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Song Wen,1,&ast; Dongxiang Xu,1,&ast; Yue Yuan,1,&ast; Zhimin Xu,1 Yanyan Li,1 Min Gong,1 Xinlu Yuan,1 Ligang Zhou1,2 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally in this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +008613611927616, Email zhouligang1n1@163.comObjective: Serum tumor markers have been discovered to be elevated in individuals with diabetes mellitus (DM); however, their significance in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia (HHS) is unknown. We evaluated these indicators in the patients with DKA and HHS.Materials and Methods: We retrospectively collected the laboratory data of 565 diabetic patients from Shanghai Pudong Hospital between Jan, 2019 and May, 2023, including 300 patients with type 2 diabetes mellitus (T2DM), 206 with DKA, and 59 with HHS. Serum tumor biomarkers and further clinical laboratory tests were compared among the three groups. Patients with conspicuous tumor evidence were excluded from the study.Results: We found significantly higher levels of carbohydrate antigen 199 (CA199) in DKA (p< 0.01), carcinoembryonic antigen (CEA), complex prostate specific antigen (CPSA) (p< 0.01), prostate specific antigen (PSA) (p< 0.05) in HHS, as well as the plasma lipid profile, iron, and electrolytes, in addition to decreased thyroid function, hepatic and renal function, and cardiac function (p< 0.05). A Spearman correlational study revealed that osmolar levels were significantly positively correlated with myoglobin (MYO) and cardiac troponin I (cTNI), whereas serum iron concentration (r=0.520) was positively correlated with CEA levels in HHS. pH was negatively correlated with CA199 (r=− 0.195), while HbA1c (r=0.22), globin (r=0.341), and total cholesterol (TC) (r=0.191) were positively correlated with elevated CA199 levels. Moreover, the multilinear regression investigation identified osmolarity as a significant determinant for CEA, as well as other parameters, and all proved to be proper predictors for CEA in HHS via ROC curve establishment.Conclusion: Elevated CA199 levels in DKA were associated with acidosis, whereas HHS with elevated CEA levels may be related to iron homeostasis and could be predicted via the osmolar degree and other predictors.Keywords: diabetes mellitus, diabetic ketoacidosis, hyperosmolar hyperglycemic state, tumor markers, osmolar, iron homeostasis

Song Wen,1,2 Yanyan Li,1 Chenglin Xu,1 Jianlan Jin,1 Zhimin Xu,1 Yue Yuan,1 Lijiao Chen,1 Yishu Ren,1 Min Gong,1 Congcong Wang,1 Meiyuan Dong,1 Yingfan Zhou,3 Xinlu Yuan,1 Fufeng Li,4 Ligang Zhou1,2,5 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Fudan Zhangjiang Institute, Fudan University, Shanghai, 201203, People’s Republic of China; 3Medical School of Tianjin University, Tianjin, 300072, People’s Republic of China; 4Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 5Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.com Fufeng Li, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email li_fufeng@aliyun.comObjective: We aim to examine and reestablish the correlational and linear regression relationships, as well as the predictive value, between the significant facial and tongue features and the metabolic parameters in type 2 diabetes mellitus (T2DM).Materials and Methods: From March to May 2024, we studied 269 patients with T2DM in the endocrinology department of Shanghai Pudong Hospital. The patients’ facial and tongue characteristics were sampling by a tongue imaging device equipped with artificial intelligence (AI) (XiMaLife, Sinology, China) of automated and advanced machine learning algorithms. Then, the imaging features were examined in relation to the blood examination.Results: Multiple facial and tongue features, as well as dimensional facial and tongue color parameters, were significantly correlated with glycated hemoglobin A1c (HbA1c) (r < 0.3, p < 0.05), glycated albumin (GA) (− 0.20 < 0.30, p < 0.05), C-peptide (− 0.20.20, p < 0.05), plasma insulin (r < 0.30, p < 0.05), fasting plasma glucose (FPG) (r < 0.3, p < 0.05), significant hepatic and renal function indicators (− 0.30 < r < 0.20, p< 0.05), cardiac injury markers (− 0.30 < r < 0.30, p < 0.05), tumor markers (− 0.5 < r < 0.5, p < 0.05), thyroid function (− 0.15 < r < 0.55, p < 0.05), and blood cell count, including white blood cells (r < 0.2, p < 0.05), and hemoglobin (Hb) (− 0.30 < r < 0.3, 0.0001. The correlational results demonstrated that the tongue’s characteristics and signs may be linked with the dynamic of the metabolic status of T2DM. In order to examine the causal relationships, we performed linear regression analyses, which revealed that various facial and tongue imaging parameters partially determined the metabolic indicators. The predictive value of imaging features was evaluated by receiver operating characteristic curve (ROC) to assess metabolic status in T2DM.Conclusion: This study demonstrated that metabolic status, renal and hepatic, cardiac, and thyroid function, the proportion of blood cells, and Hb in T2DM were intimately associated with facial and tongue features. The precise analysis of facial and tongue features through AI and advanced machine learning could be used to predict T2DM’s conditions and progression.Keywords: type 2 diabetes, tongue imaging, face imaging, cardiovascular disease, machine learning

Yuanyuan Li,1,&ast; Shanting Yi,1,&ast; Wencai Jiang,2,&ast; Meihui Gong1 1Cardiovascular Center of the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, People’s Republic of China; 2Department of Cardiology, Suining Central Hospital, Suining, 629000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meihui Gong, Cardiovascular Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, People’s Republic of China, Email yuxy69@mail.sysu.edu.cnBackground: Previous studies have established a strong association between obesity, high metabolism, and the development of hyperuricemia. However, the relationship between obesity metabolism indices and hyperuricemia in high-risk patients with hypertension and coronary heart disease (CHD) remains unclear. The purpose of this study was to investigate this relationship in patients with both hypertension and CHD, and to identify the obesity metabolism index with the best diagnostic value.Methods: A two-center study encompassed 6344 participants with hypertension and CHD. Multiple logistic regression was utilized to examine the correlation between six obesity metabolism indices and hyperuricemia, with restricted cubic spline (RCS) analysis to identify non-linear relationships. Diagnostic value was assessed via receiver operating characteristic (ROC) curves and decision curve analysis (DCA).Results: Multivariable logistic regression revealed a significant correlation between increased obesity metabolism indices and hyperuricemia. Furthermore, RCS analysis revealed a nonlinear dose-response relationship (P for nonlinear < 0.001). Moreover, ROC and DCA results showed that METS-VF index, which combined visceral obesity and metabolic parameters, became the most reliable diagnostic tool.Conclusion: The study underscores a strong association between elevated obesity metabolism indices and hyperuricemia in patients with hypertension and CHD. The METS-VF index, amalgamating visceral obesity and metabolic parameters, emerged as the most reliable diagnostic tool.Keywords: obesity metabolism indices, hypertension, coronary heart disease, uric acid, hyperuricemia

