[Characteristics and changes of cardiac injury with age in children of Duchenne muscular dystrophy: a prospective cohort study].

Objective: To explore the characteristics and changes of cardiac injury with age in Duchenne muscular dystrophy (DMD) and its clinical significance. Methods: A prospective cohort study was conducted. The 215 patients diagnosed with DMD in West China Second Hospital from January 2019 to November 2022 and aged from 6 to 18 years were enrolled. Their clinical data, myocardial injury markers, routine electrocardiogram, cardiac magnetic resonance (CMR) and echocardiography were collected. The patients were divided into five age groups: 6-<8, 8-<10, 10-<12, 12-<14 and 14-18 years of age, and matched with healthy boys respectively. Independent sample t test or Mann-Whitney U test was used to compare the clinical data and CMR indexes between DMD patients and controls in all age subgroups, and to compare the value of left ventricular ejection fraction (LVEF) measured by echocardiography and CMR in each subgroup of DMD patitents. Pearson correlation analysis or Spearman correlation analysis was used to explore the relation between the CMR indexes and age in DMD patients. Results: A total of 215 patients with DMD (all male) and 122 healthy boys were included in the study. There were 75 DMD patients and 23 controls in 6-<8 years of age group, 77 DMD and 28 controls in 8-<10 years of age group, 39 DMD and 23 controls in 10-<12 years of age group, 10 DMD and 31 controls in the 12-<14 years of age group, and 14 DMD and 17 controls in 14-18 years of age group. In the DMD patients, the older the age, the lower the levels of creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the 6-<8 years of age group, the CK level was 10 760 (7 800, 15 757) U/L, while in the group of 14-18 years of age, it was 2 369 (1 480, 6 944) U/L. As for CK-MB, it was (189±17) µg/L in the 6-<8 years of age group and (62±16) µg/L in the 14-18 years of age group. Cardiac troponin I remained unchanged in <12 years of age groups, but significantly increased in 12-<14 years of age group, reaching the highest value of 0.112 (0.006, 0.085) µg/L. In the DMD patients, the older the age, the higher the proportion of abnormal electrocardiogram (ECG). In the 6-<8 years of age group, the proportion is 29.3% (22/75), while in the 14-18 years of age group, it was 10/14. Correlation analysis showed that the left ventricular end-diastolic volume index was positively related with age (r=0.18, P=0.015), and the left ventricular stroke volume index and cardiac output index were negatively related with age (r=-0.34 and -0.31, respectively, both P<0.001). In the DMD patients, the older the age, the lower LVEF, with the LVEF decreasing to (49.3±3.1)% in the 14-18 years of age group. The LVEF of DMD cases was significantly lower than that of controls in the age subgroups of 8-<10, 10-<12, 12-<14 and 14-18 years of age groups ((57.9±5.2) % vs. (63.6±0.8)%, 60.7% (55.9%, 61.9%) vs. 63.7% (60.2%, 66.0%), 57.1% (51.8%, 63.4%) vs. 62.1 % (59.5%, 64.5)%, (49.3±3.1) % vs. (61.6±1.3)%, respectively; all P<0.01). In the DMD patients, the older the age, the higher the proportion of positive late gadolinium enhancement (LGE). In the 6-<8 years of age group, it was 22% (11/51), in the 12-<14 years of age group, it was 13/14, and in the 14-18 years of age group, all DMD showed positive LGE. The value of LVEF of DMD cases measured by echocardiography was significantly higher than that measured by CMR in 6-<8 years of age group and 8-<10 years of age group (63.2% (60.1%, 66.4%) vs. 59.1 % (55.4%, 62.9%), and (62.8±5.2) % vs. (57.9±5.2)%, all P<0.001). Conclusion: DMD patients develop cardiac injury in the early stage of the disease, and the incidence of cardiac damage gradually increases with both age and the progression of disease.

Clinical research advances of CFHR5 nephropathy: a recent review.

