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Sitong Feng,1,2,* Ziyao Wu,1,2,* Sisi Zheng,1,2 Linrui Dong,1,2 Hongxiao Jia,1,2 Yanzhe Ning1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanzhe Ning; Hongxiao Jia, Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China, Email ningzy0923@mail.ccmu.edu.cn; jhxlj@ccmu.edu.cnObjective: The thalamus plays a critical role in attentional maintenance. Previous studies have revealed the dysfunction of the thalamus in attention decline after acute sleep deprivation (SD). However, the functional connectivity (FC) between the thalamus subregions and cortical regions underlying attentional impairment after acute SD remains unclear. Here, we aimed to probe the relationship between attentional function and the altered thalamocortical FC after acute SD.Methods: In this study, 25 healthy participants with regular sleep conducted an attentional network test and received a resting-state fMRI scan before and after 24 hours of SD. Then, we analyzed the FC between the thalamus and cerebrum and relationships with attentional function in the enrolled subjects.Results: Our results showed that the participants showed a significantly lower alerting effect, a higher executive effect, and lower accuracy after acute SD. Compared to the rested wakefulness state, we observed decreased FCs between the “somatosensory” thalamic seed and left frontal pole, right frontal pole, left middle temporal gyrus (posterior division), and right middle temporal gyrus (posterior division). Furthermore, the reduced FC between the right middle temporal gyrus and “somatosensory” thalamic seed was negatively associated with the change in orienting effect of the participants.Conclusion: Our findings reveal that the disrupted FC between thalamus subregions and cortical regions may contribute to impaired attention after SD.Keywords: sleep deprivation, fMRI, attention, thalamus, functional connectivity

Jingyi Lao,1,* Yijie Zeng,1,* Zhangying Wu,1 Gaohong Lin,1 Qiang Wang,1 Mingfeng Yang,1 Si Zhang,1 Danyan Xu,1 Min Zhang,1 Kexin Yao,1 Shuang Liang,1 Qin Liu,1 Jiafu Li,1 Xiaomei Zhong,1 Yuping Ning1– 4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuping Ning; Xiaomei Zhong, The Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Email ningjeny@126.com; lovlaugh@163.comBackground: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear.Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed.Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items.Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.Keywords: late-life depression, microstate, electroencephalogram, resting-state networks

Zhao-Ting Gong,1 Yu-Yan Xiong,1,2 Yu Ning,1 Rui-Jie Tang,1 Jun-Yan Xu,3 Wen-Yang Jiang,1 Xiao-Song Li,1 Li-Li Zhang,1 Cheng Chen,1 Qi Pan,1 Meng-Jin Hu,1 Jing Xu,1 Yue-Jin Yang1 1State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Yue-Jin Yang, Email yangyjfw@126.comBackground: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI).Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism.Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway.Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation. Keywords: mesenchymal stem cell, exosomes, nicorandil, macrophage polarization, myocardial infarction

Chuan Tan,1,* Yanyan Huang,2,* Zheng Huang,2,* Yuanjia Ning,2 Lizheng Huang,2 Xianjian Wu,1 Yuan Lu,1 Huamei Wei,3 Jian Pu1 1Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 2Graduate College of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Pu, Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, Guangxi, People’s Republic of China, Email jian_pu@126.comPurpose: N6-methyladenosine (m6A) modification has shown critical roles in regulating mRNA fate. Non-coding RNAs also have important roles in various diseases, including hepatocellular carcinoma (HCC). However, the potential influences of m6A modification on non-coding RNAs are still unclear. In this study, we identified a novel m6A-modified ATP8B1-AS1 and aimed to investigate the effects of m6A on the expression and role of ATP8B1-AS1 in HCC.Methods: qPCR was performed to measure the expression of related genes. The correlation between gene expression and prognosis was analyzed using public database. m6A modification level was measured using MeRIP and single-base elongation- and ligation-based qPCR amplification method. The roles of ATP8B1-AS1 in HCC were investigated using in vitro and in vivo functional assays. The mechanisms underlying the roles of ATP8B1-AS1 were investigated by ChIRP and ChIP assays.Results: ATP8B1-AS1 is highly expressed in HCC tissues and cell lines. High expression of ATP8B1-AS1 is correlated with poor overall survival of HCC patients. ATP8B1-AS1 is m6A modified and the 792 site of ATP8B1-AS1 is identified as an m6A modification site. m6A modification increases the stability of ATP8B1-AS1 transcript. m6A modification level of ATP8B1-AS1 is increased in HCC tissues and cell lines, and correlated with poor overall survival of HCC patients. ATP8B1-AS1 promotes HCC cell proliferation, migration, and invasion, which were abolished by the mutation of m6A-modified 792 site. Mechanistic investigation revealed that m6A-modified ATP8B1-AS1 interacts with and recruits m6A reader YTHDC1 and histone demethylase KDM3B to MYC promoter region, leading to the reduction of H3K9me2 level at MYC promoter region and activation of MYC transcription. Functional rescue assays showed that depletion of MYC largely abolished the oncogenic roles of ATP8B1-AS1.Conclusion: m6A modification level of ATP8B1-AS1 is increased and correlated with poor prognosis in HCC. m6A-modified ATP8B1-AS1 exerts oncogenic roles in HCC via epigenetically activating MYC expression.Keywords: hepatocellular carcinoma, N6-methyladenosine, noncoding RNA, histone methylation, MYC signaling

Sitong Feng,1,2 Linrui Dong,1,2 Bin Yan,3 Sisi Zheng,1,2 Zhengtian Feng,1,2 Xue Li,1,2 Jiajia Li,1,2 Ning Sun,3 Yanzhe Ning,1,2 Hongxiao Jia1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Department of Andrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Hongxiao Jia; Yanzhe Ning, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Hutong, Xicheng District, Beijing, 100088, People’s Republic of China, Tel +86 010-58303065, Email jhxlj@ccmu.edu.cn; ningzy0923@mail.ccmu.edu.cnPurpose: Several studies have demonstrated that psychogenic erectile dysfunction (pED) patients potentially suffer from cognitive dysfunction. Despite that previous neuroimaging studies have reported abnormal functional connections of brain areas associated with cognitive function in pED, the underlying mechanisms of cognitive dysfunction in pED remain elusive. This study aims to investigate the underlying mechanisms of cognitive dysfunction by analyzing large-scale brain networks.Patients and Methods: A total of 30 patients with pED and 30 matched healthy controls (HCs) were recruited in this study and scanned by resting-state functional magnetic resonance imaging. The Dosenbach Atlas was used to define large-scale networks across the brain. The resting-state functional connectivity (FC) within and between large-scale brain networks was calculated to compare pED patients with HCs. The relationship among cognitive performances and altered FC of large-scale brain networks was further explored in pED patients.Results: Our results showed that the decreased FC within visual network, and between visual network and default mode network, visual network and frontoparietal network, and ventral attention and default mode network were found in pED patients. Furthermore, there was a positive correlation between immediate memory score and FC within visual network. The visuospatial score was negatively correlated with decreased FC between ventral attention network and default mode network.Conclusion: Taken together, our findings revealed the relationship between cognitive impairments and altered FC between large-scale brain networks in pED patients, providing the new evidence about the neural mechanisms of cognitive dysfunction in pED patients.Keywords: large-scale brain network, functional connectivity, cognitive impairment, psychogenic erectile dysfunction