Guojun Shen,1,&ast; Xueying Li,2,3,&ast; Anqi Zheng,2 Mingxing Gong,4 Zhanhui Wang,2 Baolin Liao5 1Hepatology Unit, the Third People′s Hospital of Jiujiang City, Jiujiang, People’s Republic of China; 2Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Gastroenterology, Shenzhen Qianhai Taikang Hospital, Shenzhen, People’s Republic of China; 4Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 5Department of Hepatology, Guangzhou Medical Research Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baolin Liao, Department of Hepatology, Guangzhou Medical Research Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 8 Huaying Road, Guangzhou, 510440, People’s Republic of China, Email polinlbl@163.com Zhanhui Wang, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Blvd, Guangzhou, 510515, People’s Republic of China, Email wangzhh@smu.edu.cnBackground: Nucleos(t)ide analogues (NAs) as the first-line treatment for chronic hepatitis B (CHB) have been shown to partially restore the antiviral immunity of the patients. However, hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients have a relatively longer duration of HBV infection and lower level of HBV DNA. Whether NAs treatments have a different effect on their immune repertoires between CHB and HCC patients remains to be determined.Patients and Methods: In this study, 126 CHB patients and 85 HBV-related HCC patients who received or did not receive NAs treatment, as well as 361 healthy individuals were enrolled to analyze the effect of NAs treatment on T cell receptor β chain (TCRβ) and B cell receptor heavy chain (BCRh) repertoires in peripheral blood of the patients.Results: We found that after NAs therapy, the richness and evenness of TCRβ and BCRh repertoires in CHB patients were significantly lower than those in untreated patients and healthy controls, while the diversity of TCRβ and BCRh repertoires was stable in HCC patients. The alanine aminotransferase and HBV DNA levels were not correlated with the TCR or BCR diversity in CHB and HCC patients.Conclusion: The results suggest that NAs therapy could influence the overall T cell and B cell repertoires diversity in CHB patients but has minimal impact on HCC patients, indicating a significant difference in the potential to restore antiviral immunity between CHB and HCC patients by NAs treatment.Keywords: chronic hepatitis B, Nucleos(t)ide analogue, T cell receptor, immune repertoire, hepatocellular carcinoma

Mingjun Gong,1 Min Sun,1 Yaqi Sun,2 Lijuan Jin,1 Shen Li3 1Sports Training College, Tianjin University of Sport, Tianjin, People’s Republic of China; 2Mental Health Institute, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Shen Li, Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +86-22-88188875, Email lishen@tmu.edu.cnObjective: Using meta-analysis to comprehensively and quantitatively evaluate the impact of acute sleep deprivation on different sports performance of athletes, this study aims to provide scientific guidance for coaches in optimizing and adjusting training and competition arrangements.Methods: Establishing literature inclusion and exclusion criteria, we conducted searches in both Chinese and English databases. Using stata 14.0, we analyzed 75 indicators from 27 included literature, focusing on three aspects: the impact of acute sleep deprivation on overall athletic performance, the impact on sporting performance across various athletic abilities, and the disparities in athletic performance between morning and afternoon following acute sleep deprivation.Results: The effect size of acute sleep deprivation on overall athletic performance was − 0.56 (P< 0.05). Sub-analyses revealed effect sizes of − 0.23 (P< 0.05) for whole night sleep deprivation, − 1.17 (P< 0.05) for partial sleep deprivation at the end of the night, and − 0.25 (P> 0.05) for partial sleep deprivation in the beginning of the night. The effect sizes of acute sleep deprivation on high intensity intermittent exercise, skill control, speed, aerobic endurance, and explosive power indicators were − 1.57, − 1.06, − 0.67, − 0.54, and − 0.39 respectively (P< 0.05). The effect sizes of acute sleep deprivation on the overall athletic performance in the morning and afternoon were − 0.30, and − 1.11, respectively (P< 0.05).Conclusion: Acute sleep deprivation significantly impairs the overall athletic performance of athletes, with a more pronounced negative impact observed with partial sleep deprivation at the end of the night. Various types of exercise performance are adversely affected by acute sleep deprivation, with magnitude of impact ranking high intensity intermittent, skill control, speed, aerobic endurance, and explosive power. Following acute sleep deprivation, athletes’ overall sporting performance in the afternoon is inferior to that in the morning.Keywords: acute sleep deprivation, athletes, athletic ability, sporting performance, meta-analysis

Chenglin Xu,1,&ast; Song Wen,1,2,&ast; Min Gong,1,&ast; Meiyuan Dong,1,3,&ast; Yue Yuan,1 Yanyan Li,1 Mingyue Zhou,4 Ligang Zhou1,3,5 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Fudan Zhangjiang Institute, Fudan University, Shanghai, 201203, People’s Republic of China; 3Hebei Medical University, Shijiazhuang, 050013, People’s Republic of China; 4Clinical Research OB/GYN REI Division, University of California, San Francisco, CA, USA; 5Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.comObjective: To investigate the implications of elevated myoglobin (MYO) in acute diabetic conditions of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).Materials and methods: This study integrates in-patient data from Shanghai Pudong Hospital from 2019 to 2023. Laboratory data were compared between stable T2D patients (without acute diabetic complications), DKA, and HHS patients. The multilinear regression explored variables relevant to the elevated MYO in DKA and HHS. The dynamics of MYO, the survival rate, and associated risk factors in HHS were determined.Results: Except for triglyceride, procalcitonin, low-density lipoprotein, islet cell autoimmune antibodies, N-terminal Pro-brain natriuretic peptide (NT-ProBNP), and brain natriuretic peptide (BNP), there were significant differences in age, gender distribution, duration of diabetes, type of diabetes, and other referred laboratory data (p< 0.05). The age, gender, creatine kinase (CK), estimated glomerular filtration rate (eGFR), and free triiodothyronine (FT3) in DKA, whereas osmolar, uric acid (UA), and cardiac troponin I (cTNI) in the HHS, were significant determinants of elevated MYO, respectively (p< 0.05). The dynamic of MYO in HHS was in line with the survival trend, where the percentage of death was 29.73%, and aging with higher procalcitonin levels was a key risk factor. Besides, the cumulative survival rates between patients with or without bone fracture or muscle injury were substantially different.Conclusion: This real-world study demonstrated DKA and HHS potentially have unique causes for increased MYO. By utilizing the appropriate regression parameters, we could forecast the progression of increased MYO in groups of DKA and HHS, while based on risk factors of aging, severity of infection, and different MYO sources, we could predict the prognosis of HHS.Keywords: diabetes mellitus, diabetic ketoacidosis, hyperosmolar hyperglycemic state, myoglobin, survival

The Chinese crocodile lizard (Shinisaurus crocodilurus) is an unusual anguimorph lizard found mainly in China. Transect surveys estimate a total wild population of about 950 individuals in China. This is a dramatic decrease compared with previous surveys. At present, there are only eight areas of distribution. No Chinese crocodile lizards have been found in four former areas for several years. Investigations have demonstrated that poaching has contributed directly to the population decline. Habitat destruction, and in particular water flow, is the second most important factor. Mining, small scale dam construction, electro-fishing and poisoning of fish in the stream also contribute to population decline. Therefore, educating local people, punishing illegal poaching, and strengthening scientific research are urgent.

