Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

OBJECTIVE To analyze the characteristics and influencing factors of patient deaths caused by non-ionic iodine contrast media and provide recommendations for safe medication， thereby providing references for clinical application. METHODS Reports of fatal cases associated with non-ionic iodine contrast media were retrieved from databases including CNKI， Wanfang， VIP， PubMed， Cochrane Library， Web of Science， Embase， and SpringerLink. Statistical analysis was performed to examine the characteristics and influencing factors of these fatalities. RESULTS A total of 43 deaths caused by non-ionic iodine contrast media were retrieved， including 21 males （48.84%） and 22 females （51.16%）. The majority of deaths occurred in 32 patients aged 51-85 years old （74.42%）. The original diseases were mostly cardiovascular and cerebrovascular diseases （30.23%） and digestive system diseases （30.23%）， and only 2 cases had a clear allergy history （4.65%）. Among the lethal drugs， iohexol （37.21%） and iopromide （25.58%） accounted for the highest proportions. The main causes of death were anaphylactic shock （51.16%）， cardiac arrest （11.63%）， and pulmonary edema （11.63%）； 48.84% of the patients’ ADR occurred within 30 minutes， and 62.79% of the patients died on the first day. It mainly involved the circulatory system， nervous system and respiratory system， and the main manifestations were breathing difficulties， low or undetectable blood pressure， vomiting， etc. CONCLUSIONS The lethal drugs of non-ionic iodine contrast media are mainly iohexol and iopromide. The adverse reactions occur quickly. Clinically， it is necessary to focus on monitoring the vital signs within 30 minutes after medication， and timely treatment of symptoms such as dyspnea and abnormal blood pressure to reduce the risk of death.

Stroke has diverse clinical manifestations and complex causes, characterized by high incidence, high disability rate, high recurrence rate, high mortality rate, and high economic burden. Currently, conventional clinical diagnostic and treatment methods face challenges such as difficulty in predicting disease and prognosis, low diagnostic accuracy, and slow treatment due to limitations in manpower and time. With the in-depth research in artificial intelligence and its application in the medical field, machine learning models can not only predict and diagnose stroke more accurately but also identify risk factors and determine high-risk populations. This paper reviews the current research status of machine learning algorithms, the identification of stroke risk factors, common machine learning algorithms for stroke prediction, and the effectiveness of these algorithms in stroke risk prediction. Findings from this paper will help provide a scientific basis for the early identification of high-risk populations, the adoption of effective preventive measures, and the formulation of precise treatment plans.

Objective To explore the effectiveness of high-definition diffusion weighted imaging(DWI)sequence combined with T1 WI-fat suppression(FS)dynamic contrast enhancement(DCE)sequence for preoperative T-stage of rectal cancer by using 3.0T MRI standardized scanning.Methods A retrospective analysis was conducted on MRI images of 57 patients with rectal cancer confirmed by pathology.Before surgery,the patients underwent 3.0T MRI standardized rectal cancer scan methods,including routine sequence,high-definition DWI sequence,and T1 WI-FS DCE sequence,etc.Then two experienced physicians evaluated the T-stage of preoperative rectal cancer through high-definition DWI(transverse and sagittal sections)and T1 WI-FS DCE sequences in the double-blind method.Using the postoperative pathological results of rectal cancer as the"gold standard",two sequences were combined to evaluate the accuracy,sensitivity,and specificity of rectal cancer T-stage.Results Among the 57 cases,there were 9 cases of upper rectal cancer,39 cases of middle rectal cancer,and 9 cases of lower rectal cancer.The accuracy rates of preoperative T-stage diagnosis for rectal cancer by two evaluator were both 85.7％(6/7)in T1 stage,88.2％(15/17)and 94.1％(16/17)in T2 stage,96.9％(31/32)and 93.8％(30/32)in T3 stage,and both 100.0％(1/1)in T4 stage.For evaluator 1,the sensitivity and specificity of the rectal cancer T-stage diagnosis were 96.1％and 83.3％,and for evaluator 2 were 94.1％and 83.3％,respectively.For rectal cancer MRI diagnosis,the accuracy rates and sensitivity were higher when combining the high-definition DWI sequence and T1 WI-FS DCE sequence,compared with a single high-definition DWI sequence or T1 WI-FS DCE sequence,and the difference was statistically significant.The average preoperative apparent diffusion coefficient(ADC)value of rectal cancer was compared between the corresponding postoperative pathological T1 to T4 stage groups,and the difference was statistically significant.Conclusion The combination of high-definition DWI sequence and T1 WI-FS DCE sequence improves the accuracy of rectal cancer T-stage,providing assistance for personalized clinical treatment.

