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1. Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial

Author

Nawal Al Kaabi, Yun Kai Yang, Yu Liang, Ke Xu, Xue Feng Zhang, Yun Kang, Yu Qin Jin, Jun Wei Hou, Jing Zhang, Tian Yang, Salah Hussein, Mohamed Saif ElDein, Ze Hua Lei, Hao Zhang, Shuai Shao, Zhao Ming Liu, Ning Liu, Xiang Zheng, Ji Guo Su, Sen Sen Yang, Xiangfeng Cong, Yao Tan, Wenwen Lei, Xue Jun Gao, Zhiwei Jiang, Hui Wang, Meng Li, Hanadi Mekki Mekki, Walid Zaher, Sally Mahmoud, Xue Zhang, Chang Qu, Dan Ying Liu, Mengjie Yang, Islam Eltantawy, Peng Xiao, Fu Jie Shen, Jin Juan Wu, Zi Bo Han, Li Fang Du, Fang Tang, Shi Chen, Zhi Jing Ma, Fan Zheng, Ya Nan Hou, Xin Yu Li, Xin Li, Zhao Nian Wang, Jin Liang Yin, Xiao Yan Mao, Jin Zhang, Liang Qu, Yun Tao Zhang, Xiao Ming Yang, Guizhen Wu, and Qi Ming Li

Subjects
Medicine, Biology (General), QH301-705.5
Abstract

Abstract An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Published
2023
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2. Epidemiological characteristics of norovirus infection in Lin’an District of Hangzhou City from 2012 to 2020

Author

SHI Shuiliang, LYU Lei, DUAN Tianxiao, ZHAO Ming, YE Yajun, YUAN Busheng, and LI Xuan

Subjects
norovirus, epidemiology, characteristics, hangzhou, Medicine
Abstract

ObjectiveTo determine the epidemiological characteristics of norovirus infections in Lin’an District， Hangzhou City from 2012 to 2020， and provide scientific evidence for improving preventive and control measures.MethodsDescriptive epidemiological methods were used to characterize the epidemic and conduct statistical analysis to determine related factors.ResultsA total of 37 clustered outbreaks of norovirus infection were reported in Lin’an District of Hangzhou from 2012 to 2020， including 8 outbreaks in kindergartens， 15 ones in elementary schools， 8 ones in middle and high schools， 2 ones in universities， and 4 other ones. The total number of cases with norovirus infection was 1 194， with the average attack rate of 3.76%. The incidence of norovirus was higher in winter and spring. It was also higher in urban areas， followed by suburban and mountainous areas neighbored to traffic lines. Moreover， attack rates differed significantly by transmission routes， including mixed contact and aerosol transmission， contact transmission， food-borne transmission， and water-borne transmission （χ2=186.91，P

Published
2022
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3. Detection rates of mental disorders in pregnant women with subjective depressive symptoms

Author

ZHAO Ming-zhe, WEI Jing, DUAN Yan-ping, ZHAO Yue, MA Liang-kun

Subjects
pregnant women, mental disorders, incidence, Medicine
Abstract

Objective To analyze the detection rates of mental disorders in women with subjective depressive symptoms during pregnancy and the postnatal period. Methods From March 1st 2020 to February 28th 2021, Patient Health Questionnaire-9 items (PHQ-9) and Edinburgh Postnatal Depression Scale (EPDS) were used to screen pregnant women and mothers who were established in a third-grade hospital. The women with PHQ-9≥5 or EPDS≥9 were followed up. Mini-International Neuropsychiatric Interview (MINI) was used to confirm the detection rates of mental disorders. Results Of the 342 women who were followed up, 24 (7.0%) were diagnosed with depressive episodes. There were 17 cases had depression in the past. Among them 3 women had a history of depression before pregnancy, and 14 had the first episode after pregnancy. The detection rate of depression in the second trimester is higher than that in the first and third trimester; 9 (2.6%)with (hypo)manic episodes; 6 (1.8%) with panic disorder; 13(3.8%) with agoraphobia; 3(0.9%) with social phobia; 15(4.4%) with generalized anxiety disorder; 6 (1.8%)with obsessive-compulsive disorder. Eighteen women suffered from two or more mental disorders, accounting for 29.0% of the total number of diagnosed mental disorders. Conclusions A variety of mental disorders occur in women with subjective depressive symptoms during pregnancy and the postnatal period, and comorbidity is a common finding. Pregnant women with depression may have several episodes during this period. So it is necessary to evaluate their mental status professionally.

Published
2022
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4. A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants

Author

Jing Zhang, Zi Bo Han, Yu Liang, Xue Feng Zhang, Yu Qin Jin, Li Fang Du, Shuai Shao, Hui Wang, Jun Wei Hou, Ke Xu, Wenwen Lei, Ze Hua Lei, Zhao Ming Liu, Jin Zhang, Ya Nan Hou, Ning Liu, Fu Jie Shen, Jin Juan Wu, Xiang Zheng, Xin Yu Li, Xin Li, Wei Jin Huang, Gui Zhen Wu, Ji Guo Su, and Qi Ming Li

Subjects
SARS-CoV-2, COVID-19, omicron variant, vaccine, broad-spectrum, Medicine, Science, Biology (General), QH301-705.5
Abstract

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

Published
2022
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5. Another treatment option for locally advanced hepatocellular carcinoma: Interventional arterial infusion of FOLFOX chemotherapy from the FOHAIC-1 study

Author

Lyu Ning and Zhao Ming

Subjects
folfox, arterial chemotherapy, advanced hepatocellular carcinoma, Medicine
Abstract

Advanced stage primary hepatocellular carcinoma (HCC) accounts for more than half of all cases worldwide. Poor prognosis is mainly attributed to intrahepatic tumor burden caused by high-risk factors, including Vp4-portal vein tumor thrombosis or tumor occupancy of >50% of the liver. In 2020, the combination of a VEGF/PD-L1 blocker was superior to a single tyrosine kinase inhibitor and associated with a median overall survival of 19.2 months. However, overall survival dramatically declined from 19.2 months to 7.6 months for patients with high-risk factors. In this present study, the FOHAIC-1 trial, interventional hepatic arterial infusion chemotherapy of FOLFOX (HAIC-FO) showed favorable survival outcomes in patients with high-risk advanced HCC. Compared with a tyrosine kinase inhibitor, in the high-risk subgroup, HAIC-FO achieved an overall survival of 10.8 months (vs. 5.7 months, hazard ratio 0.343, 95% confidence interval, 0.219–0.538). This study also observed disease downstaging in 16 (16/130) patients who received HAIC-FO; 15 (93.8%) patients received curative or regional treatments afterward. Therefore, for advanced HCC with localized high-risk factors, the clinical efficacy of HAIC-FO is significant and may be a better option than systemic therapies.

Published
2022
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6. Zonation of Microbial Communities by a Hydrothermal Mound in the Atlantis II Deep (the Red Sea).

Author

Yong Wang, Jiang Tao Li, Li Sheng He, Bo Yang, Zhao Ming Gao, Hui Luo Cao, Zenon Batang, Abdulaziz Al-Suwailem, and Pei-Yuan Qian

Subjects
Medicine, Science
Abstract

In deep-sea geothermal rift zones, the dispersal of hydrothermal fluids of moderately-high temperatures typically forms subseafloor mounds. Major mineral components of the crust covering the mound are barite and metal sulfides. As a result of the continental rifting along the Red Sea, metalliferous sediments accumulate on the seafloor of the Atlantis II Deep. In the present study, a barite crust was identified in a sediment core from the Atlantis II Deep, indicating the formation of a hydrothermal mound at the sampling site. Here, we examined how such a dense barite crust could affect the local environment and the distribution of microbial inhabitants. Our results demonstrate distinctive features of mineral components and microbial communities in the sediment layers separated by the barite crust. Within the mound, archaea accounted for 65% of the community. In contrast, the sediments above the barite boundary were overwhelmed by bacteria. The composition of microbial communities under the mound was similar to that in the sediments of the nearby Discovery Deep and marine cold seeps. This work reveals the zonation of microbial communities after the formation of the hydrothermal mound in the subsurface sediments of the rift basin.

Published
2015
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7. Optimal eukaryotic 18S and universal 16S/18S ribosomal RNA primers and their application in a study of symbiosis.

Author

Yong Wang, Ren Mao Tian, Zhao Ming Gao, Salim Bougouffa, and Pei-Yuan Qian

Subjects
Medicine, Science
Abstract

Eukaryotic 18S ribosomal RNA (rRNA) gene primers that feature a wide coverage are critical in detecting the composition of eukaryotic microscopic organisms in ecosystems. Here, we predicted 18S rRNA primers based on consecutive conserved sites and evaluated their coverage efficiency and scope of application to different eukaryotic groups. After evaluation, eight of them were considered as qualified 18S primers based on coverage rate. Next, we examined common conserved regions in prokaryotic 16S and eukaryotic 18S rRNA sequences to design 16S/18S universal primers. Three 16S/18S candidate primers, U515, U1390 and U1492, were then considered to be suitable for simultaneous amplification of the rRNA sequences in three domains. Eukaryotic 18S and prokaryotic 16S rRNA genes in a sponge were amplified simultaneously using universal primers U515 and U1390, and the subsequent sorting of pyrosequenced reads revealed some distinctive communities in different parts of the sample. The real difference in biodiversity between prokaryotic and eukaryotic symbionts could be discerned as the dissimilarity between OTUs was increased from 0.005 to 0.1. A network of the communities in external and internal parts of the sponge illustrated the co-variation of some unique microbes in certain parts of the sponge, suggesting that the universal primers are useful in simultaneous detection of prokaryotic and eukaryotic microbial communities.

Published
2014
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8. Enlarge the training set based on inter-class relationship for face recognition from one image per person.

Author

Qin Li, Hua Jing Wang, Jane You, Zhao Ming Li, and Jin Xue Li

Subjects
Medicine, Science
Abstract

In some large-scale face recognition task, such as driver license identification and law enforcement, the training set only contains one image per person. This situation is referred to as one sample problem. Because many face recognition techniques implicitly assume that several (at least two) images per person are available for training, they cannot deal with the one sample problem. This paper investigates principal component analysis (PCA), Fisher linear discriminant analysis (LDA), and locality preserving projections (LPP) and shows why they cannot perform well in one sample problem. After that, this paper presents four reasons that make one sample problem itself difficult: the small sample size problem; the lack of representative samples; the underestimated intra-class variation; and the overestimated inter-class variation. Based on the analysis, this paper proposes to enlarge the training set based on the inter-class relationship. This paper also extends LDA and LPP to extract features from the enlarged training set. The experimental results show the effectiveness of the proposed method.

Published
2013
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9. Glutamate carboxypeptidase activity in human skin biopsies as a pharmacodynamic marker for clinical studies

Author

Ebenezer Gigi J, Zhao Ming, Rudek Michelle A, Polydefkis Michael, Stathis Marigo, Rojas Camilo, and Slusher Barbara S

Subjects
Medicine
Abstract

Abstract Background Glutamate excitotoxicity is thought to be involved in the pathogenesis of neurodegenerative disease. One potential source of glutamate is N-acetyl-aspartyl-glutamate (NAAG) which is hydrolyzed to glutamate and N-acetyl-aspartate (NAA) in a reaction catalyzed by glutamate carboxypeptidase (GCP). As a result, GCP inhibition is thought to be beneficial for the treatment of neurodegenerative diseases where excess glutamate is presumed pathogenic. Both pharmacological and genetic inhibition of GCP has shown therapeutic utility in preclinical models and this has led to GCP inhibitors being pursued for the treatment of nervous system disorders in human clinical trials. Specifically, GCP inhibitors are currently being developed for peripheral neuropathy and neuropathic pain. The purpose of this study was to develop a pharmacodynamic (PD) marker assay to use in clinical development. The PD marker will determine the effect of GCP inhibitors on GCP enzymatic activity in human skin as measure of inhibition in peripheral nerve and help predict drug doses required to elicit pharmacologic responses. Methods GCP activity was first characterized in both human skin and rat paw pads. GCP activity was then monitored in both rodent paw pads and sciatic nerve from the same animals following peripheral administration of various doses of GCP inhibitor. Significant differences among measurements were determined using two-tailed distribution, equal variance student's t test. Results We describe for the first time, a direct and quantifiable assay to evaluate GCP enzymatic activity in human skin biopsy samples. In addition, we show that GCP activity in skin is responsive to pharmacological manipulation; GCP activity in rodent paws was inhibited in a dose response manner following peripheral administration of a potent and selective GCP inhibitor. Inhibition of GCP activity in rat paw pads was shown to correlate to inhibition of GCP activity in peripheral nerve. Conclusion Monitoring GCP activity in human skin after administration of GCP inhibitors could be readily used as PD marker in the clinical development of GCP inhibitors. Enzymatic activity provides a simple and direct measurement of GCP activity from tissue samples easily assessable in human subjects.

