Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension

BackgroundAberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH.MethodsFresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E₂) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA.ResultsMany circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E₂ strongly regulated it. E₂ decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E₂ reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E₂ and miR‐21‐5p antagonist.ConclusionsmiR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E₂ on MCT‐PH through ERβ.     

PPAR-γ配体抑制胆管癌的体内有效作用途径实验研究

目的探讨PPAR-γ(peroxisome proliferactor-activated receptor gamma,PPAR-γ)配体罗格列酮(rosiglitazone,RGZ)抑制胆管癌的体内有效作用途径。方法采用不同RGZ给药方法和途径对胆管癌细胞系QBC939荷瘤裸鼠进行干预,7d后处死,测量瘤体体积和重量,计算各组肿瘤生长抑制率。结果RGZ对胆管癌细胞有明显的增殖抑制作用,连续多次灌胃组[12mg/(kg.d)](临床途径组)抑制作用明显,而单次灌胃组、单次与多次腹腔灌注组抑制作用均不明显。统计学处理,连续多次灌胃组与其他给药途径比较,P<0.05,有统计学意义;而其他方法与对照组比较,P>0.05,无统计学意义。结论连续多次给药法是PPAR-γ配体RGZ对胆管癌有效抑制作用方法之一。     

Comparative analysis of transient receptor potential channel 5 opposite strand-induced gene expression patterns and protein-protein interactions in triple-negative breast cancer

In patients with triple-negative breast cancer (TNBC), high tumour mutation burden and aberrant oncogene expression profiles are some of the causes of poor prognosis. Therefore, it is necessary to identify aberrantly expressed oncogenes, since they have the potential to serve as therapeutic targets. Transient receptor potential channel 5 opposite strand (TRPC5OS) has been previously shown to function as a novel tumour inducer. However, the underlying mechanism of TRPC5OS function in TNBC remain to be elucidated. Therefore, in the present study TRPC5OS expression was first measured in tissue samples of patients with TNBC and a panel of breast cancer cell lines (ZR-75-1, MDA-MB-453, SK-BR-3, JIMT-1, BT474 and HCC1937) by using qRT-PCR and Western blotting. Subsequently, the possible effects of TRPC5OS on MDA-MB-231 cells proliferation were determined using Cell Counting Kit-8 and 5-Ethynyl-2′-deoxyuridine assays after Lentiviral transfection of MDA-MB-231. In addition, potential interaction partners of TRPC5OS were explored using liquid chromatography-mass spectrometry (LC-MS)/MS. Gene expression patterns following TRPC5OS overexpression were also detected in MDA-MB-231 cells by using High-throughput sequencing. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis were then used to systematically verify the potential interactions among the TRPC5OS-regulated genes. The potential relationship between TRPC5OS-interacting proteins and gene expression patterns were studied using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis. TRPC5OS expression was found to be significantly higher in TNBC tumour tissues and breast cancer cell lines compared with luminal tumour tissues and ZR-75-1. In addition, the overexpression of TRPC5OS significantly increased cell proliferation. High-throughput sequencing results revealed that 5,256 genes exhibited differential expression following TRPC5OS overexpression, including 3,269 upregulated genes and 1,987 downregulated genes. GO analysis results indicated that the functions of these differentially expressed genes were enriched in the categories of ‘cell division’ and ‘cell proliferation’ regulation. KEGG analysis showed that the TRPC5OS-regulated genes were associated with processes of ‘homologous recombination’ and ‘TNF signalling pathways’. Subsequently, 17 TRPC5OS-interacting proteins were found using LC-MS/MS and STRING analysis. The most important protein among interacting proteins was ENO1 which was associated with glycolysis and regulated proliferation of cancer. In summary, data from the present study suggest that TRPC5OS overexpression can increase TNBC cell proliferation and ENO1 may be a potential target protein mediated by TRPC5OS. Therefore, TRPC5OS may serve as a novel therapeutic target for TNBC.     

