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Jing Ye,1,2,* Ping Li,1,2,* Pengcheng Liu,1,2 Wenjing Pei,1,2 Ruowen Wang,1,2 Hui Liu,1,2 Changxiu Ma,1,2 Dahai Zhao1,2 1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 2Institute of Respiratory Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dahai Zhao, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Email zhaodahai@ahmu.edu.cnBackground: Anxiety and depression are two of the most common comorbidities of COPD, which can directly lead to the number of acute exacerbations and hospitalizations of COPD patients and reduce their quality of life. At present, there are many studies on anxiety and depression in stable COPD, but few studies on anxiety and depression in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Objective: We aim to explore the changes of serum metabolomics in AECOPD complicated with anxiety and depression and to provide some clues for further understanding its pathogenesis.Methods: This is an observational high-throughput experimental study based on retrospective data extraction. Twenty-one AECOPD with anxiety and depressive patients and 17 healthy controls (HCs) were retrospectively enrolled in the Second Affiliated Hospital of Anhui Medical University. Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) for anxiety and depression were used to assess the patients with AECOPD. Untargeted metabolomics analysis was carried out to investigate different molecules in the serum of all participants. General information of all participants, baseline data and clinical measurement data of AECOPD patients were collected. Statistical analysis and bioinformatics analysis were performed to reveal different metabolites and perturbed metabolic pathways.Results: A total of 724 metabolites in positive ionization mode and 555 metabolites in negative ionization mode were different in AECOPD patients with anxiety and depression. The 1,279 serum metabolites could be divided into 77 categories. Based on multivariate and univariate analysis, 74 metabolites were detected in positive ionization mode, and 60 metabolites were detected in negative ionization as differential metabolites. The 134 metabolites were enriched in 18 pathways, including biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, protein digestion and absorption, ovarian steroidogenesis, long−term depression, retrograde endocannabinoid signaling, and so on.Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in AECOPD patients with anxiety and depression. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in AECOPD patients with anxiety and depression.Keywords: metabolomics, AECOPD, anxiety, depression, exacerbation

Bin Cao,1,2,&ast; Kun Li,1,2,&ast; Jing Ke,1,2 Dong Zhao1,2 1Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 2Beijing Key Laboratory of Diabetes Research and Care, Beijing, 101149, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Ke; Dong Zhao, Email kejing@ccmu.edu.cn; zhaodong@ccmu.edu.cnObjective: This study aimed to investigate the potential association between long-term variations in remnant cholesterol (RC) levels and the development of diabetic foot ulcers (DFU) in participants with type 2 diabetes (T2D).Methods: This was a retrospective cohort study. Variation in RC was assessed by the following metrics: mean, standard deviation (SD), coefficient of variation (CV) and trajectories pattern of RC. To identify RC trajectories, we employed the latent class mixture model. The primary endpoint was the development of DFU, and the time-to-event data were analyzed using Cox regression.Results: A total of 1874 patients with T2D were included, with a median follow-up duration of 4.7 years. Among them, 129 individuals (6.9%) developed DFU. The proportion of DFU was significantly higher in the U-shaped group compared to the median group (P for trend < 0.001). Upon adjustment for confounding variables, the U-shaped trajectory correlated with a higher risk of DFU, demonstrating a hazard ratio (HR) of 2.57 (95% CI, 1.54– 4.27). Subgroup analysis showed the U-shaped trajectory had a higher DFU risk regardless of gender (HR=2.40 and 2.81, respectively), glycemic control (HR=1.89 and 7.41, respectively), smoking (HR=2.36 and 2.93, respectively), or hypertension (HR=2.30 and 2.97, respectively). No association was found between mean, SD and CV of RC and DFU.Conclusion: A U-shape trajectory of RC was independently associated with an elevated risk of DFU among patients with T2D.Keywords: diabetic foot ulcer, remnant cholesterol, trajectories, type 2 diabetes