CFHR5 nephropathy is a type of clinical C3 glomerulopathy, which is a monogenic genetic disease caused by the internal replication of CFHR5 gene, a protein related to the complement regulatory factor H family. The disease seems to be prevalent only in people of Greek Cypriot descent. Because of the special variation of the internal replication of exon 2 and exon 3 of CFHR5 protein in the occurrence of disease, it has had a serious impact on local residents. At present, the mechanism of glomerular damage caused by CFHR5 protein mutations is still unclear. The purpose of this article is to review the clinical research advances of this disease in the past 10 years, including the study of mutant genes, the analysis of mutant proteins and the role of alternative pathways in glomerular injury. It covers the progress in diagnosis and clinical treatment of the disease and looks forward to the future development prospects of its treatment. It is hoped that the recent results will be summarized for the follow-up in-depth study of CFHR5 nephropathy.

The effects of computer-aided cognitive rehabilitation combined with virtual reality technology on event-related potential P300 and cognitive function of patients with cognitive impairment after stroke.

OBJECTIVE: The aim of this study was to explore the effects of computer-aided cognitive rehabilitation (CACR) combined with virtual reality (VR) technology on event-related potential P300 and cognitive function in patients with cognitive impairment after stroke. PATIENTS AND METHODS: Clinical data from 94 patients with post-stroke cognitive impairment, admitted to our hospital from January 2020 to March 2023, were retrospectively analyzed. Of them, 45 patients received routine rehabilitation training (Control group), and 49 patients received CACR combined with VR technology (Observation group). Cognitive rehabilitation status, event-related potential P300 examination status, biochemical indices levels, and daily living activity scores of the two groups were evaluated and compared. RESULTS: After treatment, cognitive function significantly improved in the Observation group compared to the Control group. The amplitude of P300 in the Observation group was significantly higher, and the latency was significantly lower compared to the Control group. The levels of brain-derived neurotrophic factor (BDNF) in the Observation group were significantly higher (p<0.05), while the levels of cystatin C (Cys-C) and neuron-specific enolase (NSE) were significantly lower than those in the Control group (p<0.05 each). Patients in the Observation group demonstrated a significantly higher ability to perform daily living activities compared to the Control group (p<0.05). CONCLUSIONS: Compared with conventional rehabilitation training, the combination of CACR and VR technology in the treatment of stroke-induced cognitive impairment is more effective in improving patients' cognitive function, regulating BDNF, Cys-C, and NSE levels, and enhancing patients' ability to perform daily living activities.

[Clinical study on early predictors of concurrent bile duct injury following TACE in patients with liver cancer].

Objective: To explore the predictive factors of concurrent bile duct injury following transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 483 HCC patients in relation to TACE postoperative complications. A total of 21 cases of bile duct injury were observed following the TACE procedure. Laboratory data, imaging data, and clinically relevant medical histories were recorded before and after one week following the TACE procedure and follow-up. The χ (2) test, or Fisher's exact probability method, was used for categorical variables. The mean of the two samples was compared using a paired t-test or Wilcoxon rank sum test. The comparison of multiple mean values was conducted using an analysis of variance. Results: Twenty-one cases with bile duct injury had intrahepatic bile duct dilatation, bile tumors, hilar biliary duct stenoses, and other manifestations. 14.3% (3/21) of patients showed linear high-density shadows along the bile duct on a plain CT scan, while 76.2% (16/21) of patients had ALP > 200 U/L one week following TACE procedure, and bile duct injury occurred in later follow-up. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased in all patients following TACE procedure (t = -2.721, P = 0.014; t = -2.674, P = 0.015; t = -3.079, P = 0.006; t = -3.377, P = 0.003, respectively). Conclusion: The deposition of iodized oil around the bile duct on plain CT scan presentation or the continuous increase of ALP (> 200 U/L) one week following TACE procedure has a certain predictive value for the later bile duct injury.

[The research of liver failure in Banna miniature pigs caused by amanita exitialis].