Dawei Ren,1 Yan Zhang,1 Bo Du,1 Lina Wang,2 Meiheng Gong,1 Wei Zhu1 1Department of Otorhinolaryngology, the First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pediatric Respiration, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Wei Zhu, Email zhuwei@jlu.edu.cnBackground: Electrical stimulation (ES) can effectively promote skin wound healing; however, single-electrode-based ES strategies are difficult to cover the entire wound area, and the effectiveness of ES is often limited by the inconsistent mechanical properties of the electrode and wound tissue. The above factors may lead to ES treatment is not ideal.Methods: A multifunctional conductive hydrogel dressing containing methacrylated gelatin (GelMA), Ti3C2 and collagen binding antimicrobial peptides (V-Os) was developed to improve wound management. Ti3C2 was selected as the electrode component due to its excellent electrical conductivity, the modified antimicrobial peptide V-Os could replace traditional antibiotics to suppress bacterial infections, and GelMA hydrogel was used due to its clinical applicability in wound healing.Results: The results showed that this new hydrogel dressing (GelMA@Ti3C2/V-Os) not only has excellent electrical conductivity and biocompatibility but also has a durable and efficient bactericidal effect. The modified antimicrobial peptides V-Os used were able to bind more closely to GelMA hydrogel to exert long-lasting antibacterial effects. The results of cell experiment showed that the GelMA@Ti3C2/V-Os hydrogel dressing could enhance the effect of current stimulation and significantly improve the migration, proliferation and tissue repair related genes expression of fibroblasts. In vitro experiments results showed that under ES, GelMA@Ti3C2/V-Os hydrogel dressing could promote re-epithelialization, enhance angiogenesis, mediate immune response and prevent wound infection.Conclusion: This multifunctional nanocomposite hydrogel could provide new strategies for promoting infectious wound healing. Keywords: MXene, GelMA, electrical stimulation, antimicrobial peptides, wound healing

Tao Sun,1,2 Shilin Xiao,1 Miaomiao Wang,1 Qian Xie,1 Liang Zhang,1 Mingfu Gong,1 Dong Zhang,1 Chunyu Zhou1 1Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, People’s Republic of ChinaCorrespondence: Dong Zhang; Chunyu Zhou, Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing, People’s Republic of China, Tel +86 23 68763842, Email hszhangd@tmmu.edu.cn; zhouchy@tmmu.edu.cnAbstract: Acute liver injury (AIL), a fatal clinical disease featured with a swift deterioration of hepatocyte functions in the short term, has emerged as a serious public health issues that warrants attention. However, the effectiveness of existing small molecular antioxidants and anti-inflammatory medications in alleviating AIL remains uncertain. The unique inherent structural characteristics of liver confer it a natural propensity for nanoparticle capture, which present an opportunity to exploit in the formulation of nanoscale therapeutic agents, enabling their selective accumulation in the liver and thereby facilitating targeted therapeutic interventions. Significantly increased reactive oxygen species (ROS) accumulation and inflammation response have been evidenced to play crucial roles in occurrence and development of AIL. Nanozymes with ROS-scavenging capacities have demonstrated considerable promise in ROS elimination and inflammation regulation, thereby offering an appealing therapeutic instrument for the management of acute liver injury. In this review, the mechanisms of different type of ALI were summarized. In addition, we provide a comprehensive summary and review of the available ROS-scavenging nanozymes, including transition metal-based nanozymes, noble metal nanozymes, carbon-based nanozymes, and some other nanozymes. Furthermore, the challenges still need to be solved in the field of ROS-scavenging nanozymes for ALI alleviation are also discussed.Keywords: acute liver injury, nanozyme, ROS-scavenging, antioxidant, anti-inflammation

Xiucai Li,1,&ast; Song Wen,1,&ast; Meiyuan Dong,1,2 Yue Yuan,1 Min Gong,1 Congcong Wang,1 Xinlu Yuan,1 Jianlan Jin,1 Mingyue Zhou,3 Ligang Zhou1,2,4 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Hebei Medical University, Shijiazhuang, 050013, People’s Republic of China; 3Clinical Research OB/GYN REI Division, University of California, San Francisco, CA, USA; 4Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang@yahoo.comBackgrounds and Objective: Diabetic foot is a relatively severe complication in patients with type 2 diabetes (T2D), with peripheral neuropathy and angiopathy frequently serving as risk factors. However, it is unknown how the other major systemic metabolic factors impacted the profile of these patients, besides glucose management. Thus, we investigated the distinct characteristics of patients with diabetic foot ulcers and their relationships with angiopathy.Materials and Methods: We obtained the laboratory data of 334 diabetic patients at Shanghai Pudong Hospital from 2020 to 2023. The comparisons were performed between the groups with or without diabetic foot, including glucose metabolism, lipids profile, liver and kidney function, thyroid function, and serum iron. The association between metabolic factors and lower extremity computed tomography angiography (CTA) was analyzed.Results: We found significant disparities between groups in relation to age, serum protein content, liver transferase, serum creatinine, estimated glomerular filtration rate (eGFR), serum uric acid (UA), small dense low-density lipoprotein (sdLDL), lipoprotein A (LP(a)), apolipoprotein A1 (APOA1), thyroid function, serum iron, and hemoglobin (Hb) (p< 0.05). The Spearman correlational analyses showed that the severity of CTA, categorized by the unilateral or bilateral plaque or occlusion, was positively significantly correlated with UA (r=0.499), triglyceride (TG) (r=0.751), whereas inversely correlated with serum albumin (r=− 0.510), alanine aminotransferase (r=− 0.523), direct bilirubin (DBil) (r=− 0.494), total bilirubin (TBil) (r=− 0.550), Hb (r=− 0.646).Conclusion: This cross-section investigation showed that compared to T2D only, the patients with diabetic foot ulcer (DFU) might display similar glucose metabolic control context but adverse metabolic profiles, and this profile is associated with macrovascular angiopathy characteristics and their severity.Keywords: diabetic foot, macrovascular angiopathy, CTA, thyroid function, serum iron, serum bilirubin

