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1. Identification of conserved skeletal enhancers associated with craniosynostosis risk genes

Author

He, Xuan Anita, Berenson, Anna, Bernard, Michelle, Weber, Chris, Cook, Laura E, Visel, Axel, Bass, Juan I Fuxman, and Fisher, Shannon

Subjects
Biological Sciences, Genetics, Human Genome, Congenital Structural Anomalies, Rare Diseases, Dental/Oral and Craniofacial Disease, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Craniosynostoses, Animals, Zebrafish, Enhancer Elements, Genetic, Humans, Mice, Genome-Wide Association Study, Bone Morphogenetic Protein 2, Genetic Predisposition to Disease, Conserved Sequence, Zebrafish Proteins, Animals, Genetically Modified, Mutation, conserved regulatory elements, zebrafish transgenesis, craniosynostosis, enhanced yeast one-hybrid assay, BMP signaling, Medical and Health Sciences, Genetics & Heredity
Abstract

Craniosynostosis, defined by premature fusion of one or multiple cranial sutures, is a common congenital defect affecting more than 1/2000 infants and results in restricted brain expansion. Single gene mutations account for 15%-20% of cases, largely as part of a syndrome, but the majority are nonsyndromic with complex underlying genetics. We hypothesized that the two noncoding genomic regions identified by a GWAS for craniosynostosis contain distal regulatory elements for the risk genes BMPER and BMP2. To identify such regulatory elements, we surveyed conserved noncoding sequences from both risk loci for enhancer activity in transgenic Danio rerio. We identified enhancers from both regions that direct expression to skeletal tissues, consistent with the endogenous expression of bmper and bmp2. For each locus, we also found a skeletal enhancer that also contains a sequence variant associated with craniosynostosis risk. We examined the activity of each enhancer during craniofacial development and found that the BMPER-associated enhancer is active in the restricted region of cartilage closely associated with frontal bone initiation. The same enhancer is active in mouse skeletal tissues, demonstrating evolutionarily conserved activity. Using enhanced yeast one-hybrid assays, we identified transcription factors that bind each enhancer and observed differential binding between alleles, implicating multiple signaling pathways. Our findings help unveil the genetic mechanism of the two craniosynostosis risk loci. More broadly, our combined in vivo approach is applicable to many complex genetic diseases to build a link between association studies and specific genetic mechanisms.

Published
2024

2. Modeling multi-species RNA modification through multi-task curriculum learning

Author

Xiong, Yuanpeng, He, Xuan, Zhao, Dan, Tian, Tingzhong, Hong, Lixiang, Jiang, Tao, and Zeng, Jianyang

Subjects
Networking and Information Technology R&D (NITRD), Genetics, Human Genome, Biotechnology, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Adenosine, Animals, Databases, Genetic, Datasets as Topic, Gene Expression Regulation, Humans, Machine Learning, RNA, RNA-Binding Proteins, Sequence Analysis, RNA, Software, Transcriptome, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Developmental Biology
Abstract

N6-methyladenosine (m6A) is the most pervasive modification in eukaryotic mRNAs. Numerous biological processes are regulated by this critical post-transcriptional mark, such as gene expression, RNA stability, RNA structure and translation. Recently, various experimental techniques and computational methods have been developed to characterize the transcriptome-wide landscapes of m6A modification for understanding its underlying mechanisms and functions in mRNA regulation. However, the experimental techniques are generally costly and time-consuming, while the existing computational models are usually designed only for m6A site prediction in a single-species and have significant limitations in accuracy, interpretability and generalizability. Here, we propose a highly interpretable computational framework, called MASS, based on a multi-task curriculum learning strategy to capture m6A features across multiple species simultaneously. Extensive computational experiments demonstrate the superior performances of MASS when compared to the state-of-the-art prediction methods. Furthermore, the contextual sequence features of m6A captured by MASS can be explained by the known critical binding motifs of the related RNA-binding proteins, which also help elucidate the similarity and difference among m6A features across species. In addition, based on the predicted m6A profiles, we further delineate the relationships between m6A and various properties of gene regulation, including gene expression, RNA stability, translation, RNA structure and histone modification. In summary, MASS may serve as a useful tool for characterizing m6A modification and studying its regulatory code. The source code of MASS can be downloaded from https://github.com/mlcb-thu/MASS.