Published
2011
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10. C-Reactive Protein Protects Against Acetaminophen-Induced Liver Injury by Preventing Complement Overactivation

Author

Zhe Wang, Bin Cheng, Jian-Min Lv, Shang-Rong Ji, Xiao-Ling Liu, Hai-Yun Li, Zhao-Ming Tang, Yi Wu, Yu-Lin Liang, and Ning Gao

Subjects
Inflammation, RC799-869, Pharmacology, Mice, Animals, Medicine, Receptor, Acetaminophen, Liver injury, Hepatology, biology, business.industry, C-reactive protein, Pattern Recognition Receptor, Gastroenterology, Pattern recognition receptor, Biomarker, Diseases of the digestive system. Gastroenterology, medicine.disease, Rats, Mice, Inbred C57BL, C-Reactive Protein, Editorial, Chemical and Drug Induced Liver Injury, Chronic, Knockout mouse, Hepatocytes, biology.protein, Biomarker (medicine), Chemical and Drug Induced Liver Injury, medicine.symptom, business, medicine.drug
Abstract

Background and aims C-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI). Methods The effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post–AILI induction in wild-type mice. Results CRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus–mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine. Conclusion Our results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.

Published
2022

11. Nicorandil, an ATP-sensitive potassium channel activation, attenuates myocardial injury in rats with ischemic cardiomyopathy

Author

Li Shaoqing, Yu Wang, Zhao Ting, Zhao Ming, Liu Hao, and Zhihui He

Subjects
ATP-sensitive potassium channel, Myocardial Ischemia, Pharmacology, Pathology and Forensic Medicine, KATP Channels, Western blot, medicine, Animals, Nicorandil, Molecular Biology, Ischemic cardiomyopathy, medicine.diagnostic_test, business.industry, Myocardium, General Medicine, medicine.disease, Potassium channel, Rats, Apoptosis, Heart failure, cardiovascular system, Cardiomyopathies, business, VDAC1, medicine.drug
Abstract

Ischemic cardiomyopathy is a common but underestimated cause of heart failure. This study investigated the myocardial-protective effects of nicorandil on rats with ischemic cardiomyopathy. In the present study, ischemic cardiomyopathy rats model were used to evaluate the effects of nicorandil. Cardiac ultrasonography was employed to examine the changes of heart structure and heart function. Electron microscopy was employed to observe the changes of pathological ultrastructure of the myocardium. Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels and Mitochondrial Ca2+ concentration. The heart color ultrasound and myocardial pathology of the rats in the nicorandil group were improved significantly, the mitochondrial Ca2+ concentration was decreased, the expressions of MFN-1, OPA-1, and Bcl were increased, and the expressions of the mitochondrial mitotic proteins DRP-1, VDAC1, CytC, and Bax were decreased in ICM rats' heart treatment with nicorandil, compared with ICM rats. Nicorandil can reduce myocardial pathological damage in ICM rats, which may be caused by promoting the opening of mitochondrial ATP-sensitive potassium channel and inducing the changes of mitochondrial dynamics to induce the reduction of myocardial cell apoptosis.

Published
2021

12. Doxorubicin-loaded hydrogen peroxide self-providing copper nanodots for combination of chemotherapy and acid-induced chemodynamic therapy against breast cancer

Author

Qian-ni Wu, Yugang Huang, Gui-ning Feng, Songpei Li, Xue-ping Lei, Jie-xia Li, Zhao-ming Guo, Jijun Fu, Xian-qiang Sun, Xi-Yong Yu, Ling-min Zhang, and Cheng-cheng Liu

Subjects
medicine.medical_treatment, Breast Neoplasms, Photodynamic therapy, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biomaterials, chemistry.chemical_compound, Colloid and Surface Chemistry, Cell Line, Tumor, Tumor Microenvironment, medicine, Humans, Doxorubicin, Hydrogen peroxide, chemistry.chemical_classification, Reactive oxygen species, Singlet oxygen, Sonodynamic therapy, Hydrogen Peroxide, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, chemistry, Cancer cell, Cancer research, Female, Hydroxyl radical, 0210 nano-technology, Copper, medicine.drug
Abstract

In recent years, chemodynamic therapy (CDT) has gained increasing interest in cancer treatment. In contrast to photodynamic therapy and sonodynamic therapy, extrinsic excitations such as laser or ultrasound are not required in CDT. As a result, the CDT performance is not limited by the penetration depth of the external irritation. However, CDT relies heavily on hydrogen peroxide (H2O2) in the tumour microenvironment (TME). Insufficient H2O2 in the TME limits the CDT performance, and the most reported methods to produce H2O2 in the TME are dependent on oxygen supply, which is restricted by the hypoxic TME. In this study, H2O2 self-providing copper nanodots were proposed, and the drug doxorubicin (DOX) was successfully loaded to construct DOX-nanodots. Our results showed that the nanodots produced H2O2 in the weakly acidic TME due to the peroxo group and further generated the most active hydroxyl radical (OH) through the Fenton-like reaction. This process was pH-dependent and did not occur in a neutral environment. In addition to OH, the nanodots also produced singlet oxygen (1O2) and superoxide anions (O2-) in the cancer cells. The copper nanodots performed promising CDT against breast cancer in vitro and in vivo, with enhanced cell apoptosis and decreased cell proliferation. The combination of chemotherapy and CDT using DOX-nanodots further improved the therapeutic effects. The treatments showed good biocompatibility with no obvious toxicity in major tissues, possibly due to the specific OH generation in the weakly acidic TME. In summary, the H2O2 self-providing copper nanodots in combination with DOX showed promising cancer-curing effects due to the oxygen-independent and tumour-specific production of reactive oxygen species and the cooperation of chemotherapy.

Published
2021

13. Anti-apoptotic Effect of MiR-223-3p Suppressing PIK3C2A in Cardiomyocytes from Myocardial Infarction Rat Through Regulating PI3K/Akt Signaling Pathway

Author

Jia Guowei, Zhao Ming, Liu Xiaoyu, and Zhang Wei

Subjects
Male, Myocardial Infarction, Apoptosis, 030204 cardiovascular system & hematology, Toxicology, Rats, Sprague-Dawley, Andrology, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Western blot, medicine, Animals, Myocytes, Cardiac, Ventricular remodeling, Molecular Biology, Protein kinase B, Cells, Cultured, PI3K/AKT/mTOR pathway, TUNEL assay, medicine.diagnostic_test, business.industry, Akt/PKB signaling pathway, Transfection, medicine.disease, Disease Models, Animal, MicroRNAs, 030220 oncology & carcinogenesis, Apoptosis Regulatory Proteins, Cardiology and Cardiovascular Medicine, business, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract

We aimed to explore the regulatory mechanism of the axis of miR-223-3p-PIK3C2A-PI3K/Akt on cardiomyocyte apoptosis in rats with myocardial infarction. Thirty 8-week-old healthy male SD rats were used for establishing the sham group and the model group, with HE staining, TUNEL staining, and TTC staining performed. After the identification of the targeting relationship between PIK3C2A and miR-223-3p, experimental rats were randomly divided into seven groups by plasmid transfection, including the Blank group, negative control (NC) group, miR-223-3p mimic group, miR-223-3p inhibitor group, siRNA-PIK3C2A group, oe-PIK3C2A group, and miR-223-3p inhibitor + oe-PIK3C2A group. Four weeks after transfection, the expression levels of miR-223-3p and PIK3C2A in tissues as well as PI3K, Akt, Bax, and bcl-2 mRNA in cells were detected by qRT-PCR and western blot, in combination with the detection of apoptosis rate by flow cytometry. Compared with the sham group, the model group showed typical myocardial injury and abnormal staining, higher apoptotic index, and larger myocardial infarction area (all P 0.05). PIK3C2A was the target gene of miR-223-3p. The expression level of miR-223-3p in model group was significantly lower than that in sham group, while the mRNA and protein expression levels of PIK3C2A increased significantly (all P 0.05). In cell tests, the expression level of miR-223-3p increased significantly in miR-223-3p mimic group (P 0.05), which, however, showed no significant change in siRNA-PIK3C2A group (P 0.05). MiR-223-3p inhibitor group and siRNA-PIK3C2A group had obviously increased PI3K, Akt, mTOR and Bcl-2 mRNA, and protein expression, while decreased mRNA and protein expression of PIK3C2A and Bax (all P 0.05); miR-223-3p mimic groups had the opposite trends (all P 0.05). siRNA-PIK3C2A + miR-223-3p mimic showed no obvious change relative to the control groups (all P 0.05). Low expression of miR-223-3p may downregulate PIK3C2A expression, resulting in the inhibition of myocardial cell apoptosis in rats with myocardial infarction via the activation of PI3K/Akt signaling pathway.

Published
2021

14. Correlation between serum renin-angiotensin system (RAS) level and depression and anxiety symptoms in patients with Parkinson's disease

Author

Chong-Chong Zhao, Huan Wang, Hong-Bin Cai, and Zhao-Ming Ge

Subjects
0106 biological sciences, 0301 basic medicine, medicine.medical_specialty, Parkinson's disease, ACE2, Anxiety, 01 natural sciences, Gastroenterology, 03 medical and health sciences, Internal medicine, Renin–angiotensin system, Hamd, medicine, lcsh:QH301-705.5, AngⅠ, Ace, Depression (differential diagnoses), biology, Depression, business.industry, Stomach, Ang Ⅱ, Angiotensin-converting enzyme, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), biology.protein, Original Article, Ang (1–7), medicine.symptom, General Agricultural and Biological Sciences, business, hormones, hormone substitutes, and hormone antagonists, Anxiety disorder, 010606 plant biology & botany
Abstract

To investigate the correlation between serum renin-angiotensin system (RAS) level and Symptoms of anxiety and depression in Parkinson disease patients (PD). A number of 90 PD patients (47 males and 43 females) were collected on an empty stomach 12 h after stopping taking anti-PD medicines. ELISA has been found in Serum RAS ((Ang) I, Ang II, Ang (1–7), Angiotensin converting enzyme (ACE), ACE2). Depression scale (HAMD) and Anxiety scale (HAMA) in Hamilton are used for the assessment of signs of depression and anxiety. The 90 patients were diagnosed with moderate depression (HAMD score 8 ~ 19); in 32 of those (35.56 percent), and 12 (13.33%) were diagnosed as moderate and severe depression (HAMD score ≥ 20). 20 cases (22.22%) were diagnosed as possible anxiety disorder (HAMA score 7 ~ 13) and 16 cases (17.78%) as definite anxiety disorder (HAMA score ≥ 14). The association of serum Ang I, Ang II and Ang (1–7) with HAMD (r= − 0.820, P 0.05) were not associated to the serum ACE and ACE2. The serum Ang I, Ang II, and Ang (1–7) were found to be adversely associated with HAMD score (r = 0.826, P >0,001; r = −0.876, P 0.001; The HAMD score and the HAMA score (all P > 0.05) were not correlated to the serum ACE and ACE2. Finally, in PD patients, non-engine signs, including depression and anxiety, are normal. Thus, Serum levels Ang I, Ang II and Ang (1–7) were substantially decreased in female and male patients and associated with symptoms of depression and anxiety, ACE and ACE2 levels have not been attributed to signs of depression and anxiety. Serum Ang I, Ang II, and Ang (1–7) are important markers of depression and anxiety prevention and diagnosis in patients with DP.

Published
2021

15. Diabetes-Induced H3K9 Hyperacetylation Promotes Development of Alzheimer’s Disease Through CDK5

Author

Zi-Chao Li, Zhen-Zhen Fan, Ting Tian, Wen-Ting Guo, Chon-Chon Zhao, Hong-Bin Cai, and Zhao-Ming Ge

Subjects
Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Tau protein, Hyperphosphorylation, Diet, High-Fat, Diabetes Mellitus, Experimental, Histones, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Alzheimer Disease, Diabetes mellitus, Internal medicine, medicine, Animals, Maze Learning, biology, business.industry, General Neuroscience, Cyclin-dependent kinase 5, nutritional and metabolic diseases, Acetylation, Cyclin-Dependent Kinase 5, General Medicine, Histone acetyltransferase, Streptozotocin, medicine.disease, Rats, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Endocrinology, Histone, nervous system, biology.protein, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

The connection between diabetes and Alzheimer’s disease (AD) is not fully determined. Hyperphosphorylation of tau protein is mediated by binding and stabilization of truncated p25 with cyclin-dependent kinase-5 (CDK5) in AD. We recently showed that diabetes-associated hyperglycemia increased the CDK5 levels to promote development of AD. Here, we examined the underlying mechanisms. Hyperglycemia and glucose intolerance were induced in rats that had received a low dose of streptozotocin (STZ) and a high fat diet (HFD). Compared to the control rats that received no STZ and were fed a normal diet, the STZ + HFD rats exhibited poorer performance in the behavioral test and showed hyperacetylation of H3K9 histone on the CDK5 promoter, likely resulting from upregulation of a histone acetyltransferase, GCN5. Inhibition of acetylation of H3K9 histone by a specific GCN5 inhibitor, MB3, attenuated activation of CDK5, resulting in decreased tau phosphorylation in rat brain and improved performance of the rats in the behavior test. Thus, these data suggest that diabetes may promote future development of AD through hyperacetylation of H3K9 histone on CDK5 promoter.