Mingqiang Gong,1,2,&ast; Yunxia Shen,2,&ast; Wenbin Liang,2 Zhen Zhang,3 Chunxue He,4 Mingwu Lou,2 ZiYu Xu2 1Department of Acupuncture and Moxibustion, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang Central Hospital, Shenzhen, People’s Republic of China; 3Department of Radiology, The Third People’s Hospital of Longgang District, Shenzhen, People’s Republic of China; 4Department of Radiology, Shenzhen Clinical Medicine College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwu Lou; ZiYu Xu, Department of Radiology, Longgang Central Hospital, No. 6082, Longgang Avenue, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86 13808854650 ; +86 13824321925, Email mingwulou@sina.com; xuziyu82@163.comPurpose: Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment.Methods: Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively.Results: Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs.Conclusion: Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.Keywords: methamphetamine, abstinence, network, Granger causality analysis, independent component analysis

Chuanzhen Hao,&ast; Jiachen Luo,&ast; Baoxin Liu,&ast; Wei Xu, Zhiqiang Li, Mengmeng Gong, Xiaoming Qin, Beibei Shi, Yidong Wei Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yidong Wei, Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Tel +86-21-66307249, Fax +86-21-66301771, Email ywei@tongji.edu.cnPurpose: The prognostic impact of new-onset atrial fibrillation (NOAF) among different heart failure (HF) subtypes including HF with preserved (HFpEF, ejection fraction [EF] ≥ 50%), mid-range (HFmrEF, EF 40%∼ 49%), and reduced (HFrEF, EF < 40%) EF following acute myocardial infarction (AMI) remains unclear. We aimed to investigate the incidence and prognostic implication of post-MI NOAF across HF subtypes.Patients and Methods: We included 1413 patients with post-MI HF (743 with HFpEF, 342 with HFmrEF and 328 with HFrEF) between February 2014 and March 2018. NOAF was considered as patients without a preexisting AF who developed AF during the AMI hospitalization. The primary endpoint was all-cause mortality.Results: Of 1413 patients (mean age 66.8 ± 12.6 years, 72.9% men) analyzed, 200 (14.2%) developed post-MI NOAF. Patients with HFrEF were more likely to experience NOAF compared to those with HFmrEF or HFrEF (18.9%, 13.7% and 12.2% in HFrEF, HFmrEF and HFpEF, respectively; p for trend = 0.006). During a median follow-up of 28.5 months, 192 patients died (70 with HFrEF, 35 with HFmrEF and 87 with HFpEF) and 195 patients experienced HF rehospitalization (79 with HFrEF, 37 with HFmrEF and 79 with HFpEF). After multivariable adjustment, NOAF was independently associated with all-cause mortality (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.03– 3.12) only in the HFrEF group compared to sinus rhythm (SR), whereas an increased risk of HF rehospitalization was found in all HF subtypes, particularly in HFmrEF (HR: 5.08, 95% CI: 2.29– 11.25) and HFpEF (HR: 2.83 95% CI: 1.64– 4.90).Conclusion: In patients with post-MI HF, NOAF carried a worse prognosis for all-cause death in the HFrEF group and for HF rehospitalization in all HF subtypes.Keywords: heart failure, acute myocardial infarction, atrial fibrillation, left ventricular ejection fraction, mortality

Jin Chen,1,&ast; Min Gong,1,&ast; Zhuo Huang,1 Fang Wang,2 Yajing Wang,3 Zuquan Hu,1 Zhu Zeng,1 Yun Wang2 1Key Laboratory of Biology and Medical Engineering/Immune Cells and Antibody Engineering Research Center of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 2Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 3The Affiliated Stomatological Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhu Zeng, Key Laboratory of Biology and Medical Engineering/Immune Cells and Antibody Engineering Research Center of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, People’s Republic of China, Email zengzhu@gmc.edu.cn Yun Wang, Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, People’s Republic of China, Tel/Fax +86851-88174044, Email wangyun@gmc.edu.cnPurpose: Gastric injury is a major issue for long-term administration of aspirin. In this work, we tried to explore the possibility of using BLG to alleviate aspirin-induced gastric injury, because of excellent abilities of BLG in loading drug molecules.Methods: Various spectroscopic techniques and molecular docking methods were applied to investigate the interaction mechanism between BLG and aspirin. Animal experiments were performed to figure out the effects of taking aspirin-BLG on the stomach.Results: Our results demonstrate that aspirin could bind with BLG to form stable aspirin-BLG complex (the binding constant Kb= 2.051 × 103 M− 1). The formation process is endothermic (∆H> 0) and the main acting force is hydrophobic force. Our data also show that the aspirin-BLG complex is formed with a higher affinity in simulated gastric fluid and could remain stable for several hours, which might arise from its special binding mode under acidic condition and the resistance of BLG to gastric digestion. Furthermore, animal models (rats with aspirin-induced gastric damage) were built. The results of animal experiments reveal that the oral administration of aspirin-BLG could cause less damage to gastric tissue, and it also hardly triggers obvious inflammatory responses.Conclusion: This study would contribute to an in-depth understanding of the interaction mechanism between BLG and aspirin. It is reasonable to believe that using BLG to bind with aspirin would be a potential way to alleviate the aspirin-induced gastric injury.Graphical Abstract: Keywords: beta-lactoglobulin, aspirin, gastric injury, static quenching, molecular docking

Bian Hu,1,2 Jingyu Zhang,3 Mengdan Gong,1 Yongqin Deng,1 Yujie Cao,1 Yizhen Xiang,1 Dong Ye1 1Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, People’s Republic of China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Ninghai First Hospital, Ningbo, 315699, Zhejiang, People’s Republic of China; 3Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of ChinaCorrespondence: Dong Ye, Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, People’s Republic of China, Tel +86 13819861213, Fax +86 574-87392232, Email yedong518@sina.comAbstract: The olfactory nerve (ON) is the only cranial nerve exposed to the external environment. Hence, it is susceptible to damage from head trauma, viral infection, inflammatory stimulation, and chemical toxins, which can lead to olfactory dysfunction. However, compared with all other cranial nerves, the ON is unique due to its inherent ability to regenerate. This characteristic provides a theoretical basis for treatment of olfactory dysfunction. Olfactory training (OT) is one of the main treatments for olfactory dysfunction. It is easy to apply and has few side-effects, and has been shown to be efficacious for patients with olfactory dysfunction of various causes. To further understand the application value of ON regeneration and OT on olfactory dysfunction, we review the research progress on the mechanism of ON regeneration and OT.Keywords: olfaction, regeneration, olfactory training, olfactory dysfunction