Qiming Gan,1,&ast; Quanzhen Liu,1,2,&ast; Yanjuan Wu,1,&ast; Xiaofeng Zhu,1,2 Jingcun Wang,1 Xiaofen Su,1 Dongxing Zhao,1 Nuofu Zhang,1 Kang Wu1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Disease, Department of Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2Nanshan School, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kang Wu; Nuofu Zhang, Department of Pulmonary and Critical Care Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No. 28 Qiaozhong Mid Road, Guangzhou, Guangdong, 510160, People’s Republic of China, Email d102_wk@126.com; nfzhanggird@163.comPurpose: Obstructive sleep apnea (OSA) had been associated with asthma in observational studies, but the effect of OSA on the onset of asthma in childhood or adulthood remains unclear, and the causal inferences have not been confirmed. This study aims to investigate the potential causal association between OSA with asthma, including different age-of-onset subtypes, providing reliable basis for the clinical treatment of OSA and asthma.Patients and Methods: Causality between OSA and asthma was assessed using a two-sample bi-directional Mendelian randomization (MR) analysis. OSA data were obtained from the FinnGen consortium R9, while asthma and its subtypes (adult-onset asthma, child-onset asthma, and moderate-to-severe asthma) were sourced from the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was chosen as the primary analysis and was complemented by various sensitivity analyses. The MR-PRESSO outlier test was employed to systematically identify and remove outlier variants, mitigating heterogeneity and potential effects of horizontal pleiotropy.Results: The MR analyses provided evidence of genetically predicted OSA having a promoting effect on child-onset asthma (OR,1.49; 95% CI, 1.05– 2.11; P=0.025) and moderate-to-severe asthma (OR,1.03; 95% CI, 1.00– 1.06; P=0.046). However, no causal association between OSA with asthma and adult-onset asthma was observed.Conclusion: Our study revealed a causal association between OSA and child asthma, but not in adults. Moderate-to-severe asthma may have a potential promoting effect on OSA. These findings underscore the importance of age-specific considerations in managing asthma and suggests the need for personalized approaches in clinical practice.Keywords: asthma, obstructive sleep apnea, Mendelian randomization, genetic

Weiwei Guan,1,2 Congyue Zhang,1 Tongguo Miao,1 Chen Dong,1 Lu Li,1 Xiwei Yuan,1 Dandan Zhao,1 Rong Ai,1 Xiaoxiao Zhang,1 Mengjiao Sun,1 Haiyan Kang,2,&ast; Yuemin Nan1,&ast; 1Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, 050023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, No. 139, Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 18533112266, Email nanyuemin@163.com Haiyan Kang, Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, No. 42, Tanan Road, Shijiazhuang, Hebei Province, 050023, People’s Republic of China, Tel +86 13315952782, Email kanghaiyan1976@126.comPurpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC.Materials and Methods: High‐throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated.Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors.Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.Keywords: ADAMTSL4-AS1, AC067931, SOCS2-AS1, HBV-associated HCC, diagnostic biomarkers

Jiachen Yu,1,&ast; Yingchun Zhang,1,&ast; Rong Ran,2,&ast; Zixiao Kong,3 Duoyi Zhao,1 Wei Zhao,1 Yingxin Yang,4 Lianbo Gao,5 Zhiyu Zhang1 1Department of Orthopedics, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 2Department of Anesthesia, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 3China Medical University, Shen Yang, 110032, People’s Republic of China; 4General Hospital of Northern Theater Command, China Medical University, Shen Yang, 110032, People’s Republic of China; 5Department of Neurology, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyu Zhang; Lianbo Gao, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan Road, Huanggu District, Shenyang, Liaoning, People’s Republic of China, Email zyzhang@cmu.edu.cn; lbgao@cmu.edu.cnAbstract: The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.Keywords: bioprinting, bioink, organoids, tumor spheroids, tumor chips