Published
2021

3. Metabolic phenotype of breast-fed infants, and infants fed standard formula or bovine MFGM supplemented formula: a randomized controlled trial

Author

He, Xuan, Parenti, Mariana, Grip, Tove, Domellöf, Magnus, Lönnerdal, Bo, Hernell, Olle, Timby, Niklas, and Slupsky, Carolyn M

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Nutrition, Pediatric, Clinical Trials and Supportive Activities, Clinical Research, 3.3 Nutrition and chemoprevention, Prevention of disease and conditions, and promotion of well-being, Metabolic and endocrine, Breast Feeding, Feeding Behavior, Female, Humans, Infant, Infant Formula, Infant, Newborn, Male, Metabolome, Metabolomics, Plasma
Abstract

Formula-fed (FF) infants exhibit a different metabolic profile than breast-fed (BF) infants. Two potential mechanisms are the higher protein level in formula compared with breast milk and the removal of the milk fat and associated milk fat globule membranes (MFGM) during production of infant formula. To determine whether MFGM may impact metabolism, formula-fed infants were randomly assigned to receive either an MFGM isolate-supplemented experimental formula (EF) or a standard formula (SF) from 2 until 6 months and compared with a BF reference group. Infants consuming EF had higher levels of fatty acid oxidation products compared to infants consuming SF. Although the protein level in the study formula was approximately 12 g/L (lower than most commercial formulas), a metabolic difference between FF and BF remained such that FF infants had higher levels of amino acid catabolism by-products and a low efficiency of amino acid clearance (preference for protein metabolism). BF infants had higher levels of fatty acid oxidation products (preference for fat metabolism). These unique, energy substrate-driven metabolic outcomes did not persist after diet was shifted to weaning foods and appeared to be disrupted by complementary feeding. Our results suggest that MFGM may have a role in directing infant metabolism.

Published
2019

4. Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial

Author

He, Xuan, Parenti, Mariana, Grip, Tove, Lönnerdal, Bo, Timby, Niklas, Domellöf, Magnus, Hernell, Olle, and Slupsky, Carolyn M

Subjects
Microbiology, Biological Sciences, Biomedical and Clinical Sciences, Medical Biochemistry and Metabolomics, Clinical Trials and Supportive Activities, Prevention, Pediatric Research Initiative, Pediatric, Clinical Research, Nutrition, Prevention of disease and conditions, and promotion of well-being, 3.3 Nutrition and chemoprevention, Animals, Breast Feeding, Cattle, Dietary Supplements, Feces, Glycolipids, Glycoproteins, Humans, Infant, Infant, Newborn, Lipid Droplets, Metabolome, Microbiota
Abstract

Human milk delivers an array of bioactive components that safeguard infant growth and development and maintain healthy gut microbiota. Milk fat globule membrane (MFGM) is a biologically functional fraction of milk increasingly linked to beneficial outcomes in infants through protection from pathogens, modulation of the immune system and improved neurodevelopment. In the present study, we characterized the fecal microbiome and metabolome of infants fed a bovine MFGM supplemented experimental formula (EF) and compared to infants fed standard formula (SF) and a breast-fed reference group. The impact of MFGM on the fecal microbiome was moderate; however, the fecal metabolome of EF-fed infants showed a significant reduction of several metabolites including lactate, succinate, amino acids and their derivatives from that of infants fed SF. Introduction of weaning food with either human milk or infant formula reduces the distinct characteristics of breast-fed- or formula-fed- like infant fecal microbiome and metabolome profiles. Our findings support the hypothesis that higher levels of protein in infant formula and the lack of human milk oligosaccharides promote a shift toward amino acid fermentation in the gut. MFGM may play a role in shaping gut microbial activity and function.

Published
2019

5. Postprandial metabolic response of breast-fed infants and infants fed lactose-free vs regular infant formula: A randomized controlled trial.