Zhihan Jiang,1,* Xiaosen Wang,1,* Lijiao Zhang,1,* Drolma Yangzom,2,* Yanping Ning,2 Baiyan Su,3,4 Meijiao Li,5 Meilang ChuTso,2 Yahong Chen,1,6 Ying Liang,1,2,6 Yongchang Sun1,6 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, 850000, People’s Republic of China; 3Radiology Department, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 4Radiology Department, Tibet Autonomous Region People’s Hospital, Lhasa, 850000, People’s Republic of China; 5Radiology Department, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 6Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, 100083, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Liang; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of China, Tel +86 138 1096 4766 ; +86 139 1097 9132, Email bysyliangying@126.com; suny@bjmu.edu.cnBackground: COPD patients living in Tibet are exposed to specific environments and different risk factors and probably have different characteristics of COPD from those living in flatlands. We aimed to describe the distinction between stable COPD patients permanently residing at the Tibet plateau and those in flatlands.Methods: We conducted an observational cross-sectional study that enrolled stable COPD patients from Tibet Autonomous Region People’s Hospital (Plateau Group) and Peking University Third Hospital (Flatland Group), respectively. Their demographic information, clinical features, spirometry test, blood routine and high-resolution chest CT were collected and evaluated.Results: A total of 182 stable COPD patients (82 from plateau and 100 from flatland) were consecutively enrolled. Compared to those in flatlands, patients in plateau had a higher proportion of females, more biomass fuel use and less tobacco exposure. CAT score and frequency of exacerbation in the past year were higher in plateau patients. The blood eosinophil count was lower in plateau patients, with fewer patients having an eosinophil count ≥ 300/μL. On CT examination, the proportions of previous pulmonary tuberculosis and bronchiectasis were higher in plateau patients, but emphysema was less common and milder. The ratio of diameters of pulmonary artery to aorta ≥ 1 was more often in plateau patients.Conclusion: Patients with COPD living at Tibet Plateau had a heavier respiratory burden, lower blood eosinophil count, less emphysema but more bronchiectasis and pulmonary hypertension. Biomass exposure and previous tuberculosis were more common in these patients.Keywords: chronic obstructive pulmonary disease, plateau, phenotype, computed tomography, emphysema

The ecological threshold concept describes how changes in one or more factors at thresholds can result in a large shift in the state of an ecosystem. This concept focuses attention on limiting factors that affect the tolerance of systems or organisms and changes in them. Accumulating empirical evidence for the existence of ecological thresholds has created favorable conditions for practical application to wildlife conservation. Applying the concept has the potential to enhance conservation of two large carnivores, Amur tiger and leopard, and the knowledge gained could guide the construction of a proposed national park. In this review, ecological thresholds that result from considering a paradigm of bottom-up control were evaluated for their potential to contribute to the conservation of Amur tiger and leopard. Our review highlights that large carnivores, as top predators, are potentially affected by ecological thresholds arising from changes in climate (or weather), habitat, vegetation, prey, competitors, and anthropogenic disturbances. What's more, interactions between factors and context dependence need to be considered in threshold research and conservation practice, because they may amplify the response of ecosystems or organisms to changes in specific drivers. Application of the threshold concept leads to a more thorough evaluation of conservation needs, and could be used to guide future Amur tiger and leopard research and conservation in China. Such application may inform the conservation of other large carnivores worldwide.

Ying Ning,* Yanju Gong,* Tianyan Zheng, Ya Xie, Shiqing Yuan, Weijun Ding School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijun Ding; Shiqing Yuan, Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Road, Chengdu, 611137, People’s Republic of China, Tel + 86-28-61800219, Fax + 86-28-61800225, Email Dingweijun@cdutcm.edu.cn; yuanshiqing@cdutcm.edu.cnBackground: The increasing incidence of obesity and its complications has become a global public health problem. Lingguizhugan decoction (LGZGD) is a representative compound of traditional Chinese medicine (TCM) for metabolic diseases, such as nonalcoholic fatty liver disease, but its role in insulin resistance (IR) treatment is still less known. This study aims to evaluate the therapeutic properties of LGZGD on obesity-induced IR and explore the potential mechanism of LGZGD on gut microbiota and its metabolites in the treatment of IR.Methods: In this study, we induced an IR model in the form of high-fat diet (HFD) rats gavaged with LGZGD (1.64 g/kg BW) for three weeks. The IR status was measured by biochemical assays and oral glucose tolerance tests. The degrees of damage to liver function and the intestinal barrier were observed by hematoxylin and eosin (H&E) staining and immunohistochemistry. Alterations in intestinal microbiota and metabolites were assessed by 16S rRNA and an untargeted metabolomics platform.Results: Our results showed that after LGZGD treatment, the body weight, plasma insulin concentration and blood lipids were significantly decreased, and glucose tolerance and hepatic steatosis were ameliorated. In addition, small intestinal villi were restored, and the expression of Occludin was upregulated. The relative abundance of Akkermansia, Faecalibacterium and Phascolarctobacterium in the HFD-LGZG group was upregulated. Obesity-related metabolic pathways, such as bile secretion, biosynthesis of amino acids, phenylalanine metabolism, serotonergic synapse, protein digestion and absorption, taurine and hypotaurine metabolism, and primary bile acid biosynthesis, were changed. After LGZGD intervention, metabolites developed toward the healthy control group. In addition, the expression of bile acid metabolism related genes was also regulated in IR rats.Conclusion: We showed that LGZGD relieved IR, possibly by regulating the composition of the fecal microbiota and its metabolites. The above studies provide a basis for further study of LGZGD in the treatment of IR and its clinical application.Keywords: insulin resistance, IR, lingguizhugan decoction, LGZGD, intestinal microbiota, nontargeted metabolomics, high-fat diet, HFD