Changxiu Ma,1 Ying Zhang,1 Tingchao Tian,2 Ling Zheng,1 Jing Ye,1 Hui Liu,1 Dahai Zhao1 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huoqiu First People’s Hospital, Huoqiu, 237400, People’s Republic of ChinaCorrespondence: Dahai Zhao, Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Tel +86-13721027959, Email zhaodahai@ahmu.edu.cnPurpose: To explore the role of the mean apnea–hypopnea duration (MAD) and apnea–hypopnea duration per hour (HAD) in hypoxemia and evaluate whether they can effectively predict the occurrence of hypoxemia among adults with OSA.Patients and Methods: A total of 144 participants underwent basic information gathering and polysomnography (PSG). Logistic regression models were conducted to evaluate the best index in terms of hypoxemia. To construct the prediction model for hypoxemia, we randomly divided the participants into the training set (70%) and the validation set (30%).Results: The participants with hypoxemia tend to have higher levels of obesity, diabetes, AHI, MAD, and HAD compared with non-hypoxemia. The most relevant indicator of blood oxygen concentration is HAD (r = 0.73) among HAD, MAD, and apnea–hypopnea index (AHI). The fitness of HAD on hypoxemia showed the best. In the stage of establishing the prediction model, the area under the curve (AUC) values of both the training set and the validation set are 0.95. The increased HAD would elevate the risk of hypoxemia [odds ratio (OR): 1.30, 95% confidence interval (CI): 1.13– 1.49].Conclusion: The potential role of HAD in predicting hypoxemia underscores the significance of leveraging comprehensive measures of respiratory disturbances during sleep to enhance the clinical management and prognostication of individuals with sleep-related breathing disorders.Keywords: mean apnea–hypopnea duration, obstructive sleep apnea, apnea–hypopnea duration per hour, polysomnography, apnea–hypopnea index

Yuanhang Pan,1,&ast; Di Zhao,1,&ast; Xinbo Zhang,1,&ast; Na Yuan,1 Lei Yang,1 Yuanyuan Jia,2 Yanzhao Guo,3 Ze Chen,1 Zezhi Wang,1 Shuyi Qu,1 Junxiang Bao,4 Yonghong Liu1 1Department of Neurology, Xijing Air Force Medical University, Xi’an, People’s Republic of China; 2Encephalopathy Department No.2, Baoji Hospital of Traditional Chinese Medicine, Baoji, People’s Republic of China; 3Encephalopathy Department No.10, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, People’s Republic of China; 4Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Liu, Department of Neurology, Xijing hospital, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 13991236602, Email liuyhong@fmmu.edu.cn Junxiang Bao, Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 02984711241, Email baojunx@fmmu.edu.cnBackground: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1.Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early.Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP).Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA.Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices.Keywords: obstructive sleep apnea, narcolepsy, machine learning, prediction model, sleep disorder

Donghao Wang,1,&ast; Yuting Zhang,1,&ast; Qiming Gan,1,&ast; Xiaofen Su,1,&ast; Haojie Zhang,1,2,&ast; Yanyan Zhou,1 Zhiyang Zhuang,1 Jingcun Wang,1 Yutong Ding,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang; Dongxing Zhao, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13600460056 ; +86-13650901411, Email nfzhanggird@163.com; rieast@163.comObjective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea–hypopnea index (AHI).Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR).Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07– 1.62, P < 0.01) and 1.45 (95% CI = 1.01– 2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02– 3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes.Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.Keywords: obstructive sleep apnea, arousal threshold, apnea–hypopnea index, hypertension, diabetes

Xiu-Li Xiao,1,&ast; Qian-Xue Yang,2,&ast; Hui-Zhong Niu,1 Li-Jing Li,1 Jian-Lei Geng,1 Dan Zhao,1 Hui Ren,1 Pan-Pan Yang1 1Department of General Surgery I, Hebei Children’s Hospital, Shijiazhaung, 050000, People’s Republic of China; 2Department of Operating Room, Hebei Children’s Hospital, Shijiazhaung, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiu-Li Xiao, Department of General Surgery I, Hebei Children’s Hospital, No. 133 Jianhuanan Street, Shijiazhuang, Yuhua District, 050000, People’s Republic of China, Tel +86 0311 8591 1321, Email xxlwwvt7@email.cnPurpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD).Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test.Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23± 6.17 VS 7.89± 2.38). The difference between the two groups had statistical significance (P < 0.05).Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.Keywords: catheter blockage rate, catheter sealing fluid volume, pain, puncture method, totally implantable venous access device