Chenglin Xu,1,&ast; Min Gong,1,&ast; Song Wen,1,&ast; Mingyue Zhou,2 Yanyan Li,1 Ligang Zhou1,3 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Clinical Research OB/GYN REI Division, University of California, San Francisco, CA, USA; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Tel +8613611927616, Email zhouligang@yahoo.comPurpose: This study aims to identify changes in bone turnover markers and thyroid function in diabetic ketosis (DK) and diabetic ketoacidosis (DKA).Materials and Methods: We compared data from the Department of Endocrinology at Shanghai Pudong Hospital from 2018 to 2020 on the pancreatic status and previous glucose control, bone transformation, calcium homeostasis, and thyroid function in groups with diabetes (DM alone, n=602), DK (n=232), and DKA (n=60). Similar comparisons were made in recurrent DK (A) (n=17) and single DK (A) (n=272).Results: The fasting C-peptide level decreased significantly, but hemoglobin A1c (HbA1c) levels were higher in DK or DKA (p< 0.05). Blood calcium and 25-hydroxyvitamin D3 (25-OH-VitD3) levels were significantly lower in DKA (p< 0.05), but parathyroid hormone (PTH) levels remained constant across all three groups. The N-terminal middle molecular fragment of osteocalcin (N-MID) and β-C terminal cross-linking telopeptide of type 1 collagen (β-CTX) showed significant inverse alterations in DKA, regardless of gender or age (p< 0.05). Otherwise, DKA significantly inhibited thyroid function (p< 0.05). Furthermore, Spearman correlation analyses revealed a relationship between N-MID and HbA1c in DM alone (r=− 0.27, p< 0.01), while total triiodothyronine (TT3, r=0.62, p< 0.01) or free T3 (FT3, r=0.61, p< 0.01) in DK, and DKA (TT3, r=0.45, p< 0.01; FT3, r=0.43, p< 0.01). Multilinear regression analyses revealed that β-CTX (β=0.564), HbA1c (β=− 0.196), TT3 (β=0.183), and 25-OH-VitD3 (β=− 0.120) were the only independent determinants of N-MID in DM, whereas FT3 (β=0.491), β-CTX (β=0.315) in DK, and FT3 (β=0.420), β-CTX (β=0.367), TG (β=− 0.278) in DKA. Only 25-OH-VitD3 was found to be significantly lower in recurrent DK (A) than in single onset DK (A) (p< 0.05), and β-CTX (β=0.745) was found to be significantly independently associated with N-MID.Conclusion: Our preliminary findings show a dramatic change in bone turnover markers in DM patients with DK and DKA, and this change may be related to thyroid function.Keywords: bone turnover marker, diabetes mellitus, thyroid function, DKA

Chunxue He,1,2,&ast; Mingqiang Gong,3,4,&ast; Gengxiao Li,1,2 Yunxia Shen,2 Longyin Han,5 Bin Han,6 Mingwu Lou2 1Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang District Central Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 4Department of Acupuncture, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China; 5Department of Neurology, Beijing Longfu Hospital, Beijing, People’s Republic of China; 6Department of Rehabilitation Medicine, Longgang District Central Hospital of Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Han; Mingwu Lou, Tel +86 13928488998 ; +86 13808854650, Email hhbb08@163.com; mingwulou@sina.comPurpose: To investigate white matter alterations in post-stroke cognitive impairment (PSCI) patients at the subacute stage employing diffusion kurtosis and tensor imaging.Methods: Thirty PSCI patients at the subacute phase and 30 healthy controls (HC) underwent diffusion kurtosis imaging (DKI) scans and neuropsychological assessments. Based on the tract-based spatial statistics and atlas-based ROI analysis, fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), kurtosis fractional anisotropy (KFA), axial kurtosis (AK), and radial kurtosis (RK) were compared in specific white matter fiber bundles between the groups (with family-wise error correction). Adjusting for age and gender, a partial correlation was conducted between neurocognitive assessments and DKI metrics in the PSCI group.Results: In comparison with the HC, PSCI patients significantly showed decreased MK, RK, and FA and increased MD values in the genu of corpus callosum, anterior limb internal capsule, and left superior corona radiata. In addition, DKI detected more white matter region changes in MK (31/48), KFA (40/48), and RK (25/48) than DTI with FA (28/48) and MD (21/48), which primarily consisted of the right cingulum, right superior longitudinal fasciculus, and left posterior limb of internal capsule. In the left anterior limb of internal capsule, MK and RK values were significantly negatively correlated with TMT-B (r = − 0.435 and − 0.414, P < 0.05), and KFA values (r = − 0.385, P < 0.05) of corpus callosum negatively associated with TMT-B.Conclusion: Combing DTI, DKI, and neuropsychological tests, we found extensive damaged white matter microstructure and poor execution performance in subacute PSCI patients. DKI could detect more subtle white matter changes than DTI metrics. Our findings provide added information for exploring the mechanisms of PSCI and conducting cognitive rehabilitation in the subacute stage.Keywords: diffusion kurtosis imaging, diffusion tensor imaging, subacute ischemic stroke, cognitive impairment