Yanzhe Ning,1– 3 Sisi Zheng,1– 3 Sitong Feng,1– 3 Kuangshi Li,4 Hongxiao Jia1– 3 1The Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 4Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Hongxiao Jia, The Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China, Email jhxlj@ccmu.edu.cn Kuangshi Li, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China, Email likuangshi89@hotmail.comIntroduction: Sleep deprivation (SD) has a detrimental effect on cognitive functions. Numerous studies have indicated the mechanisms underlying cognitive impairments after SD in brain networks. However, the findings based on the functional connectivity (FC) and topological architecture of brain networks are inconsistent.Methods: In this study, we recruited 30 healthy participants with regular sleep (aged 25.20 ± 2.20 years). All participants performed the repeatable battery for the assessment of neuropsychological status and resting-state fMRI scans twice, during the rested wakefulness (RW) state and after 24 h of total SD. Using the Dosenbach atlas, both large-scale FC and topological features of brain networks (ie nodal, global and local efficiency) were calculated for the RW and SD states. Furthermore, the correlation analysis was conducted to explore the relationship between the changes in FC and topological features of brain networks and cognitive performances.Results: Compared to the RW state, the large-scale brain network results showed decreased between-network FC in somatomotor network (SMN)-default mode network (DMN), SMN-frontoparietal network (FPN), and SMN-ventral attention network (VAN), and increased between-network FC in the dorsal attention network (DAN)-VAN, DAN-SMN after SD. The clustering coefficient, characteristic path length and local efficiency decreased after SD. Moreover, the decreased attention score positively correlated with the decreased topological measures and negatively correlated with the FC of DAN-SMN.Conclusion: Our results suggested that the increased FC of DAN-SMN and decreased topological features of brain networks may act as neural indicators for the decrease in attention after SD.Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR2000039858, China.Keywords: brain network, functional connectivity, sleep deprivation, cognitive impairment, topological feature

Yao Yao,&ast; Yumeng Jia,&ast; Yan Wen, Bolun Cheng, Shiqiang Cheng, Li Liu, Xuena Yang, Peilin Meng, Yujing Chen, Chun’e Li, Jingxi Zhang, Zhen Zhang, Chuyu Pan, Huijie Zhang, Cuiyan Wu, Xi Wang, Yujie Ning, Sen Wang, Feng Zhang Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng ZhangKey Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaEmail fzhxjtu@mail.xjtu.edu.cnPurpose: Most previous genetic studies of sleep behaviors were conducted individually, without comprehensive consideration of the complexity of various sleep behaviors. Our aim is to identify the genetic architecture and potential biomarker of the sleep health score, which more powerfully represents overall sleep traits.Patients and Methods: We conducted a genome-wide association study (GWAS) of sleep health score (overall assessment of sleep duration, snoring, insomnia, chronotype, and daytime dozing) using 336,463 participants from the UK Biobank. Proteome-wide association study (PWAS) and transcriptome-wide association study (TWAS) were then performed to identify candidate genes at the protein and mRNA level, respectively. We finally used linkage disequilibrium score regression (LDSC) to estimate the genetic correlations between sleep health score and other functionally relevance traits.Results: GWAS identified multiple variants near known candidate genes associated with sleep health score, such as MEIS1, FBXL13, MED20 and SMAD5. HDHD2 (PPWAS = 0.0146) and GFAP (PPWAS = 0.0236) were identified associated with sleep health score by PWAS. TWAS identified ORC4 (PTWAS = 0.0212) and ZNF732 (PTWAS = 0.0349) considering mRNA expression level. LDSC found significant genetic correlations of sleep health score with 3 sleep behaviors (including insomnia, snoring, dozing), 4 psychiatry disorders (major depressive disorder, attention deficit/hyperactivity disorder, schizophrenia, autism spectrum disorder), and 9 plasma protein (such as Stabilin-1, Stromelysin-2, Cytochrome c) (all LDSC PLDSC < 0.05).Conclusion: Our results advance the comprehensive understanding of the aetiology and genetic architecture of the sleep health score, refine the understanding of the relationship of sleep health score with other traits and diseases, and may serve as potential targets for future mechanistic studies of sleep phenotype.Keywords: sleep, sleep health score, genome-wide association study, genetics, complex-traits

Jie Zhong,1,2,&ast; Hong Zhu,1,2,&ast; Dongqing Yin,1,2 Yanzhe Ning,1,2 Sisi Zheng,1,2 Yanbo Zhang,3 Hongxiao Jia1,2 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine, and Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada&ast;These authors contributed equally to this workCorrespondence: Yanbo ZhangDepartment of psychiatry, Faculty of Medicine, and Dentistry, College of Health Sciences, University of Alberta, Alberta, Edmonton, CanadaEmail yanbo.zhang@usask.caHongxiao JiaThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel +86-010-58303065Email jhxlj@ccmu.edu.cnPurpose: Theory of mind (ToM) is an important part of social cognitive function and is associated with medial prefrontal cortical (mPFC) activity. This study aimed to evaluate the efficacy of paliperidone in improving ToM task performance in patients with schizophrenia compared with haloperidol.Patients and Methods: This study was a single-center, single-blinded (assessor), parallel-group randomized clinical trial of patients with schizophrenia randomized to paliperidone or haloperidol. ToM was assessed at weeks 0, 8, 12, and 16 using the first-order belief, higher-order belief, faux-pas, and Reading the Mind in the Eyes tests. The primary outcome was the change in the ToM performance scores from baseline to after 16 weeks of treatment.Results: The participants received paliperidone (n = 29) or haloperidol (n = 31). For the first-order belief task, there were no between-group differences (P > 0.05) but time differences in both groups (P < 0.05). For the higher-order belief task, there were no between-group differences (P > 0.05), but there were time differences in both groups (P < 0.05) and a time×group interaction in the paliperidone group only (P < 0.05). For the faux-pas task, there was a difference between groups at week 16 (P < 0.05), and the improvement in time was significant for the paliperidone group only (P < 0.05). For the Reading the Mind in the Eyes task, there was an improvement over time for the paliperidone group only (P < 0.05). Safety was manageable in both groups.Conclusion: Paliperidone treatment might be more effective than haloperidol in improving ToM task performance in schizophrenia.Trial Registration: chictr.org.cn_identifier ChiCTR-IPR-15007635.Keywords: schizophrenia, theory of mind, longitudinal study, paliperidone, haloperidol