Zhongyin Zhou,1,&ast; Feiyan Ma,2,&ast; Jianxiang Zhu,1 Jialing Wang,1 Jing Zhang,3 Dongsheng Zhao4 1Department of Echocardiography, Affiliated Hospital 2 of Nantong University, First People’s Hospital of Nantong City, Nantong, 226000, People’s Republic of China; 2Department of Ultrasound, the People’s Hospital of Rugao, Nantong, 226000, People’s Republic of China; 3Department of Electroencephalogram, Affiliated Hospital 2 of Nantong University, First People’s Hospital of Nantong City, Nantong, 226000, People’s Republic of China; 4Department of Cardiology, Affiliated Hospital 2 of Nantong University, First People’s Hospital of Nantong City, Nantong, 226000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Zhao, Department of Cardiology, Affiliated Hospital 2 of Nantong University, First People’s Hospital of Nantong City, No. 666 Shengli Road, Nantong, 226006, People’s Republic of China, Tel +86 13814710785, Email dongshengzhaoss@126.comObjective: Left ventricular (LV) mechanical dyssynchrony (LVMD) is fundamental to the progression of heart failure and ventricular remodeling. The status of LVMD in different patterns of bundle branch blocks (BBB) is unclear. In this study, we analyzed the relationship between LVMD and left ventricular systolic dysfunction using real-time three-dimensional echocardiography (RT-3DE).Methods: RT-3DE and conventional two-dimensional echocardiography were performed on 68 patients with left bundle branch block (LBBB group), 106 patients with right bundle branch block (RBBB group), and 103 patients without BBB (Normal group). The RT-3DE data sets provided time-volume analysis for global and segmental LV volumes. The LV systolic dyssynchrony index (LVSDI) was calculated using the standard deviation (SD) and maximal difference (Dif) of time to minimum segmental volume (tmsv) for LV segments adjusted by the R-R interval. LVMD was considered if the LVSDI (Tmsv-16-SD) was greater than or equal to 5%.Results: LVSDI is negatively and significantly correlated with left ventricular ejection fraction (LVEF), but not with BBB or QRS duration. The proportion of LVMD in the LBBB, RBBB, and Normal group was 30.88%, 28.30%, and 25.24%, respectively, and there was no significant difference.Conclusion: In dilated cardiomyopathy, LVMD is more closely related to LVEF reduction than QRS morphology and duration.Keywords: bundle branch block, dilated cardiomyopathy, mechanical dyssynchrony