Author

Slupsky, Carolyn M, He, Xuan, Hernell, Olle, Andersson, Yvonne, Rudolph, Colin, Lönnerdal, Bo, and West, Christina E

Subjects
Humans, Insulin, Blood Glucose, Energy Metabolism, Breast Feeding, Postprandial Period, Time Factors, Infant Formula, Aged, 80 and over, Infant, Infant, Newborn, Female, Male, Biomarkers, Clinical Research, Pediatric, Nutrition, Breast Cancer, Cancer, Metabolic and Endocrine, Aged, and over, Newborn, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Lactose intolerance is a major concern driving the growth of lactose-free foods including lactose-free infant formula. It is unknown what the metabolic consequence is of consumption of a formula where lactose has been replaced with corn syrup solids (CSS). Here, a randomized double-blinded intervention study was conducted where exclusively formula-fed infants were fed formula containing either lactose or CSS-based infant formula and compared with an equal number of exclusively breast-fed infants. Plasma metabolites and insulin were measured at baseline, 15, 30, 60, 90 and 120 min after feeding. Differences in plasma metabolite profiles for formula-fed infants included a rapid increase in circulating amino acids, creatinine and urea compared with breast-fed infants. At 120 min post-feeding, insulin was significantly elevated in formula-fed compared with breast-fed infants. Infants fed lactose-based formula had the highest levels of glucose at 120 min, and leucine, isoleucine, valine and proline at 90 and 120 min, whereas infants fed CSS-based formula had the lowest levels of non-esterified fatty acids at all time points, and glucose at 120 min. Overall, these differences highlight that changes in infant formula composition impact infant metabolism, and show that metabolomics is a powerful tool to help with development of improved infant formulas.

Published
2017

6. Cross-talk between E. coli strains and a human colorectal adenocarcinoma-derived cell line.

Author

He, Xuan, Mishchuk, Darya O, Shah, Jigna, Weimer, Bart C, and Slupsky, Carolyn M

Subjects
Cell Line, Tumor, Caco-2 Cells, Humans, Escherichia coli, Adenocarcinoma, Colorectal Neoplasms, Lactic Acid, Coculture Techniques, Citric Acid Cycle, Host-Pathogen Interactions, Cell Line, Tumor, Infectious Diseases, Digestive Diseases, 2.1 Biological and endogenous factors, 2.2 Factors relating to physical environment, Infection, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Although there is great interest in the specific mechanisms of how gut microbiota modulate the biological processes of the human host, the extent of host-microbe interactions and the bacteria-specific metabolic activities for survival in the co-evolved gastrointestinal environment remain unclear. Here, we demonstrate a comprehensive comparison of the host epithelial response induced by either a pathogenic or commensal strain of Escherichia coli using a multi-omics approach. We show that Caco-2 cells incubated with E. coli display an activation of defense response genes associated with oxidative stress. Indeed, in the bacteria co-culture system, the host cells experience an altered environment compared with the germ-free system that includes reduced pH, depletion of major energy substrates, and accumulation of fermentation by-products. Measurement of intracellular Caco-2 cell metabolites revealed a significantly increased lactate concentration, as well as changes in TCA cycle intermediates. Our results will lead to a deeper understanding of acute microbial-host interactions.

Published
2013

7. Emerging Aspects of Food and Nutrition on Gut Microbiota

Author

He, Xuan, Marco, Maria L, and Slupsky, Carolyn M

Subjects
Agricultural, Veterinary and Food Sciences, Engineering, Chemical Sciences, Genetics, Nutrition, Aetiology, 2.2 Factors relating to the physical environment, Oral and gastrointestinal, Good Health and Well Being, Biological Evolution, Diet, Gastrointestinal Tract, Humans, Microbiota, Nutritional Status, Symbiosis, gut microbiome, diet, nutrition, food, colon, dietary fiber, Agricultural and Veterinary Sciences, Food Science, Agricultural, veterinary and food sciences, Chemical sciences
Abstract

The human gastrointestinal tract contains a highly complex ecosystem that harbors various microorganisms, which together create a unique environment within each individual. There is growing awareness that dietary habits are one of the essential factors contributing to the microbial diversity and community configuration that ultimately affects human health. From an evolutionary perspective, human dietary history can be viewed as a central factor in the selection of the gut microbial community and stabilization of the mutualistic host-microbial interaction, that together drive host phenotype. Herein, current knowledge concerning the influence of major dietary macrostructure and individual food ingredients is presented. This knowledge will provide perspectives for personalized gut microbiota management and, ultimately, movement toward an era of personalized nutrition and medicine.