Published
2020

16. MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways

Author

He Zhefeng, Lan Yaliang, Xue Junlin, Xiao Peng, Liu Lianxin, Li Jian, Sun Boshi, Lang Qingfu, Liu Guoxing, Zhao Ming, Meng Fanzheng, Han Jihua, Guo Zihao, Meng Qinghui, Song Ruipeng, Liang Desen, Wang Yan, and Pei Tiemin

Subjects
Male, 0301 basic medicine, Mice, Nude, Biology, Transfection, Metastasis, Cholangiocarcinoma, Mice, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Cell Movement, Epidermal growth factor, Cell Line, Tumor, medicine, Animals, Humans, Epidermal growth factor receptor, Protein kinase B, PI3K/AKT/mTOR pathway, Retrospective Studies, Mice, Inbred BALB C, Phosphoinositide 3-kinase, Hepatology, Akt/PKB signaling pathway, Mucins, Middle Aged, medicine.disease, Xenograft Model Antitumor Assays, Tumor Burden, Up-Regulation, ErbB Receptors, MicroRNAs, 030104 developmental biology, Bile Duct Neoplasms, Disease Progression, Cancer research, biology.protein, Female, 030211 gastroenterology & hepatology, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract

Background & Aims Mucin 13 (MUC13) is reportedly overexpressed in human malignancies. However, the clinicopathological and biological significance of MUC13 in human intrahepatic cholangiocarcinoma (iCCA) remain unclear. The aim of this study was to define the role of MUC13 in the progression of iCCA. Methods Expression levels of MUC13 in human iCCA samples were evaluated by immunohistochemistry, western blot, and real-time PCR. In vitro and in vivo experiments were used to assess the effect of MUC13 on iCCA cell growth and metastasis. Crosstalk between MUC13 and EGFR/PI3K/AKT signaling was analyzed by molecular methods. The upstream regulatory effects of MUC13 were evaluated by Luciferase and DNA methylation assays. Results MUC13 was overexpressed in human iCCA specimens and iCCA cells. MUC13 overexpression positively correlated with clinicopathological characteristics of iCCA, such as vascular invasion and lymph node metastasis, and was independently associated with poor survival. Results from loss-of-function and gain-of-function experiments suggested that knockdown of MUC13 attenuated, while overexpression of MUC13 enhanced, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Mechanistically, we found that the phosphatidylinositol 3-kinase-AKT signal pathway and its downstream effectors, such as tissue inhibitor of metalloproteinases 1 and matrix metallopeptidase 9, were required for MUC13-mediated tumor metastasis of iCCA. MUC13 interacted with epidermal growth factor receptor (EGFR) and subsequently activated the EGFR/PI3K/AKT signaling pathway by promoting EGFR dimerization and preventing EGFR internalization. We also found that MUC13 was directly regulated by miR-212-3p, whose downregulation was related to aberrant CpG hypermethylation in the promoter area. Conclusions These findings suggest that aberrant hypermethylation-induced downregulation of miR-212-3p results in overexpression of MUC13 in iCCA, leading to metastasis via activation of the EGFR/PI3K/AKT signaling pathway. Lay summary Mucin 13 overexpression has been implicated in the development of malignancies, although its role in intrahepatic cholangiocarcinoma has not been studied. Herein, we show that mucin 13 plays a critical role in intrahepatic cholangiocarcinoma. Mucin 13 could have therapeutic value both as a prognostic marker and as a treatment target.

Published
2020

17. Mantle cell lymphoma relapsed after autologous stem cell transplantation: a single-center experience

Author

Robert E. Richard, Thomas R. Chauncey, Aaron Wu, Jonathan E. Grim, Zhao Ming Dong, Solomon A. Graf, and Nicholas Burwick

Subjects
Oncology, medicine.medical_specialty, Mantle cell lymphoma, Subsequent Relapse, business.industry, Disease progression, Hematology, Single Center, medicine.disease, chemistry.chemical_compound, Autologous stem cell transplant, Autologous stem-cell transplantation, Real-world, chemistry, Internal medicine, Ibrutinib, medicine, Original Article, Progression-free survival, business, Veterans Affairs
Abstract

Background Autologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging. Methods We examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37). Results Ten patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3–7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib. Conclusion Our findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.

Published
2020

18. Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ε/γ binding

Author

Zhao Ming Zhong, Xuemin Wang, Mu Sheng Zeng, Shiqi Wang, Jin Liang, Chuan Zheng Sun, Xue Chen, Ru Jia Qin, Xiao Qi, and Chunyan Li

Subjects
Cancer Research, LNK, Adaptor protein, lcsh:RC254-282, 03 medical and health sciences, Cell growth, 0302 clinical medicine, Western blot, Genetics, medicine, lcsh:QH573-671, Thyroid cancer, 030304 developmental biology, 0303 health sciences, Gene knockdown, medicine.diagnostic_test, Chemistry, lcsh:Cytology, In vitro toxicology, Anaplastic thyroid carcinoma, Signal transducing adaptor protein, 14-3-3 ε/γ, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Haematopoiesis, Oncology, 030220 oncology & carcinogenesis, Cancer research, Immunohistochemistry, Primary Research
Abstract

Background Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. In a preliminary study, we demonstrated that some hematopoietic factors may be involved in the progression of ATC. The adaptor protein LNK, which is a negative regulator of hematopoietic cytokine signalling, has been studied extensively in malignant hematopoietic cells. However, there are few studies on LNK in solid tumours. Methods Real-time PCR, immunohistochemistry (IHC) and western blot analysis of LNK were performed on ATC cells, differentiated thyroid cancer (DTC) cells and normal thyroid cells. In vitro assays (including pull-down, liquid chromatography-mass spectrometry (LC–MS), co-IP, MTT and colony formation) were performed to validate the effect of LNK on ATC progression and elucidate the molecular mechanisms. Results Compared with DTC cells and normal thyroid cells, ATC cells exhibit overexpression of LNK. In addition, LNK overexpression results in increased proliferation of ATC cells. Conversely, LNK knockdown significantly suppresses ATC cell proliferation. LC–MS identified the 14-3-3 ε/γ protein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ε/γ binding. Conclusions The present study elucidated the important role of LNK in the growth of ATC opposite to its behaviour in the hematopoietic system and indicates that LNK is a potential target for the treatment of ATC.

Published
2020

19. miR‐15a regulates oxygen glucose deprivation/reperfusion (OGD/R)‐induced neuronal injury by targeting BDNF

Author

Li-Jun Qin, Hao-Yue Wang, Pei Liu, Chong-Chong Zhao, Jie-Jie Hu, Hai-Ping Wei, Zhi-Yan Liu, and Zhao-Ming Ge

Subjects
Untranslated region, Cell Survival, Blotting, Western, Apoptosis, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Western blot, Neurotrophic factors, microRNA, Animals, Medicine, PI3K/AKT/mTOR pathway, Neurons, Messenger RNA, lcsh:R5-920, medicine.diagnostic_test, business.industry, Brain-Derived Neurotrophic Factor, miR‐15a, Computational Biology, General Medicine, neuron, Rats, Cell biology, Oxygen, PI3K/AKT pathway, MicroRNAs, Glucose, medicine.anatomical_structure, BDNF, nervous system, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Neuron, business, lcsh:Medicine (General)
Abstract

Multiple microRNAs (miRs) have also been implicated in ischemic brain injury. This research intended to probe the regulatory function and the mechanism of miR‐15a on the ischemic brain injury induced by oxygen‐glucose deprivation/reoxygenation (OGD/R) in neurons of rats. The OGD/R model was established with the cortical neurons separated from rats. After transfection with miR‐15a mimic negative control (NC), miR‐15a mimic, miR‐15a inhibitor NC and miR‐15a inhibitor, the OGD/R‐induced apoptosis were detected. Using bioinformatic softwares including TargetScan, miRanda, and miRWalk to predict the underlying targets of miR‐15a, and the binding of miR‐15a with brain‐derived neurotrophic factor (BDNF) were validated with double‐fluorescein reporter assay system. The expression levels of BDNF mRNA and protein were detected with qRT‐PCR and western blot. The effect of miR‐15a on PI3K/AKT pathway in neurons submitted to OGD/R was also investigated. The findings showed that miR‐15a may mediate the apoptosis of neurons submitted to OGD/R, and lower expression of Bcl‐2 and higher expression of Bax and cleaved caspase‐3 were observed. BDNF was screened as the candidate target, and the direct binding of miR‐15a with 3′‐UTR of BDNF were verified. Further research showed that miR‐15a downregulated the expression of BDNF mRNA and protein, thus exerted negative regulatory effect on the OGD/R injury. PI3K/AKT pathway may be related to the regulatory effect of miR‐15a. Our findings contribute to uncovering novel pathogenesis for ischemic brain injury.

Published
2020

20. A preliminary study of a novel robotic system for pedicle screw fixation: A randomised controlled trial

Author

Yongjian Zhu, Zhao-Ming Zhong, Jincheng Yang, Jianting Chen, Dehong Yang, Wei Huang, Shaoli Zheng, Zongze Li, Hui Jiang, Jiarui Chen, Wangsheng Jiang, Qingan Zhu, and Donghui Sun

Subjects
0301 basic medicine, musculoskeletal diseases, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Statistical difference, law.invention, 03 medical and health sciences, 0302 clinical medicine, Spine surgery, Randomized controlled trial, law, Operation time, Medicine, Orthopedics and Sports Medicine, Accurcay, Pedicle screw fixation, Pedicle screw, Robotic system, Conventional technique, 030203 arthritis & rheumatology, Posterior lumbar interbody fusion, business.industry, Surgery, 030104 developmental biology, Robotic systems, surgical procedures, operative, Preoperative planning, Original Article, lcsh:RC925-935, business
Abstract

Background and objective: Existing orthopaedic robotic systems are almost restricted to provide guidance for trajectory direction. In the present study, a novel spinal robotic system with automatic drilling power was introduced. The aim of this study is to evaluate the feasibility and safety in pedicle screw ​insertion of posterior lumbar interbody fusion assisted by this novel robotic system. Methods and materials: A randomised controlled trial was conducted for 17 participants who were required posterior lumbar interbody fusion process. Seven (3 M/4 F) were randomly assigned to the robot-assisted group (RA group), and the other ten (4 M/6 F) were assigned to the conventional technique group (FH group). A novel robotic system was used in the RA group. All measurements were based on postoperative computed tomography (CT) data. Accuracy of screw insertion was determined using the Gertzbein and Robbins Scale. Precision was measured by the entry point deviation distance and the trajectory rotation. Other variables included operation time, radiation time, length of stay, and screw-related complications. Result: A total of 82 pedicle screws were placed in the 17 participants. In the RA group, 90.6% of screws placed were Grade A, and 9.4% were Grade B. In the FH group, 78.0% of screws were Grade A, 20.0% were Grade B, and 2.0% were Grade C. No statistical difference was found in the operation time, radiation time per case, and length of stay between both groups. The radiation time per screw is significantly lower in the RA group. No screw-related complications or revision occurred in the present study. Conclusion: The outcome of screw accuracy of this robotic system was comparable with that of experienced surgeons, and no screw-related complication was found in the RA group during hospitalisation. In addition, radiation time per screw in the robotic group was significantly lower than that in the conventional group, which shows the potential to reduce radiation exposure of pedicle screw fixation assisted by this robotic system. Translational potential: Our study shows that pedicle screw fixation assisted by “Orthbot” system is accurate and safe. It is concluded that this novel robotic system offers a new option for internal implantation in spine surgery. Keywords: Robotic system, Pedicle screw fixation, Posterior lumbar interbody fusion, Preoperative planning, Accurcay

Published
2020

21. Oxidative Stress Contributes to Hyperalgesia in Osteoporotic Mice

Author

Ji-Huan Zeng, Di-Zheng Wu, Ping Xu, Ting-Ting Meng, Zhao-Ming Zhong, Jing-Shen Zhuang, Chen Tu, and Yu-Sheng Huang

Subjects
medicine.medical_specialty, business.industry, Osteoporosis, TRPV1, Chronic pain, Stimulation, Calcitonin gene-related peptide, medicine.disease, Malondialdehyde, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Anesthesiology and Pain Medicine, Endocrinology, chemistry, 030202 anesthesiology, Internal medicine, Hyperalgesia, medicine, medicine.symptom, business, 030217 neurology & neurosurgery, Oxidative stress
Abstract

Purpose Chronic pain is one of the most common complications of postmenopausal osteoporosis. Since oxidative stress is involved in the pathogenesis of postmenopausal osteoporosis, we explored whether oxidative stress contributes to postmenopausal osteoporotic pain. Methods Osteoporosis was induced in mice by ovariectomy (OVX). Pain-related behaviours were assessed by measuring sensitivity to mechanical, thermal and cold stimulation. The expression of pain-related transcripts, such acid-sensing ion channel 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP), was evaluated. Plasma markers of oxidative stress were also measured. In addition, the effects of the reactive oxygen species scavenger phenyl N-tert-butylnitrone (PBN) on these parameters were assessed. Results The OVX mice presented hyperalgesia, as demonstrated by decreased paw withdrawal thresholds to mechanical stimulation and withdrawal latencies to thermal and cold stimulation, along with upregulated expression of ASIC3, TRPV1 and CGRP in the dorsal root ganglia, spinal cord and thalamus tissue. OVX elevated the plasma levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPPs). However, the administration of PBN alleviated these effects. Conclusion Our results indicated that oxidative stress contributes to hyperalgesia in OVX mice. Enhanced oxidative stress may be associated with osteoporotic pain. Antioxidant treatment could help alleviate chronic pain in postmenopausal osteoporotic patients.