Miaomiao Li,1,2 Xiaoyu Wang,1,2 Fang Wang,3 Fengqi Wang,1,2 Dehua Zhao,4 Shiguo Liu1,2 1Department of Medical Genetic, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Prenatal Diagnosis Center, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Endocrinology Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Neonatal Screening Center, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Dehua Zhao, The Third Affiliated Hospital of Zhengzhou University, Neonatal Screening Center, Zhengzhou, Henan, 450052, People’s Republic of China, Email zhaodehua369@163.com Shiguo Liu, The Affiliated Hospital of Qingdao University, Department of Medical Genetic, Prenatal Diagnosis Center, Qingdao, Shandong, 266003, People’s Republic of China, Email liushiguo@qdu.edu.cnBackground and Objective: Congenital hypothyroidism (CH) is indeed a prevalent neonatal endocrine disorder, affecting approximately 1 in 2000– 3000 newborns worldwide, and 1 in 2400 newborns in China. Despite its high incidence, the genetic causes of CH, particularly those related to thyroid dysgenesis (TD), are still not well understood. However, previous studies have suggested that JAG1 may be a potential susceptibility gene for congenital thyroid defects. To explore the association between JAG1 and CH, we screened JAG1 variants in a large cohort of 813 CH patients.Methods: We performed genetic analysis of JAG1 using next-generation sequencing in 813 CH cases. The pathogenicity of the variants was assessed by bioinformatics softwares, protein sequence conservation analysis, and hydrophobic analysis. Further genetic analysis was conducted targeting 20 CH-related genes in these 25 JAG1 variant carriers.Results: We identified 10 pathogenic missense mutations (p.V45L, p.V272I, p.P552L, p.G610E, p.G852D, p.A891T, p.E1030K, p.R1060W, p.A1131T, p.P1174L) carried by 25 patients, the mutation rate of JAG1 in CH was 3.08%. Among these 25 patients, 16 with 1 variant, 6 with 2 variants, and the other 3 with 3 variants. Our findings indicated that JAG1 variants confer genetic susceptibility to both TD and DH, but with different inheritance models. JAG1 variants lead to TD mainly through monogenic model, while for DH cases, both monogenic mechanisms and oligogenic mechanisms play a pivotal role. Oligogenicity may contribute to the disease severity of DH.Conclusion: JAG1 is a shared genetic factor in TD and DH, with a detection rate of 3.08% in Chinese individuals with CH. A comparison between the oligogenic and monogenic groups suggests a gene dosage effect in CH. Patients with the same JAG1 mutation exhibit diverse clinical phenotypes, indicating complex mechanisms underlying phenotypic heterogeneity.Keywords: congenital hypothyroidism, JAG1, pathogenic variant, inheritance model, phenotypic heterogeneity

Donghao Wang,1,&ast; Yating Chen,1,&ast; Yutong Ding,1,&ast; Yongkang Tang,1,&ast; Xiaofen Su,1,&ast; Shiwei Li,1 Haojie Zhang,1,2 Yanyan Zhou,1 Zhiyang Zhuang,1 Qiming Gan,1 Jingcun Wang,1 Yuting Zhang,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China, Tel +86-13600460056, Email nfzhanggird@163.comBackground: Obstructive sleep apnea (OSA) is a common chronic disease with various comorbidities. The cardiometabolic index (CMI) reflects visceral fat tissue distribution and function, assessing the risk of obesity-related conditions such as metabolic syndrome (MetS) and stroke, which are strongly connected to OSA. The relationship between CMI with OSA and OSA combined with MetS (OMS) remains unclear. This study aims to evaluate the screening value of CMI for OSA and OMS, compared to the lipid accumulation product (LAP).Methods: A total of 280 participants who underwent polysomnography were finally included, with the measurements of metabolic-related laboratory test results such as total cholesterol and triglyceride. Receiver operating curve (ROC) analysis and calculation of the area under the curve (AUC) were conducted to assess the screening potential of CMI, LAP, and the logistic regression models established based on them for OSA and OMS. The Youden index, sensitivity, and specificity were used to determine the optimal cutoff points.Results: ROC curve analysis revealed that the AUCs for CMI in screening OSA and OMS were 0.808 and 0.797, and the optimal cutoff values were 0.71 (sensitivity 0.797, specificity 0.776) and 0.89 (sensitivity 0.830, specificity 0.662), respectively, showing higher Youden index than LAP. The AUCs of screening models based on CMI for OSA and OMS were 0.887 and 0.824, respectively.Conclusion: CMI and LAP can effectively screen for OSA and OMS, while CMI has more practical cutoff values for identifying the diseased states. Screening models based on CMI demonstrate a high discriminatory ability for OSA and OMS, which needs verification in a large-scale population.Keywords: obstructive sleep apnea, metabolic syndrome, cardiometabolic index, lipid accumulation products, screening model