Published
2013

8. Patterns of cardiometabolic multimorbidity and the risk of depressive symptoms in a longitudinal cohort of middle-aged and older Chinese

Author

Zi-Ting Huang, Yan Luo, Ling Han, Kaipeng Wang, Shan-Shan Yao, He-Xuan Su, Sumin Chen, Gui-Ying Cao, Carson M. De Fries, Zi-Shuo Chen, Hui-Wen Xu, Yong-Hua Hu, and Beibei Xu

Subjects
China, Psychiatry and Mental health, Clinical Psychology, Depression, Hypertension, Humans, Multimorbidity, Longitudinal Studies, Middle Aged, Aged
Abstract

Cardiometabolic diseases (CMDs) are associated with depression. However, it is unclear whether coexisting CMDs may increase the risk of depression. We examined associations between cardiometabolic multimorbidity and depressive symptoms among middle-aged and older Chinese.Participants aged ≥45 years were enrolled from the China Health and Retirement Longitudinal Study 2011-2018 (N = 18,002). Cardiometabolic multimorbidity was defined as the coexistence of ≥2 CMDs, including stroke, heart disease, diabetes, hypertension, and dyslipidemia. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. We used generalized estimating equation models to examine associations between cardiometabolic multimorbidity and depressive symptoms, including the dose effect of disease count and prevalent disease combinations, as well as individual and additive effects of specific CMDs.The prevalence of cardiometabolic multimorbidity was 24.5%. A higher number of CMDs had an additive dose effect on depressive symptoms that persisted consistently in specific CMDs. Stroke only, heart disease only, and diabetes only were each associated with a higher risk of depressive symptoms compared with no CMDs. CMD combinations involving stroke, heart disease, or diabetes were each associated with an increased risk of depressive symptoms compared with the absence of stroke, heart disease, or diabetes.Self-reported chronic conditions.Stroke, heart disease, and diabetes showed individual and additive effects on CMD combinations, whereas hypertension and dyslipidemia only showed associations with depressive symptoms in combinations with other CMDs. These results suggest person-centered healthcare of mental health prevention and treatment for middle-aged and older adults with individual or multiple CMDs.

Published
2022

9. Multimorbidity measures differentially predicted mortality among older Chinese adults

Author

Shan-Shan Yao, Hui-Wen Xu, Ling Han, Kaipeng Wang, Gui-Ying Cao, Nan Li, Yan Luo, Yu-Ming Chen, He-Xuan Su, Zi-Shuo Chen, Zi-Ting Huang, Yong-Hua Hu, and Beibei Xu

Subjects
Adult, China, Epidemiology, Health Status, Chronic Disease, Humans, Multimorbidity, Longitudinal Studies, Middle Aged, Aged
Abstract

This study aimed to examine and compare the associations between different multimorbidity measures and mortality among older Chinese adults.Using the Chinese Longitudinal Healthy Longevity Survey 2002-2018, data on fourteen chronic conditions from 13,144 participants aged ≥65 years were collected. Multimorbidity measures included condition counts, multimorbidity patterns (examined by exploratory factor analysis), and multimorbidity trajectories (examined by a group-based trajectory model). Mortality risk associated with different multimorbidity measures was each analyzed using Cox regression. C-statistic, the Integrated Discrimination Improvement (IDI), and the Net Reclassification Index (NRI) were used to compare the performance of different multimorbidity measures.Participants with multimorbidity, regardless of measurements, had a higher risk of death compared with people without multimorbidity. Compared with the mortality prediction model using age and sex, C-statistics showed added discrimination (over 0.77, all P .05) for models with multimorbidity measures. Multimorbidity trajectory showed integrated discrimination and net reclassification improvement for mortality prediction compared to condition count (IDI = 0.042, NRI = 0.033) and multimorbidity pattern (IDI = 0.041, NRI = 0.069).Adding multimorbidity measures significantly improved the performance of a mortality prediction model using age and sex as predictors. Trajectory-based measures of multimorbidity performed better than count- and pattern-based measures for mortality prediction.