Objective: To explore the characteristics of Banna miniature pig liver failure induced by amanita exitialis. Methods: From September to October 2020, a reverse high performance liquid chromatography (RP-HPLC) method was used to determine the toxin content of amanita exitialis solution, and 2.0 mg/kg amanita exitialis solution (α-amanitins+ß-amanitins) was administered orally to Banna miniature pigs. Toxic symptoms, blood biochemical indexes and histopathological changes of liver, heart and kidney were observed at each time point. Results: All Banna miniature pigs died within 76 h of exposure, and different degrees of digestive tract symptoms such as nausea, vomiting and diarrhea appeared between 6 and 36 h. The biochemical indexes of alanine aminotransferase, aspartate aminotransferase, total bilirubin, lactate dehydrogenase, myoglobin, creatine kinase isoenzyme, blood urea nitrogen and creatinine increased significantly at 52 h after exposure, and the differences were statistically significant compared with 0 h (P<0.05). The bleeding of liver and heart was obvious under macroscopic and microscopic observation, hepatocyte necrosis, renal tubule epithelial cell swelling. Conclusion: Large dose of amanita exitialis can cause acute liver failure of Banna miniature pigs, which is in line with the pathophysiological characteristics of acute liver failure, and lays a foundation for further research on the toxic mechanism and detoxification drugs of amanita exitialis induced liver failure.

[Progress of clinical application in extraocular muscle transposition].

Extraocular muscle transposition, including adjacent extraocular muscle transposition and transmuscular transposition, is often used to correct different types of strabismus, especially special forms of strabismus, instead of conventional surgery, which could not correct large-angle strabismus or improve the eye movement function. With the popularity of individualized surgical schemes, various types of extraocular muscle transposition procedures are available. In this article, the research progress of extraocular muscle transposition in the treatment of strabismus is reviewed, and the indications, advantages and disadvantages of various extraocular muscle transposition procedures are discussed, so as to provide reference for clinicians to further understand and reasonably carry out the treatment.

Impact of prior extrapulmonary cancer on survival after lung cancer: a systematic review and meta-analysis.

OBJECTIVE: This review aimed to examine the impact of previous extrapulmonary malignancies on the overall survival (OS) of lung cancer patients. MATERIALS AND METHODS: The online databases of PubMed, Embase, Scopus, and Web of Science were explored for studies published up to 22nd December 2022 and comparing outcomes of first lung cancer vs. second primary lung cancer with a history of previous extrapulmonary malignancy. Studies were to report adjusted data on OS. Meta-analysis was performed in a random-effects model. RESULTS: Nine retrospective studies were eligible. A total of 267,892 lung cancer patients with prior extrapulmonary malignancy and 1,351,245 primary lung cancer patients were analyzed in the studies. Meta-analysis of all studies showed that prior extrapulmonary malignancy results in poor OS in lung cancer patients as compared to those with no history of such cancer (HR: 1.27 95% CI: 1.07, 1.50 I2=83%). The results did not change on sensitivity analysis. No publication bias was noted. CONCLUSIONS: The result of this meta-analysis indicates that a history of prior extrapulmonary malignancy results in poor OS in patients with lung cancer. Caution is needed in the interpretation of the results owing to high interstudy heterogeneity. Further research is needed to assess how factors like the type of extrapulmonary malignancy, time interval of diagnosis, cancer stage, and treatment modality impact this relationship.

[Internal carotid artery embolization in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma: a single-center retrospective study].

Objective: To evaluate the efficiency of internal carotid artery (ICA) embolization technology in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma (rNPC) invading the ICA. Methods: From January 2016 to March 2021, 83 patients with rNPC who invaded the ICA and underwent endoscopic extended nasopharyngectomy were retrospectively collected from the Eye & ENT Hospital in Fudan University, including 60 males and 23 females. The age of the patients ranged from 27 to 77 years. The standard of ICA invasion was that the distance from the lesion to the ICA on enhanced MRI was ≤ 1.8 mm. The clinical characteristics, ICA management strategy and survival prognosis of patients were analyzed, and the effectiveness of ICA embolization was evaluated. Kaplan-Meier method was used to calculate the survival rate and Log-rank test was used to compare the difference. Results: In 83 patients with rNPC, there were 13 patients with rT2, 38 patients with rT3, 32 patients with rT4, and 16 patients had lymph node metastasis. A total of 37 patients (44.6%) underwent ICA coil embolization before surgery, of which 2 cases underwent external carotid-middle cerebral artery artery bypass grafting and ICA embolization due to positive balloon occlusion test (BOT). Patients with positive surgical margin accounted for 24.1% (20/83). Among them, patients with rT4 and patients without ICA embolization had a higher positive rate of surgical margin (P value was 0.001, 0.043, respectively). The 3-year overall survival (OS) and progression free survival (PFS) rate of all patients was 46.5% and 26.7%, respectively. In addition, the 3-year OS and PFS of patients with ICA embolization was significantly higher than those without ICA embolization, respectively (69.1% vs 27.8%, P=0.003; 33.9% vs 18.9%, P=0.018). Only 2 patients (2/37, 5.4%) had cerebral infarction complications after coil embolization of the affected ICA due to negative BOT. Conclusion: Preoperative ICA embolization can be used to treat patients with rNPC invading the ICA, improve the total removal rate and survival rate of patients, which is an effective salvage treatment.

