1.Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window.
Shuai XIONG ; Hui XIAO ; Meng SUN ; Yunjie LIU ; Ling GAO ; Ke XU ; Haiying LIANG ; Nan JIANG ; Yuhui LIN ; Lei CHANG ; Haiyin WU ; Dongya ZHU ; Chunxia LUO
Acta Pharmaceutica Sinica B 2023;13(7):3008-3026
Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.
2.Clinical characteristics and prognosis of severe coronal virus disease 2019 pneumonia combined with coronary artery disease in the elderly
Ruijin XU ; Ge LIU ; Yuying SU ; Juan CHEN ; Yunjie GE ; Junjie GAO ; Liu LIU
Chinese Journal of Geriatrics 2022;41(8):961-964
Objective:To investigate the clinical manifestations and prognosis of severe coronal virus disease 2019(COVID-19)pneumonia combined with coronary artery disease(CAD)in the elderly.Methods:A total of 351 old patients(≥60 years)with severe COVID-19 pneumonia combined with CAD admitted to Tongji Hospital of Wuhan from February 2020 to March 2020 were enrolled in this retrospective study.The patients were divided into CAD group(n=52)and non-CAD group(n=299). The clinical data, the changes of blood tests and cardiovascular complications were observed.Results:Compared with non-CAD group, CAD group showed a longer time of stay in hospital[(12.3±2.6)d and(9.3±2.1)d, t=3.24, P=0.002], and higher incidence of cardiovascular complications, such as myocardial infarction(7.7% and 0.0%, χ2=21.6, P<0.001), heart failure(15.4% and 0.3%, χ2=34.7, P<0.001), arrhythmia(50.0% and 12.4%, χ2=24.45, P<0.001)and all-cause mortality(15.4% and 4.3%, χ2=7.94, P=0.005). The serum levels of interleukin-2 receptor, interleukin 6, CK-MB, cTnI, NT-proBNP, D-dimer and fibrinogen were higher in CAD group than in non-CAD group.The oxygenation index was significantly lower and the blood lactic acid level was higher in CAD group than in non-CAD group. Conclusions:The aged patients with severe COVID-19 pneumonia combined with CAD show obvious inflammatory reaction, high incidence of cardiovascular complications and high mortality.
3.Related factors of pulmonary embolism recurrence and research progress on its prevention
Yunjie XU ; Feifei FANG ; Liyuan XU
Chinese Journal of Primary Medicine and Pharmacy 2022;29(12):1917-1920
Pulmonary embolism is the cardiovascular disease caused by endogenous or exogenous emboli blocking the pulmonary artery system. Pulmonary embolism is clinically very common and has a high recurrence rate. Its etiology is complicated. Pulmonary embolism recurrence can be caused by many factors, which affect its prognosis. Complicated diseases, residual thrombosis, anticoagulation therapy and respiratory disorders are the main factors that lead to pulmonary embolism recurrence. Some blood test indicators can also reflect the recurrence of pulmonary embolism. This paper reviews the risk factors and prevention strategies of pulmonary embolism recurrence, with the purpose of reducing recurrence rate, improving prognosis and thereby providing objective evidence for clinical practice.
4. Reseach progress on the role of ErbB2 in cardiac disease
Yunjie CHEN ; Xuan ZHOU ; Yuanbin ZHANG ; Zhu LIN ; Suyan ZHU ; Yunjie CHEN ; Xu WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(10):1182-1189
Cardiac disease is the general term of diseases, caused by damage to the structure or abnormal function of the heart. Its morbidity and mortality have remained high, seriously threatening the lives and health of people. The tyrosine kinase receptor ErbB2 (also known as EGFR2 or HER2) was originally discovered for its oncogenic activity, however, recent studies have found that ErbB2 have protective effects in various heart diseases. Therefore, this article reviews the role and underlying mechanism of ErbB2 in myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, heart failure, doxorubicin-induced cardiotoxic injury and diabetic cardiomyopathy. Furthermore, this article also preliminarily discusses the application prospects, limitations and development directions of ErbB2 as a clinical diagnostic marker and therapeutic target for heart disease.