Effects of Internet-Based Nutrition and Exercise Interventions on the Prevention and Treatment of Sarcopenia in the Elderly

Effective nutrition and exercise interventions may improve sarcopenia in the elderly. The purpose of our study was to investigate the effectiveness of Internet-based nutrition and exercise interventions in the elderly with sarcopenia. Participants were divided into 4 groups: control, nutrition, exercise, and comprehensive (nutrition plus exercise) groups; there was at least 50 participants in each group. Our trial lasted 12 weeks. We conducted dietary and exercise interventions through an app and collected feedback from the participants every three weeks. Information on the diet, skeletal muscle mass, and muscle function was collected before and after the interventions. The comprehensive group had higher high-quality protein intake than the control (p = 0.017) and exercise (p = 0.012) groups. After the interventions, we obtained differences in skeletal muscle mass, skeletal muscle mass/height², skeletal muscle mass/weight, muscle mass/BMI, and skeletal muscle mass/body fat percentage (p < 0.05). Changes in average daily energy and total daily protein intakes were not significantly different; however, there was an overall improvement in the intervention groups relative to baseline data. There were no changes in the average daily time of moderate physical activity. The Internet was an effective tool of nutrition intervention in the elderly with sarcopenia. The Internet-based nutrition intervention improved high-quality protein intake and skeletal muscle mass in the elderly with sarcopenia.     

Risk factors of perioperative complications and management with enhanced recovery after primary surgery in women with epithelial ovarian carcinoma in a single center

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I–IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4–5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3–5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3–5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3–5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3–5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.     

异维A酸联合左旋咪唑治疗扁平疣疗效观察

临床上常外用维甲酸类药物治疗扁平疣,但系统用药的报道较少见。笔者于2004年7月~2005年3月使用口服异维A酸(又称13-顺式维甲酸,商品名:泰尔丝,上海信谊延安药业有限公司生产)、左旋咪唑联合治疗扁平疣,取得了满意的疗效,现报道如下。1资料和方法1.1病例选择临床确诊为扁平疣的     

Recovery of complete left bundle branch block in a dilated cardiomyopathy patient after treatment with sacubitril/valsartan: A case report

Rationale:The treatment of dilated cardiomyopathy (DCM) has recently been greatly improved, especially with the widespread use of sacubitril/valsartan (ARNI) combination therapy. We know that ARNI-like drugs can significantly improve the symptoms of heart failure with reducing ejection fraction. However, clinical studies evaluating the safety and efficacy of ARNI in DCM-associated arrhythmia are limited, and whether individuals with arrhythmia would benefit from ARNI remains controversial. In this case, we report a patient with complete left bundle branch block (CLBBB) associated with DCM whose CLBBB returned to normal after treatment with ARNI.Patient concerns:A 38-year-old man was admitted to the hospital for 20 days for idiopathic paroxysmal dyspnea. He presented with exacerbated dyspnea symptoms at night, accompanied by cough and sputum.Diagnosis:Physical examination revealed a grade 4/6 systolic murmur could be heard in the apical area of the heart and mild edema was present in both lower limbs. Laboratory examination found that the B-type natriuretic peptide was significantly increased. Echocardiography indicated left atrial internal diameter, right ventricular internal diameter, and left ventricular diastolic diameter were enlarged and ejection fraction was significantly decreased. Besides, the pulsation of the wall was diffusely attenuated. Electrocardiogram was suggestive of tachycardia and CLBBB. A diagnosis of DCM with CLBBB was considered based on a comprehensive evaluation of the physical examination, laboratory examination, echocardiography and electrocardiogram.Interventions:The patient was treated with ARNI at a dose of 50 mg (twice a day) at first, gradually increasing to the target dose (200 mg, twice a day) in the following 9 months as shown in Table ​Table1,1, along with metoprolol 25 mg (once a day [qd]), diuretics 20 mg (qd), and aldosterone 20 mg (qd).Table 1Specific medications used in treatment.