[Assessment of disease burden related to non-optimal temperature across China].

Objective: To estimate the excess mortality attributed to non-optimal ambient temperature in China. Methods: Mortality data and meteorological data from 239 counties in 2013-2018 were collected to simulate the quantitative exposure-response relationship between the temperature and mortality using distributed lag nonlinear models for time series studies. Then the number of non-optimal-temperature-related excess deaths was assessed and the spatial distribution was explored. Results: There were averagely (12±8) cases of all-cause deaths per day per county from 2013 to 2018. The average daily temperature was (14.98±10.31)℃, and the daily average relative humidity was (68.79±17.25)%. The daily average O3 concentration was (58.95±34.96) µg/m³, and the daily average PM2.5 concentration was (54.97±45.56) µg/m³. The exposure-response curve between daily average temperature and all-cause mortality showed a "U" shape, and the theoretical minimum mortality temperature (MMT) corresponding to the minimum number of deaths was 21.60 ℃. When the temperature was higher than MMT, the heat-related health effect increased with the temperature rising. When the temperature was lower than MMT, the cold-related effect increased with the temperature decreasing. The attributable fraction (AF) of death caused by non-optimal temperature was 8.76% (95%CI: 8.07%-9.10%), and the AF of death caused by cold effect and heat effect was 7.21% (95%CI: 6.51%-7.57%) and 1.55% (95%CI: 1.46%-1.61%), respectively. The excess deaths from non-optimal temperature in 2015 were 519 122, 72.98% of which could be attributed to low temperature. The number of excess deaths caused by non-optimal temperature mainly showed a decreasing trend from the east to the west, relatively high (117 522) in East China. Heilongjiang Province (in Northeast China) had the most excess deaths (26 924) caused by low temperature, and Guangdong Province(in South China) had the most excess deaths (27 763) caused by high temperature. Conclusion: The non-optimal temperature has a significant impact on health and causes a considerable burden of disease in China with obvious spatial heterogeneity.

Influence of light supplement on duck sternal calcification from integrated analysis of metabolome and transcriptome.

Calcification of bones is the critical process of bone development in birds, which is very important for sustaining the normal biological function of bones. Light is one of the vital factors affecting bone development, but whether light intensity affects bone calcification and the underlying mechanism is still unknown. In this study, we used duck sternum as a model to analyze the calcification process under different light regimes. In addition, the underlying mechanism was also illustrated by integrating metabolomics and transcriptome methods. The experiment lasted from 14 to 51 d of duck age. The control group (LP1) kept light intensity 2 lx during the whole experiment. The two light supplement groups (LP2, LP3) were given light with the intensity of 70 lx at different time (14-29 d for LP2, 14-43 d for LP3). Samples were collected at 52 d of duck age. Sternal calcification analysis showed no significant difference in proportion of area of cartilage matrix and trabecular bone in keel tissue among the 3 groups, but the degree of keel calcification in LP3 was higher than in the other 2 groups. Serum metabolomics showed 32 and 28 differentially accumulated metabolites (DAMs) in the 2 comparison groups, LP1 vs. LP3 and LP1 vs. LP2, respectively. Carboxylic acids and derivatives were the most abundant among the DAMs. Sternal transcriptome analysis showed 231 differentially expressed genes (DEGs), including 177 upregulated genes and 54 downregulated genes in group LP1 vs. LP3, and 22 DEGs in group LP1 vs. LP2. Protein-protein interaction (PPI) network analysis on DEGs between LP1 and LP3 showed that genes BTRC, GLI1, BMP4, and FOS were in the core position of the interaction network, and are also involved in bone development. KEGG pathway analysis of DAMs and DEGs showed that differences in Hedgehog signaling pathway, MAPK signaling pathway, apoptosis, energy metabolism, and amino acid metabolism following light treatment seem likely to have contributed to the observed difference in calcification of duck sternum.