Yudong Ning,1 Hong Yang,2 Sheng Qin,2 Bangrong Cao,3 Zuxian Zhong,4 Chuanshi He,5 Guiquan Zhu6 1Department of Head and Neck Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Pathology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Department of Head and Neck Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Sichuan Key Laboratory of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, People’s Republic of China; 6Department of Head and Neck Oncology, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Guiquan ZhuDepartment of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaEmail zhugq@scu.edu.cnObjective: We aimed to identify new prognostic factors of oral squamous cell carcinoma (OSCC) among platelet-related parameters, establish a survival prediction model to predict the survival status of OSCC patients, and analyze the therapeutic effect of neoadjuvant chemotherapy on OSCC patients on the basis of real-world data.Materials and Methods: The real-world data of patients with OSCC confirmed by pathologic examination at Cancer Hospital from January 2011 to January 2015 and May 2017 to January 2020 were collected. We analyzed clinicopathologic factors using a Cox regression analysis, the Kaplan-Meier method, and propensity score matching (PSM).Results: The multivariate Cox regression analysis of not only validated the traditional prognostic factors such as tumor site, neural invasion, poor differentiation, and tumor-node-metastasis (TNM) stage but also identified a new prognostic factor, preoperative mean platelet volume (MPV) for overall survival (OS, HR, 0.47; 95% CI: 0.25– 0.89, P = 0.020). A nomogram was created to predict the probability of 3-year and 5-year OS. We found that neoadjuvant chemotherapy improved OS in patients with OSCC.Conclusion: Preoperative MPV, being associated with female, neoadjuvant chemotherapy, and advanced stage (Stage III and IV), may be a new prognostic factor for OS of patients with OSCC. The nomograms provided useful prediction for OS in OSCC patients. Neoadjuvant chemotherapy may improve the OS of patients with OSCC.Keywords: oral squamous cell carcinoma, overall survival, nomogram, mean platelet volume, neoadjuvant chemotherapy, induction chemotherapy

Pregnant persons are at higher risk of severe COVID-19. Although vaccination is recommended, COVID-19 vaccination rates are lower among pregnant persons compared to the non-pregnant population. We aimed to evaluate acceptance of any dose of COVID-19 vaccine during pregnancy. A national online cross-sectional survey of US adults who were pregnant between December 2020 and July 2021 was used to measure COVID-19 vaccine behaviors, attitudes, and beliefs. Post-stratification weighting was used to ensure representativeness to the US population. Marginal log-binomial models were used to estimate adjusted prevalence ratios (aPR) of COVID-19 vaccine acceptance, accounting for sociodemographic factors. Of 5,660 who responded to survey advertisements, 2,213 met eligibility criteria and completed the survey; 55.4% of respondents received or planned to receive COVID-19 vaccine prior to or during pregnancy, 27.0% planned to vaccinate after pregnancy, 8.8% were unsure and 8.7% had no plans to vaccinate. Individuals were more likely to receive or plan to receive COVID-19 vaccine if they had group prenatal care (aPR 1.57; 95% CI 1.40, 1.75), were employed in a workplace with a policy recommending vaccination (aPR 1.15; 95% CI 1.06, 1.26), and believed COVID-19 vaccines are safe (aPR 2.86; 95% CI 2.49, 3.29). Pregnant persons who were recommended COVID-19 vaccination by their healthcare provider less commonly reported concerns about vaccine safety (35.5% vs 55.9%) and were more likely to accept COVID-19 vaccines (aPR 1.52; 95% CI 1.31, 1.76). COVID-19 vaccine acceptance during pregnancy is not universal and public health intervention will be needed to continue to increase vaccine coverage.

Ying Liang,1,2 Drolma Yangzom,2 Lhamo Tsokyi,2 Yanping Ning,2 Baiyan Su,3,4 Shuai Luo,4 Bian Ma Cuo,2 Meilang ChuTso,2 Yanling Ding,1 Yahong Chen,1 Yongchang Sun1 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, 850000, People’s Republic of China; 3Radiology Department, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 4Radiology Department, Tibet Autonomous Region People’s Hospital, Lhasa, 850000, People’s Republic of ChinaCorrespondence: Yongchang SunDepartment of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of ChinaTel +86 139 1097 9132Fax +86 108 226 6989Email suny@bjmu.edu.cnBackground: COPD at high altitude may have different risk factors and unique clinical and radiological phenotypes. We aimed to investigate the demographic data, clinical and radiological features of COPD patients permanently residing at the Tibet Plateau (≥ 3000 meters above sea level).Methods: We conducted an observational cross-sectional study which consecutively enrolled COPD patients visiting the outpatient of Respiratory Medicine at Tibet Autonomous Region People’s Hospital from January 2018 to March 2021. All patients were Tibetan permanent residents aging ≥ 40 years and met the diagnosis of COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Data including demographic characteristics, altitude of residence, risk factors, respiratory symptoms, comorbidities and medications, as well as computed tomography (CT) measurements were collected.Results: Eighty-four patients with definite COPD were enrolled for analysis. Their mean age was 64.7 (± 9.1) years. All patients lived at ≥ 3000 m above sea level and 34.5% of them lived at ≥ 4000 m. About 8.3% of the patients were current smokers and 44.0% were ex-smokers. Up to 88.1% of the patients reported long-term exposure to indoor biomass fuels. Most of the patients were classified as having mild-to-moderate (GOLD I: 27.4%; GOLD II: 51.2%) COPD, while 89.3% had a CAT score ≥ 10. Only 36.9% of the patients received regular long-term medications for COPD in the past year, in whom ICS/LABA and oral theophylline were the most common used pharmacological therapy. On CT scanning, the majority of our patients (70.7%) showed no or minimal emphysema, while signs of previous tuberculosis were found in 45.1% of the patients.Conclusion: COPD patients living at the Tibet Plateau had a heavy respiratory symptom burden, but most of them did not receive adequate pharmacological treatment. Indoor biomass fuel exposure and previous tuberculosis were prevalent, while the emphysema phenotype was less common in this population.Keywords: chronic obstructive pulmonary disease, high altitude, phenotype, computed tomography