Published
2021

10. Acute cardiac complications and subclinical myocardial injuries associated with pheochromocytoma and paraganglioma

Author

Junting Hu, Yunxiang Miao, He Xuan, Jing Zhou, and Yunlang Dai

Subjects
Adult, Male, medicine.medical_specialty, China, Time Factors, Heart Diseases, Cardiomyopathy, Adrenal Gland Neoplasms, 030209 endocrinology & metabolism, Pheochromocytoma, 030204 cardiovascular system & hematology, Longitudinal strain, Gastroenterology, behavioral disciplines and activities, Risk Assessment, Paraganglioma, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Takotsubo Cardiomyopathy, Internal medicine, Prevalence, Medicine, Diseases of the circulatory (Cardiovascular) system, Humans, Cardiac complication, Subclinical infection, Angiology, Retrospective Studies, Heart Failure, biology, business.industry, Middle Aged, medicine.disease, Troponin, Cardiac surgery, nervous system, RC666-701, Myocardial injury, Acute Disease, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, Heart failure with preserved ejection fraction, psychological phenomena and processes, Research Article
Abstract

Background Catecholamine excess arising from pheochromocytomas and paragangliomas (PPGLs) can cause a wide spectrum of cardiac manifestations, including acute cardiac complications (ACCs) and subclinical myocardial injuries (SMIs). In this study, we aimed to conduct a comprehensive analysis of ACCs and SMIs in a large cohort of patients with PPGLs. Methods We retrospectively analyzed the clinical data of consecutive patients with PPGLs admitted between January 2013 and July 2020 (n = 189). The prevalence of ACCs and SMIs and characteristics of patients identified with ACCs and SMIs were investigated. Moreover, comparisons were performed between patients with and without ACCs. Results Fourteen patients (7.4%) fulfilled the criteria for ACCs, including nine (4.8%) who presented with Takotsubo-like cardiomyopathy, four (2.1%) with heart failure with preserved ejection fraction, and finally one (0.5%) with catecholamine-induced cardiomyopathy. Compared to those without ACCs (n = 175), patients with ACCs had a higher prevalence of epinephrine-producing PPGLs (81.8% vs 33.9%, P = 0.006) and were more likely to show invasive behavior (61.5% vs 27.3%, P = 0.022) or hemorrhage/necrosis (53.9% vs 17.4%, P = 0.005) on histology. The apical sparing pattern (5/7, 71.4%) was the dominant impairment pattern of longitudinal strain (LS) for patients displaying Takotsubo-like cardiomyopathy. In patients without cardiac symptoms, a fairly high proportion (21/77, 27.3%) of patients who underwent screening for troponin and/or natriuretic peptide and/or echocardiography had SMIs. Conclusions One in every fourteen PPGL patients presented with ACCs, and in the patients with Takotsubo-like cardiomyopathy, the apical sparing pattern was the primary impairment pattern of LS. Additionally, nearly one-third of patients without symptoms had SMIs. The diagnosis of PPGLs should be considered in patients with acute reversible cardiomyopathy, especially in those exhibiting an apical sparing pattern of LS.

Published
2021

11. Metabolic Fingerprint of Dimethyl Sulfone (DMSO2) in Microbial–Mammalian Co-metabolism

Author

He, Xuan and Slupsky, Carolyn M

Subjects
Microbiology, Biological Sciences, Chemical Sciences, Digestive Diseases, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Animals, Dimethyl Sulfoxide, Host-Pathogen Interactions, Humans, Intestinal Mucosa, Intestines, Mammals, Metabolic Networks and Pathways, Metabolome, Metabolomics, Microbiota, Sulfones, DMSO2, dimethyl sulfone, methylsulfonylmethane, dimethyl sulfoxide, dimethyl sulfide, methanethiol, hydrogen sulfide, intestinal microbiota, metabolism, metabolome, Biochemistry & Molecular Biology, Biological sciences, Chemical sciences
Abstract

There is growing awareness that intestinal microbiota alters the energy harvesting capacity of the host and regulates metabolism. It has been postulated that intestinal microbiota are able to degrade unabsorbed dietary components and transform xenobiotic compounds. The resulting microbial metabolites derived from the gastrointestinal tract can potentially enter the circulation system, which, in turn, affects host metabolism. Yet, the metabolic capacity of intestinal microbiota and its interaction with mammalian metabolism remains largely unexplored. Here, we review a metabolic pathway that integrates the microbial catabolism of methionine with mammalian metabolism of methanethiol (MT), dimethyl sulfide (DMS), and dimethyl sulfoxide (DMSO), which together provide evidence that supports the microbial origin of dimethyl sulfone (DMSO2) in the human metabolome. Understanding the pathway of DMSO2 co-metabolism expends our knowledge of microbial-derived metabolites and motivates future metabolomics-based studies on ascertaining the metabolic consequences of intestinal microbiota on human health, including detoxification processes and sulfur xenobiotic metabolism.