[Survival analysis of different kinds of tyrosine kinase inhibitors in the treatment of patients with epidermal growth factor receptor mutated non-small cell lung cancer and leptomeningeal metastasis].

Objective: To explore the prognosis of patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC) treated with different kinds of tyrosine kinase inhibitors (TKIs). Methods: From January 2016 to June 2021, the clinicopathological data of 70 patients confirmed by histologically or cytologically EGFRm LM who received different types of TKIs in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. According to treatment patterns, patients were divided into the first-and second-generation EGFR-TKIs treatment group and the third-generation EGFR-TKIs treatment group [Osimertinib 80 mg once a day], and the prognosis and prognostic factors (with Cox proportional hazards model) of patients in different treatment group were assessed. The next-generation sequencing (NGS) of paired samples of cerebrospinal fluid (CSF) and plasma from 64 patients at the time of LM diagnosis was performed simultaneously. Results: There were 20 males and 50 females in 70 EGFRm NSCLC patients with LM. The age ranged from 35 to 69 years, with a median age of 56 years. A total of 24 patients received the first-and second-generation EGFR-TKIs treatment, and 46 received the third-generation EGFR-TKIs treatment. Twenty-four patients developed disease progression on the first-and second EGFR-TKIs treatments, followed by treatment with the third-generation EGFR-TKIs (Osimertinib) in 12 cases, chemotherapy or anti-angiogenesis therapy in 4 cases, and the optimal supportive treatment in 8 cases. Among the 70 patients, 18 had partial response (PR), 48 had stable disease (SD), and 4 had progressive disease (PD). The objective response rate (ORR) and disease control rate (DCR) were 26% (18/70) and 94% (66/70), respectively. The median follow-up time was 16.5 months. The median progression-free survival (PFS) was 5.3 months(95%CI: 2.8-7.8)in the first-and second-generation EGFR-TKIs and 10.8 months (95%CI: 7.9-13.6) in the third-generation EGFR-TKIs, and the difference was statistically significant (P=0.019). The median overall survival (OS) was 14.9 months (95%CI: 9.7-20.0) and 15.7 months (95%CI: 13.3-18.1) in the two groups, respectively, but no statistical differences was observed (P=0.713). Univariate analysis showed that the PFS of patients with EGFRm LM were related to gender and different types of EGFR-TKIs (P˂0.05). Multivariate analysis demonstrated that male (HR=2.30, 95%CI: 1.31-4.03, P=0.004) and the first-and second-generation EGFR-TKIs (HR=2.03, 95%CI: 1.20-3.41, P=0.008) were independent risk factors for PFS in patients with EGFRm LM. The EGFR mutation was detected in 61 (95%) CSF and in 27 (42%) plasma samples. Conclusion: In EGFRm NSCLC patients with LM, the dose of Osimertinib 80 mg (once a day) has a significant PFS benefit compared with the first-and second-generation EGFR-TKIs.

[Preliminary effects of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma].

