1.A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses.
Yuhan LI ; Xiangqing DING ; Xianxian WU ; Longfei DING ; Yuhui YANG ; Xiaoliang JIANG ; Xing LIU ; Xu ZHANG ; Jianrong SU ; Jianqing XU ; Zhiwei YANG
Acta Pharmaceutica Sinica B 2023;13(11):4461-4476
Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.
2.Application of artificial intelligence based on multimodal fundus image data in the diagnosis and treatment of cardiovascular diseases
Yan WANG ; Xue HE ; Hanpeng ZHAO ; Cong LI ; Yun REN ; Jianrong JIANG ; Zhenchao DU ; Xiaohong YANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(09):1344-1350
Cardiovascular diseases is the leading cause of threat to human life and health worldwide. Early risk assessment, timely diagnosis, and prognosis evaluation are critical to the treatment of cardiovascular diseases. Currently, the evaluation of diagnosis and prognosis of cardiovascular diseases mainly relies on imaging examinations such as coronary CT and coronary angiography, which are expensive, time-consuming, partly invasive, and require high professional competence of the operator, making it difficult to promote in the community or in areas where medical resources are scarce. The fundus microcirculation is a part of the human microcirculation and has similar embryological origins and physiopathological features to cardiovascular circulation. Several studies have revealed fundus imaging biomarkers associated with cardiovascular diseases, and developed and validated intelligent diagnosis and treatment models for cardiovascular diseases based on fundus imaging data. Fundus imaging is expected to be an important adjunct to cardiovascular disease diagnosis and treatment given its noninvasive and convenient nature. The purpose of this review is to summarize the current research status, challenges, and future prospects of the application of artificial intelligence based on multimodal fundus imaging data in cardiovascular disease diagnosis and treatment.
3.Nanopolyphenol rejuvenates microglial surveillance of multiple misfolded proteins through metabolic reprogramming.
Dayuan WANG ; Xiao GU ; Xinyi MA ; Jun CHEN ; Qizhi ZHANG ; Zhihua YU ; Juan LI ; Meng HU ; Xiaofang TAN ; Yuyun TANG ; Jianrong XU ; Minjun XU ; Qingxiang SONG ; Huahua SONG ; Gan JIANG ; Zaiming TANG ; Xiaoling GAO ; Hongzhuan CHEN
Acta Pharmaceutica Sinica B 2023;13(2):834-851
Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.
4.Pneumomediastinum secondary to diabetes ketoacidosis in high altitude: a case report
Haibo LI ; Jie YANG ; Jianrong JIANG ; Zeren GURONG ; Ga LONG
Clinical Medicine of China 2023;39(2):130-133
Diabetic ketoacidosis (DKA), a serious acute complication of diabetes mellitus, mainly manifests as hyperglycemia, ketosis, and acidosis. It is a metabolic syndrome resulting from insulin deficiency and increased insulin-antagonistic hormone levels. While type 2 diabetes mellitus complicated by DKA is relatively uncommon, secondary pneumomediastinum in DKA is extremely rare. Following alveolar rupture, air can travel through various routes to reach the hilum, causing anterior, middle, or posterior pneumomediastinum or even leading to intracranial epidural pneumatosis. The diagnosis of pneumomediastinum is mainly dependent on chest computed tomography findings. After the successful treatment of DKA, pneumomediastinum usually resolves spontaneously within 5-10 days with a good prognosis. One DKA patient admitted to Dege County People's Hospital developed Kussmaul respirations, followed by an increase in intra-alveolar pressure, an elevation in intra and extra-alveolar pressure difference, and protein decomposition in the alveolus wall, which promoted alveolar rupture and induced mediastinal emphysema. After rapid fluid replacement, blood glucose control with insulin, and maintenance of acid-base balance (correction DKA), the mediastinal emphysema was spontaneously absorbed. Through the analysis of the clinical data of this case, the purpose is to improve the clinicians' internal understanding of the relationship between mediastinal emphysema and DKA, avoid over-examination and over-treatment, and provide strategies for correct diagnosis and treatment.