Published
2014

12. Clinicopathological evidence of hepatitis B virus infection in the development of gastric adenocarcinoma

Author

Yao Liu, Yongsheng Zhang, Yizi Jin, Wei Deng, Caihong Hu, Yudong Xu, Fang Chen, He Xuan, Hongxia Cui, Duanmin Hu, and Hengli Ni

Subjects
Male, Hepatitis B virus, Adenocarcinoma, medicine.disease_cause, B7-H1 Antigen, Virus, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Virology, Atypia, Humans, Medicine, Viral Regulatory and Accessory Proteins, 030212 general & internal medicine, Aged, biology, business.industry, virus diseases, Cancer, Middle Aged, Helicobacter pylori, Hepatitis B, medicine.disease, biology.organism_classification, Hepatitis B Core Antigens, Immunohistochemistry, digestive system diseases, HBx, HBcAg, Infectious Diseases, Gastric Mucosa, Case-Control Studies, Immunology, Trans-Activators, Female, 030211 gastroenterology & hepatology, business
Abstract

Gastric cancer (GC) is one of the infection-related cancers. Helicobacter pylori and Epstein-Barr virus (EBV) were established risk factors for GC. Recently, there are several reports showing the inconsistent association between hepatitis B virus (HBV) infection and the development of GC. To explore the relationship between HBV infection and the development of GC, we designed a meta-analysis of previous epidemiological studies, a hospital-based case-control study, followed by an immunohistochemistry (IHC) assay of HBV-exposed GC samples. We found that HBV infection was associated with an increased risk of GC based on the meta-analysis. No significant association between HBV infection and GC was detected according to our hospital-based case-control study. Histological examination showed that the gastric epithelium positive for HBx demonstrated a higher nuclear-cytoplasmic ratio compared to those HBx-negative cells. HBx and HBcAg were expressed more in tumors than those in normal counterparts in HBV-exposed subjects, and PD-L1 was lower in GC tissues from HBV carriers than those in HBV clearances. In conclusion, HBV infection may contribute to a higher risk for GC based on the meta-analysis and to the morphological atypia of gastric epithelium by the histological assessment, and GC patients among HBV carriers showed lower expression of PD-L1 may lose the chance for immune checkpoint blockade therapy.

Published
2019

13. Associations between Multimorbidity and Physical Performance in Older Chinese Adults

Author

He-Xuan Su, Xiangfei Meng, Yonghua Hu, Ling Han, Gui-Ying Cao, Yan Luo, Beibei Xu, Zi-Ting Huang, Zi-Shuo Chen, Shan-Shan Yao, and Kaipeng Wang

Subjects
Longitudinal study, Asia, multimorbidity, Health, Toxicology and Mutagenesis, Population, lcsh:Medicine, Article, 03 medical and health sciences, Grip strength, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, education, Generalized estimating equation, Aged, education.field_of_study, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Odds ratio, physical performance, Middle Aged, Physical Functional Performance, Confidence interval, Exploratory factor analysis, Walking Speed, Quartile, grip strength, Chronic Disease, Female, business, gait speed, 030217 neurology & neurosurgery, Demography
Abstract