Objective: To analyze the efficacy and safety of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma. Methods: Clinical data of 50 patients with advanced renal cell carcinoma who received axitinib combined with toripalimab were retrospectively collected from the database of Peking University Cancer Hospital. ORR, DCR, PFS, and OS were analyzed. Results: Among the 50 patients, 37 were males; median age was 56 (22-73) years; 38 were pathologically diagnosed as clear cell renal cell carcinoma and 12 were non-clear cell carcinoma. Common metastatic sites included lung, bone, lymph node, liver, and so on. 90% of the patients had received at least one-line of systemic therapy. With a median follow-up time of 11.9 months (0.8-24), 27 of the 50 patients are still on treatment, ORR was 34%, DCR was 86%, median PFS was 13.1 months (95%CI 5.8-20.4), and median OS has not yet reached. One-year OS rate was 84.6%. Common adverse reactions were proteinuria, diarrhea, hypertension, abnormal thyroid function, elevated transaminase, and hand-foot syndrome. Most adverse events were grade 1-2. Conclusion: Toripalimab combined with axitinib was efficient in the treatment of advanced renal cell carcinoma, and had manageable adverse reactions.

[Gender differences in cardiovascular risk factors in patients with acute myocardial infarction in China].

Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.

Theoretically exploring selective-binding mechanisms of BRD4 through integrative computational approaches.

The origin of cancer is related to the dysregulation of multiple signal pathways and of physiological processes. Bromodomain-containing protein 4 (BRD4) has become an attractive target for the development of anticancer and anti-inflammatory agents since it can epigenetically regulate the transcription of growth-promoting genes. The synthesized BRD4 inhibitors with new chemical structures can reduce the drug resistance, but their binding modes and the inhibitory mechanism remain unclear. Here, we initially constructed robust QSAR models based on 68 reported tetrahydropteridin analogues using topomer CoMFA and HQSAR. On the basis of QSAR results, we designed 16 novel tetrahydropteridin analogues with modified structures and carried out docking studies. Instead of significant hydrogen bondings with amino acid residue Asn140 as reported in previous research, the molecular docking modelling suggested a novel docking pose that involves the amino acid residues (Trp81, Pro82, Val87, Leu92, Leu94, Cys136, Asp144, and Ile146) at the active site of BRD4. The MD simulations, free energy calculations, and residual energy contributions all indicate that hydrophobic interactions are decisive factors affecting bindings between inhibitors and BRD4. The current study provides new insights that can aid the discovery of BRD4 inhibitors with enhanced anti-cancer ability.

Integrated microRNA-mRNA analysis reveals the roles of microRNAs in the muscle fat metabolism of Yanbian cattle.

Fat deposition is an important economic trait in farm animals. However, it is difficult to genetically improve intramuscular fat deposition via trait-based cattle breeding. The main objectives of this study were to analyze the factors about beef flavor, and to detect functional microRNA (miRNA, miR) associated with intramuscular fat deposition in Yanbian cattle. Longissimus dorsi samples from six steers were separated into high- and low-fat groups (n = 3 each) based on the marbling score, and transcriptomic analysis was performed using miRNA sequencing. A total of 33 miRNAs and 38 genes were found to be differentially expressed in the high- and low-fat groups. Quantitative real-time polymerase chain reaction was performed to validate the sequencing results. Integrated miRNA-mRNA analysis revealed that miRNA-associated target genes were primarily associated with skeletal muscle development. However, some of the miRNAs (miR-424 etc.) and genes (ATF3 etc.) were also associated with fat metabolism. A targeted relationship between miR-22-3p and the WFIKKN2 gene and its involvement in adipocyte differentiation were confirmed experimentally. The study findings may provide potential candidate molecular targets for the selection of cattle with improved meat quality.

Quantification of peak blood flow velocity at the cardiac valve and great thoracic vessels by four-dimensional flow and two-dimensional phase-contrast MRI compared with echocardiography: a systematic review and meta-analysis.