Yuan Ning,1 Yushuang Shao,1 Jiangyue Zhao,1 Jinsong Zhang,1 Mingwu Wang,2 Yu Qin1 1Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang, 110005, People’s Republic of China; 2Department of Ophthalmology and Vision Science, The University of Arizona College of Medicine, Tucson, Arizona, 85711-1824, USACorrespondence: Yu QinDepartment of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, No. 11 Xinhua Road, Heping District, Shenyang, 110005, People’s Republic of ChinaTel +86 24 62035015Fax +86 24 62035015Email yuqin_3620@163.comObjective: The aim of the present study was to evaluate the stability of four different types of aspheric intraocular lenses (IOLs) after implantation.Methods: This retrospective study included 124 eyes implanted with four different types of aspheric IOLs including a one-piece four-loop fixed hydrophilic acrylic IOL, a one-piece flat fixed acrylic IOL, a one-piece two-loop fixed acrylic IOL, and a three-piece two-loop fixed silicone IOL. IOL decentration, tilt, and ocular coma‐like aberration (coma) at one-week, one-month, three-month, and one-year time points were evaluated postoperatively.Results: IOL decentration, tilt, and coma in the AO, 36A, IQ, and KS-AiN implantation groups were statistically significantly different one week and one year postoperatively (p < 0.01). There were significant differences between each of the pairs of groups (p < 0.01), except for coma between the AO and 36A implantation groups one week postoperatively (p > 0.05). When comparing the different time points (ie, one week, one month, three months, and one year postoperatively), IOL decentration, tilt, and coma were significantly different in each group (p < 0.05). IOL decentration, tilt, and coma in each group increased over the period from one week to one year postoperatively. A positive linear correlation was observed between IOL decentration or tilt and coma one year postoperatively (p < 0.01).Conclusion: One-piece multi-point fixed acrylic IOLs demonstrate better stability when compared with three-piece two-point fixed silicone IOLs. IOL decentration, tilt, and coma increase gradually over time. Ocular coma‐like aberrations are influenced by the stability of IOLs.Keywords: stability, aspheric intraocular lens, IOL, decentration, tilt, coma

Yi Liu,1 Taiyong Bi,2 Qijie Kuang,1 Bei Zhang,3 Huawang Wu,1 Haijing Li,1 Bin Zhang,1 Jingping Zhao,4 Yuping Ning,1 Shenglin She,1 Yingjun Zheng1 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, 510370, People’s Republic of China; 2Centre for Mental Health Research in School of Management, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3General and Experimental Psychology, Department of Psychology, LMU, Munich, Germany; 4Mental Health Institute of the Second Xiangya Hospital, Central South University; Chinese National Clinical Research Center on Mental Disorders; Chinese National Technology Institute on Mental Disorders; Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Yingjun Zheng; Shenglin She Email brainzheng@gzhmu.edu.cn; shenglinshe@gzhmu.edu.cnObjective: Impaired face perception is considered as a hallmark of social disability in schizophrenia. It is widely believed that inverted faces and upright faces are processed by distinct mechanisms. Previous studies have identified that individuals with schizophrenia display poorer face processing than controls. However, the mechanisms underlying the face inversion effect (FIE) in patients with first-episode schizophrenia (FSZ) remain unclear.Methods: We designed an fMRI task to investigate the FIE mechanism in patients with schizophrenia. Thirty-four patients with FSZ and thirty-five healthy controls (CON) underwent task-related fMRI scanning, clinical assessment, anhedonia experience examination, and social function and cognitive function evaluation.Results: The patients with FSZ exhibited distinct functional activity regarding upright and inverted face processing within the cortical face and non-face network. These results suggest that the differences in quantitative processing might mediate the FIE in schizophrenia. Compared with controls, affected patients showed impairments in processing both upright and inverted faces; and for these patients with FSZ, upright face processing was associated with more severe and broader impairment than inverted face processing. Reduced response in the left middle occipital gyrus for upright face processing was related to poorer performance of social function outcomes evaluated using the Personal and Social Performance Scale.Conclusion: Our data suggested that patients with FSZ exhibited similar performance in processing inverted faces and upright faces, but were less efficient than controls; and for these patients, inverted faces are processed less efficiently than upright faces. We also provided a clue that the mechanism under abnormal FIE might be related to an aberrant activation of non-face-selective areas instead of abnormal activation of face-specific areas in patients with schizophrenia. Finally, our study indicated that the neural pathway for upright recognition might be relevant in determining the functional outcomes of this devastating disorder.Keywords: first-episode schizophrenia, face inversion effect, task-related fMRI, face recognition, social functional outcome

Yuanyuan Huang,1,* Yongjie Zhou,2,* Yi Wei,1 Lingyun Zeng,2 Jiezhi Yang,3 Yi Li,2 Xiuli Song,4 Hehua Li,1 Hongbo He,1 Ting Li,1 Kai Wu,5 Mingzhe Yang,1 Fengchun Wu,1,6,7 Yuping Ning,1,7 Xiangyang Zhang1,8 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, People’s Republic of China; 2Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 3Department of Psychiatry, Shenzhen Health Development Research Center, Shenzhen, People’s Republic of China; 4Clinical Psychology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People’s Republic of China; 5Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (scUT), Guangzhou, People’s Republic of China; 6Department of Psychiatry, Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 7The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 8CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuping NingDepartment of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), 36 Mingxin Road, Liwan District, Guangzhou, 510370, People’s Republic of ChinaEmail ningjeny@126.comXiangyang ZhangCAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaEmail zhangxy@psych.ac.cnBackground: During the outbreak of coronavirus disease 2019 (COVID-19), occupational differences were recognized with respect to psychological issues, but there are no reports regarding the insomnia and anxiety comorbidities and their related factors among the general public and medical staff. Our study aimed to compare the prevalence of anxiety and anxiety with insomnia, as well as the relationship between different psychological symptoms between the two groups.Methods: A total of 605 medical staff and 1091 public respondents were assessed through an online questionnaire survey, including the 7-item Insomnia Severity Index (ISI), the somatization subscale of Symptom Checklist 90-Revised (SCL-90-R), and the 7-item Generalized Anxiety Disorder scale (GAD-7).Results: Compared with the general public, medical staff had a higher incidence of anxiety (45.5% vs 32.4%). The incidence of insomnia in anxious participants was 52.7% in medical staff and 44.6% in the general public, and the difference was significant (p < 0.05). The GAD-7 score and somatization subscore of the SCI-90 were independently associated with insomnia among anxiety participants in both groups (all p < 0.001).Conclusion: Our findings suggest that during the epidemic period of COVID-19, medical staff experienced more anxiety and anxiety with insomnia. Somatization, anxiety and insomnia are highly correlated among medical staff and the general public.Keywords: somatic symptom, anxiety, insomnia, medical staff, COVID-19