Background: Evidence on the association between physical performance and multimorbidity is scarce in Asia. This study aimed to identify multimorbidity patterns and their association with physical performance among older Chinese adults. Methods: Individuals aged &ge, 60 years from the China Health and Retirement Longitudinal Study 2011&ndash, 2015 (N = 10,112) were included. Physical performance was measured by maximum grip strength (kg) and average gait speed (m/s) categorized as fast (&gt, 0.8 m/s), median (&gt, 0.6&ndash, 0.8 m/s), and slow (&le, 0.6 m/s). Multimorbidity patterns were explored using exploratory factor analysis. Generalized estimating equation was conducted. Results: Four multimorbidity patterns were identified: cardio&ndash, metabolic, respiratory, mental&ndash, sensory, and visceral&ndash, arthritic. An increased number of chronic conditions was associated with decreased normalized grip strength (NGS). Additionally, the highest quartile of factor scores for cardio&ndash, metabolic (&beta, = &minus, 0.06, 95% Confidence interval (CI) = &minus, 0.07, &minus, 0.05), respiratory (&beta, 0.03, 95% CI = &minus, 0.05, &minus, 0.02), mental&ndash, sensory (&beta, 0.04, 0.03), and visceral&ndash, arthritic (&beta, 0.02) patterns were associated with lower NGS compared with the lowest quartile. Participants with &ge, 4 chronic conditions were 2.06 times more likely to have a slow gait speed. Furthermore, the odds ratios for the highest quartile of factor scores of four patterns with slow gait speed compared with the lowest quartile ranged from 1.26&ndash, 2.01. Conclusion: Multimorbidity was related to worse physical performance, and multimorbidity patterns were differentially associated with physical performance. A shift of focus from single conditions to the requirements of a complex multimorbid population was needed for research, clinical guidelines, and health-care services. Grip strength and gait speed could be targeted to routinely measure clinical performance among older adults with multimorbidity, especially mental&ndash, sensory disorders, in clinical settings.

Published
2020
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14. Different doses of galcanezumab versus placebo in patients with migraine and cluster headache: a meta-analysis of randomized controlled trials

Author

Bixi Gao, Yanbo Yang, Zilan Wang, Zhouqing Chen, Yun Zhu, He Xuan, and Zhong Wang

Subjects
medicine.medical_specialty, Cluster headache, Calcitonin Gene-Related Peptide, Injections, Subcutaneous, Migraine Disorders, lcsh:Medicine, Lower risk, Placebo, Antibodies, Monoclonal, Humanized, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, 030212 general & internal medicine, Adverse effect, Migraine, Randomized Controlled Trials as Topic, business.industry, lcsh:R, General Medicine, medicine.disease, Galcanezumab, Meta-analysis, Anesthesiology and Pain Medicine, Treatment Outcome, Relative risk, Neurology (clinical), business, 030217 neurology & neurosurgery, Research Article
Abstract

Background Galcanezumab is a novel monoclonal antibody that target to calcitonin gene-related peptide (CGRP). It has been tested for the preventive treatment of migraine and episodic cluster headache by multiple randomized clinical trials (RCTs) and have been found to reduce headache frequency. Methods We systematically searched PubMed and Embase on Cochrane Central Register of Controlled Trials (CENTRAL) from the earliest date to August 1, 2019. Relative risk (RR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. Results Seven studies were pooled with 3889 patients. Subcutaneous injection of Galcanezumab at 120 mg, 240 mg leads to a statistically significant response rate for the treatment of migraine compared with placebo (120 mg: RR = 1.51; 95% CI, 1.33 to 1.70; P P P = 0.425; 75% response: RR = 1.07; 95% CI, 0.94 to 1.23; P = 0.301; 100% response; RR = 1.06; 95% CI, 0.81 to 1.37; P = 0.682; MHD: RR = − 0.08; 95% CI, − 0.55 to − 0.40; P = 0.748) while related to a lower risk for adverse events for the treatment of migraine (120 mg RR = 1.06; 95% CI, 0.99 to 1.14; P = 0.084; 240 mg: RR = 1.17; 95% CI, 1.09 to 1.25; P P = 0.048). Conclusions Use of galcanezumab is related to a significantly reduced monthly headache frequency compared with placebo for the treatment of migraine and episodic cluster headache, 120 mg has the same treatment efficacy with 240 mg group while related to a lower risk for adverse effects for the treatment of migraine. 300 mg per month galcanezumab is effective for the prevention of episodic cluster headache with no significantly increased adverse events.

Published
2019

15. Associations Between Somatic Multimorbidity Patterns and Depression in a Longitudinal Cohort of Middle-Aged and Older Chinese

Author

Yonghua Hu, He-Xuan Su, Zi-Shuo Chen, Ling Han, Gui-Ying Cao, Shan-Shan Yao, Beibei Xu, and Zi-Ting Huang

Subjects
Male, medicine.medical_specialty, Longitudinal study, China, Odds, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, medicine, Multimorbidity, Humans, 030212 general & internal medicine, Longitudinal Studies, Generalized estimating equation, General Nursing, Depression (differential diagnoses), Aged, business.industry, Depression, Health Policy, General Medicine, Odds ratio, Middle Aged, Confidence interval, Chronic Disease, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Demography
Abstract

