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Jiangtao Dong,1– 4,* Meilin Liu,1– 3,* Qianwen Chen,1– 3,5 Lingfeng Zha1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-15827177185, Email zhalf@hust.edu.cnBackground: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy, with variable pathogenesis, clinical presentation, and prognosis. Although mutations in genes encoding sarcomere proteins have been reported to explain the genetic etiology of 40%-60% of HCM patients, the etiology of approximately 1/3 of HCM patients remains unknown. Whole-exome sequencing (WES) is an effective method for identifying the genes that cause genetic diseases. In the present study, WES and systematic genetic screening were performed to determine the genetic causes of HCM in Chinese HCM family.Materials and Methods: Peripheral blood genomic DNA was collected from 9 family members of a Chinese Han HCM pedigree, including an HCM proband. Candidate variants obtained by WES were verified using Sanger sequencing, pathogenic mutation screening was conducted among family members, and the mutations were systematically analyzed using bioinformatics.Results: WES revealed a novel heterozygous missense mutation, c.20233 C>T (p.R6745C), located in exon 80 of the HCM-related gene TTN, which may be a pathogenic mutation in the family. In addition, this mutation was predicted to damage protein function. WES combined with Sanger sequencing results showed that the other two HCM patients in this family carried this TTN mutation, while none of the healthy family members carried the mutation except for a 3 years old girl.Conclusion: In this study, a new pathogenic mutation of TTN was found in a Chinese family with HCM, and disease-causing gene carriers in the family members were identified through pedigree screening. These findings have theoretical and application value for understanding the genetic basis of HCM, as well as for early risk stratification and early prevention and intervention of patients, and highlight the important role of genetic testing in the diagnosis and treatment of genetic diseases.Keywords: cardiomyopathy, HCM, whole exome sequencing, TTN, genetic testing

Jiangtao Dong,1– 4,* Wenjuan Zhang,5,* Qianwen Chen,1– 3,6 Lingfeng Zha1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Geriatrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-15827177185, Email zhalf@hust.edu.cnObjective: Restrictive cardiomyopathy (RCM) is a heterogenous cardiomyopathy with various causes, and genetic variants take an important part of the pathogenesis. Whole-exome sequencing (WES) is effective to discover genes that cause genetic diseases. By using WES, we attempted to identify the genetic cause of an RCM family and clarify the clinical diagnosis of the patient and then provide a personalized treatment plan.Materials and Methods: Blood samples were obtained from the proband and his healthy parents. WES and Sanger sequencing were performed to identify the possible pathogenic gene. Co-segregation analysis was conducted for candidate variants, and the allele frequency was checked in databases including Ensembl, Exome Aggregation Consortium (ExAC) and Human Gene Mutation Database (HGMD). Furthermore, the potential effect of variant was predicted using various-free software such as SIFT, Polyphen-2 and Mutation Taster and the conservation was tested using multiple sequence alignments by ClustalX.Results: The proband was a 20 years old boy with severe heart failure symptoms including dyspnea, massive ascites, edema of both lower limbs and chest congestion. Echocardiography showed significant biatrial enlargement, normal left ventricular wall thickness and preserved systolic function of both ventricles. A missense mutation in FLNC (c.6451G>A, p.G2151S), encoded filamin-C was detected in proband by WES and Sanger sequencing, while it was not be found in his parents, we supposed that the FLNC mutation (c.6451G>A, p.G2151S) may be a de-novo mutation. Through multiple functional predictions, we found that it is a deleterious mutation and the mutation in filamin-C could alter its structure and normal function, contributing to RCM.Conclusion: Here, an FLNC missense mutation (c.6451G>A, p.G2151S) known to be pathogenic in hypertrophic cardiomyopathy, was found to be associated with RCM, indicating the genetic overlap among cardiomyopathies. This study provides insights into Phenotype-Genotype Correlations of RCM in patients with FLNC mutations.Keywords: restrictive cardiomyopathy, whole-exome sequencing, filamin-C, FLNC