5.Electrophysiological analysis of early warning information processing in children with transient tic disorder
Lina LIAO ; Ting WU ; Jianrong LIU ; Yang YI ; Chaoqun WANG ; Xiaoping JIANG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(12):1099-1103
Objective:To explore the changing characteristics of early warning information ability in children with transient tic disorder(TTD).Methods:A total of 32 children with TTD(TTD group) diagnosed and treated at Changzhou Children's Hospital from 2018 to 2022 and 36 healthy control children(HC group) recruited from ordinary primary schools in Changzhou city were tested with CPT-Go/Nogo task and their behavioral data and cue/uncue-N2, P3b and CNV components of event related potential(ERP) were analyzed and compared by SPSS 25.0 software.Results:(1)Comparison of behavioral data: there was no statistical difference in the correct number(37(34, 39) vs 38(37, 40)), false number(1(0, 2) vs 1(0, 2))and correct reaction time((511.27±99.27)ms vs(504.88±92.23)ms)between TTD and HC group(all P>0.05). (2) Comparison of ERP components: in the HC group, the amplitudes of cue-CNV were higher than those in uncue-CNV in lead Cz((-4.61±4.67)μV vs(-1.07±3.20)μV)and Pz((-4.17±3.74)μV vs(-1.79±3.49)μV) and the differences were statistically significant(both P<0.01). The amplitude of cue-P3b in lead Pz were higher than that in uncue-P3b((9.13±4.99)μV vs(6.12±6.24)μV) and the difference was statistically significant( P<0.01). Compare with HC group((-4.12±4.25)μV, (-4.61±4.67)μV, (9.13±4.99)μV), the amplitudes of uncue-N2, cue-CNV and cue-P3b in TTD group((-1.29±4.48)μV, (-2.03±3.19)μV, (6.59±3.41)μV) were respectively lower, and the differences were statistically significant(all P<0.05). Conclusion:Children with TTD may have dysfunction in conflict monitoring, attention allocation, and maintaining alertness when processing early warning information, but there may be corresponding compensation mechanisms for brain function.
6.Correlation between physical fitness and reading ability among school aged children
XIAO Pei, ZHOU Xinhong, ZHOU Jianrong,JIANG Qi,FENG Yanan,WU Xiaoqian,XIANG Zhen,ZOU Li,SONG Ranran
Chinese Journal of School Health 2022;43(5):784-787
Objective:
To determine the association between physical health fitness with Chinese reading ability of schoolaged children, so as to provide evidence for improving children s reading ability.
Methods:
A questionnaire survey was conducted among 1 923 school aged children in grades 2-6 in a primary school in Wuhan, Hubei Province, China. The questionnaire included basic demographic information and Dyslexia Checklist for Chinese Children and the Pupil Rating Scale Revised Screening. At the same time, participants underwent physical fitness tests which included an assessment of height, weight, and lung capacity, as well as a 50 meter run, sit forward bend, one minute skipping rope task, sit ups, and a 50 × 8 round trip.
Results:
A total of 59 children were identified with dyslexia. Normal children achieved higher scores than children with dyslexia in the total physical health score, as well as the one minute skipping rope score, one minute sit up score, and sitting forward score ( P <0.05). Multiple linear regression analyses showed that the reading ability of girls was higher than that of boys ( β =-3.04, P <0.01), and the children who regularly participated in more intense physical activity and who had higher fitness scores had a higher reading ability ( β =-1.68, -0.08, P <0.01). Children s reading ability increased significantly with parental educational level( P <0.05).
Conclusion
Gender, parents education level, physical exercise intensity, and children s physical fitness were identified as influencing factors of school age children s reading ability. A positive correlation was found between children s physical health level and reading ability.
7.Survey on blood donation related self-efficacy and blood donation willingness with different demographic characteristics
Jianrong HUANG ; Huiying HU ; Huiying HAN ; Ruqiong ZHENG ; Qin HE ; Xin CHENG ; Yingjia JIANG ; Ming ZHU
Chinese Journal of Blood Transfusion 2022;35(2):201-205
【Objective】 To investigate the effect of blood donation related self-efficacy on blood donation intention, in order to provide valuable reference for formulating the recruitment and service strategy for blood donors with different demographic characteristics. 【Methods】 A questionnaire was designed based on psychological self-efficacy theory, and respondents in Nanchong city were taken as the research objects. The data of demographic characteristics, blood donation related self-efficacy measurement and blood donation intention measurement of the respondents who were randomly selected by convenient sampling method were collected and analyzed by rank sum test. 【Results】 The number of previous blood donation was significantly correlated with blood donation related self-efficacy and blood donation intention, and there was a strong positive correlation between blood donation related self-efficacy and blood donation intention (r=0.618). There are significant differences in blood donation related self-efficacy or blood donation intention of respondents with different blood donation experiences (P<0.05), and respondents who donated blood twice or more showed relatively strong blood donation related self-efficacy and blood donation intention. Significant differences in blood donation related self-efficacy or blood donation intention among respondents were noticed in gender, age or education level(P<0.05), and males or 30~39 years old respondents, or respondents with bachelor degree or above have relatively strong blood donation related self-efficacy and blood donation intention. Significant differences in blood donation related self-efficacy were noticed among respondents with different occupations (P<0.05), but no significant difference was noticed in blood donation intention (P>0.05). 【Conclusion】 Blood donation intention can be increased by enhancing the blood donation related self-efficacy of respondents. We can focus on the recruitment of respondents with high self-efficacy in the areas covered by the survey during the practice of blood donor recruitment and service to achieve higher recruitment efficiency. In the meantime, special attention should also be paid to the people with relatively low self-efficacy and high-quality services should be provided t to expand blood donor team. Furthermore, blood donor recruitment and services can be appropriately expanded to the countryside as needed.