AIM: To objectively examine the agreement and correlation between four-dimensional (4D) flow magnetic resonance imaging (MRI) and traditional two-dimensional (2D) phase-contrast (PC) MRI with the reference standard of Doppler echocardiography for measuring peak blood velocity at the cardiac valve and great arteries, and to assess if 4D flow MRI offers an advantage over the traditional 2D method. MATERIALS AND METHODS: The literature was searched systematically for studies that evaluate the degree of correlation and agreement between 4D flow MRI or 2D PC MRI and Doppler retrieved from PubMed, EMBASE, and the Cochrane Library. A meta-analysis was conducted to determine the peak velocity pooled bias with 95% limits of agreement (LoA) and correlation coefficient (r) for 4D flow MRI and 2D PC MRI compared with Doppler. RESULTS: Ten studies that compared 4D flow MRI with Doppler and 12 studies that compared 2D PC MRI with Doppler were included. 4D flow MRI showed an underestimation with bias and 95% LoA of -0.09 (-0.41, 0.24) m/s (p=0.079) while 2D PC MRI showed a poorer agreement with a bias and 95% LoA of -0.25 (-0.53, 0.03), p=0.596. 4D flow MRI and 2D PC MRI showed a strong correlation with R=0.80 (95% CI 0.75, 0.84; p<0.001) and R=0.83 (95% CI 0.79, 0.87; p<0.001), respectively. CONCLUSION: In this meta-analysis, 4D flow MRI provides improved assessment of peak velocity when compared with traditional 2D PC MRI. 4D flow MRI can be considered an important complement or substitute to Doppler echocardiography for peak velocity assessment.

Effect of different types of sugar on gut physiology and microbiota in overfed goose.

To explored the difference of goose fatty liver formation induced-by different types of sugar from the intestinal physiology and the gut microflora, an integrated analysis of intestinal physiology and gut microbiota metagenomes was performed using samples collected from the geese including the normal-feeding geese and the overfed geese which were overfed with maize flour or overfeeding dietary supplementation with 10% sugar (glucose, fructose or sucrose, respectively), respectively. The results showed that the foie gras weight of the fructose group and the sucrose group was heavier (P < 0.05) than other groups. Compared with the control group, the ileum weight was significantly higher (P < 0.01), and the cecum weight was significantly lower in the sugar treatment groups (P < 0.001). Compared with the control group, the ratio of villi height to crypt depth in the fructose group was the highest in jejunum (P < 0.05); the trypsin activity of the ileum was higher in the fructose group and the sucrose group (P < 0.05). At the phylum level, Firmicutes, Proteobacteria and Bacteroidetes were the main intestinal flora of geese; and the abundance of Firmicutes in the jejunum was higher in the sugar treatment groups than that of the maize flour group. At the genus level, the abundance of Lactobacillus in the jejunum was higher (P < 0.05) in the sugar treatment groups than that of the maize flour group. In conclusion, forced-feeding diet supplementation with sugar induced stronger digestion and absorption capacity, increased the abundance of Firmicutes and Bacteroidetes and the abundance of Lactobacillus (especially fructose and sucrose) in the gut. So, the fructose and sucrose had higher induction on hepatic steatosis in goose fatty liver formation.

Myocardial motion-corrected phase-sensitive inversion recovery late gadolinium enhancement in free breathing paediatric patients: a comparison with single-shot coherent gradient echo ("TrueFISP") phase-sensitive inversion recovery.

AIM: To investigate the value of motion-corrected (MOCO) phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) compared with single-shot balanced steady-state gradient echo ("TrueFISP", Siemens) PSIR in free breathing paediatric patients. MATERIALS AND METHODS: In this retrospective study, 238 paediatric patients underwent clinical contrast-enhanced cardiovascular magnetic resonance imaging (CMRI). Both the single-shot TrueFISP PSIR and MOCO PSIR sequences were performed on each child. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Two radiologists rated the quality of the images on a scale of 1-5 (1 = poor, 5 = very good). Bland-Altman, linear regression, and intraclass correlation coefficient were used to compared the extent of LGE of the single-shot TrueFISP PSIR and MOCO PSIR. Imaging artefacts were described and compared. RESULTS: Children ranged in age from 60 days to 17 years with an average age of 8.1 ± 3.8 years. MOCO PSIR had higher SNR and CNR than the single-shot TrueFISP PSIR (p<0.001). Mean quality ratings for short-axis imaging were 4 (interquartile range, 3-4) for single-shot TrueFISP PSIR and 4 (interquartile range, 4-5) for MOCO PSIR (p<0.001). The scan time was faster for single-shot TrueFISP PSIR than for MOCO PSIR. The myocardial LGE results were similar with high agreement between the single-shot TrueFISP PSIR and MOCO PSIR (ICC = 0.955-0.986). CONCLUSION: The MOCO PSIR sequence is feasible in children. MOCO PSIR is robust at high heart rates and can be performed without breath-holding with higher image-quality ratings than the single-shot TrueFISP PSIR.