Kristin Kostka,1,2 Talita Duarte-Salles,3 Albert Prats-Uribe,4 Anthony G Sena,5,6 Andrea Pistillo,3 Sara Khalid,4 Lana YH Lai,7 Asieh Golozar,8,9 Thamir M Alshammari,10 Dalia M Dawoud,11 Fredrik Nyberg,12 Adam B Wilcox,13,14 Alan Andryc,5 Andrew Williams,15 Anna Ostropolets,16 Carlos Areia,17 Chi Young Jung,18 Christopher A Harle,19 Christian G Reich,1,2 Clair Blacketer,5,6 Daniel R Morales,20 David A Dorr,21 Edward Burn,3,4 Elena Roel,3,22 Eng Hooi Tan,4 Evan Minty,23 Frank DeFalco,5 Gabriel de Maeztu,24 Gigi Lipori,19 Hiba Alghoul,25 Hong Zhu,26 Jason A Thomas,13 Jiang Bian,19 Jimyung Park,27 Jordi Martínez Roldán,28 Jose D Posada,29 Juan M Banda,30 Juan P Horcajada,31 Julianna Kohler,32 Karishma Shah,33 Karthik Natarajan,16,34 Kristine E Lynch,35,36 Li Liu,37 Lisa M Schilling,38 Martina Recalde,3,22 Matthew Spotnitz,14 Mengchun Gong,39 Michael E Matheny,40,41 Neus Valveny,42 Nicole G Weiskopf,21 Nigam Shah,29 Osaid Alser,43 Paula Casajust,42 Rae Woong Park,27,44 Robert Schuff,21 Sarah Seager,1 Scott L DuVall,35,36 Seng Chan You,45 Seokyoung Song,46 Sergio Fernández-Bertolín,3 Stephen Fortin,5 Tanja Magoc,19 Thomas Falconer,16 Vignesh Subbian,47 Vojtech Huser,48 Waheed-Ul-Rahman Ahmed,33,49 William Carter,38 Yin Guan,50 Yankuic Galvan,19 Xing He,19 Peter R Rijnbeek,6 George Hripcsak,16,34 Patrick B Ryan,5,16 Marc A Suchard,51 Daniel Prieto-Alhambra4 1IQVIA, Cambridge, MA, USA; 2OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, USA; 3Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 4Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK; 5Janssen Research & Development, Titusville, NJ, USA; 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; 7School of Medical Sciences, University of Manchester, Manchester, UK; 8Regeneron Pharmaceuticals, Tarrytown, NY, USA; 9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 10College of Pharmacy, Riyadh Elm University, Riyadh, Saudi Arabia; 11National Institute for Health and Care Excellence, London, UK; 12School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 13Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA; 14Unviersity of Washington Medicine, Seattle, WA, USA; 15Tufts Institute for Clinical Research and Health Policy Studies, Boston, MA, USA; 16Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA; 17Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 18Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea; 19University of Florida Health, Gainesville, FL, USA; 20Division of Population Health and Genomics, University of Dundee, Dundee, UK; 21Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA; 22Universitat Autònoma de Barcelona, Barcelona, Spain; 23O’Brien Institute for Public Health, Faculty of Medicine, University of Calgary, Calgary, Canada; 24IOMED, Barcelona, Spain; 25Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine; 26Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 27Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea; 28Director of Innovation and Digital Transformation, Hospital del Mar, Barcelona, Spain; 29Department of Medicine, School of Medicine, Stanford University, Redwood City, CA, USA; 30Georgia State University, Department of Computer Science, Atlanta, GA, USA; 31Department of Infectious Diseases, Hospital del Mar, Institut Hospital del Mar d’Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Universitat Pompeu Fabra, Barcelona, Spain; 32United States Agency for International Development, Washington, DC, USA; 33Botnar Research Centre, NDORMS, University of Oxford, Oxford, UK; 34New York-Presbyterian Hospital, New York, NY, USA; 35VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA; 36Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 37Biomedical Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 38Data Science to Patient Value Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 39Institute of Health Management, Southern Medical University, Guangzhou, People’s Republic of China; 40Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USA; 41Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; 42Real-World Evidence, TFS, Barcelona, Spain; 43Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 44Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea; 45Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea; 46Department of Anesthesiology and Pain Medicine, Catholic University of Daegu, School of Medicine, Daegu, South Korea; 47College of Engineering, The University of Arizona, Tucson, AZ, USA; 48National Library of Medicine, National Institutes of Health, Bethesda, MD, USA; 49College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter, UK; 50DHC Technologies Co. Ltd., Beijing, People’s Republic of China; 51Departments of Biostatistics, Computational Medicine, and Human Genetics, University of California, Los Angeles, CA, USACorrespondence: Daniel Prieto-Alhambra, Botnar Research Centre, Windmill Road, Oxford, OX37LD, UK, Email daniel.prietoalhambra@ndorms.ox.ac.ukPurpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.Keywords: OHDSI, OMOP CDM, descriptive epidemiology, real world data, real world evidence, open science

Mingkai Gong,1 Xiangping Liu,2 Wu Yang,3 Hongming Song,1 Xian Zhao,1 Xiancheng Ai,1 Shuo Wang,1 Haibo Wang1 1Center of Diagnosis and Treatment of Breast Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 3Department of International Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Haibo WangCenter of Diagnosis and Treatment of Breast Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaEmail hbwang66@126.comBackground: Cancer metabolism and specifically lipid metabolism play an important role in breast cancer (BC) progression and metastasis. However, the role of lipid metabolism-associated genes (LMGs) in the prognosis of breast cancer remains unknown.Methods: The expression profiles and clinical follow-up information of 1053 BC were downloaded from The Cancer Genome Atlas (TCGA), and metabolic genes were downloaded from the Gene Set Enrichment Analysis (GSEA) dataset. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. Finally, we analyzed the expression, interaction and correlation among the lipid metabolism-associated genes risk model.Results: The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in TCGA, and single-sample gene set enrichment analysis (ssGSEA) shows it is plausible that lipid metabolism is highly correlated with tumor immunity.Conclusion: Lipid metabolism-associated genes may become a new prognostic indicator predicting the survival of BC patients. The prognostic genes (n = 16) may help provide new strategies for tumor therapy.Keywords: bioinformatics, lipid metabolism-associated genes, breast cancer, lipid metabolism, TCGA

Xun Kang, Tao Sun, Liang Zhang, Chunyu Zhou, Zhongsheng Xu, Mengmeng Du, Shilin Xiao, Yun Liu, Mingfu Gong, Dong Zhang Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Mingfu Gong; Dong ZhangDepartment of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing, People’s Republic of ChinaTel +86 2368763843Fax +86 2368755306Email hummer198625@163.com; hszhangd@163.comBackground: Satisfactory prognosis of breast cancer (BC) is limited by difficulty in early diagnosis and insufficient treatment. The combination of molecular imaging and photothermal therapy (PTT) may provide a solution.Methods: Fe3O4-Aushell nanoparticles (NPs) were prepared by thermal decomposition, seeded growth and galvanic replacement and were comprehensively characterized. After conjugated to PEG, NPs were used as MRI and PTT agents in vitro and in vivo.Results: Fe3O4-Aushell NPs which had uniform Janus-like morphology were successfully synthesized. The Fe3O4 had a size of 18 ± 2.2 nm, and the Aushell had an outer diameter of 25 ± 3.3 nm and an inner diameter of 20 ± 2.9 nm. The NPs showed superparamagnetism, a saturation magnetization of 36 emu/g, and an optical absorption plateau from 700 to 808 nm. The Fe3O4-Aushell NPs were determined to possess good biocompatibility. After PEG coating, the zeta potential of NPs was changed from − 23.75 ± 1.37 mV to − 13.93 ± 0.55 mV, and the FTIR showed the characteristic C–O stretching vibration at 1113 cm− 1. The NPs’ MR imaging implied that the T2 can be shortened by Fe3O4-Aushell NPs in a concentration-dependent manner, and the Fe3O4-Aushell NPs coated with PEG at the molar ratio of 160 (PEG: NPs) showed the highest transverse relaxivity (r2) of 216 mM− 1s− 1. After irradiation at 0.65 W/cm2 for 5 min, all cells incubated with the Fe3O4-Aushell-PEG160 NPs (Fe: 30 ppm, Au: 70 ppm) died. After administrated intratumorally, Fe3O4-Aushell-PEG160 notably decreased the signal intensity of tumor in T2WI images. Under the same irradiation, the temperature of tumors injected with Fe3O4-Aushell-PEG160 quickly rose to 54.6°C, and the tumors shrank rapidly and were ablated in 6 days.Conclusion: Fe3O4-Aushell-PEG NPs show good r2 and PTT performance and are promising synergistic theranostic agents of MRI and PTT for BC.Keywords: magnetic resonance imaging, photothermal therapy, nanoparticle, early breast cancer theranostics, gold nanoshells