Objectives Depressive symptoms are commonly seen among patients with multiple chronic somatic conditions, or somatic multimorbidity (SMM); however, little is known about the relationships between depressive symptoms and different SMM combinations. Our study aimed to delineate the patterns of SMM and their longitudinal associations with depressive symptoms among a nationally representative sample of middle-aged and older Chinese adults. Design We employed a longitudinal design. Setting and Participants Older adults (N = 10,084) aged ≥45 years from the China Health and Retirement Longitudinal Study 2011-2015 participated (mean age = 57.7 years at baseline; 53.3% men). Methods Sixteen chronic somatic conditions were ascertained at baseline via questionnaires. Depression was assessed with the Center for Epidemiological Studies Depression Scale at baseline and during follow-up. Patterns of SMM were identified via exploratory factor analyses. Generalized estimating equations were used to evaluate the longitudinal associations between patterns of SMM and the presence of depressive symptoms at follow-up. Results Compared with participants with no somatic condition, those with 1, 2, and 3 or more somatic conditions had a 21%, 66%, and 111% greater risk, respectively, for the presence of depressive symptoms. Increased factor scores for 4 patterns identified, cardio-metabolic pattern [adjusted odds ratio (AOR) 1.12, 95% confidence interval (CI) 1.06, 1.20], respiratory pattern (AOR 1.25, 95% CI 1.17, 1.33), arthritic-digestive-visual pattern (AOR 1.29, 95% CI 1.22, 1.37), and hepatic-renal-skeletal pattern (AOR 1.09, 95% CI 1.02, 1.16), were all associated with a higher risk of having depressive symptoms. Conclusions and Implications All SMM patterns were independently associated with depression among middle-aged and older Chinese adults, with greater odds for people with comorbid arthritic-digestive-visual conditions and respiratory conditions. Clinical practitioners should treat the middle-aged and older population under a multiple-condition framework combining SMM and mental disorders.

Published
2019

16. Mental health and psychological impact of COVID-19: Potential high-risk factors among different groups

Author

Lijie Mi, Yufeng Jiang, He Xuan, and Yafeng Zhou

Subjects
China, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Preventive Psychiatry, Risk Assessment, Vulnerable Populations, Sex Factors, Risk Factors, Surveys and Questionnaires, Environmental health, Adaptation, Psychological, Pandemic, Humans, Medicine, Letter to the Editor, Psychological impact, General Psychology, SARS-CoV-2, business.industry, Mental Disorders, Age Factors, COVID-19, General Medicine, High risk factors, Mental health, Psychiatry and Mental health, Mental Health, business
Published
2020

17. Short-segment fixation with a cement-augmented pedicle screw for Kummell disease

Author

Di, He-Xuan, Liu, Feng-Yu, Yang, Si-Dong, Wang, Hui, Yang, Da-Long, and Ding, Wen-Yuan

Subjects
musculoskeletal diseases, Lumbar Vertebrae, Bone Cements, Osteonecrosis, Middle Aged, equipment and supplies, Thoracic Vertebrae, Fracture Fixation, Internal, short-segment fixation, Kummell disease, Back Pain, Pedicle Screws, cement-augmented pedicle screw, Fractures, Compression, Humans, Spinal Fractures, Female, Clinical Case Report, Osteoporotic Fractures, Research Article
Abstract

Rationale: Kummell disease is described as avascular necrosis of a vertebral body that occurred in a delayed fashion after a minor trauma. Anterior, posterior, and anterior–posterior approaches have been reported. Nevertheless, there is no standard treatment for patients with Kummell disease. Patient concerns: We reported a successful cement-augmented pedicle screw placement in a patient with Kummell disease. A 63-year-old woman with serious osteoporosis complained persistent back pain with progressive lower extremities weakness for almost 2 years. Diagnoses: The diagnosis of Kummell disease was mainly depended on clinical symptoms and imaging examinations. Interventions: The application of a cement-augmented pedicle screw was designed to treat this illness. Outcomes: The operation was successful without any complications. The patient stated that symptoms were obviously improved in 1 week after operation. Lessons: The application of a cement-augmented pedicle screw is an effective treatment option for Kummell disease.

Published
2017

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