Hui Huang,1– 3,* Qing Ye,1– 4,* Yulan Xu,1– 3,* Baoming Tao,1– 3 Junlan Liu,1– 3 Tian Xie,1– 3 Lingfeng Zha1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4School of Nursing, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian Xie; Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-15972150162 ; +86-15827177185, Email xietian@hust.edu.cn; zhalf@hust.edu.cnPurpose: We investigated the risk factors and characteristic clinical features of peripartum cardiomyopathy (PPCM) to lay the groundwork for early identification, screening, diagnosis, and intervention in high-risk pregnant women.Patients and methods: A retrospective case-control study was conducted to analyze data from 44 patients with PPCM and 226 normal pregnant women from a Chinese population.Results: Significant differences were found between the groups in terms of various factors such as age, body mass index (BMI), heart rate, and medical history. Logistic regression models identified abnormal electrocardiography (OR=18.852), upper respiratory tract infection (OR=41.822), gestational hypertension (OR=18.188), and cesarean section (OR=8.394) as risk factors for PPCM. Common clinical features observed in patients with PPCM included cough, wheezing, and chest tightness (68.18%), left heart enlargement (56.82%) and valvular insufficiency (81.82%). Additionally, cardiotropic virus was detected in a subset of patients (43.18%) and NT-proBNP was elevated ≥ 400 pg/mL (81.82%).Conclusion: In the Chinese population, the presence of abnormal electrocardiograms during pregnancy, history of upper respiratory tract infection, gestational hypertension, and maternal choice of cesarean section suggest the possibility of PPCM development. Factors such as advanced age, family history of cardiovascular disease, gestational diabetes mellitus, eclampsia, anemia, and hypoproteinemia should be considered. Clinically, patients present with cough, wheezing, chest tightness, enlarged left heart, valvular insufficiency and NT-proBNP elevated ≥ 400 pg/mL. This study could serve as a valuable reference for medical practitioners for the early identification and screening of patients with PPCM.Keywords: peripartum cardiomyopathy, risk factors, clinical features, early identification

Daniyal H Mirza,1,* Lucy Zha,1,* Claudia See,2 Isabella N Paoletti,1 Feng Dai,3 Mark Hocevar,4 Jinlei Li,5 Daniel Wiznia6 1Yale College, New Haven, CT, 06520-8241, USA; 2Yale School of Medicine, New Haven, CT, 06520, USA; 3Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, 06520, USA; 4Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA; 5Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, 06510, USA; 6Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT, USA; Department of Mechanical Engineering & Materials Science, School of Engineering & Applied Science, Yale University, New Haven, CT, USA*These authors contributed equally to this workCorrespondence: Jinlei Li, Department of Anesthesiology, Yale University School of Medicine, 20 York Street, New Haven, CT, 06510, USA, Tel +1 917-601-6828, Email jinlei.li@yale.eduBackground: The most common route of opioid delivery is nurse-administered pills. However, there are numerous challenges such as nursing burden, opioid diversion, medication delay, and patient dissatisfaction. In this study, we conducted two surveys, first to assess patients’ and nurses’ opinions on the current administration of opioids in pill form, followed by their attitudes towards an innovative concept of oral medication delivery based on a medical device currently undergoing research and development within the University, patient-controlled dispenser and deactivator (PCDD) that allows patients to self-administer liquid oral opioids on demand based on physician prescription.Methods: Questionnaires were developed, verified and deployed to assess nurse and post-surgical patient opinions on the current administration of opioids in pill form, as well as the proposed new concept of patient -controlled administration of oral liquid medication via an illustration of PCDD, from September 2022 through July 2023 at a major academic tertiary care center. Quantitative and qualitative data were collected from postoperative patients and nurses from surgical specialties including General Surgery, Surgical Oncology, Trauma Surgery, Orthopedics, and Neurosurgery.Results: Forty-three patients and 53 nurses were interviewed. Seventy percent of patients frequently called nurses for pain medication post-surgery 1– 4 times daily, and 32% of patients were told each day by nurses that they could not receive medication because they were not due yet. Medication delay caused 24% of patients to worry about nursing availability for medication delivery. Likewise, nurses reported that half of patients receive delayed medication (22 minutes median delay time) and half of nursing time was spent administering pain medication. Nurses expressed moderate satisfaction with their current delivery of medication (median satisfaction score 6.5 out of 10). When being introduced to the concept of PCDD via a product illustration, 15% of patients said that they prefer liquid medication and 51% said they prefer PCDD or were interested in trying it.Conclusion: Nurse-administered pills are a common but suboptimal method for postoperative pain management. Based on patient and nurse feedback, patient controlled self-administered liquid oral opioid delivery is conceptually innovative, practically viable and potentially a preferred alternative for timely and less nurse-exhaustive pain management.Keywords: pain management, opioid, survey, nursing, patient-controlled analgesia pump