Published
2020

22. Psychophysiological and cognitive effects of strawberry plants on people in isolated environments

Author

Hong Liu, Wenzhu Zhang, Zhao-ming Li, and Hui Liu

Subjects
Adult, Male, 0301 basic medicine, Hydrocortisone, Emotions, Crew, Environment, Profile of mood states, Affect (psychology), Fragaria, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Cognition, 0302 clinical medicine, Heart Rate, medicine, Humans, General Pharmacology, Toxicology and Pharmaceutics, Bioregenerative life support system, Saliva, General Veterinary, fungi, General Medicine, Negative mood, Affect, 030104 developmental biology, Mood, 030220 oncology & carcinogenesis, Anxiety, Female, medicine.symptom, Psychology, Clinical psychology
Abstract

In manned deep-space exploration, extremely isolated environments may adversely affect the mood and cognition of astronauts. Horticultural plants and activities have been proven to be effective in improving their physical, psychological, and cognitive states. To assess the effects of applying horticultural plants and activities in isolated environments, this study investigated the influence of viewing strawberry plants on the mood of people in a laboratory experiment as indicated by heart rate, salivary cortisol, and psychological scales. The results showed that heart rate and salivary cortisol were significantly decreased after viewing strawberry plants for 15 min. "Tension" and "confusion" scored using the Profile of Mood States negative mood subscales, and anxiety levels measured using the State-Trait Anxiety Inventory scale were also significantly reduced. This study further explored the impact of viewing strawberry plants on cognition. A notable reduction of the subjects' reaction time after 15-min plant viewing was observed. Based on these findings, a long-duration isolated experiment in a bioregenerative life support system-"Lunar Palace I"-was conducted. A similar trend was obtained that crew members' mood states were improved by viewing the strawberry plants, but no significant change was observed. This study provided some experimental evidence for the benefits of interacting with strawberry plants in isolated environments.

Published
2019

23. Circular RNA circPDSS1 promotes osteosarcoma progression by sponging miR-502-3p and miR-4436a

Author

Laijie Wang, Chao Liu, Zhengping Jin, Xinhai Tang, Shaolong Tang, Zhao-ming Ye, Qinghua Huang, and Diarra Mohamed Diaty

Subjects
Cancer Research, Clone (cell biology), Bone Neoplasms, Biology, medicine.disease_cause, Mice, Downregulation and upregulation, Circular RNA, Cell Line, Tumor, medicine, Animals, Humans, Pharmacology (medical), Cell Proliferation, Pharmacology, Gene knockdown, Osteosarcoma, RNA, RNA, Circular, medicine.disease, Gene Expression Regulation, Neoplastic, MicroRNAs, Oncology, Cell culture, Cancer research, Carcinogenesis
Abstract

Background Osteosarcoma (OS) is a highly aggressive bone cancer. Patients with OS frequently develop drug resistance in clinical treatment, and the prognosis has not been improved significantly. There is an urgent need to identify novel markers and therapeutic targets. Methods In this study, we focused on the highly expressed noncoding circular RNA circPDSS1 in OS, and studied its functional roles and downstream targets in OS cells by CCK-8, clone formation assay, transwell assays. Additionally, we performed luciferase reporter assay, RNA pull-down experiment and qRT-PCR to validate the micoRNA targets of circPDSS1. The involvement of circPDSS1 in tumorigenesis was also investigated in mouse xenografts model. Results The expression of circPDSS1 was significantly upregulated in OS tissues and cell lines. Patients with high circPDSS1 expression were associated with poorer progression-free survival (PFS) and overall survival (OS) as compared to those with low circPDSS1 expression. CircPDSS1 knockdown significantly inhibited the viability, clone formation ability and invasion ability of OS cells, and induced cell apoptosis, which were associated with the upregulation of proapoptotic proteins and the impairment of prosurvival signaling. Molecular mechanism study further demonstrated that circPDSS1 modulates OS cell functions by regulating the expression of miR-502-3p and miR-4436a. Conclusion Our data suggest that circPDSS1 acts as a molecular sponge of miR-502-3p and miR-4436a regulates the proliferation and invasion of OS cells and promote the malignant progression of OS.

Published
2021

24. Exhaled Volatile Organic Compounds for Identifying Patients With Chronic Pulmonary Aspergillosis

Author

Zheng-Tu Li, Pei-Ying Zeng, Zhao-Ming Chen, Wei-Jie Guan, Tong Wang, Ye Lin, Shao-Qiang Li, Zhi-Juan Zhang, Yang-Qing Zhan, Ming-Die Wang, Guo-Bin Tan, Xue Li, and Feng Ye

Subjects
Antifungal, Medicine (General), medicine.medical_specialty, medicine.drug_class, Gastroenterology, R5-920, chronic pulmonary aspergillosis, volatile organic compounds, Internal medicine, medicine, In patient, Original Research, business.industry, Chronic pulmonary aspergillosis, exhalation, Antibody titer, Exhalation, General Medicine, medicine.disease, Serum samples, metabolomics, single-photon ionization-mass spectrometry, Pneumonia, Medicine, Differential diagnosis, business
Abstract

Background: Diagnosing chronic pulmonary aspergillosis is a major challenge in clinical practice. The development and validation of a novel, sensitive and specific assay for diagnosing chronic pulmonary aspergillosis is urgently needed.Methods: From April 2018 to June 2019, 53 patients with chronic pulmonary aspergillosis (CPA), 32 patients with community-acquired pneumonia (CAP) and 48 healthy controls were recruited from the First Affiliated Hospital of Guangzhou Medical University. Clinical characteristics and samples were collected at enrollment. All exhaled breath samples were analyzed offline using thermal desorption single-photon ionization time-of-flight mass spectrometry; to analyze the metabolic pathways of the characteristic volatile organic compounds, serum samples were subjected to ultrahigh-performance liquid chromatography.Results: We identified characteristic volatile organic compounds in patients with chronic pulmonary aspergillosis, which mainly consisted of phenol, neopentyl alcohol, toluene, limonene and ethylbenzene. These compounds were assessed using a logistic regression model. The sensitivity and specificity were 95.8 and 96.9% for discriminating patients in the CPA group from those in the CAP group and 95.8 and 97.9% for discriminating patients in the CPA group from healthy controls, respectively. The concentration of limonene (m/z 136) correlated significantly positively with anti-Aspergillus fumigatus IgG antibody titers (r = 0.420, P < 0.01). After antifungal treatment, serum IgG and the concentration of limonene (m/z 136) decreased in the subgroup of patients with chronic pulmonary aspergillosis.Conclusions: We identified VOCs that can be used as biomarkers for differential diagnosis and therapeutic response prediction in patients with chronic pulmonary aspergillosis.

Published
2021

25. Reflection on Improving the Quality Management System for Experimental Animal Waste Disposal: National Institutes for Food and Drug Control as an Example

Author

MA Liying, ZHAO Minghai, LIANG Chunnan, YUE Bingfei, and WANG Hong

Subjects
waste, quality management, laboratory animal, inspection and testing organizations, Medicine
Abstract

Science and technological advancements drive human progress, with laboratory animals serving as essential resources for developments in life sciences and medicine. However, the waste generated by these animals presents new challenges for urban management. Issues such as classification, recycling, effective utilization, and biohazard elimination must be addressed, necessitating the development of regulations, standards, and norms to keep pace with advancements. The construction of quality management system is the foundation and framework for the management of inspection and testing organizations. It should have strong operability and inspectability, enabling continuous improvement of the management level and enhancing the stability of basic management. However, current quality management systems often lack clarity in managing laboratory animal waste, including undefined disposal processes for non-medical institutions, inaccurate waste classification, and inadequate disposal methods for different waste categories. This paper addresses these challenges by identifying necessary processes to be added or removed in the quality management system of National Institutes for Food and Drug Control, developing effective SOPs, proposing practical measures to strengthen supervision and management, and integrating 6S management principles into our quality management system. In conclusion, effective management of laboratory animal waste should be centered on improving the quality management system, emphasizing waste classification and management at the source, controlling biological hazards, minimizing environmental pollution and promoting conditions for sustainable development.

Published
2024
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26. SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

Author

Zhao-Ming Xiao, Dao-Jun Lv, Yu-zhong Yu, Chong Wang, Tao Xie, Tao Wang, Xian-Lu Song, and Shan-Chao Zhao

Subjects
0301 basic medicine, QH301-705.5, proliferation, epithelial-mesenchymal-transition, Metastasis, Cell and Developmental Biology, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, medicine, Epithelial–mesenchymal transition, Biology (General), PI3K/AKT/mTOR pathway, Original Research, Chemistry, Cell growth, Akt/PKB signaling pathway, Cell migration, Cell Biology, SMARCC1, prostate cancer, medicine.disease, PI3K/AKT pathway, 030104 developmental biology, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, Developmental Biology
Abstract

BackgroundSWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms.MethodsThe expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.ResultsOur finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells.ConclusionSMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.

Published
2021

27. Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2

Author

Fu Jie Shen, Wei Zhen, Zhang Xuefeng, Weijin Huang, Zhao Ming Liu, Shuo Liu, Gui Zhen Wu, Li Fang Du, Hao Zhang, Jin Juan Wu, Shao Shuai, Mei Yu Wang, Zi Bo Han, Ji Guo Su, Jing Zhang, Qi Ming Li, Ze Hua Lei, Zhi Jing Ma, Ya Nan Hou, Chang Wen Ke, Wei Min Zhou, Zheng Fan, Shi Chen, Zhong Yu Hu, Yu Qin Jin, Peng He, Si Yu Ren, Jun Wei Hou, Fang Tang, Yu Liang, Run Yu Yuan, Xiang Zheng, and Ning Liu

Subjects
Mutation, biology, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.disease_cause, Virology, Neutralization, Titer, Protein trimer, medicine, biology.protein, Antibody, Neutralizing antibody, Adjuvant
Abstract

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the “immune-escape” Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

Published
2021

28. Development of new endovascular stent-graft system for type B thoracic aortic dissection with finite element analysis and experimental verification

Author

Zhou Xiaochen, Zhao Ming, Gong Xiaoyan, Sun Zhili, Yang Fan, and Zheng Yufeng

Subjects
medicine.medical_specialty, Materials science, Polymers and Plastics, medicine.medical_treatment, Less invasive, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Fatigue resistance, medicine.artery, Materials Chemistry, medicine, Thoracic aorta, cardiovascular diseases, Mechanical Engineering, Metals and Alloys, Stent, equipment and supplies, 021001 nanoscience & nanotechnology, Alternative treatment, Finite element method, 0104 chemical sciences, Clinical trial, surgical procedures, operative, Mechanics of Materials, Ceramics and Composites, Thoracic aortic dissection, Radiology, 0210 nano-technology
Abstract

Endovascular repair of the thoracic aorta with self-expanding stent-grafts has been emerging as a less invasive alternative treatment compared with conventional open surgeries. Despite the promising efficacy and safety of endovascular stent grafting, the stent-graft failure remains a major concern in terms of stent migration, device fatigue, and the risk of endoleaks. Challenges associated with the stent-grafts involve optimized geometrical structure, lifetime fatigue resistance, and adequate radial support. In this work, a novel endovascular stent-graft system is developed specially for the treatment of Stanford type B thoracic aortic dissections (TAD). Numerical study with finite element analysis (FEA) was utilized to evaluate the mechanical behaviors of the individual stent component. Results of the simulation were validated by experimental tests. Based on the systematic analysis of the parametric variations, a final stent-graft system was developed by the selection and arrangement of the individual stent components, targeting an optimal performance for treatment of TAD. The optimized solution of the stent-graft system was tested in clinical trials, showing advantageous therapeutic efficacy.

Published
2019

29. Severe and prolonged cyclophosphamide-induced hepatotoxicity in a breast cancer patient carrying a CYP2B6*7 variant

Author

Xu Yan, Tian Xiaoxin, Zhao Ming, Zhang Yongqiang, Zhang Zijin, and Chen Di

Subjects
Pharmacology, Oncology, medicine.medical_specialty, Chemotherapy, Cyclophosphamide, CYP2B6, business.industry, medicine.medical_treatment, medicine.disease, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Internal medicine, Genetics, Molecular Medicine, Medicine, Allele, business, Adverse effect, Genotyping, Pharmacogenetics, medicine.drug
Abstract

As a widely used alkylating agent, cyclophosphamide often leads to various toxicities. Severe hepatotoxicity has been rarely reported in breast cancer patients receiving chemotherapy containing cyclophosphamide. Differences in cyclophosphamide metabolism may contribute to variability in adverse events of patients. Here, we report on a case of a 68-year-old Chinese female with breast cancer who experienced severe and prolonged hepatotoxicity induced by cyclophosphamide. Pharmacogenetic tests showed that she was a carrier of CYP2B6*7 allele and this is the first case of a CYP2B6*7 variant in the Han Chinese population so far reported. In addition, the patient was also a carrier of an ALDH3A1*2 variant potentially contributing to the occurrence of hepatotoxicity. CYP2B6 and ALDH3A1 genotyping may play a role in guiding cyclophosphamide therapy.

