1.Preliminary study on delaying aging induced thymus degeneration in SAMP6 mice with Bazi Bushen capsule
Zhao-Dong LI ; Yin-Xiao CHEN ; Bo-Yang GONG ; Zhe XU ; Zhi-Xian YU ; Yue-Xuan SHI ; Yan-Fei PENG ; Yu-Hong BIAN ; Yun-Long HOU ; Xiang-Ling WANG ; Shu-Wu ZHAO
Chinese Pharmacological Bulletin 2024;40(6):1186-1192
Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P<0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P<0.01);the proportion of CD3+T cells apparently increased(P<0.05);the level of p16 protein signifi-cantly decreased(P<0.05);the level of Bcl-2 pro-tein significantly increased(P<0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P<0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P<0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.
2.Study on Traditional Chinese Medicine Syndrome Characteristics of 1676 Heart Failure Inpatients: A Cross-Sectional Survey Based on Real-World Electronic Medical Record Information
Yi DU ; Zheng LI ; Guanlin YANG ; Shuqi DONG ; Wenshuai HUANG ; Nanxing XIAN ; Puyu GUO ; Jiajie QI ; Bohang CHEN ; Xin XU ; Zhe ZHANG ; Yi YANG
Journal of Traditional Chinese Medicine 2024;65(3):299-307
ObjectiveTo analyse the clinical characteristics of different traditional Chinese medicine (TCM) syndromes in patients with heart failure based on information from electronic medical record. MethodsA cross-sectional study was conducted to collect clinical data of all inpatients with heart failure in the Department of Cardiology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 1, 2019 to December 31, 2020. A database of clinical TCM data was established to explore the characteristics of clinical data of basic information, syndromes and syndrome element types, and biochemical indexes. The distribution of TCM syndromes and syndrome elements in heart failure patients were also analysed, and the basic information and biochemical indexes of the patients with top 7 different TCM syndrome types were compared. ResultsA total of 1676 inpatients with heart fai-lure were included. The top 7 TCM syndromes of heart failure were syndrome of phlegm turbidity and blood stasis (477 cases, 28.46%), syndrome of qi deficiency and blood stasis (439 cases, 26.19%), syndrome of qi deficiency and blood stasis with water retention (274 cases, 16.35%), syndrome of yang deficiency with water retention (145 cases, 8.65%), syndrome of qi and yin deficiency (104 cases, 6.21%), syndrome of qi and yin deficiency with blood stasis (80 cases, 4.77%), syndrome of heart yang deficiency (59 cases, 3.52%). Among the 1676 patients, 6 syndrome elements accounted for more than 5%. Blood stasis accounted for the highest proportion of TCM syndrome element type (1292 cases, 77.09%), followed by qi deficiency (919 cases, 54.83%), phlegm (498 cases, 29.71%), water retention (434 cases, 25.89%), yang deficiency (215 cases, 12.82%) and yin deficiency (191 cases, 11.40%). Among the 1676 patients, 1308 cases of acute heart failure mainly showed syndrome of phlegm turbidity and blood stasis (386 cases, 29.51%), and 368 of chronic heart fai-lure mainly showed syndrome of qi deficiency and blood stasis (118 cases, 32.07%). Patients with syndrome of phlegm turbidity and blood stasis had the shortest disease duration of 0.3 months, while those with syndrome of heart yang deficiency had the longest disease duration of 15 months. The proportion of syndrome of phlegm turbidity and blood stasis was the highest in patients with heart failure combined with coronary artery disease, the proportion of syndrome of qi deficiency and blood stasis with water retention was the highest in patients with heart failure combined with atrial fibrillation, and the proportion of patients with syndrome of qi deficiency and blood stasis with water retention and syndrome of yang deficiency with water retention in those applying diuretics during the hospital stay was the highest with more than 86%. The different 7 TCM syndromes showed statistically difference in patients with complications including coronary artery disease, old myocardial infarction, atrial fibrillation, pre and post-admission medication usage including intravenous vasodilators, cardiac stimulants, diuretics, and level of blood chloride, blood urea, blood creatinine, blood bicarbonate, blood albumin, and blood total bilirubin (P<0.05). ConclusionThe most common TCM syndromes in patients with heart failure are syndrome of phlegm turbidity and blood stasis and syndrome of qi deficiency and blood stasis. Different TCM syndromes have different characteristics in gender, disease complications, medication before and after admission, and blood indexes.