Mou-chun Gong,&ast; Wei-qing Chen,&ast; Zhao-qing Jin, Jia Lyu, Li-hao Meng, Hai-yan wu, Fei-hua Chen Department of General Surgery, First People’s Hospital of Hangzhou Lin’an District, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this work.Correspondence: Fei-hua ChenDepartment of General Surgery, First People’s Hospital of Hangzhou Lin’an District, 548 Yijin Road, Street Jincheng, Hangzhou, Zhejiang, 311300, People’s Republic of ChinaEmail 13396510518@189.cnBackground: Topoisomerase 2-alpha (TOP2A) has been identified as a hub gene that played an important role in the initiation and progression of thyroid carcinoma (THCA). However, the exact function of TOP2A in papillary thyroid cancer (PTC) remained elusive. The current study aimed to evaluate the TOP2A expression, prognosis significance and key signaling pathways involved in PTC.Methods: We firstly evaluated the expression of TOP2A in PTC via UALCAN, cBioportal, HPA and LinkdedOmics databases. Genetic alteration of TOP2A in PTC was then explored in cBioportal. Prognostic impacts of TOP2A expression on disease-free survival (DFS) of PTC patients were subsequently evaluated using Kaplan–Meier plotter and Gepia databases. Taking gender, age, cancer stage, T, N and M stages into consideration, we compared survival difference between TOP2A high and low expression groups. KEGG pathway analysis in WebGestalt and GSEA analysis were further performed to reveal the potential TOP2A-associated signaling pathways involved in PTC. Finally, the upstream microRNAs of TOP2A were assessed using DIANA, TargetScan, miRDB and miRWALK database, followed by mechanism exploration of upstream microRNAs.Results: 1) The mRNA and protein of TOP2A were highly expressed in PTC tissue compared with normal thyroid tissue. TOP2A expression was associated with patient’s age, N stage and cancer stage (all P< 0.05). TOP2A protein was mainly localized to nucleoplasm. 2) Most of samples occurred the missense substitution, and mutation site was located at K1199E. Nucleotide mutations were mainly presented as G>A (35.29%). 3) TOP2A high expression significantly influenced the DFS of PTC patients (P=0.015). Restricted survival analysis showed that TOP2A high expression caused poorer DFS of female patients (P=0.003) and those with age < 60 years old (P=0.002), early clinical stage (P=0.012), N0 stage (P=0.002) or M0 stage (P=0.040). 4) Pathway analysis suggested that TOP2A positively participated in the cell cycle, oocyte meiosis and p53 signaling pathways (all P< 0.05) involved in thyroid cancer.Conclusion: The expression of TOP2A was higher in PTC tissue, which resulted in a worse DFS of patients with PTC. TOP2A might act as an effective therapeutic target for PTC treatment.Keywords: TOP2A, high expression, poor prognosis, pathway

Xu Zhai,1 Meihua Gong,1,2 Yixuan Peng,1 Daping Yang1 1Department of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Plastic and Cosmetic Surgery, Shenzhen People’s Hospital, Second Affiliated Hospital of Jinan University Medical College, Shenzhen, People’s Republic of ChinaCorrespondence: Daping YangDepartment of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaTel/Fax +86-0451-86297062Email dapingyang1223@hotmail.comPurpose: To study the changes in the hair follicle cycle and related stem cells induced by photoaging to establish a mouse model of senescence in hair follicles.Methods: There were 54 C57BL6/J mice randomly divided into three groups. The UVA group and the UVB group underwent photoaging induced by UV lamps for 8 weeks. Changes in skin and the hair follicle cycle were compared by physical signs, dermoscopy, and hematoxylin and eosin and Masson’s staining in each group. Western blot, immunohistochemistry, and RT-qPCR were carried out to test canonical proteins and gene expression of the Wnt signaling pathway in the samples. Immunofluorescence was chosen to show variations in the stem cells related to the hair follicle cycle.Results: There were more gray hairs in the UVA group than the other groups (P< 0.05). Both diameter of the hair shaft and depth of hair root were significantly decreased in the UV groups (P< 0.05). Stem cells and melanocytes of the hair follicles were reduced in the UVA group. UV, especially UVB, up-regulated the expression of the Wnt signaling pathway and prolonged anagen and telogen phases in the hair follicles, compared with the control group (P< 0.05).Conclusion: By decreasing the number of stem cells related to hair follicles, UVA induces hair follicle photoaging characterized by hair follicle miniaturization and gray hairs. UV up-regulated the expression of the Wnt signaling pathway, and the hair follicle cycle was significantly prolonged by UVB.Keywords: UVA, photoaging, hair follicle cycle, HFSCs, Wnt

Baoxin Liu,1,* Jiachen Luo,1,* Mengmeng Gong,1 Zhiqiang Li,1 Beibei Shi,1 Xingxu Zhang,1 Xinqiang Han,2 Yidong Wei1 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Electrophysiology and Arrhythmia Services, Reid Health, Indiana University School of Medicine, Richmond, IN, 47374, USA*These authors contributed equally to this workCorrespondence: Yidong WeiDepartment of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Jingan District, Shanghai, People’s Republic of ChinaTel +86-021-66307249Fax +86-021-66301771Email ywei@tongji.edu.cnPurpose: LAAO has been an alternative therapy to oral anticoagulants (OACs) for stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF) with elevated CHA2DS2-Vasc score, but the long-term outcomes of LAAO and its impacts on cardiac electrical and mechanical remodeling remain to be learned. We aimed to describe the impact of left atrial appendage occlusion (LAAO) on atrial remodeling and cardiovascular outcomes within 5-year follow-up.Patients and Methods: A total of 107 patients with nonvalvular atrial fibrillation (NVAF) undergoing LAAO in the Shanghai Tenth People’s Hospital between January 2014 and July 2017 were included. All participants were followed for ECG, transthoracic echocardiography (TTE), and clinical outcomes (including cardiovascular death, heart failure, ischemic stroke/systemic embolism, and pericardial effusion) at 6 and 12 months, and thereafter every 12 months after LAAO discharge until 5 years.Results: After LAAO, the left atrial diameter significantly increased at 6 months (48.6 ± 6.7 vs 46.5 ± 7.0 mm); heart rate decreased immediately after the procedure (78.5 ± 14.7 vs 85.3 ± 21.7 bpm) when compared with the pre-procedure level. The QTc interval prolongated to the highest value of 460.7 ± 46.8 ms at 6 months (pre-procedure level of 433.7± 49.0 ms). All these changes return to the pre-procedure level within the follow-up. For clinical outcomes, 51 patients suffered the composite of cardiovascular death (n=4, 3.7%), heart failure (n=25, 23.4%), ischemic stroke/systemic embolism (n=22, 20.6%), and pericardial effusion (n=26, 26.2%).Conclusion: LAAO did not change ECG or TTE characteristics and nonprocedure-related pericardial effusion is common during long-term follow-up. Further studies are warranted to investigate the optimal time frame of anticoagulation in patients undergoing LAAO.Keywords: atrial fibrillation, left atrial appendage occlusion, ECG, echocardiogram