Yiyang Tang,1 Qin Chen,1 Lihuang Zha,1 Yilu Feng,1 Xiaofang Zeng,1 Zhenghui Liu,2 Famei Li,1 Zaixin Yu1 1Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Zaixin YuDepartment of Cardiology, Xiangya Hospital, Central South University, Xiangya Road, Kaifu District, Changsha, 410008, People’s Republic of ChinaTel/Fax +86 731-8432749Email yuzaixin@126.comPurpose: Acute myocardial infarction (AMI) is a common cardiovascular disease with a poor prognosis. The aim of this study was to construct a nomogram for predicting the long-term survival of critically ill patients with AMI. This nomogram will help in assessing disease severity, guiding treatment, and improving prognosis.Patients and Methods: The clinical data of patients with AMI were extracted from the MIMIC-III v1.4 database. Cox proportional hazards models were adopted to identify independent prognostic factors. A nomogram for predicting the long-term survival of these patients was developed on the basis of the results of multifactor analysis. The discriminative ability and accuracy of the multifactor analysis were evaluated according to concordance index (C-index) and calibration curves.Results: A total of 1202 patients were included in the analysis. The patients were randomly divided into a training set (n = 841) and a validation set (n = 361). Multivariate analysis revealed that age, blood urea nitrogen, respiratory rate, hemoglobin, pneumonia, cardiogenic shock, dialysis, and mechanical ventilation, all of which were incorporated into the nomogram, were independent predictive factors of AMI. Moreover, the nomogram exhibited favorable performance in predicting the 4-year survival of patients with AMI. The training set and the validation set had a C-index of 0.789 (95% confidence interval [CI]: 0.765– 0.813) and 0.762 (95% CI: 0.725– 0.799), respectively.Conclusion: The nomogram constructed herein can accurately predict the long-term survival of critically ill patients with AMI.Keywords: acute myocardial infarction, nomogram, long-term prognosis, MIMIC-III, retrospective study

Peihan Li, 1, 2,* Yanfeng Lin, 1, 2,* Xiaofeng Hu, 2,* Yuqi Liu, 1, 2 Mei Xue, 3 Lang Yang, 1, 2 Jinhui Li, 2 Lei Zha, 2 Kaiying Wang, 1 Kezong Qi, 3 Shaofu Qiu, 2 Peng Li, 2 Hongbin Song 2 1Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, People’s Republic of China; 2Center for Disease Control and Prevention of PLA, Beijing, People’s Republic of China; 3Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Li; Hongbin SongCenter for Disease Control and Prevention of PLA, 20 DongDa Street, Fengtai District, Beijing 100071, People’s Republic of ChinaTel/Fax +86-10-66948475Email jiekenlee@126.com; hongbinsong@263.netPurpose: Carbapenem-resistant Enterobacter cloacae complex has been reported worldwide and becomes a new challenge for clinical management. The present study was to characterize the IncX3 plasmid encoding blaNDM-1 and blaSHV-12 gene in E. hormaechei sequence.Materials and Methods: EcHK001 was recovered from the sputum sample of a patient. Species identification and antimicrobial susceptibility testing were performed using the VITEK 2 system, while further classification was carried out by hsp60 typing. The presence of NDM-1 was detected by PCR and sequencing. Conjugation experiments and southern blotting were carried out to determine the transferability of the NDM-1-carrying plasmid. Whole-genome sequencing and analysis were conducted to better understand the molecular characteristics of the multi-drug resistant isolate.Results: Strain EcHK001 was classified as E. hormaechei of new sequence type 1000. Multiple drug-resistant genes were detected. The blaNDM-1 and blaSHV-12 genes were located on a self-transferable IncX3 plasmid. Synonymous mutations were identified in the genes encoding TEM-1 and ACT-17. Phylogenetic analysis indicated that EcHK001 clustered into a different clade from domestic strains.Conclusion: The rapid spread of the recurrent IncX3 plasmid highlights the need for continuous surveillance of the NDM-1 dissemination. The presence of mutations in existing carbapenem-resistant genes may generate potential new variants and raise serious challenges for clinical treatment.Keywords: multidrug-resistant, NDM-1, SHV-12, enterobacter hormaechei