Jun Cheng,&ast; Jinjin Pan,&ast; Dongmei Zhao, Xuejiao Ma, Qiulin Sun, Jiabin Li Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiabin Li, Tel/Fax +86-551-62922281, Email lijiabin@163.comAbstract: The global prevalence of hepatitis C virus (HCV) infection is approximately 3%, with a post-infection chronicity rate of up to 50%– 85%. HCV reactivation can occur when anti-HCV positive individuals receive antineoplastic therapy. In this study, we report a case of an anti-HCV positive patient with negative HCV RNA after 12 weeks of direct antiviral therapy. Two months later, sorafenib was used to treat hepatocellular carcinoma, and HCV reactivation occurred after 8 months of the treatment. HCV RNA was negative after 12 weeks of antiviral treatment with Sofosbuvir-velpatasvir. We also discussed the mechanism of HCV reactivation caused by sorafenib and the antiviral treatment regimen after HCV reactivation with the relevant literature.Keywords: hepatocellular carcinoma, sorafenib, HCV-RNA, anti-HCV therapy, reactivation

Xiaotian Ji,1 Shuhui Wu,1 Dan Zhao,1 Qi Bai,1 Yun Wang,1 Ke Gong,2 Huie Zheng,1 Mingfang Zhu1 1Department of Dermatology, the Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2Department of Traditional Chinese Medicine, Cangzhou Central Hospital, Cangzhou, People’s Republic of ChinaCorrespondence: Mingfang Zhu, Department of Dermatology, the Second Affiliated Hospital of Hunan University of Chinese Medicine, 233 Cai E North Road, Kaifu District, Changsha, People’s Republic of China, Tel +86-13907317358, Fax +86-731-84917727, Email 320492@hnucm.edu.cnBackground: The association between acne and gut microbiota has garnered considerable attention; nevertheless, given the substantial diversity within gut microbiota, the precise cause-and-effect relationship linking specific microbial species to acne remains elusive. To address this gap in knowledge, our study utilized Mendelian randomization analysis to elucidate a potential causal link between gut microbiota composition and acne development while also investigating underlying mechanisms involving microbial factors associated with metabolic disorders.Materials and Methods: The independent single nucleotide polymorphisms (SNPs) closely associated with 196 gut microbiota samples (N=18340) were selected as variable tools. The relationship between gut microbiota and acne (N=212438) was analyzed using the Twosample package in R4.3.1, employing various methods including inverse variance weighting (IVW), weighted median, MR-Egger, Simple-mode, and Weighted-mode. To ensure the stability of the estimates, a series of sensitivity analyses were conducted, such as Cochran’s Q-test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Additionally, the impact of each instrumental variable was calculated.Results: In the Mendelian randomization analysis, we identified twelve microbial taxa potentially associated with acne: family.Bacteroidaceae, family.Clostridiaceae1, genus.Allisonella, genus.Bacteroides, genus.Butyricimonas, genus.Clostridiumsensustricto1, and genus.Coprococcus3. These seven bacterial groups were found to be potential risk factors for acne. Conversely, family.Lactobacillaceae and genus.Ruminococcustorquesgroup along with genus.CandidatusSoleaferrea, genus.Fusicatenibacter, family.Lactobacillaceae, and genus.Lactobacillus exhibited a protective effect against acne. Furthermore, our investigation revealed that some of these microbial taxa have been implicated in metabolic diseases through previous studies. Importantly though, no causal relationship was observed in the reverse Mendelian randomization analysis.Keywords: acne, gut microbiota, Mendelian randomization, metabolic disease

The preparation and realization of highly reliable thermal barrier coatings (TBCs) on the internal surface of complex cavities is a bottleneck problem. Traditional coating methods are difficult to deposit and fulfil service requirements. In this study, a novel structure of YSZ and Ce-doped YSZ (CeYSZ) TBCs was prepared by a newly cathode plasma electrolytic deposition (CPED) technology. The results suggested that both the CPED-YSZ and CPED-CeYSZ coatings exhibited porous cross-linked dendritic structures. Because Ce doping significantly improved the phase stability of tetragonal structure and enhanced thermal insulation temperature during a burner-rig test at 1300 °C, resulting in a threefold increase in the thermal cycling life of the CPED-CeYSZ coating compared to the CPED-YSZ coating. This work provided a new strategy for tailoring multiple rare-earth principal components of high-performance TBCs and depositing them on the inner surface of complex cavities with high aspect ratios. [ABSTRACT FROM AUTHOR]