Objective:To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN).Methods:Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed.Results:(1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment.Conclusions:PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.

Objective To understand the genotypes of hepatitis C virus (HCV) circulating in intravenous drug users (IDUs) in Pudong new district,Shanghai,and explore the population growth and selection pressure of the HCV strains isolated.Methods A total of 200 serum specimens sampled from IDUs in local methadone maintenance treatment clinic in Pudong were used for amplification of a HCV NS5B 377-nt partial sequence.Mean evolutionary rate and effective number of infections were estimated based on the 377-nt partial sequences of the HCV strains isolated from IDUs and isolated contemporarily from local voluntary blood donors,men who have sex with men and reported hepatitis C cases by using BEAST software.Selection pressure sites were identified with online Datamonkey software for subsequent comparison with direct-acting antiviral (DAA) drug binding sites.Results A total of 39 (19.5％) serum specimens were positive for HCV RNA.The genotypes were determined based on the HCV NS5B 377-nt partial sequences as follows:subtype 3a (n=14),3b (n=13),lb (n=7),6a (n=4) and 6n (n=1).The partial sequences of the HCV strains isolated in IDUs shared high homology with the sequences of the HCV strains isolated in other populations.The Bayesian Skyline Plot indicated that the estimated infections with HCV subtype 1b increased exponentially during the 1990s,whereas that of subtypes 3a and 3b increased slowly since the mid-1990s.In the NS5B 377-nt partial sequences of the HCV strains isolated in IDUs,there were two positive selection sites and seventy-eight negative selection sites recognized.The mutation rate was as low as 2.2％ in the 377-nt partial sequences corresponding to the known seven DAA drug binding sites.Conclusions HCV subtype 3a and 3b were the predominant genotypes in the IDUs in Pudong.Subtype lb was prevalent in different populations and evolved very rapidly,and more infections might be caused,suggesting further attention to its prevention,control and treatment.Although DAA treatment based on HCV NS5B binding sites targeting local IDUs might be effective,it is still necessary to strengthen the surveillance.

Objective To analyze the influencing factors of strain ratio in diagnosing thyroid lesions of thyroid imaging reporting and data system (TI-RADS) 4-6 categories, and explore the application value of elastic strain ratio in differentiating malignant thyroid nodules from benign ones under different influencing factors.Methods A retrospective analysis was made on the pathologic data of 278 nodules undergone TI-RADS ultrasonography stratification and ultrasound elestography, and 105 nodules of TI-RADS 4-6 categories were selected as research objects. A receiver-operating characteristic (ROC) curve was used to identify the cut-off point for differential diagnosis of thyroid nodules. A logistic regression model was established to analyze the factors affecting strain ratio in the differential diagnosis on thyroid nodules of TI-RADS 4-6 categories. Analyses were made in groups to judging the sensitive, specificity, accuracy, positive predictive value and negative predictive of strain ratio under the impact of different factors. Results The best cut-off point of ROC curve for benign and malignant nodules was 0.54. It was found through the logistic regression model that the strain ratio value was closely related to the size, calcification, and thyroid diffuse disease, and strain ration was of higher value in the thyroid nodules which were less than 1 cm without calcification and thyroid diffuse disease.Conclusions Three factors including size, calcification, and diffuse lesions of the thyroid nodules can influence the elastic strain ratio of TI-RADS 4-6 thyroid nodules. Comprehensive analysis of these three influencing factors can improve the application value of elastic strain ratio in differential diagnosis of benign and malignant thyroid nodules.