Gang Gui,1,* Ziqi Fan,1,* Yihuan Ning,1 Cancan Yuan,2 Baolin Zhang,3 Qin Xu1 1College of Pharmacy, Guilin Medical University, Guilin, 541004, People’s Republic of China; 2Department of Pharmacy, Luohe City People’s Hospital, Luohe, 462000, People’s Republic of China; 3College of Materials Science and Engineering, Guilin University of Technology, Guilin, 541004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin XuCollege of Pharmacy, Guilin Medical University, Guilin, 541004, People’s Republic of ChinaEmail xuqincpu@126.comBaolin ZhangCollege of Materials Science and Engineering, Guilin University of Technology, Guilin, 541004, People’s Republic of ChinaEmail zhangbaolin@glut.edu.cnBackground: Paclitaxel (PTX) has interesting anticancer activity. However, it is insoluble in water, which seriously hinders its use in clinical. Superparamagnetic iron oxide nanoparticles (SPIONs) are used as an ideal drug delivery system. Therefore, we proposed a folic acid (FA) targeting drug-loaded SPIONs to reduce its adverse reaction.Methods: To improve the hydrophilicity of PTX, the structure of PTX was modified by succinic anhydride to obtain 2ʹ-succinate paclitaxel (SPTX). FA conjugated Polyethylene glycol (PEG)/polyethyleneimine (PEI)-SPIONs SPTX-loaded nanoparticles (SPTX@FA@PEG/PEI-SPIONs) were prepared by solvent volatilization and hydrogen bond adsorption, and the nano-formulation was optimized by response surface methodology (RSM). The characteristics, antitumor effect in vitro, pharmacokinetics, and biodistribution of SPTX@FA@PEG/PEI-SPIONs were evaluated.Results: SPTX was successfully loaded on the surface of FA@PEG/PEI-SPIONs. The formation of SPTX@FA@PEG/PEI-SPIONs was exhibited water-dispersive monodispersity with high stability by RSM, and dynamic light scattering (DLS) was 178.1± 3.12 nm, particle size observed in the transmission electron microscope (TEM) was 13.01± 1.10 nm, and the encapsulation efficiency (EE) and loading efficiency (LE) were 81.1± 1.66% and 14.8± 1.46%, respectively. It enhanced the stability in normal physiological condition, accelerated drug release at tumorous pH, and preferentially prolonged the circulation time. In vitro, the SPTX@FA@PEG/PEI-SPIONs significantly targeted to folate receptor (FR) positive cancers cell (HNE-1) via the receptor-ligand mediated pathway, resulting in effective cytotoxic activity. Pharmacokinetic results demonstrated that SPTX@FA@PEG/PEI-SPIONs (t1/2=3.41 h) had longer than free SPTX or PTX (t1/2=1.67 h) in rats in vivo. Tissue distribution studies showed that SPTX@FA@PEG/PEI-SPIONs were present at high levels in the liver and help in targeting the folate receptors present on the kidneys.Conclusion: These results suggest that SPTX@FA@PEG/PEI-SPIONs offer a highly promising approach to control drug release, improve drug pharmacokinetics and actively target the nasopharyngeal carcinoma.Keywords: paclitaxel, folic acid, superparamagnetic iron oxide nanoparticles, targeted drug delivery, response surface methodology, anti-nasopharyngeal carcinoma

Yilin Ning,1,2 Peh Joo Ho,3,4 Nathalie C Støer,5,6 Ka Keat Lim,7,8 Hwee-Lin Wee,3,9 Mikael Hartman,1– 3,10 Marie Reilly,11 Chuen Seng Tan3 1NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore; 2Yong Loo Lin School of Medicine, Department of Surgery, National University of Singapore and National University Health System, Singapore, Singapore; 3Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; 4Genome Institute of Singapore, Singapore, Singapore; 5Norwegian National Advisory Unit on Women’s Health, Oslo University Hospital, Oslo, Norway; 6Department of Research, Cancer Registry of Norway, Oslo, Norway; 7Department of Population Health Sciences, School of Population Health & Environmental Sciences (SPHES), Faculty of Life Sciences & Medicine, King’s College London, London, UK; 8Programme in Health Services & Systems Research, Duke-NUS Medical School, Singapore, Singapore; 9Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore; 10Department of Surgery, National University Hospital, Singapore, Singapore; 11Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenCorrespondence: Chuen Seng TanSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Tahir Foundation Building, 12 Science Drive 2, #10-01, Singapore, 117549, SingaporeTel +65-66013206Email ephtcs@nus.edu.sgPurpose: Assessing the clinical importance of an exposure effect on a quality of life (QoL) score often requires quantifying the effect in terms of a difference in scores. Using the linear regression model (LRM) for this purpose assumes the ordinal score is a proxy for an underlying continuous variable, but the analysis offers no assessment for the validity of the assumption. We propose an approach that assesses the proxy assumption and estimates the exposure effect by using the cumulative link model (CLM).Patients and methods: CLM is a well-established regression model that assumes an ordinal score is an ordered category generated from applying thresholds to a latent continuous variable. Our approach assesses the proxy assumption by testing whether these thresholds are equidistant. We compared the performance of CLM and LRM using simulated ordinal data and illustrated their application to the effect of time since diagnosis on five subscales of fatigue among breast cancer survivors measured using the Multidimensional Fatigue Inventory.Results: CLM had good performance in estimating the difference in means with simulated ordinal data satisfying the proxy assumption, even when the outcome had only a few categories. When the proxy assumption was inadequate, both the CLM and LRM had biased estimates with poor coverage. The proxy assumption was appropriate for four of the five subscales in our real data application to fatigue scores, which highlighted the importance of assessing the proxy assumption to avoid reporting invalid estimates in terms of the difference in scores.Conclusion: The proxy assumption is critical to the interpretation of the exposure effect on the difference in mean QoL scores. CLM offers a valid test for the presence of an association, a method for assessing the proxy assumption, and when the assumption is adequate, an assessment for clinical significance using the difference in means.Keywords: cumulative link model, ordered probit model, ordinal outcome, ordinal regression, probit link, quality of life