Published
2019

30. Epigenetic Control of CDK5 Promoter Regulates Diabetes-Associated Development of Alzheimer’s Disease

Author

Zhen-Zhen Fan, Ting Tian, Chon-Chon Zhao, Zhao-Ming Ge, and Hong-Bin Cai

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Tau protein, Morris water navigation task, Hyperphosphorylation, tau Proteins, Diet, High-Fat, Methylation, Epigenesis, Genetic, Diabetes Complications, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Alzheimer Disease, Internal medicine, Glucose Intolerance, medicine, Animals, Epigenetics, Phosphorylation, Maze Learning, Promoter Regions, Genetic, CA1 Region, Hippocampal, biology, General Neuroscience, Cyclin-dependent kinase 5, Neurodegeneration, Acetylation, Cyclin-Dependent Kinase 5, Recognition, Psychology, General Medicine, medicine.disease, Rats, Psychiatry and Mental health, Clinical Psychology, Glucose, 030104 developmental biology, Endocrinology, nervous system, biology.protein, Insulin Resistance, Geriatrics and Gerontology, 030217 neurology & neurosurgery
Abstract

Cyclin-dependent kinase-5 (CDK5) is activated by p35 and then binds to both p35 and its truncated form p25 to promote hyperphosphorylation of tau protein, thereby facilitating the pathological progression of Alzheimer's disease (AD). However, it is unknown whether a patient's diabetic status promotes the later onset of AD in a CDK5-dependent manner. Here, we induced pro-diabetic insulin resistance and glucose intolerance in rats using a combined high fat and high glucose diet. Compared to normal diet-fed rats, these pro-diabetic rats exhibited poorer behavioral performance in the Morris water maze test and the novel object recognition test. Increased phosphorylation of tau protein was detected in the hippocampal CA1 region of the rat brain, suggesting neurodegeneration. Moreover, CDK5 transcriptional activity was significantly increased in the HFGD-rat brain, likely resulting from an increase in acetylation and a decrease in methylation of the CDK5 promoter. Together, these data suggest that epigenetic control of the CDK5 promoter by acetylation and methylation may regulate the diabetes-associated development of AD.

Published
2019

31. Predictors for Poor Outcomes After Percutaneous Endoscopic Lumbar Discectomy: A Retrospective Study of 241 Patients

Author

Jianting Chen, Xing Shen, Qian Wu, Zhao-Ming Zhong, Shuai Zheng, and Zetao Shen

Subjects
Adult, Male, medicine.medical_specialty, Percutaneous, Physical examination, 03 medical and health sciences, 0302 clinical medicine, Lumbar, Rating scale, medicine, Back pain, Humans, Diskectomy, Percutaneous, Retrospective Studies, Lumbar Vertebrae, medicine.diagnostic_test, business.industry, Endoscopy, Modic changes, Retrospective cohort study, Middle Aged, Oswestry Disability Index, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Neurology (clinical), medicine.symptom, business, Intervertebral Disc Displacement, 030217 neurology & neurosurgery
Abstract

Percutaneous endoscopic lumbar discectomy (PELD) is a popular surgical procedure for the treatment of lumbar disc herniation (LDH). However, a small proportion of patients will have poor surgical outcomes. We sought to identify the predictors for poor outcomes after PELD.A total of 241 patients who had undergone PELD were followed up. Their numerical rating scale (NRS) for pain and Oswestry Disability Index scores were analyzed. They were divided by outcome (excellent, good, fair, poor) using the MacNab criteria. Their clinical history, physical examination, imaging, and surgical findings were compared among the groups. Ordinal logistic regression analysis was used to identify independent predictors for poor outcomes.The preoperative mean total NRS for back pain, NRS for leg pain, and Oswestry Disability Index scores were 4.3 ± 2.6, 5.6 ± 2.5, and 52.1% ± 23.0%. At 2 years after PELD, the corresponding scores had decreased to 1.2 ± 1.7, 0.9 ± 1.5, and 8.4% ± 11.2% (P0.001). The excellent, good, fair, and poor outcome rates were 44.4%, 31.5%, 17.4%, and 6.6%, respectively. Ordinal logistic regression analysis revealed that 2-level PELD (P = 0.001), a history of lumbar fusion (P = 0.007), and Modic changes (P = 0.011) were independent predictors for poor outcomes. Numbness was an independent predictor for excellent outcomes (P = 0.014).PELD appears to be an effective surgery for LDH. Two-level PELD, a history of lumbar fusion, and Modic changes at the same level were independent predictors for poor outcomes after PELD. Patients with LDH with numbness were more likely to have excellent outcomes.

Published
2019

32. Is anterior decompression and fusion superior to laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament? A systematic review and meta-analysis

Author

Jianting Chen, Yu-Sheng Huang, Zhao-Ming Zhong, Jing-Shen Zhuang, and Ping Xu

Subjects
medicine.medical_specialty, medicine.medical_treatment, Reviews, Context (language use), Ossification of Posterior Longitudinal Ligament, Spinal Cord Diseases, Laminoplasty, 03 medical and health sciences, Myelopathy, 0302 clinical medicine, Osteogenesis, medicine, Humans, Posterior longitudinal ligament, Spinal Cord Injuries, Retrospective Studies, 030222 orthopedics, business.industry, Ossification, Anterior decompression, Surgical procedures, Decompression, Surgical, medicine.disease, Longitudinal Ligaments, Surgery, Spinal Fusion, Treatment Outcome, Meta-analysis, Cervical Vertebrae, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL). Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL. Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL. Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%. Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation

Published
2019

33. Application of Immune Infiltration Signature and Machine Learning Model in the Differential Diagnosis and Prognosis of Bone-Related Malignancies

Author

Guo-Qi Li, Yi-Kai Wang, Hao Zhou, Lin-Guang Jin, Chun-Yu Wang, Mugahed Albahde, Yan Wu, Heng-Yuan Li, Wen-Kan Zhang, Bing-Hao Li, and Zhao-Ming Ye

Subjects
immune microenvironment, Context (language use), Metastasis, Cell and Developmental Biology, Immune system, bone metastases, osteosarcoma, medicine, lcsh:QH301-705.5, Multiple myeloma, Original Research, business.industry, Cancer, Ewing's sarcoma, Cell Biology, medicine.disease, multiple myeloma, lcsh:Biology (General), Cancer research, Osteosarcoma, Sarcoma, Ewing’s sarcoma, ssGSEA, business, random forest, Developmental Biology
Abstract

Bone-related malignancies, such as osteosarcoma, Ewing’s sarcoma, multiple myeloma, and cancer bone metastases have similar histological context, but they are distinct in origin and biological behavior. We hypothesize that a distinct immune infiltrative microenvironment exists in these four most common malignant bone-associated tumors and can be used for tumor diagnosis and patient prognosis. After sample cleaning, data integration, and batch effect removal, we used 22 publicly available datasets to draw out the tumor immune microenvironment using the ssGSEA algorithm. The diagnostic model was developed using the random forest. Further statistical analysis of the immune microenvironment and clinical data of patients with osteosarcoma and Ewing’s sarcoma was carried out. The results suggested significant differences in the microenvironment of bone-related tumors, and the diagnostic accuracy of the model was higher than 97%. Also, high infiltration of multiple immune cells in Ewing’s sarcoma was suggestive of poor patient prognosis. Meanwhile, increased infiltration of macrophages and B cells suggested a better prognosis for patients with osteosarcoma, and effector memory CD8 T cells and type 2 T helper cells correlated with patients’ chemotherapy responsiveness and tumor metastasis. Our study revealed that the random forest diagnostic model based on immune infiltration can accurately perform the differential diagnosis of bone-related malignancies. The immune microenvironment of osteosarcoma and Ewing’s sarcoma has an important impact on patient prognosis. Suppressing the highly inflammatory environment of Ewing’s sarcoma and promoting macrophage and B cell infiltration may have good potential to be a novel adjuvant treatment option for osteosarcoma and Ewing’s sarcoma.

Published
2021

34. Puerarin induces Nrf2 as a cytoprotective mechanism to prevent cadmium-induced autophagy inhibition and NLRP3 inflammasome activation in AML12 hepatic cells

Author

Chuan Zheng, Zhao-Ming Yu, Xue-Lei Zhou, Min Xiao, and Xue-Mei Wan

Subjects
Autophagosome, Inflammasomes, NF-E2-Related Factor 2, Inflammation, 010402 general chemistry, environment and public health, 01 natural sciences, Biochemistry, Antioxidants, Cell Line, Inorganic Chemistry, chemistry.chemical_compound, Mice, Puerarin, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Autophagy, Gene silencing, Animals, Gene knockdown, 010405 organic chemistry, respiratory system, KEAP1, Isoflavones, 0104 chemical sciences, Cell biology, Oxidative Stress, chemistry, Hepatic stellate cell, medicine.symptom, Cadmium, Signal Transduction
Abstract

Liver is the main target organ of cadmium (Cd) toxicity and puerarin (PU) has been shown to prevent Cd-induced hepatic cell damage via its antioxidant activity. Nrf2 acts as a critical regulator of cellular defense against various oxidative insults, but its role in the protection of PU against Cd-induced hepatic damage has not yet been clarified. Hereby, this study was designed to investigate the underlying mechanism using mouse hepatocyte line AML-12. Data firstly showed that Cd-inhibited Nrf2 pathway was markedly restored by PU treatment, assessed by Nrf2 nuclear translocation, protein levels of Keap1 and Nrf2 downstream target genes. Accordingly, Cd-reduced protein levels of antioxidant enzymes were significantly up-regulated by PU. Next, Nrf2 silencing cellular model was established to further elucidate the role of Nrf2 in the protection of PU against Cd-induced hepatic damage. Attenuation of Cd-induced autophagy inhibition and autophagosome accumulation by PU was remarkably countered by Nrf2 silencing. Moreover, alleviation of Cd-induced NLRP3 inflammasome activation by PU was distinctly prevented by Nrf2 knockdown, assessed by protein levels of NLRP3 inflammosome complex and downstream IL-18 and IL-1β production. Collectively, our data suggest that PU restores Cd-induced Nrf2 inhibition to prevent autophagy inhibition and NLRP3 inflammasome activation, providing novel insights into the protection of PU against Cd-induced hepatic cell damage.

Published
2020

35. Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and mendelian randomization study

Author

Han-Qi Yang, James T. Elder, Zhi-Hua Yang, Peikuan Cong, Jiangwei Xia, Zhi-Min Ying, Ke-Qi Liu, Bin Wang, Mo-Chang Qiu, Rajan P. Nair, Zhao-Ming Ye, Pian-Pian Zhao, Wei-Yang Bai, Xiao-Wei Zhu, Jin-Qiu Zhao, Yan-Ping Zhu, Philip E. Stuart, Si-Rui Gai, Kaijing Mao, Lin Xu, Shu-Yang Xie, Bin Hu, Hou-Feng Zheng, Peng-Lin Guan, Yu-Ting Liao, and Lam C. Tsoi

Subjects
030203 arthritis & rheumatology, 0301 basic medicine, medicine.medical_specialty, Bone density, business.industry, Immunology, Osteoporosis, Confounding, Arthritis, medicine.disease, Logistic regression, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Psoriatic arthritis, 030104 developmental biology, 0302 clinical medicine, Rheumatology, Psoriasis, Internal medicine, medicine, Immunology and Allergy, Risk factor, business
Abstract

Objectives and methodsWith 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them.ResultsLower eBMD were observed in patients with PsA than in controls in both model0 (β-coefficient=−0.014, p=0.0006) and model1 (β-coefficient=−0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (β-coefficient=−0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (pConclusionsThe effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

Published
2020

36. Straighter low lumbar curvature in isthmic spondylolisthesis at L4

Author

Shuai Zheng, Zongze Li, Xinqiang Yao, Qingan Zhu, Si-Yuan Zhu, Jianting Chen, Shaoli Zheng, Yongjian Zhu, Congrui Liao, and Zhao-Ming Zhong

Subjects
Pelvic tilt, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Sports medicine, L5 incidence, Urology, 03 medical and health sciences, 0302 clinical medicine, Lumbar, Rheumatology, Humans, Medicine, Orthopedics and Sports Medicine, Lower lumbar lordosis, Aged, Retrospective Studies, 030222 orthopedics, Lumbar Vertebrae, business.industry, Incidence (epidemiology), Lumbosacral Region, Sagittal plane, Sagittal lumbo-pelvic alignment, Oswestry Disability Index, Cross-Sectional Studies, medicine.anatomical_structure, Orthopedic surgery, Lumbosacral angle, Roussouly type, Isthmic spondylolisthesis, Spondylolisthesis, lcsh:RC925-935, business, 030217 neurology & neurosurgery, Research Article
Abstract

Background: This study was conducted to compare differences in imaging features and clinical symptoms between patients with single-level isthmic spondylolisthesis (IS) at L4 and at L5 and to investigate the correlation between imaging and clinical parameters. Methods: This cross-sectional study evaluated patients with single-level IS who were enrolled between June 2011 and June 2018. A total of 139 patients, 44 in the L4 IS group and 95 in the L5 IS group, met the study criteria and were included. Imaging and clinical parameters obtained from the two groups were compared and analyzed.Results: Patients in the L4 IS group had smaller lower lumbar lordosis (LLL) (27.1 ± 8.2 vs. 30.9 ± 9.3, P = 0.021) and were of older age (58.5 ± 8.7 vs. 52.8 ± 10.1, P < 0.01) than those in the L5 IS group. As per the Roussouly classification system, most patients with L4 IS were classified as Type 2 (43.2%), whereas most patients with L5 IS fell under Type 3 (44.2%). In the L5 IS group, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), and L5 incidence (L5I) were positively associated with slippage rate (SR), but the lumbosacral angle (LSA) was negatively associated with SR (P < 0.01). In the L4 IS group, only L5I showed a positive association with SR (P < 0.01). More significant associations were found among sagittal lumbo-pelvic parameters in the L5 IS group, but none were found between SR and Oswestry Disability Index (ODI) in either group.Conclusions: When compared with patients with L5 IS, patients with L4 IS were of older age and had straighter low lumbar curvature when they were obviously symptomatic. PI was an important parameter for patients with L5 IS while for those with L4 IS, L5I deserved more attention for its significantly positive correlation with the degree of slippage.