OBJECTIVE: Air pollution is affecting the health of millions of people all over the world. The causal correlations of PM2.5, PM10, and nitrogen dioxide (NOx), as the main fine particulate matter, and coronary heart disease (CHD) are yet to be explored. Low-density lipoprotein (LDL) has been a principal factor in the pathogenesis of CHD. It is an interesting issue to consider whether LDL mediates the effect of air pollutants in CHD pathogenesis. MATERIALS AND METHODS: A genome-wide association study (GWAS) on the European population, followed up from 2010 to 2018, involving over 400,000 participants, was based on a land-use regression model. The annual mean concentrations of major air pollutant particles, PM2.5 (n=423,796), PM10 (n=423,796), and NOx (n=456,380), were recorded. The large GWAS database of CHD covered over ten million SNPs with independent single nucleotide polymorphisms (SNPs). LDL database collected major biochemical blood parameters from over 400,000 patients (n=440,546). Taken together, we conducted independent two-sample Mendelian randomization (MR) analyses for the causality between air pollutants (PM2.5, PM10, and NOx) and CHD. Multivariate MR analysis was conducted using causal relationships to determine the direct effects of exposure on outcome. The fixed-effect inverse variance weighted (IVW2) method was mainly employed to assess this relationship, with a confi- dence interval of 95% for the odds ratio (OR). Also, MR-Egger, weighted median, maximum likelihood ratio method, and random-effects inverse variance-weighted (IVW1) method were adopted as supplementary methods. RESULTS: T wo-sample M R r esults b ased o n the IVW2 method suggested positive correlations between PM2.5 and CHD [OR 1.875 (1.279-2.748), p=0.001], PM10 and CHD [OR 2.586 (1.479-4.523), p=0.001], and NOx and CHD [OR 2.991 (2.021- 4.427), p=4.37E-08]. The direct effect and mediating proportion were calculated using multivariable Mendelian randomization (MVMR). Lastly, the mediating proportions of LDL in the regulatory roles of PM2.5, PM10, and NOx in CHD were 2.82%, 4.73%, and 9.54%, respectively. CONCLUSIONS: PM2.5, PM10, and NOx share direct causal associations with CHD, and LDL performs a mediating role in this pathogenic process. Early prevention against air pollution (such as increasing green areas and reducing large-scale industrial dust emissions) and early lipid-lowering treatment can effectively prevent the occurrence of CHD. [ABSTRACT FROM AUTHOR]

Artificial sweeteners can bind to the sweet taste receptors T1R2/T1R3 on the cell membrane of taste receptor cells, including intestinal enteroendocrine cells, and induce an increase in intracellular Ca2+ concentration ([Ca2+]i). Acute adaptation or a reduction in receptor signalling was observed after prolonged exposure to a taste stimulus in an animal model. However, at the cell level, it remains unclear whether the expression level of T1R2/T1R3 will be changed by pre-exposure to sweetener molecules, and whether the corresponding change in [Ca2+]i induced by the altered expression of sweet taste receptors varies. In the present work, western blotting and qPCR analysis showed that the expression level of T1R2/T1R3 in NCI-H716 cells was upregulated by sucralose stimulation. In the sucralose-treated cells, the accumulation of intracellular Ca2+ in the sweetener pre-treated cells was significantly enhanced as compared to that in cells without sweetener pre-treatment, although the sweet response differed between acesulfame K and sucralose with the same sweetness. Collectively, the increased expression of T1Rs in sweetener pre-incubated cells enhanced the sweet taste signal response, which implies that long-term administration of artificial sweeteners in beverages or foods could alter the sensitivity of taste receptor cells to sweetener molecules. [ABSTRACT FROM AUTHOR]