Liang Zhang, Shilin Xiao, Xun Kang, Tao Sun, Chunyu Zhou, Zhongsheng Xu, Mengmeng Du, Ya Zhang, Guangxian Wang, Yun Liu, Dong Zhang, Mingfu Gong Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Dong Zhang; Mingfu GongDepartment of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing, People’s Republic of ChinaTel +86 2368763843Fax +86 2368755306Email hszhangd@163.com; hummer198625@163.comBackground: Manganese Ferrite Nanoparticles (Mn-IONPs) are widely used in biomedical field and their cytotoxicity has been initially explored, but the mechanism remains obscure. The nano-bio interactions are believed to be crucial for cytotoxicity mechanism, while little data have been acquired.Methods: Mn-IONPs were synthesized by thermal decomposition of acetylacetonate precursor. After physicochemical characterization, we analyzed the metabolic conversion and removal of Mn-IONPs in RAW264.7 cells by Prussian blue staining, TEM, HRTEM and elemental quantitative analysis, followed by gene expression evaluation using quantitative RT-PCR.Results: Mn-IONPs were successfully synthesized. Both the uptake and cytotoxicity of Mn-IONPs on RAW264.7 cells were time- and dose-dependent. After internalized, Mn-IONPs were passed to daughter cells with passages on. Meanwhile, Mn-IONPs were exocytosed and digested to metal ions and further excreted out, resulted in the labeling rate and ions contents decreased gradually. As ion influx related genes, the expressions of ZIP14, IRP2, FtH and DMT1 were suppressed within 24 hours but overexpressed to a plateau at the 48th hour in a dose-dependent manner. At the 72nd hour, ZIP14 and DMT1 mRNA levels decreased toward normal, while IRP2 and FtH kept up-regulated. As efflux related genes, FPN, SLC30A10 and Hamp2 genes were up-regulated within 24– 72 hours; SPCA1 was suppressed at the 24th and 72nd hour, while overexpressed at the 48th hour. All the efflux related genes’ mRNA had a dose-dependent increasing manner at the corresponding time points.Conclusion: Mn-IONPs showed time- and dose-dependent cytotoxicity and cell labeling rate in RAW264.7 cells. Accompanying with the intracellular catabolic breakdown and exocytosis of Mn-IONPs, RAW264.7 cells also secreted and re-uptook manganese and iron ions to maintain intracellular homeostasis in the succeeding passages. And the metabolic conversion of Mn-IONPs in RAW264.7 cells can affect the expression of ZIP14, DMT1, FPN, SLC30A10, IRP2, FtH, Hamp2 and SPCA1 genes.Keywords: manganese ferrite nanoparticles, cytotoxicity, metabolism, metal transporter genes, RAW264.7 macrophage cells

ObjectiveAlthough intrauterine nutritional stress is known to result in offspring obesity and the metabolic phenotype, the underlying cellular/molecular mechanisms remain incompletely understood. We tested the hypothesis that compared with the controls, the bone marrow-derived mesenchymal stem cells (BMSCs) of the intrauterine growth-restricted (IUGR) offspring exhibit a more adipogenic phenotype.MethodsA well-established rat model of maternal food restriction (MFR), that is, 50% global caloric restriction during the later-half of pregnancy and ad libitum diet following birth that is known to result in an obese offspring with a metabolic phenotype was used. BMSCs at 3 weeks of age were isolated, and then molecularly and functionally profiled.ResultsBMSCs of the intrauterine nutritionally-restricted offspring demonstrated an increased proliferation and an enhanced adipogenic molecular profile at miRNA, mRNA and protein levels, with an overall up-regulated PPARγ (miR-30d, miR-103, PPARγ, C/EPBα, ADRP, LPL, SREBP1), but down-regulated Wnt (LRP5, LEF-1, β-catenin, ZNF521 and RUNX2) signaling profile. Following adipogenic induction, compared with the control BMSCs, the already up-regulated adipogenic profile of the MFR BMSCs, showed a further increased adipogenic response.ConclusionsMarkedly enhanced adipogenic molecular profile and increased cell proliferation of MFR BMSCs suggest a possible novel cellular/mechanistic link between the intrauterine nutritional stress and offspring metabolic phenotype. This provides new potential predictive and therapeutic targets against these conditions in the IUGR offspring.

Thiquynhnga Nguyen,* Song Wen,* Min Gong,* Xinlu Yuan, Dongxiang Xu, Chaoxun Wang, Jianlan Jin, Ligang Zhou Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of ChinaTel +86 13611927616Email zhouligang@yahoo.comPurpose: This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity.Material and Methods: Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence.Results: Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin.Conclusion: This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function.Keywords: sodium glucose co-transporter-2, dapagliflozin, c-Fos, cardiovascular activity, brain nuclei

Min Gong, Song Wen, Thiquynhnga Nguyen, Chaoxun Wang, Jianlan Jin, Ligang Zhou Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of ChinaCorrespondence: Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, ChinaTel +8613611927616Email zhouligang@yahoo.comBackground: Obesity and hyperuricemia mutually influence metabolic syndrome. This study discusses the metabolic relationships between obesity and hyperuricemia in terms of pathophysiology, complications, and treatments.Methods: We searched for preclinical or clinical studies on the pathophysiology, complications, and therapy of obesity and hyperuricemia on the PubMed database.Results: In this systemic review, we summarized our searching results on topics of pathophysiology, complications and therapeutic strategy. In pathophysiology, we firstly introduce genetic variations for obesity, hyperuricemia and their relationships by genetic studies. Secondly, we talk about the epigenetic influences on obesity and hyperuricemia. Thirdly, we describe the central metabolic regulation and the role of hyperuricemia. Then, we refer to the character of adipose tissue inflammation and oxidative stress in the obesity and hyperuricemia. In the last part of this topic, we reviewed the critical links of gut microbiota in the obesity and hyperuricemia. In the following part, we review the pathophysiology of major complications in obesity and hyperuricemia including insulin resistance and type 2 diabetes mellitus, chronic kidney disease, cardiovascular diseases, and cancers. Finally, we recapitulate the therapeutic strategies especially the novel pharmaceutic interventions for obesity and hyperuricemia, which concurrently show the mutual metabolic influences between two diseases.Conclusion: The data reviewed here delineate the metabolic relationships between obesity and hyperuricemia, and provide a comprehensive overview of the therapeutic targets for the management of metabolic syndromes.Keywords: obesity, hyperuricemia, pathophysiology, complication, pharmacotherapy