8.A case of 16p13.11 microdeletion syndrome with febrile convulsion as the main manifestation.
Ting WU ; Li'na LIAO ; Xiaoping JIANG ; Jianrong LIU ; Wangyang CHEN ; Min SHENG ; Ning GUO
Chinese Journal of Medical Genetics 2021;38(10):981-984
OBJECTIVE:
To explore the genetic basis for a girl with febrile convulsion as the main manifestation.
METHODS:
The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family.
RESULTS:
The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR.
CONCLUSION
16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.
Child
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DNA Copy Number Variations
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Epilepsy
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Female
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Humans
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Seizures/genetics*
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Seizures, Febrile/genetics*
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Whole Exome Sequencing
9. Clinical application and research progress of remimazolam
Baowei JIN ; Zongming JIANG ; Jianrong GUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(12):1444-1448
Remimazolam is a new ultra-short-acting sedative, with rapid onset and recovery, metabolism independent of liver and kidney function, light respiratory inhibition, stable hemodynamics, long time application without accumulation. Carboxylic acid metabolites have no pharmacological effects, and can be rapidly reversed by antagonist flumazenil, which is expected to become a new choice of clinical sedative. In this paper, pharmacological characteristics and recent research progress of remimazolam are reviewed, which can provide reference for clinical safe drug use.
10.Establishment and evaluation of rat obesity model induced by electrical damage of ventromedial hypothalamic nucleus and arcuate nucleus
Junjie PENG ; Zhanpeng FENG ; Xingqin WANG ; Yichao OU ; Mingfeng ZHOU ; Guangsen WU ; Haodong GONG ; Kai LI ; Peirong NIU ; Yusheng LIU ; Jianrong JIANG ; Songtao QI
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(7):659-665
Objective:To construct a rat model of hypothalamic obesity by two point electrical damage to the ventromedial hypothalamus and arcuate nucleus.Methods:Twenty adult male SD rats of SPF grade were randomly divided into experimental group and sham operation group.A 25GA (0.45 mm) solid iron needle was used, the needle was coated with an insulating layer, and the tip exposed a 0.5 mm conductive area.With reference to The Rat Brain in Stereotaxic Coordinates and using the stereotactic instrument (AP: -2.6 mm, ML: ± 0.6 mm, DV: -9.6 mm) as the coordinate, 1.5 mA current was continuously applied for 25 s, the ventromedial nucleus (VMH) and arcuate nucleus (ARC) of bilateral brain in SD rats was damaged.During the experiment, the body weight(BW), food intake(FI) and water intake(WI) of the two groups were recorded regularly.The rats were sacrificed on the 28th day after the operation, and the changes of periprenal fat mass and body length were measured.The changes of liver and adipose tissue were detected by HE staining method, leptin by ELISA, leptin receptor(LEPR) by Western blot.Results:(1) The body weight of rats in the experimental group ((427.5±17.7)g) and weight gain ((208.5±14.8)g) were significantly increased compared with the rats in the control group((349.2±17.7)g), ((136.2±21.4)g)on the 28th day after operation ( t=7.661, 6.806, both P<0.001). (2) The daily food intake of rats in the experimental group ((44.2±6.6)g) on the 28th day after surgery was significantly higher than that in the control group ((23.0±3.6)g) ( t=6.918, P<0.001). There was no significant difference of the daily drinking water of rats between experimental group((37.5±12.1)ml) and the control group ((35.0±11.8)ml) ( t=0.361, P=0.726). (3) Perikidney fat mass of experimental group rats ((13.4±2.7)g) significantly increased 28 days after operation compared with control group rats((6.3±0.9)g)( t=4.250, P<0.05). The naso-anal length of experimental group((21.8±0.4)cm) was significantly decreased compared with the control group ((23.4±0.2)cm) ( t=-6.788, P<0.01). The Lee index of the experimental group (348.9±8.5) was significantly higher than that of the control group(305.5±4.3)( t=7.898, P<0.01). (4) The serum leptin content ((8 324.10±159.00)μg/L) of the experimental group rats at 28 days after surgery was significantly higher than that of the control group((2 705.31±407.10)μg/L) ( t=25.712, P<0.001). The lateral hypothalamus area (LHA) LEPR protein expression (1.3±0.1) in the experimental group was significantly higher than that in the control group (0.9±0.1) ( t=4.932, P<0.01). Conclusion:Two-point electrical damage to bilateral VMH and ARC of rats can establish hypothalamic obese rat model.


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