3.Study on the Distribution of Traditional Chinese Medicine Syndromes in Patients with Type 2 Diabetic Retinopathy and Its Correlation with Serum Inflammatory Factors and Adiponectin Levels
Hong-Yun WU ; Zhen-Xuan YUAN ; Fang CHEN ; Wei YE ; Li-Qun HU ; Xian-Zhong ZENG ; Zhe XU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1371-1379
Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in patients with type 2 diabetic retinopathy(T2DR)and to explore the correlation of TCM syndromes with serum inflammatory factors and adiponectin(APN)levels,so as to provide evidence for TCM syndrome differentiation of T2DR.Methods A cross-sectional case-control study was conducted in 42 patients(involving 84 eyes)diagnosed as T2DR in the Department of Ophthalmology,Ganzhou People's Hospital from September 2022 to March 2023.The correlation between fundus fluorescein angiography(FFA)staging and TCM syndrome differentiation in patients with T2DR was explored.The relationship between TCM syndrome types and serum levels of inflammatory factors and APN,as well as the differences in serum inflammatory factors and APN levels of the patients with various FFA stages were analyzed.The correlation between each variable and TCM syndrome types in patients with T2DR was investigated.Results(1)Among the 42 patients with T2DR,27 cases were male and 15 cases were female,and their age averaged(54.0±12.0)years old.Among them,14 cases(33.3%)were differentiated as liver-kidney deficiency with malnutrition of eye collateral syndrome,15 cases(35.7%)were differentiated as yin-essence deficiency with internal dry-heat syndrome,9 cases(21.4%)were differentiated as qi-yin deficiency with collateral stasis and obstruction syndrome,4 cases(9.5%)were differentiated as yin-yang deficiency with blood stasis and phlegm coagulation syndrome,and none case(0.0%)was differentiated as spleen dysfunction and water-damp obstruction syndrome.(2)FFA staging showed that FFA staging ≥ 4[i.e.,having proliferative diabetic retinopathy(PDR)]was found in 78.6%(11/14)of the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome,73.3%(11/15)of the patients with yin-essence deficiency with internal dry-heat syndrome,100%(9/9)of the patients with qi-yin deficiency with collateral stasis and obstruction syndrome,and 100%(4/4)of the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome.But the intergroup comparison showed no significant differences among various syndrome types(P=0.272).(3)Among the 42 patients with T2DR,35 patients(83.3%)had higher level of tumor necrosis factor-α(TNF-α),28 patients(68.3%)had higher level of C-reactive protein(CRP)and 38 patients(90.5%)had higher level of glycosylated hemoglobin(HbA1c)than the normal.However,there was no significant difference in the levels of serum inflammatory factors of TNF-α,CRP,interleukin-6(IL-6)and vascular endothelial growth factor(VEGF),APN and HbA1c among the patients with different FFA stages(P>0.05),neither did the difference in serum APN,TNF-α,CRP,IL-6 and VEGF levels among the patients with different TCM syndrome types(P>0.05).(4)The correlation analysis showed that the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome had a shorter course of eye diseases than the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome(r=-0.467,P=0.051),had higher CRP level than the patients with yin-essence deficiency with internal dry-heat syndrome(r=0.592,P=0.010),and had higher CRP level(r=0.668,P=0.013)and a longer course of diabetes(r=0.629,P=0.021)than the patients with qi-yin deficiency with collateral stasis and obstruction syndrome.Conclusion Increased serum TNF-α and CRP expressions are presented in the patients with T2DR.Liver-kidney deficiency with malnutrition of eye collaterals syndrome and yin-essence deficiency with internal dry-heat syndrome are the common syndromes in T2DR.Yin-yang deficiency with blood stasis and phlegm coagulation syndrome is closely correlated with CRP level,and the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome have a longer course of diabetes.