Hehua Li,1,* Yaping Zhang,2,3,* Honggang Wang,4 Jing Liang,4 Yongjie Zhou,2,3 Yuanyuan Huang,1 Tianyi Zhai,1 Qiong Yang,1 Mingzhe Yang,1 Yuping Ning,1,5 Hongbo He,1 Kai Wu,6 Fengjuan Chen,7 Fengchun Wu,1,5,8 Xiangyang Zhang1,9 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Research Center for Psychological and Health Sciences, China University of Geosciences, Wuhan, People’s Republic of China; 3Affiliated Wuhan Mental Health Center, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, People’s Republic of China; 4Qingdao Mental Health Center, Qingdao University, Qingdao, People’s Republic of China; 5The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 6Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (scUT), Guangzhou, People’s Republic of China; 7Department of Medical, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 8Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 9CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengchun WuInstitute of Psychology, The Affiliated Brain Hospital of Guangzhou Medical University, Liwan District, Guangzhou 510370, People’s Republic of ChinaEmail 13580380071@163.comXiangyang ZhangInstitute of Psychology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, People’s Republic of ChinaEmail zhangxy@psych.ac.cnBackground: The pandemic of coronavirus disease 2019 (COVID-19) has posed a threat to global health. Increasing studies have shown that the mental health status of health professionals is very poor during the COVID-19 epidemic. At present, the relationship between somatic symptoms and symptoms of anxiety of health professionals during the COVID-19 has not been reported. The purpose of this study was to explore the frequency of somatic symptoms and its related factors in health professionals with symptoms of anxiety during COVID-19 in China.Methods: A total of 606 health professionals were assessed online with the Chinese version of the 7-item Generalized Anxiety Disorder (GAD-7) scale, 7-item Insomnia Severity Index (ISI) and the somatization subscale of Symptom Checklist 90 (SCL-90).Results: The percentage of symptoms of anxiety, somatic symptoms and insomnia in all health professionals was 45.4%, 12.0%, and 32%, respectively. The frequency of somatic symptoms in health professionals with symptoms of anxiety was 22.9%. The SCL-90 somatization subscale score was significantly positively correlated with history of somatic diseases, GAD-7 score and ISI score in participants with symptoms of anxiety.Conclusion: During the COVID-19, symptoms of anxiety, insomnia, and somatic symptoms are commonly observed in health professionals. Insomnia and symptoms of anxiety are independently associated with somatic symptoms of health professionals with symptoms of anxiety.Keywords: somatic symptoms, coronavirus disease 2019, health professionals, frequency, related factors

Chunyu Yang,1– 4,* Xiaomei Zhong,2,4,* Huarong Zhou,2,4 Zhangying Wu,2,4 Min Zhang,2,4 Yuping Ning1,2,4 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3The Third People’s Hospital of Zhongshan, Zhongshan, Guangdong, People’s Republic of China; 4Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuping NingThe Affiliated Brain Hospital of Guangzhou Medical University, Mingxin Road #36, Liwan District, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-8126-8720Fax +86 20-8189-1391Email ningjeny@126.comBackground: In people with psychosis, physical comorbidities are highly widespread and leading contributors to the untimely death encountered. Readmission rates in psychiatric patients are very high. Somatic comorbidities could be one of the considerable risk factors for psychiatric rehospitalization. Nevertheless, much less is known about the relation between physical comorbidities and psychiatric readmission. We aimed to investigate the association between physical comorbidities and psychiatric readmission in Han Chinese patients with psychiatric disorders.Methods: We used administrative data for January 1, 2009 to December 31, 2018 from the headquarters of the Affiliated Brain Hospital of Guangzhou Medical University to identify adults with schizophrenia, unipolar depression or bipolar disorder discharged from hospital. Data were extracted on sociodemographic and clinical characteristics. The Charlson comorbidity index (CCI) was used to assess the existence of significant physical comorbidity. Cox proportional hazards regression estimated rehospitalization risk after discharge.Results: A total of 15,620 individuals were included in this study, with the mean age of 35.1 years (SD = 12.8), and readmission occurred for 23.6% of participants. Survival analysis showed that physical comorbidities were statistically and significantly associated with psychiatric readmission, even after the adjustment for the number of psychiatric comorbidities, other sociodemographic and clinical variables.Conclusion: Our results suggest that somatic comorbidities are related with higher rates of psychiatric readmission. Hence, to treat psychosis more effectively and to reduce rehospitalization, it is crucial to treat physical comorbidities promptly and adequately. It is absolutely necessary to bring somatic comorbidities to the forefront of psychiatric treatment and research.Keywords: psychiatric disorder, physical comorbidity, readmission, survival analysis

Dongfang Chen,1 Zhongke Huang,2 Yanli Ning,1 Cen Lou2 1Department of Nuclear Medicine, Xiasha Branch of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Nuclear Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Cen LouDepartment of Nuclear Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, People’s Republic of ChinaTel 86-0571-86090073 Email 3194110@zju.edu.cnBackground: LncRNAs play important roles in papillary thyroid carcinoma (PTC). LINC02471 has been reported to be related to PTC prognosis. The current study aimed to investigate the effects of LINC02471 on human PTC cells.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine LINC02471 expression in PTC tissues and cells and miR-375 expression in PTC cells. SiLINC02471, miR-375 mimic and miR-375 inhibitor were used for cell transfection. Cell proliferation, apoptosis, migration, and invasion were detected by performing Cell Counting Kit-8 (CCK-8), clone formation assay, flow cytometry, scratch assay, and transwell assay. Western blot was carried out to detect protein levels of E-cadherin, N-cadherin and Snail. The target gene for LINC02471 was verified by dual-luciferase reporter assay.Results: LINC02471 was highly expressed in PTC tissues and cells. After silencing LINC02471, cell proliferation, migration and invasion were reduced, but cell apoptosis was increased. SiLINC02471 increased the expressions of E-cadherin and miR-375, and inhibited the expressions of N-Cadherin and Snail. LINC02471 directly targeted miR-375 in PTC cells. Overexpression of miR-375 inhibited the proliferation, migration, invasion of PTC cells and reduced the expressions of N-Cadherin and Snail but promoted the cell apoptosis and increased E-cadherin expression, while miR-375 inhibitor produced opposite effects to overexpressed miR-375. After inhibiting miR-375 expression, siLINC02471 reversed the effect of miR-375 inhibitor.Conclusion: LINC02471 could promote the development of PTC. Knocking down LINC02471 could inhibit invasion and metastasis and promote PTC cell apoptosis through directly targeting miR-375.Keywords: papillary thyroid carcinoma, long non-coding RNAs, miR-375, epithelial-mesenchymal transition, EMT