The nanocomposite magnets attract great interest in the study of high-performance magnets. Here, the micromagnetic simulations have been performed to investigate the effects of various microstructural factors such as grain geometry, grain size, and volume fraction on the performance of a soft-in-hard-matrix nanostructured Nd2Fe14B/α-Fe isotropic magnet. It is found that there is very little dependence of remanence on the geometry of the soft phase. The coercivity decreases with increasing the soft grain size, whereas it has a variation tendency depending on the size of hard grain size. In contrast to a significant role of soft-sphere geometry in anisotropic nanocomposites (Skomski et al 2013 IEEE Trans. Magn. 49 3215), the energy product of the soft-sphere system simulated here is slightly increased (8 kJ m−3), compared with that of the soft-cylinder system. In the meantime, a significant enhancement in energy product with increasing the soft grain size is observed only when the hard grain size is less than 15 nm. Our simulation predicts the highest energy product of 347 kJ m−3 with a hard grain size of 5 nm and a soft-sphere size of 12.4 nm (30 vol% of the soft phase). It is shown that the effective magnetocrystalline anisotropy is responsible for the variation in coercivity, based on its quantitative evaluation for the soft-sphere system. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To detect the expression of long non-coding ribonucleic acid (lncRNA) NCK1-AS1 in non-small cell lung cancer (NSCLC), analyze the association between its expression and the clinicopathological characteristics of NSCLC patients, and study the biological function of NCK1-AS1 in vitro. PATIENTS AND METHODS: The relative expression of NCK1-AS1 in NSCLC tissues and cells was detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between the expression of NCK1-AS1 and the clinicopathological characteristics of NSCLC was statistically analyzed. The effects of interference in the expression of NCK1-AS1 on the biological behaviors of NSCLC cells were detected via in vitro experiments, including Cell Counting Kit-8 (CCK-8) assay, colony formation assay and flow cytometry. After interference in the expression of NCK1-AS1, the expression of cyclin-dependent kinase 1 (CDK1) was determined using Western blotting. RESULTS: The results of qRT-PCR showed that the expression of NCK1-AS1 was up-regulated in 50 out of 64 cases of NSCLC tissues. It was found via statistical analysis that highly expressed NCK1-AS1 was positively correlated with tumor size, TNM stage and lymph node metastasis. The results of qRT-PCR revealed that the expression of NCK1-AS1 was also up-regulated in NSCLC cells. After interference in the expression of NCK1-AS1, the proliferation of NSCLC cells was inhibited, and the cell cycle was arrested at G2/M phase. The results of Western blotting manifested that the expression of CDK1 was suppressed after interference in the expression of NCK1-AS1. CONCLUSIONS: The expression of NCK1- AS1 is up-regulated in NSCLC, which indicates a poor prognosis. Highly expressed NCK1- AS1 promotes the proliferation of NSCLC cells through activating CDK1. [ABSTRACT FROM AUTHOR]

The magnetic and microwave absorption properties of Nd2Co16.5Si0.5 and Nd2Co16.5Si0.5–paraffin composite have been investigated. The Nd2Co16.5Si0.5 compound shows a planar anisotropy with a saturation magnetization of 114 emu/g at room temperature. The Nd2Co16.5Si0.5–paraffin composite exhibits a permeability of 2.1 at a frequency of 100 MHz, together with a microwave reflection loss (RL) up to −38 dB at a frequency of 4 GHz with a thickness of 2.8 mm and a qualified bandwidth (QB, RL ≤ −10 dB) of 3.2 GHz at a frequency of 14 GHz with a thickness of 1 mm. This composite exhibits both high working frequency and permeability due to its high saturation magnetization. A strong microwave absorption was achieved for the composite through a better impedance match. Hence, it is possible that this composite can be used as a high-performance thin-layer microwave absorber. [ABSTRACT FROM AUTHOR]