Comparison of overfeeding effects on gut physiology and microbiota in two goose breeds.

To have a better understanding of how the "gut-liver axis" mediates the lipid deposition in the liver, a comparison of overfeeding influence on intestine physiology and microbiota between Gang Goose and Tianfu Meat Goose was performed in this study. After force-feeding, compared with Gang Goose, Tianfu Meat Goose had better fat storage capacity in liver (397.94 vs. 166.54 for foie gras weight (g), P < 0.05; 6.37 vs. 2.92% for the ratio of liver to body, P < 0.05; 60.01 vs. 46.64% for fat content, P < 0.05) and the less subcutaneous adipose tissue weight (1240.96 g vs. 1440.46 g, P < 0.05). After force-feeding, the digestion-absorption capacity of Tianfu Meat Goose was higher than that of Gang Goose (5.56 vs. 3.64 and 4.63 vs. 3.68 for the ratio of villus height to crypt depth in duodenum and ileum, respectively, P < 0.05; 1394.96 vs. 782.59 and 1314.76 vs. 766.17 for the invertase activity (U/mg-prot), in duodenum and ileum, respectively, P < 0.05; 6038.36 vs. 3088.29 and 4645.29 vs. 3927.61 for the activity of maltase (U/mg-prot), in duodenum and ileum, respectively, P < 0.05). Force-feeding decreased the gene expression of Escherichia coli in the ileum of Tianfu Meat Goose; force-feeding increased the number of gut microbiota Enterobacterial Repetitive Intergenic Consensus-Polymerase Chain Reaction band in Tianfu Meat Goose and decreased the number in Gang Goose. In conclusion, compared with Gang Goose, the lipid deposition in the liver and the intestine digestion-absorption capacity and stability were higher in Tianfu Meat Goose. Thereby, Tianfu Meat Goose is the better breed for foie gras production for prolonged force-feeding; Gang Goose possesses better fat storage capacity in subcutaneous adipose tissue. However, Gang Goose has lower gut stability responding to force-feeding, so Gang Goose is suited to force-feeding in a short time to gain the body weight and subcutaneous fat as an overfed duck for roast duck.

Late gadolinium enhancement is a risk factor for major adverse cardiac events in unrecognised myocardial infarction without apparent symptoms: a meta-analysis.

AIM: To assess the prognostic role of unrecognised myocardial infarction (UMI) detected at late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRII). MATERIALS AND METHODS: Electronic databases including PubMed, EMBASE, Medline, and Cochrane were searched systematically for studies exploring the predictive value of UMI detected by LGE-CMRI for major adverse cardiac events (MACEs) and all-cause mortality in patients without apparent symptoms. Pooled hazard ratios (HRs) along with their 95% confidence intervals (CIs) were obtained from a random-effects model. Subgroup analyses were performed according to the different participants and outcomes. RESULTS: Eight studies (2,009 participants) were identified comprising 442 patients with UMI detected at LGE-CMRI and 1,567 without UMI. The presence of UMI on LGE was associated with a significantly increased risk for MACEs (HRs: 3.44, 95% CI: 2.06 to 5.75; p<0.001) and all-cause mortality (HRs: 2.43, 95% CI: 1.00 to 5.87; p=0.05). In the subgroup analysis, the presence of UMI on LGE remained significantly associated with the risk of MACEs in patients with suspected coronary artery disease (HRs: 3.82, 95% CI: 2.49 to 5.85; p<0.01) and diabetes mellitus (HRs: 4.97, 95% CI: 3.02 to 8.18; p<0.01). CONCLUSION: The presence of UMI detected by LGE-CMRI is associated with an increased risk of MACEs and all-cause mortality in patients without symptoms. LGE-CMRI could provide important prognostic information and guide risk stratification in patients with UMI.