5.Investigation and analysis of thyroid nodules and goiter in school-age children in different water iodine areas of Jiangsu Province
Yuting XIA ; Li SHANG ; Yunjie YE ; Yang WANG ; Mao LIU ; Peihua WANG ; Yan XU
Chinese Journal of Endemiology 2022;41(10):819-823
Objective:To analyze the detection rate of thyroid nodules and goiter in school-age children in different water iodine regions and investigate the difference of thyroid nodule and goiter in school-age children with different age, gender and body mass index (BMI) in Jiangsu Province.Methods:In 2017, three villages with water iodine values of 8.1, 51.2 and 115.4 μg/L (iodine deficient group, iodine appropriate group and iodine high group) were selected as survey sites in Xuzhou City, Jiangsu Province, where the supply of iodized salt was suspended. One primary school was selected from each village, and children aged 8 to 10 years old (age balance, half male and half female) were selected from each primary school as the survey subjects. Urine sample were collected, urinary iodine level was determined, height and weight were measured, and neck B ultrasound was performed.Results:A total of 131, 140 and 138 school-age children aged 8 to 10 years old were investigated in the iodine deficient group, iodine appropriate group and iodine high group, respectively, with a total of 409 children. The detection rates of thyroid nodules were 6.9% (9/131), 15.0% (21/140) and 16.7% (23/138), respectively, and the detection rates of goiter were 1.5% (2/131), 1.4% (2/140) and 6.5% (9/138) in the three groups, respectively. There were statistically significant differences in the detection rates of thyroid nodules and goiter in different water iodine groups (χ 2 = 6.92, 6.37, P < 0.05). The detection rates of thyroid nodules in different age groups were 9.5% (12/126), 11.3% (16/142) and 17.7% (25/141), the differences were statistically significant (χ 2 = 9.05, P < 0.05). The detection rates of thyroid nodules were 11.6% (24/207), 14.4% (29/202), and 12.5% (39/313), 16.9% (14/83), 0/9 and 0/4 in the subjects of different gender and BMI, the differences were not statistically significant (χ 2 = 0.69, P > 0.05). The detection rates of goiter in the subjects of different gender, age and BMI were 1.4% (3/207), 5.0% (10/202); 2.4% (3/126), 6.3% (9/142), 0.7% (1/141); 1.6% (3/313), 4.8% (4/83), 3/9 and 1/4. The differences were statistically significant (χ 2 = 4.07, 7.66, P < 0.05). Conclusion:The detection rate of thyroid nodules in school-age children in different water iodine regions in Jiangsu Province may have a certain relationship with age, and the detection rate of goiter may have a certain relationship with age, gender and BMI.
6.A novel PGAM5 inhibitor LFHP-1c protects blood-brain barrier integrity in ischemic stroke.
Chenglong GAO ; Yazhou XU ; Zhuangzhuang LIANG ; Yunjie WANG ; Qinghong SHANG ; Shengbin ZHANG ; Cunfang WANG ; Mingmin NI ; Dalei WU ; Zhangjian HUANG ; Tao PANG
Acta Pharmaceutica Sinica B 2021;11(7):1867-1884
Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate
7.Progress in the national talent training program for inheritance of characteristic traditional Chinese medicine technology
Huayao CHENG ; Yiqun LIU ; Heling MA ; Xiaohua CHENG ; Yunjie XU ; Peipeng WEI ; Facheng YANG
Chinese Journal of Primary Medicine and Pharmacy 2021;28(5):791-796
To alleviate the shortage of excellent talents of traditional Chinese medicine (TCM), the State Administration of Traditional Chinese Medicine has decided to cultivate a group of talents with strong theoretical foundation, rich practical experience and exquisite skills who would like to devote themselves to TCM technology research. The national talent training program for inheritance of characteristic TCM technology is a major breakthrough in the history of new China in the cultivation of high-level TCM technology talents. A retrospective analysis was performed on the national talent training program for inheritance of characteristic TCM technology hold in training bases from Beijing, Shanghai, Guangdong Province, Jiangsu Province, Anhui Province, Xinjiang Uygur Autonomous Region, Inner Mongolia Autonomous Region, Heilongjiang Province, Yunnan Province, Sichuan Province, Shaanxi Province and Fujian Province. Based on the completion assessment work of 2014 and 2015 national talent training program for inheritance of characteristic TCM technology, and after knowledge exchange and discussion with the training subjects from 30 provinces and some teaching experts in the field of characteristic TCM technology, this paper summarizes the work of the national talent training program for inheritance of characteristic TCM technology. After trained in bases in China, training subjects' theoretical knowledge and practical skills as well as their comprehensive capacity have been greatly promoted. At the same time, there are also some problems and shortages. For example, characteristic TCM technology in some training bases is not prominent enough, some characteristic TCM technologies are not well inherited, and the affiliations of some training subjects do not pay enough attention to it. All of these problems should be solved and improved in future work.