Published
2020

37. M2-Like Microglia Polarization Attenuates Neuropathic Pain Associated with Alzheimer's Disease

Author

Chong-Chong Zhao, Zhi-Yan Liu, Zhao-Ming Ge, Jing Jin, Jia Guo, Hong-Bin Cai, and Huan Wang

Subjects
0301 basic medicine, Small hairpin RNA, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Alzheimer Disease, medicine, Animals, Humans, Secretion, Microglia, business.industry, General Neuroscience, General Medicine, Phenotype, In vitro, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, medicine.anatomical_structure, Neuropathic pain, DNMT1, Cancer research, Cytokines, Neuralgia, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Signal Transduction
Abstract

Many Alzheimer's disease (AD) patients suffer from persistent neuropathic pain (NP), which is mediated, at least partially, but microglia. Nevertheless, the exact underlying mechanism is unknown. Moreover, a clinically translatable approach through modulating microglia for treating AD-associated NP is not available. Here, in a doxycycline-induced mouse model (rTg4510) for AD, we showed development of NP. We found that the total number of microglia in the CA3 region was not increased, but polarized to pro-inflammatory M1-like phenotype, with concomitant increases in production and secretion of pro-inflammatory cytokines. To examine whether this microglia polarization plays an essential role in the AD-associated NP, we generated an adeno-associated virus (AAV) serotype PHP.B (capable of crossing the blood-brain barrier) carrying shRNA for DNA methyltransferase 1 (DNMT1) under a microglia-specific TMEM119 promoter (AAV-pTMEM119-shDNMT1), which specifically targeted microglia and induced a M2-like polarization in vitro and in vivo in doxycycline-treated rTg4510 mice. Intravenous infusion of AAV-pTMEM119-shDNMT1 induced M2-polarization of microglia and attenuated both AD-associated behavior impairment but also NP in the doxycycline-treated rTg4510 mice. Thus, our data suggest that AD-associated NP may be treated through M2-polarization of microglia.

Published
2020

38. Dysregulation of the miR-148a–GLUT1 axis promotes the progression and chemoresistance of human intrahepatic cholangiocarcinoma

Author

Xiao Peng, Xue Junlin, Pei Tiemin, Lang Qingfu, Liang Desen, Zhao Ming, He Zhefeng, Wang Yan, and Meng Qinghui

Subjects
0301 basic medicine, endocrine system, Cancer Research, Biology, lcsh:RC254-282, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Western blot, Downregulation and upregulation, In vivo, medicine, Gene silencing, Molecular Biology, Gene knockdown, medicine.diagnostic_test, Cell growth, nutritional and metabolic diseases, Cancer, Oncogenes, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, carbohydrates (lipids), 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Immunohistochemistry, hormones, hormone substitutes, and hormone antagonists
Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of iCCA progression is critical for the identification of new therapeutic targets. The present study explored the role of the miR-148a–GLUT1 axis in the progression of iCCA. The expression of GLUT1 was detected by using immunohistochemistry, western blot assays, and real-time polymerase chain reaction. The effects of GLUT1 on cell proliferation, invasion, and chemoresistance were investigated both in vitro and in vivo. A luciferase reporter assay was used to explore the effect of miR-148a on GLUT1 expression. GLUT1 was overexpressed in iCCA tissues. GLUT1 overexpression was associated with shorter overall and disease-free survival. Knockdown of GLUT1 reduced, while overexpression of GLUT1 promoted, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Silencing GLUT1 significantly sensitized iCCA cells to gemcitabine in vitro and in vivo. GLUT1 was directly regulated by miR-148a, whose downregulation was associated with the proliferation, migration, and invasion of iCCA cells. WZB117, a GLUT1 inhibitor, inhibited tumor growth in an iCCA patient-derived xenograft model. These results indicate that downregulation of miR-148a levels results in GLUT1 overexpression in iCCA, leading to iCCA progression and gemcitabine resistance.

Published
2020

39. Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)

Author

Solomon A. Graf, Daniel Y Wu, Robert E. Richard, Nicholas Burwick, Craig O'Brien, Thomas R. Chauncey, Heather Klocke, and Zhao Ming Dong

Subjects
Oncology, medicine.medical_specialty, Myeloid, Decitabine, Case Report, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Diseases of the blood and blood-forming organs, Acute leukemia, business.industry, Venetoclax, Not Otherwise Specified, General Medicine, medicine.disease, Leukemia, medicine.anatomical_structure, Hypomethylating agent, chemistry, 030220 oncology & carcinogenesis, Stem cell, RC633-647.5, business, 030215 immunology, medicine.drug
Abstract

T/myeloid mixed-phenotype acute leukemia not otherwise specified (MPAL NOS) is an uncommon and aggressive leukemia without well-established treatment guidelines, particularly when relapsed. Venetoclax plus a hypomethylating agent offers a promising option in this situation since studies support its use in both acute myeloid and, albeit with fewer data to date, acute T-cell-lymphoblastic leukemias. We report the successful eradication of T/myeloid MPAL NOS relapsed after allogeneic stem cell transplant with venetoclax plus decitabine. A consolidative allogeneic stem cell transplant from a second donor was subsequently performed, and the patient remained without evidence of disease more than one year later. Further investigation is indicated to evaluate venetoclax combined with hypomethylating agents and/or other therapies for the management of T/myeloid MPAL NOS.