Xing-Bing Huang, Xiong Huang, Hong-Bo He, Fang Mei, Bin Sun, Su-Miao Zhou, Su Yan, Wei Zheng, Yuping Ning The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, People’s Republic of ChinaCorrespondence: Yuping Ning; Wei Zheng 36 Mingxin Road, Liwan District, Guangzhou, People’s Republic of ChinaTel +86-13322214239; +86-13322214239Fax +86-20-81891391; +86-20-81778169Email ningjeny@126.com; zhengwei0702@163.comObjective: Ketamine and propofol have become increasingly popular in electroconvulsive therapy (ECT) anaesthesia. This study was conducted to examine whether changes in serum levels of brain-derived neurotrophic factor (BDNF) are associated with the antidepressant effects of ketofol, a combination of ketamine and propofol, in ECT for patients with treatment-resistant depression (TRD).Methods: Thirty patients with TRD (18– 65 years) were enrolled and underwent eight ECT sessions with ketamine (0.5 mg/kg) plus propofol (0.5 mg/kg) (ketofol). Symptom severity was monitored using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Brief Psychiatric Rating Scale (BPRS), and serum levels of BDNF were examined by enzyme-linked immunosorbent assay (ELISA) at baseline and after 2, 4, and 8 ECT treatments. Serum levels of BDNF were also collected from thirty healthy controls.Results: At baseline, there were no significant differences in serum levels of BDNF between patients with TRD and healthy controls. The response and remission rates in patients with TRD were 100% (30/30) and 53.3% (16/30) after ECT treatment, respectively. Despite a significant reduction in HAMD-17 and BPRS scores after ECT, no changes in serum levels of BDNF were observed after ECT treatment when compared to baseline. No association was found between serum levels of BDNF and changes in illness severity.Conclusion: Serum levels of BDNF did not represent a suitable candidate biomarker for determining the antidepressant effects of ketofol during ECT for patients with TRD.Keywords: BDNF, ketamine, propofol, electroconvulsive therapy, treatment-resistant depression

Xingbing Huang, 1, 2,* Wenhua Ding, 2,* Fengchun Wu, 2 Sumiao Zhou, 2 Shuhua Deng, 2 Yuping Ning 1– 3 1First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuping Ning 36 Mingxin Road, Liwan District, Guangzhou, People’s Republic of ChinaTel +86 20 8189 1425Fax +86 20 8189 1391Email ningjeny@126.comObjective: Preclinical studies have reported that abnormal kynurenic acid (KYNA) may play a role in cognitive deficits. Schizophrenia (SCZ) is characterized by a wide range of cognitive deficits that may evolve from abnormal KYNA. This study aimed to explore the relationship between KYNA and cognitive impairment in SCZ, which has not yet been reported.Methods: We recruited 30 SCZ patients and 34 healthy controls, measured clinical symptoms by using the Positive and Negative Syndrome Scale and performed cognitive tests using the MATRICS Consensus Cognitive Battery (MCCB). Plasma levels of tryptophan, kynurenine, and KYNA were determined by high-performance liquid chromatography–tandem mass spectrometry.Results: We found that plasma KYNA levels were significantly higher in patients than in healthy controls (p=0.009). The cognitive performance of patients in the total MCCB scores and the scores of all subscales were significantly lower than those in healthy controls (all P < 0.01). Correlation analysis showed that KYNA levels were negatively correlated with attention/vigilance (r=– 0.457, p=0.019) and social cognition (r=– 0.481, p=0.013) only in SCZ patients.Conclusion: Our results indicate that elevated plasma KYNA levels may serve as a biomarker of cognitive impairment in SCZ patients.Keywords: schizophrenia, kynurenic acid, cognitive impairment, symptom

Carlin Rafie,1,* Yi Ning,2,* Aiping Wang,3 Xiang Gao,4 Robert Houlihan4,5 1Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 2GlaxoSmithKline Institute of Infectious Disease and Public Health, Beijing, China; 3Apex Life Science, Richmond, VA, USA; 4Department of Nutritional Sciences, Pennsylvania State University, University Park, PA, USA; 5UF Health Cancer Center, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Background: Lifestyle behaviors may impact quality of life (QoL). The relative impact of physical activity and sleep quality on QoL of individuals with and without a history of cancer living in underserved rural communities requires further study to inform health care and public health initiatives.Methods: Individuals with and without a history of cancer were recruited from rural Virginia. We collected information on physical activity level (PAL), sleep quality (Pittsburgh Sleep Quality Index), and QoL (Short Form-36). Additional dimensions of physical activity and sleep were measured including ambient light exposure and sleep duration via Actiwatch2, and serum vitamin D and urine melatonin, which are markers of outdoor activity and sleep.Results: A total of 124 cancer survivors and 48 cancer-free individuals were enrolled in the study. Mean age was 59 years, with the majority being women (89%) and Caucasian (76%). Breast cancer was the most common cancer (72%), and mean time from diagnosis to the survey was 8.1 years. Survivors were significantly less active, more likely to be inactive, and had significantly worse sleep quality and physical and mental health relative to cancer-free individuals (P

Fengchun Wu,1,2,* Yue Zhang,2,3,* Yongzhe Yang,2–4 Xiaobing Lu,1,2 Ziyan Fang,1 Jianwei Huang,1 Lingyin Kong,3 Jun Chen,5,6 Yuping Ning,1,2 Xiaobo Li,7,8 Kai Wu2,3,5,6,9 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China; 2Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; 3Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (SCUT), Guangzhou, China; 4School of Medicine, South China University of Technology (SCUT), Guangzhou, China; 5Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou, China; 6National Engineering Research Center for Healthcare Devices, Guangzhou, China; 7Department of Biomedical Engineering, New Jersey Institute of Technology, NJ, USA; 8Department of Electric and Computer Engineering, New Jersey Institute of Technology, NJ, USA; 9Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan *These authors contributed equally to this work Background: Structural and functional brain abnormalities in schizophrenia (SZ) have been widely reported. However, a few studies have investigated both structural and functional characteristics in SZ patients at different stages to understand the neuropathology of SZ. Methods: In this study, we recruited 44 first-episode drug-naive SZ (FESZ) patients, 44 medicated chronic SZ (CSZ) patients, and 56 normal controls (NCs) and acquired their structural and resting-state functional magnetic resonance imaging (MRI). We then made group comparisons on structural and functional characteristics, including regional gray matter volume (GMV), regional homogeneity, amplitude of low-frequency fluctuation, and degree centrality. A linear support vector machine (SVM) combined with a recursive feature elimination (RFE) algorithm was implemented to discriminate three groups.Results: Our results indicated that the regional GMV was significantly decreased in patients compared with that in NCs; CSZ patients have more diffused GMV decreases primarily involved in the frontal and temporal lobes when compared with FESZ patients. Both FESZ and CSZ patients showed significant functional alterations compared with NCs; when compared with FESZ patients, CSZ patients showed significant reductions in functional characteristics in several brain regions associated with auditory, visual processing, and sensorimotor functions. Moreover, a linear SVM combined with a RFE algorithm was implemented to discriminate three groups. The accuracies of the three classifiers were 79.80%, 83.16%, and 81.71%, respectively. The performance of classifiers in this study with multimodal MRI was better than that of previous discriminative analyses of SZ patients with single-modal MRI.Conclusion: Our findings bring new insights into the understanding of the neuropathology of SZ and contribute to stage-specific biomarkers in diagnosis and interventions of SZ. Keywords: multimodal MRI, schizophrenia, support vector machine, SVM, classification