8.Inter-patient arrhythmia ECG signal classification based on SVM+XGBoost ensemble classifier
Chenhua XU ; Sichao YE ; Yunjie FENG ; Qingli QIAO
International Journal of Biomedical Engineering 2020;43(5):366-371,375
Objective:To study a classifier used to classify arrhythmia electrocardiogram (ECG) signals under the inter-patient paradigm to improve the accuracy of automatic classification and solve the limitations of manual diagnosis of arrhythmia.Methods:A SVM+XGBoost ensemble classifier with four modules including preprocessing, feature extraction, support vector machine (SVM) training and ensemble classification was constructed. ECG signal was preprocessed, and R-R interval, high-order statistics, local binary patterns and wavelet components were used as features to train independent SVM classifiers. Then, XGboost algorithm was used to integrate independent SVM classifiers and output arrhythmia classification results. The integrated classifiers were trained and tested on MIT-BIH database.Results:The overall classification accuracy of the ensemble classifier for arrhythmia was 0.867 and the average sensitivity was 0.782.Conclusions:The proposed ensemble classifier can realize automatic and accurate classification of arrhythmia ECG signals under the inter-patient paradigm, and can be used for clinical auxiliary diagnosis.
9. Multi-site analysis of acute effects of air pollutants combination exposure on mortality in Jiangsu Province, China
Qingqing WANG ; Yunjie YE ; Jiayao ZHANG ; Hong SUN ; Lian ZHOU ; Zhen DING ; Yan XU
Chinese Journal of Preventive Medicine 2019;53(1):86-92
Objective:
To explore the acute effect of fine particulate matters (PM2.5), O3, NO2 on daily non-accidental mortality, cardiovascular disease mortality and respiratory mortality data in thirteen cities of Jiangsu province.
Methods:
Daily average concentrations of non-accidental mortality, cardiovascular disease mortality, respiratory mortality data and environmental data were collected from January 1, 2015 to December 31, 2017 in thirteen cities of Jiangsu Province. Daily air quality, mortality and meteorology data were collected from the Information System of Air Pollution and Health Impact Monitoring of Chinese Center for Disease Control and Prevention. We used generalized additive model to evaluate the association between daily concentrations of air pollutants and mortality at single-city level and multi-city level, after adjusting the long-term and seasonal trend, as well as meteorological factors and the effect of "days and weeks" . A multivariate Meta-analysis with random effects was applied to estimate dose-response relationship between air pollutants and mortality.
Results:
At multi-city level, per interquartile range increase of PM2.5, O3, NO2 was associated with an increase of 1.10% (95
10.Analysis of water iodine content in Jiangsu rural water factory
Yuting XIA ; Kuikui LU ; Li SHANG ; Yunjie YE ; Peihua WANG ; Yang WANG ; Mao LIU ; Yan XU ; Ran LIU
Chinese Journal of Endemiology 2019;38(10):818-822
Objective To further understand and master the distribution and influencing factors of water iodine in Jiangsu Province.Methods From 2012 to 2014,half of the water plants in rural centralized water supply monitoring plants in 63 counties (cities,districts) of Jiangsu Province were selected as survey sites,and the types of monitoring,types of water plants,types of water sources,self-inspection ability,disinfection situation,water treatment methods were investigated and analyzed.One sample of peripheral water was collected from each survey site to determine the water iodine content.Results From 2012-2014,there were 938 samples of river water were monitored,and the median water iodine was 5.9 μg/L.There were 57 samples of lake water were monitored,the median water iodine was 6.8 μg/L.There were 228 samples of reservoir water were monitored,and the median water iodine was 7.1 μg/L.There were 43 samples of gully pond water were monitored,and the median water iodine was 6.9 μg/L.There were 5 474 samples of deep well water were monitored,and the median water iodine was 28.2 μg/L.There were 162 samples of shallow well water were monitored,and the median water iodine was 30.9 μg/L.There was a statistically significant difference in the median iodine content of water samples from different water sources (x2 =844.9,P < 0.05).The differences of median iodine of lake water,reservoir water,gully pond water,deep well water and shallow well water among different monitoring types were significant (x2 =9.6,6.3,9.7,121.2,38.1,P < 0.05).The differences of median iodine of river water,reservoir water,deep well water and shallow well water among different types of water plants were significant (x2 =109.5,39.0,153.3,7.6,P < 0.05).The iodine contents of fiver water,lake water,deep well water and shallow well water had significant difference in selfinspection ability of different water plants (x2 =62.5,5.1,29.9,10.1,P < 0.05).The iodine content of reservoir water,deep well water and shallow well water were significandy different in different disinfection situation (x2 =12.1,12.4,35.7,P < 0.05).The medians iodine of river water,reservoir water,deep well water and shallow well water had significant difference in different water treatment methods (x2 =9.5,21.2,102.4,46.9,P < 0.05).Conclusions The water iodine contents of water samples in different types of water sources in rural area of Jiangsu Province are different.The level of water iodine is affected by factors such as monitoring type,type of water plant,self-inspection ability,disinfection situation and water treatment method.

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