Published
2020

40. Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Author

Rodriguez-Martinez, Andrea, Zhou, Bin, Sophiea, Marisa K, Bentham, James, Paciorek, Christopher J, Iurilli, Maria LC, Carrillo-Larco, Rodrigo M, Bennett, James E, Di Cesare, Mariachiara, Taddei, Cristina, Bixby, Honor, Stevens, Gretchen A, Riley, Leanne M, Cowan, Melanie J, Savin, Stefan, Danaei, Goodarz, Chirita-Emandi, Adela, Kengne, Andre P, Khang, Young-Ho, Laxmaiah, Avula, Malekzadeh, Reza, Miranda, J Jaime, Moon, Jin Soo, Popovic, Stevo R, Sorensen, Thorkild IA, Soric, Maroje, Starc, Gregor, Zainuddin, Ahmad A, Gregg, Edward W, Bhutta, Zulfiqar A, Black, Robert, Ezzati, Majid, Abarca-Gomez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A, Agyemang, Charles, Ahmad, Mohamad Hasnan, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmed, Soheir H, Ahrens, Wolfgang, Aitmurzaeva, Gulmira, Ajlouni, Kamel, Al-Hazzaa, Hazzaa M, Al-Othman, Amani Rashed, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M, Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N, Amiri, Parisa, Amougou, Norbert, Amouyel, Philippe, Andersen, Lars Bo, Anderssen, Sigmund A, Angquist, Lars, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Aounallah-Skhiri, Hajer, Araujo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assuncao, Maria Cecilia F, Aung, May Soe, Auvinen, Juha, Avdicova, Maria, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V, Jorgensen, Maja Baeksgaard, Baharudin, Azli, Bahijri, Suhad, Baker, Jennifer L, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, Jose R, Baran, Joanna, Barbagallo, Carlo M, Barcelo, Alberto, Barkat, Amina, Barros, Aluisio JD, Barros, Mauro Virgilio Gomes, Basit, Abdul, Bastos, Joao Luiz D, Bata, Iqbal, Batieha, Anwar M, Batista, Rosangela L, Battakova, Zhamilya, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Bel-Serrat, Silvia, Belavendra, Antonisamy, Ben Romdhane, Habiba, Benedics, Judith, Benet, Mikhail, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bi, Hongsheng, Bi, Yufang, Bia, Daniel, Lele, Elysee Claude Bika, Bikbov, Mukharram M, Bista, Bihungum, Bjelica, Dusko J, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Bjorkelund, Cecilia, Bloch, Katia V, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boddy, Lynne M, Boehm, Bernhard O, Boeing, Heiner, Boggia, Jose G, Bogova, Elena, Boissonnet, Carlos P, Bojesen, Stig E, Bonaccio, Marialaura, Bongard, Vanina, Bonilla-Vargas, Alice, Bopp, Matthias, Borghs, Herman, Bovet, Pascal, Braeckevelt, Lien, Braeckman, Lutgart, Bragt, Marjolijn CE, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Breda, Joao, Brenner, Hermann, Brewster, Lizzy M, Brian, Garry R, Brinduse, Lacramioara, Brophy, Sinead, Bruno, Graziella, Bueno-de-Mesquita, H Bas, Bugge, Anna, Buoncristiano, Marta, Burazeri, Genc, Burns, Con, de Leon, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cama, Tilema, Cameron, Christine, Camolas, Jose, Can, Gunay, Candido, Ana Paula C, Canete, Felicia, Capanzana, Mario V, Capkova, Nadezda, Capuano, Eduardo, Capuano, Vincenzo, Cardol, Marloes, Cardoso, Viviane C, Carlsson, Axel C, Carmuega, Esteban, Carvalho, Joana, Casajus, Jose A, Casanueva, Felipe F, Celikcan, Ertugrul, Censi, Laura, Cervantes-Loaiza, Marvin, Cesar, Juraci A, Chamukuttan, Snehalatha, Chan, Angelique W, Chan, Queenie, Chaturvedi, Himanshu K, Chaturvedi, Nish, Rahim, Norsyamlina Che Abdul, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Cheraghian, Bahman, Chetrit, Angela, Chikova-Iscener, Ekaterina, Chiolero, Arnaud, Chiou, Shu-Ti, Chirlaque, Maria-Dolores, Cho, Belong, Christensen, Kaare, Christofaro, Diego G, Chudek, Jerzy, Cifkova, Renata, Cilia, Michelle, Cinteza, Eliza, Claessens, Frank, Clarke, Janine, Clays, Els, Cohen, Emmanuel, Concin, Hans, Confortin, Susana C, Cooper, Cyrus, Coppinger, Tara C, Corpeleijn, Eva, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L, Crampin, Amelia C, Crujeiras, Ana B, Csilla, Semanova, Cucu, Alexandra M, Cui, Liufu, Cureau, Felipe V, D'Arrigo, Graziella, d'Orsi, Eleonora, Dacica, Liliana, Saavedra, Maria Angeles Dal Re, Dallongeville, Jean, Damasceno, Albertino, Damsgaard, Camilla T, Dankner, Rachel, Dantoft, Thomas M, Dasgupta, Parasmani, Dastgiri, Saeed, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Ridder, David, De Ridder, Karin, de Rooij, Susanne R, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D, DeGennaro, Vincent, Dehghan, Abbas, Delisle, Helene, Delpeuch, Francis, Demarest, Stefaan, Dennison, Elaine, Deren, Katarzyna, Deschamps, Valerie, Dhana, Klodian, Dhimal, Meghnath, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soares, Diaz-Sanchez, Maria Elena, Diaz, Alejandro, Dika, Zivka, Djalalinia, Shirin, Djordjic, Visnja, Do, Ha TP, Dobson, Annette J, Donati, Maria Benedetta, Donfrancesco, Chiara, Donoso, Silvana P, Doring, Angela, Dorobantu, Maria, Dorosty, Ahmad Reza, Doua, Kouamelan, Drygas, Wojciech, Duan, Jia Li, Duante, Charmaine A, Duboz, Priscilla, Duda, Rosemary B, Duleva, Vesselka, Dulskiene, Virginija, Dumith, Samuel C, Dushpanova, Anar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eddie, Ricky, Eftekhar, Ebrahim, Egbagbe, Eruke E, Eggertsen, Robert, Eghtesad, Sareh, Eiben, Gabriele, Ekelund, Ulf, El-Khateeb, Mohammad, El Ati, Jalila, Eldemire-Shearer, Denise, Eliasen, Marie, Elliott, Paul, Engle-Stone, Reina, Enguerran, Macia, Erasmus, Rajiv T, Erbel, Raimund, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, Escobedo-de la Pena, Jorge, Eslami, Saeid, Esmaeili, Ali, Evans, Alun, Faeh, David, Fakhretdinova, Albina A, Fall, Caroline H, Faramarzi, Elnaz, Farjam, Mojtaba, Sant'Angelo, Victoria Farrugia, Farzadfar, Farshad, Fattahi, Mohammad Reza, Fawwad, Asher, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, Fernandez-Berges, Daniel, Ferrante, Daniel, Ferrao, Thomas, Ferrari, Marika, Ferrario, Marco M, Ferreccio, Catterina, Ferrer, Eldridge, Ferrieres, Jean, Figueiro, Thamara Hubler, Fijalkowska, Anna, Fink, Gunther, Fischer, Krista, Foger, Bernhard, Foo, Leng Huat, Forsner, Maria, Fouad, Heba M, Francis, Damian K, Franco, Maria do Carmo, Franco, Oscar H, Frikke-Schmidt, Ruth, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujiati, Isti I, Fujita, Yuki, Fumihiko, Matsuda, Furusawa, Takuro, Gaciong, Zbigniew, Gafencu, Mihai, Galbarczyk, Andrzej, Galenkamp, 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Zampelas, Antonis, Zamrazilova, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Zaw, Ko Ko, Zdrojewski, Tomasz, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zocalo, Yanina, Cisneros, Julio Zuniga, Zuziak, Monika, Faculdade de Ciências da Nutrição e Alimentação, Instituto de Saúde Pública da Universidade do Porto, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Environnement, Santé, Sociétés (ESS), Centre National de la Recherche Scientifique (CNRS), European Project: 774548, Reproductive Origins of Adult Health and Disease (ROAHD), Rodriguez-Martinez A, Zhou B, Sophiea MK, Bentham J, Paciorek CJ, Iurilli ML, Carrillo-Larco RM, Bennett JE, Di Cesare M, Taddei C, Bixby H, Stevens GA, Riley LM, Cowan MJ, Savin S, 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Ferrario MM, Ferreccio C, Ferrer E, Ferrieres J, Figueiró TH, Fijalkowska A, Fink G, Fischer K, Föger B, Foo LH, Forsner M, Fouad HM, Francis DK, Franco MDC, Franco OH, Frikke-Schmidt R, Frontera G, Fuchs FD, Fuchs SC, Fujiati II, Fujita Y, Fumihiko M, Furusawa T, Gaciong Z, Gafencu M, Galbarczyk A, Galenkamp H, Galeone D, Galfo M, Galvano F, Gao J, Garcia-de-la-Hera M, García-Solano M, Gareta D, Garnett SP, Gaspoz J-M, Gasull M, Gaya ACA, Gaya AR, Gazzinelli A, Gehring U, Geiger H, Geleijnse JM, Ghanbari A, Ghasemi E, Gheorghe-Fronea O-F, Giampaoli S, Gianfagna F, Gill TK, Giovannelli J, Gironella G, Giwercman A, Gkiouras K, Godos J, Gogen S, Goldsmith RA, Goltzman D, Gómez SF, Gomula A, Goncalves Cordeiro da Silva B, Gonçalves H, Gonzalez-Chica DA, Gonzalez-Gross M, González-Leon M, González-Rivas JP, González-Villalpando C, González-Villalpando M-E, Gonzalez AR, Gottrand F, Graça AP, Graff-Iversen S, Grafnetter D, Grajda A, Grammatikopoulou MG, Gregor RD, Grodzicki T, Grøholt EK, 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JM, Ibrahim MM, Ibrahim Wong N, Ikeda N, Ikram MA, Iotova V, Irazola VE, Ishida T, Islam M, Islam SMS, Iwasaki M, Jackson RT, Jacobs JM, Jaddou HY, Jafar T, James K, Jamil KM, Jamrozik K, Janszky I, Janus E, Jarani J, Jarvelin M-R, Jasienska G, Jelakovic A, Jelakovic B, Jennings G, Jha AK, Jiang CQ, Jimenez RO, Jöckel K-H, Joffres M, Johansson M, Jokelainen JJ, Jonas JB, Jørgensen T, Joshi P, Joukar F, Jovic DP, Józwiak JJ, Juolevi A, Jurak G, Jurca Simina I, Juresa V, Kaaks R, Kaducu FO, Kafatos A, Kajantie EO, Kalmatayeva Z, Kalter-Leibovici O, Kameli Y, Kanala KR, Kannan S, Kapantais E, Karki KB, Katibeh M, Katz J, Katzmarzyk PT, Kauhanen J, Kaur P, Kavousi M, Kazakbaeva GM, Keil U, Keinan Boker L, Keinänen-Kiukaanniemi S, Kelishadi R, Kelleher C, Kemper HC, Keramati M, Kerimkulova A, Kersting M, Key T, Khader YS, Khalili D, Khaw K-T, Kheiri B, Kheradmand M, Khosravi A, Khouw IM, Kiechl-Kohlendorfer U, Kiechl S, Killewo J, Kim DW, Kim HC, Kim J, Kindblom JM, Klakk H, Klimek M, 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Sevcikova L., Shalnova S.A., Shamah-Levy T., Shamshirgaran M., Shanthirani C.S., Sharafkhah M., Sharma S.K., Shaw J.E., Shayanrad A., Shayesteh A.A., Shengelia L., Shi Z., Shibuya K., Shimizu-Furusawa H., Shin D.W., Shin Y., Shirani M., Shiri R., Shrestha N., Si-Ramlee K., Siani A., Siantar R., Sibai A.M., Silva A.M., Silva D.A.S., Simon M., Simons J., Simons L.A., Sjoberg A., Sjostrom M., Skodje G., Slowikowska-Hilczer J., Slusarczyk P., Smeeth L., So H.-K., Soares F.C., Sobek G., Sobngwi E., Sodemann M., Soderberg S., Soekatri M.Y., Soemantri A., Sofat R., Solfrizzi V., Somi M.H., Sonestedt E., Song Y., Sorgjerd E.P., Sossa Jerome C., Soto-Rojas V.E., Soumare A., Sovic S., Sparboe-Nilsen B., Sparrenberger K., Spinelli A., Spiroski I., Staessen J.A., Stamm H., Stathopoulou M.G., Staub K., Stavreski B., Steene-Johannessen J., Stehle P., Stein A.D., Stergiou G.S., Stessman J., Stevanovic R., Stieber J., Stockl D., Stocks T., Stokwiszewski J., Stoyanova E., Stratton G., Stronks K., Strufaldi M.W., Sturua L., Suarez-Medina R., Suka M., Sun C.-A., Sundstrom J., Sung Y.-T., Sunyer J., Suriyawongpaisal P., Swinburn B.A., Sy R.G., Syddall H.E., Sylva R.C., Szklo M., Szponar L., Tai E.S., Tammesoo M.-L., Tamosiunas A., Tan E.J., Tang X., Tanser F., Tao Y., Tarawneh M.R., Tarp J., Tarqui-Mamani C.B., Taxova Braunerova R., Taylor A., Taylor J., Tchibindat F., Tebar W.R., Tell G.S., Tello T., Thankappan K.R., Theobald H., Theodoridis X., Thijs L., Thomas N., Thuesen B.H., Ticha L., Timmermans E.J., Tjonneland A., Tolonen H.K., Tolstrup J.S., Topbas M., Topor-Madry R., Torheim L.E., Tormo M.J., Tornaritis M.J., Torrent M., Torres-Collado L., Toselli S., Traissac P., Tran T.T.-H., Trichopoulos D., Trichopoulou A., Trinh O.T., Trivedi A., Tshepo L., Tsigga M., Tsugane S., Tuliakova A.M., Tulloch-Reid M.K., Tullu F., Tuomainen T.-P., Tuomilehto J., Turley M.L., Tynelius P., Tzotzas T., Tzourio C., Ueda P., Ugel E., Ukoli F.A., Ulmer H., Unal B., Usupova Z., Uusitalo H.M., Uysal N., Vaitkeviciute J., Valdivia G., Vale S., Valvi D., van Dam R.M., Van der Heyden J., van der Schouw Y.T., Van Herck K., Van Minh H., van Valkengoed I.G., Vanderschueren D., Vanuzzo D., Varbo A., Varela-Moreiras G., Varona-Perez P., Vasan S.K., Vega T., Veidebaum T., Velasquez-Melendez G., Velika B., Veronesi G., Verschuren W.M., Victora C.G., Viegi G., Viet L., Villalpando S., Vineis P., Vioque J., Virtanen J.K., Visser M., Visvikis-Siest S., Viswanathan B., Vladulescu M., Vlasoff T., Vocanec D., Volzke H., Voutilainen A., Voutilainen S., Vrijheid M., Vrijkotte T.G., Wade A.N., Wagner A., Waldhor T., Walton J., Wambiya E.O., Wan Bebakar W.M., Wan Mohamud W.N., Wanderley Junior R.D.S., Wang M.-D., Wang N., Wang Q., Wang X., Wang Y.X., Wang Y.-W., Wannamethee S.G., Wareham N., Weber A., Wedderkopp N., Weerasekera D., Weghuber D., Wei W., Weres A., Werner B., Whincup P.H., Widhalm K., Widyahening I.S., Wiecek A., Wilks R.J., Willeit J., Willeit P., Williams J., Wilsgaard T., Wojtyniak B., Wong-McClure R.A., Wong A., Wong J.E., Wong T.Y., Woo J., Woodward M., Wu F.C., Wu J., Wu L.J., Wu S., Xu H., Xu L., Yaacob N.A., Yamborisut U., Yan W., Yang L., Yang X., Yang Y., Yardim N., Yaseri M., Yasuharu T., Ye X., Yiallouros P.K., Yoosefi M., Yoshihara A., You Q.S., You S.-L., Younger-Coleman N.O., Yusof S.M., Yusoff A.F., Zaccagni L., Zafiropulos V., Zakavi S.R., Zamani F., Zambon S., Zampelas A., Zamrazilova H., Zapata M.E., Zargar A.H., Zaw K.K., Zdrojewski T., Zeljkovic Vrkic T., Zeng Y., Zhang L., Zhang Z.-Y., Zhao D., Zhao M.-H., Zhao W., Zhen S., Zheng W., Zheng Y., Zholdin B., Zhou M., Zhu D., Zocalo Y., Zuniga Cisneros J., Zuziak M., and Ezzati M.

Subjects
Male, body-mass index, ADULTHOOD, Adolescents, pituuskasvu, Pediatrics, Body Mass Index, 0302 clinical medicine, Child Development, nuoret, Public health surveillance, Medicine, Health Status Indicators, 10. No inequality, Child, 11 Medical and Health Sciences, Body mass index, ComputingMilieux_MISCELLANEOUS, education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, General Medicine, Body mass indexes, kansainvälinen vertailu, 3. Good health, Geography, Health, 030220 oncology & carcinogenesis, Child, Preschool, Medical and Health sciences, purl.org/becyt/ford/3 [https], medicine.medical_specialty, School-aged adolescents, Socio-culturale, lapset (ikäryhmät), Nursing, territories, ravinto, purl.org/becyt/ford/3.3 [https], 03 medical and health sciences, School Children, SDG 3 - Good Health and Well-being, SYSTEMATIC ANALYSIS, Humans, school-aged children and adolescents, Montenegro, education, Science & Technology, Omvårdnad, Health sciences, Medical and Health sciences, Ciências médicas e da saúde, Bayes Theorem, Anthropometry, Adolescent Development, medicine.disease, TRENDS, Height and Body-mass Index, Faculdade de Ciências Sociais, UNDERNUTRITION, Height index trajectories, Height, body mass index, children , epidemiology, risk factors, growth, Stature, Demography, Settore MED/09 - Medicina Interna, Internationality, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Body-mass index trajectories, Epidemiology, Medicine and Health Sciences, risk factors, countries, EPIDEMIOLOGY, height, children, adolescents, BMI, 030212 general & internal medicine, painoindeksi, Child development, 2. Zero hunger, Medicine(all), School age child, obestity children cardiovascular, Population Health, 1. No poverty, Pediatrik, Public Health, Global Health, Social Medicine and Epidemiology, 3142 Public health care science, environmental and occupational health, Pooled analysis, NUTRITION, Female, medicine.symptom, pooled analysis, Life Sciences & Biomedicine, terveys, height, BMI, nutrition, health, children, adolescents, Adolescent, growth, Population, body-mass, Population based, Body-mass index, Young Adult, Medicine, General & Internal, Meta-Analysis as Topic, General & Internal Medicine, parasitic diseases, Weight gain, School-aged childrens, Age trajectories, business.industry, Height, Weight, Body Height, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, ONSET, Ciências da Saúde, Ciências médicas e da saúde, School-aged children, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, terveysriskit, Estilos de Vida e Impacto na Saúde
Abstract

BACKGROUND: Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents., METHODS: For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence., FINDINGS: We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls., INTERPRETATION: The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks., Wellcome Trust, AstraZeneca Young Health Programme, EU., peer-reviewed

Published
2020

42. The change of cervical sagittal alignment after surgery for adolescent idiopathic scoliosis

Author

Jianting Chen, Si-Yuan Zhu, Shi-Gan Luo, and Zhao-Ming Zhong

Subjects
Male, Pelvic tilt, medicine.medical_specialty, Adolescent, Radiography, Posture, Idiopathic scoliosis, Thoracic kyphosis, Thoracic Vertebrae, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Sagittal alignment, Kyphosis, Postoperative Period, Child, Cervical kyphosis, 030222 orthopedics, Lumbar Vertebrae, Cobb angle, business.industry, General Medicine, Sagittal plane, Surgery, Spinal Fusion, medicine.anatomical_structure, Scoliosis, Cervical Vertebrae, Lordosis, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

The postoperative change in cervical sagittal alignment has an impact on health-related quality of life in adolescent idiopathic scoliosis (AIS) patients who have undergone deformity correction. However, the effect of deformity correction on sagittal cervical profile is still controversial in the literatures. The objective of this study was to investigate the postoperative change in the cervical sagittal alignment of patients with AIS.A total of 46 AIS patients treated by posterior instrumentation and fusion with pedicle screw constructs were included in the study. Radiographs were collected preoperatively, immediate postoperatively and at the final follow-up. The C2-C7 Cobb angle and C2-C7 sagittal vertical axis (cSVA) were used to assess the cervical sagittal alignment. Spinopelvic alignment parameters, such as thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and sagittal vertical axis (SVA), were also measured. The correlations between the cervical sagittal parameters and spinopelvic parameters were analyzed.The incidence of cervical kyphosis was 67.4% preoperatively but increased to 87% postoperatively and 69.5% at the final follow-up. The C2-C7 Cobb angle significantly increased from pre-operation (-1.5° ± 15°) to post-operation (-5.4° ± 7.3°; P 0.05) and spontaneously decreased to -2.9° ± 10.5° at the final follow up. The cSVA was 18.1 ± 13 mm preoperatively, 17 ± 12.3 mm after surgery and 18.5 ± 9.5 mm at the last follow-up, but the change was not statistically significant (P 0.05). TK decreased significantly from pre-operation (17.7° ± 14.4°) to post-operation (14.2° ± 7.6°) and spontaneously improved to 16.9° ± 8.2° at the final follow-up. TK showed a significant correlation with the C2-C7 Cobb angle, but not with cSVA, in the preoperative (r = 0.709, P 0.01), postoperative (r = 0.472, P 0.01), and last follow-up measurements(r = 0.505, P 0.01). Compared with patients with preoperative thoracic hypokyphosis or hyperkyphosis, patients with a normal thoracic spine had more significant postoperative changes in the C2-C7 Cobb angle and TK.Cervical sagittal alignment after deformity correction is altered in AIS patients. An increase in cervical kyphosis after surgery is correlated with a loss of thoracic kyphosis. The change in the cervical sagittal profile may be a compensatory mechanism in response to an abnormal thoracic sagittal profile.