Oral Health,Diabetes, and Inflammation: Effects of Oral Hygiene Behaviour

IntroductionThe aim of this research was to assess the association between inflammation and oral health and diabetes, as well as the mediating role of oral hygiene practice in this association.MethodsData were from the 2009–2010 National Health and Nutrition Examination Survey. The analytical sample consisted of 2,191 respondents aged 50 and older. Poor oral health was clinically defined by significant tooth loss (STL) and periodontal disease (PD). Diabetes mellitus (DM) was determined by glycemic levels. The outcome variable was serum C-reactive protein (CRP) level, dichotomised as ≥1 mg/dL (elevated CRP) vs <1 mg/dL (not elevated CRP). Two path models, one using STL and DM as the independent variable, the other using PD and DM as the independent variable, were estimated to assess the direct effects of having poor oral health and DM on elevated CRP and the mediating effects of dental flossing.ResultsIn path model 1, individuals having both STL and DM (adjusted odds ratio [AOR], 1.92; 95% confidence interval [CI], 1.30–2.82) or having STL alone (AOR, 2.30; 95% CI, 1.68–3.15) were more likely to have elevated CRP than those with neither STL nor DM; dental flossing (AOR, 0.92, 95% CI, 0.88–0.96) was associated with lower risk of elevated CRP. In path model 2, no significant association was found between having both PD and DM and elevated CRP; dental flossing (AOR, 0.91; 95% CI:, 0.86–0.94) was associated with lower risk of elevated CRP.ConclusionsFindings from this study highlight the importance of improving oral health and oral hygiene practice to mitigate inflammation. Further research is needed to assess the longer-term effects of reducing inflammation.Key words: Tooth loss, Periodontal disease, Diabetes, Inflammation     

Research Progress on Postoperative Minimal/Molecular Residual Disease Detection in Lung Cancer

Lung cancer is the leading cause of cancer‐related deaths worldwide. Approximately 10%–50% of patients experience relapse after radical surgery, which may be attributed to the persistence of minimal/molecular residual disease (MRD). Circulating tumor DNA (ctDNA), a common liquid biopsy approach, has been demonstrated to have significant clinical merit. In this study, we review the evidence supporting the use of ctDNA for MRD detection and discuss the potential clinical applications of postoperative MRD detection, including monitoring recurrence, guiding adjuvant treatment, and driving clinical trials in lung cancer. We will also discuss the problems that prevent the routine application of ctDNA MRD detection. Multi‐analyte methods and identification of specific genetic and molecular alterations, especially methylation, are effective detection strategies and show considerable prospects for future development. Interventional prospective studies based on ctDNA detection are needed to determine whether the application of postoperative MRD detection can improve the clinical outcomes of lung cancer patients, and the accuracy, sensitivity, specificity, and robustness of different detection methods still require optimization and refinement.     

A Damage Model of Concrete including Hysteretic Effect under Cyclic Loading

A novel damage model for concrete has been developed, which can reflect the complex hysteresis phenomena of concrete under cyclic loading, as well as other nonlinear behaviors such as stress softening, stiffness degradation, and irreversible deformation. The model cleverly transforms the complex multiaxial stress state into a uniaxial state by equivalent strain, with few computational parameters and simple mathematical expression. The uniaxial tensile and compressive stress–strain curves matching the actual characteristics are used to accommodate the high asymmetry of concrete in tension and compression, respectively. Meanwhile, an unloading path and a reloading path that can reflect the hysteresis effect under cyclic loading of concrete are established, in which the adopted expressions for the loading and unloading characteristic points do not depend on the shape of the curve. The proposed model has a concise form that can be easily implemented and also shows strong generality and flexibility. Finally, the reliability and correctness of the model are verified by comparing the numerical results with the three-point bending beam test, cyclic loading test, and a seismic damage simulation of the Koyna gravity dam.