Published
2018

43. Bafilomycin A1 increases the sensitivity of tongue squamous cell carcinoma cells to cisplatin by inhibiting the lysosomal uptake of platinum ions but not autophagy

Author

Mu Sheng Zeng, Xue Chen, Xiao Feng Zhu, Yu E. Jiang, Chuan Zheng Sun, Xiao Qi, Rui Cheng, Zhao Ming Zhong, Wei Wang, and Hong Ying Chu

Subjects
0301 basic medicine, Cancer Research, ATG5, Autophagy-Related Protein 5, Gene Knockout Techniques, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ion binding, Cell Line, Tumor, Lysosome, Autophagy, medicine, Humans, Proto-Oncogene Proteins c-abl, Cytotoxicity, Platinum, Cisplatin, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Chemistry, Bafilomycin, Drug Synergism, Tongue Neoplasms, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Cancer research, TFEB, Macrolides, Lysosomes, medicine.drug
Abstract

The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1. Furthermore, we found that cisplatin resistance of TSCC cells was related to cisplatin inducing lysosome biogenesis in a TFEB-dependent manner, which was regulated by c-Abl. In summary, this is the first study to show that Bafilomycin A1 increases the sensitivity of TSCC cells to cisplatin by inhibiting lysosomal function but not autophagy. Lysosomes may be a potential target to increase cisplatin cytotoxicity toward TSCC cells.

Published
2018

44. Intracapillary monoclonal deposits disease due to B-cell non-Hodgkin lymphoma: A case report and review of the literature

Author

Sarah F. Sanghavi, Ryan C. Lynch, Zhao Ming Dong, and Roberto F. Nicosia

Subjects
Pathology, medicine.medical_specialty, business.industry, Crescentic glomerulonephritis, Monoclonal igm, Disease, medicine.disease, Glomerular capillary, Monoclonal, Membranoproliferative glomerulonephritis, medicine, B-Cell Non-Hodgkin Lymphoma, Kidney disorder, business
Abstract

Intracapillary monoclonal deposits disease is a rare kidney disorder defined by the presence of intracapillary monoclonal IgM deposits that completely obstruct glomerular capillary lumina. It is typically associated with Waldenstrom macroglobulinemia and significant levels of circulating monoclonal IgM. We describe a patient that presented with nephrotic range proteinuria, rapidly rising serum creatinine, and low levels of biclonal IgM. Kidney biopsy showed intracapillary monoclonal deposits disease with a membranoproliferative pattern and focal crescent formation. Subsequent bone marrow biopsy revealed marginal zone lymphoma. Despite treatment, the patient rapidly progressed to end-stage renal disease. Patients with indolent lymphomas and low levels of circulating clonal IgM may present with aggressive renal disease due to IgM deposition.

Published
2018

46. How to Fill the Cavity after Curettage of Giant Cell Tumors around the Knee? A Multicenter Analysis

Author

Kai Zheng, Xiu-Chun Yu, Yong-Cheng Hu, Zhen Wang, Su-Jia Wu, Zhao-Ming Ye, and Giant Cell Tumor Group of China (GTOC)

Subjects
Adult, Male, medicine.medical_specialty, Knee Joint, medicine.medical_treatment, lcsh:Medicine, Bone Neoplasms, Bone grafting, Curettage, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Knee, Giant Cell Tumors, Tumor location, Bone Grafting, Cementation, Retrospective Studies, Giant Cell Tumor of Bone, 030222 orthopedics, Surgical complication, business.industry, lcsh:R, Retrospective cohort study, General Medicine, Giant Cell Tumor, Middle Aged, Surgery, surgical procedures, operative, Filling materials, 030220 oncology & carcinogenesis, Radiological weapon, Original Article, Female, business
Abstract

Background: Intralesional excision with curettage is the standard method of giant cell tumor (GCT) treatment, but the ideal filling material after curettage remains controversial. The purpose of this study was to compare the oncological and functional outcomes which underwent cementation or bone grafting after GCT curettage around the knee. Methods: We reported 136 cases with GCTs in distal femur or proximal tibia who accepted curettage from five clinical centers during the last 15 years. All patients were divided into two groups according to filling materials. Recurrence-free survival proportions were used to evaluate oncological outcomes while the Musculoskeletal Tumor Society (MSTS) 93 functional score was used to evaluate functional outcomes. Other parameters including surgical complication, general condition, and radiological classification had been analyzed. The valid statisitical data was analyzed using SPSS 13.0 software. Results: After GCT curettage, 86 patients (63.2%) accepted bone grafting while 50 patients (36.8%) accepted cementation. There was no statistical difference in age, gender, tumor location, radiological classification, fixation, follow-up time, and MSTS 93 functional score between cementation group and bone grafting group. The recurrence-free survival proportions showed that the recurrence rate in bone grafting group was higher than it in cementation group (P = 0.034). Surgical complication was lower in cementation group than that in bone grafting group but without statistically significant difference (P = 0.141). Conclusions: Parameters including patients’ age, gender, tumor location, and radiological classification did not affect surgeons’ treatments in cavity filling after GCT curettage. Cementation should be recommended because of easy usage, the similar postoperative knee function with bone grafting, and the better local tumor control than bone grafting. Key words: Bone Grafting; Cementation; Giant Cell Tumor; Knee

Published
2017

47. Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia

Author

Ruoting Ding, Congrui Liao, Baihui Sun, Zhao-Ming Zhong, Si-Yuan Zhu, Jianting Chen, Hui Jiang, Wei Li, and Xiaoliang Wu

Subjects
Male, 0301 basic medicine, Freund's Adjuvant, Clinical Biochemistry, Pharmacology, medicine.disease_cause, Biochemistry, Rats, Sprague-Dawley, 0302 clinical medicine, Ganglia, Spinal, lcsh:QH301-705.5, Cells, Cultured, lcsh:R5-920, NADPH oxidase, biology, Chemistry, NADPH Oxidase 1, NOX4, Hyperalgesia, NADPH Oxidase 4, NOX1, Anesthesia, Administration, Intravenous, medicine.symptom, lcsh:Medicine (General), Research Paper, Calcitonin Gene-Related Peptide, TRPV1, TRPV Cation Channels, Calcitonin gene-related peptide, 03 medical and health sciences, medicine, Animals, Organic Chemistry, Advanced oxidation protein products, Rats, Disease Models, Animal, 030104 developmental biology, lcsh:Biology (General), Gene Expression Regulation, nervous system, biology.protein, Dorsal root ganglion, Reactive Oxygen Species, 030217 neurology & neurosurgery, Oxidative stress
Abstract

Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund’s adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P, Graphical abstract Schematic representation of AOPPs-induced TRPV1 sensitization through Nox1/Nox4-dependent ROS generation, intracellular Ca2+ increase and CGRP release.fx1, Highlights • Plasma AOPPs were first found to increase in CFA-induced hyperalgesia rats. • Intravenous injection of AOPPs in rats can induce hyperalgesia. • AOPPs sensitize Nox1/Nox4 to generate abundant ROS in DRG neurons. • AOPPs exacerbate hypersensitivity through Nox1/Nox4-ROS-TRPV1- CGRP/Ca2+ pathway.

Published
2016

48. Discussion of Power System Operation Risk Control Technology in Natural Disasters

Author

Yu Chen, Jun Guo, Zhao Ming, Chang Kang, Wang Haohao, and Xu Taishan

Subjects
Warning system, Emergency management, business.industry, Computer science, Blackout, Fault (power engineering), Electric power system, Electronic stability control, Risk analysis (engineering), medicine, medicine.symptom, Natural disaster, Risk assessment, business
Abstract

It has become a common consensus that the blackout defense framework has been extended to the early warning of natural disasters. Due to the spatial and temporal distribution characteristics of natural disasters’ evolution, and fault uncertainty induced by natural disasters, it is urgent to extend the safety and stability analysis of power system based on deterministic criterion to the operation risk assessment, to extend traditional safety and stability control based on deterministic scenarios listed in three-defense-lines to risk control. In this paper, several key technologies in the field of disaster prevention, namely fault probability assessment, contingency set generation and screening, operation risk assessment and risk control decision-making, are reviewed firstly. Secondly, the risk control framework which is compatible with traditional three-defense-lines and suitable of natural disasters characteristics is discussed. Then the improved method of improving the mentioned key technologies is proposed under the risk control framework.

Published
2019

49. Elevated serum macrophage migration inhibitory factor levels correlate with benign paroxysmal positional vertigo and recurrence events

Author

Lei Duan, Hong-Bin Cai, Zhao-Ming Ge, Zi-Chao Li, Chong-Chong Zhao, and Ting Tian

Subjects
Adult, Male, medicine.medical_specialty, Supine position, Benign paroxysmal positional vertigo, recurrence, Biophysics, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Risk Factors, Vertigo, Internal medicine, medicine, otorhinolaryngologic diseases, Humans, Benign Paroxysmal Positional Vertigo, Prospective Studies, 030223 otorhinolaryngology, Molecular Biology, Macrophage Migration-Inhibitory Factors, Research Articles, biology, business.industry, Cell Biology, Odds ratio, inflammatory response, Middle Aged, biology.organism_classification, medicine.disease, Confidence interval, Intramolecular Oxidoreductases, Quartile, macrophage migration inhibitory factor, Macrophage migration inhibitory factor, Female, sense organs, business, 030217 neurology & neurosurgery, Research Article, Follow-Up Studies
Abstract

Objective: We aimed to assess the possible relations between serum levels of macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory response, and benign paroxysmal positional vertigo (BPPV) risk and BPPV recurrence events. Methods: In the present study, 154 patients with BPPV, and 100 age-and sex-matched control subjects were enrolled in the study. All the patients and controls underwent a complete audio-vestibular test battery including the Dix–Hallpike maneuver and supine roll test. In the BPPV group, measurements of MIF levels were repeated 1 month after the vertigo attack. The patients were also divided into the recurrence group and the nonrecurrence group in the 1-year follow-up. Results: The serum levels of MIF in patients with BPPV were higher than in those controls (13.9[interquartile range {IQR}, 8.9–18.4] ng/ml vs. 9.8[7.8–11.8]; P Conclusions: Elevated MIF is positively correlated with BPPV risk and BPPV recurrence events, requiring further efforts to clarify the exact mechanism.

Published
2019

50. Surgical outcomes of cervical myelopathy due to ossification of posterior longitudinal ligament: Anterior decompression and fusion versus posterior laminoplasty

Author

Jianting Chen, Jing-Shen Zhuang, Zhao-Ming Zhong, Chen Tu, Yu-Sheng Huang, and Ping Xu

Subjects
musculoskeletal diseases, Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Operative Time, macromolecular substances, Ossification of Posterior Longitudinal Ligament, Spinal Cord Diseases, Laminoplasty, 03 medical and health sciences, Myelopathy, 0302 clinical medicine, Recovery rate, lcsh:Orthopedic surgery, medicine, Posterior longitudinal ligament, Humans, Aged, Retrospective Studies, 030222 orthopedics, Ossification, business.industry, Anterior decompression, 030229 sport sciences, Middle Aged, medicine.disease, Decompression, Surgical, Surgery, lcsh:RD701-811, Spinal Fusion, Treatment Outcome, Cervical Vertebrae, Female, medicine.symptom, business
Abstract

Background: The purpose of this study was to compare the surgical outcomes of anterior decompression and fusion (ADF) with that of posterior laminoplasty (LAMP) for cervical myelopathy caused by ossification of posterior longitudinal ligament (OPLL). Methods: We retrospectively assessed the medical records of patients who underwent surgery for cervical myelopathy owing to OPLL between 2007 and 2016 at our institution. Fifty patients were included in this study, including 17 patients in ADF group and 33 patients in LAMP group. Surgical outcomes were assessed under the Japanese Orthopaedic Association (JOA) score. The radiologic and clinical data were compared between two groups. Results: There was no significant difference in age, follow-up time, operation time, blood loss, length of stay, preoperative JOA score, occupying ratio of OPLL, diameter of spinal canal, preoperative and final follow-up C2-C7 Cobb angles, and the change of C2-C7 Cobb angle before and after operation between ADF and LAMP groups. The final follow-up JOA score and the neurological recovery rate were significantly higher in ADF group than in LAMP group, particularly in patients with segmental-type OPLL. Cerebrospinal fluid leakage is a major complication after ADF, C5 paralysis, and axial pain frequently results from LAMP. Conclusion: Compared with LAMP, ADF shows better improvement of neurological function in patients with cervical myelopathy due to OPLL, especially in patients with segmental-type cervical OPLL.

Published
2019

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