4.Reactivation of PPARα alleviates myocardial lipid accumulation and cardiac dysfunction by improving fatty acid β-oxidation in Dsg2-deficient arrhythmogenic cardiomyopathy.
Yubi LIN ; Ruonan LIU ; Yanling HUANG ; Zhe YANG ; Jianzhong XIAN ; Jingmin HUANG ; Zirui QIU ; Xiufang LIN ; Mengzhen ZHANG ; Hui CHEN ; Huadong WANG ; Jiana HUANG ; Geyang XU
Acta Pharmaceutica Sinica B 2023;13(1):192-203
Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2 -/-). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2 -/- mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2 -/- mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR-4EBP1-PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.
5. The therapeutic effect of Balanophora polysaccharide on acetic acid gastric ulcer in rats and its mechanism
De-Yao XIA ; Fang-Yu ZHAO ; Xian-Bing CHEN ; De-Yao XIA ; Sheng-Zhe HUANG ; Yi-Ru ZHAO ; Jiang-Hua WANG ; Jun-Yan MOU ; Feng-Jie WANG ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2023;39(1):193-199
Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.
6.Relationship between body mass index and sexual development in Chinese children.
Xiao Qin XU ; Jian Wei ZHANG ; Rui Min CHEN ; Jing Si LUO ; Shao Ke CHEN ; Rong Xiu ZHENG ; Di WU ; Min ZHU ; Chun Lin WANG ; Yan LIANG ; Hui YAO ; Hai Yan WEI ; Zhe SU ; Mireguli MAIMAITI ; Hong Wei DU ; Fei Hong LUO ; Pin LI ; Shu Ting SI ; Wei WU ; Ke HUANG ; Guan Ping DONG ; Yun Xian YU ; Jun Fen FU
Chinese Journal of Pediatrics 2022;60(4):311-316
Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent
;
Body Mass Index
;
Child
;
Child, Preschool
;
China/epidemiology*
;
Cross-Sectional Studies
;
Female
;
Humans
;
Male
;
Obesity/epidemiology*
;
Overweight/epidemiology*
;
Puberty
;
Puberty, Precocious
;
Sexual Development
7.Characteristics of fusion gene expression in acute lymphoblastic leukemia.
Xian Qi HUANG ; Ya Ni LIN ; En Bin LIU ; Fei XING ; Zhe WANG ; Xue Jing CHEN ; Long CHEN ; Jing Ting MA ; Ying Chang MI ; Kun RU
Chinese Journal of Pathology 2022;51(4):307-313
Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.
Adolescent
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Adult
;
Aged
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Aged, 80 and over
;
Child
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Child, Preschool
;
Gene Expression
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Genes, ras
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Humans
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Infant
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Infant, Newborn
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Middle Aged
;
Oncogene Fusion
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*
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Retrospective Studies
;
Young Adult
8.Comparative study between 3D guide plate assisted and free-hand insertion of anterior cervical transpedicular screw.
Jie LI ; Liu-Jun ZHAO ; Min-Zhe ZHENG ; Kai-Feng GAN ; Yi-Lei CHEN ; Zong-Xian FENG ; Ling-Xiao PAN ; Jun-Xiang XU ; Teng-di FAN ; Jing-Yang CHEN ; Feng-Dong ZHAO
China Journal of Orthopaedics and Traumatology 2021;34(1):45-50
OBJECTIVE:
To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods.
METHODS:
Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups.
RESULTS:
Two screws were inserted in each segment from C
CONCLUSION
The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.
Adult
;
Aged
;
Bone Plates
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Cervical Vertebrae/surgery*
;
Cross-Sectional Studies
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Female
;
Humans
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Male
;
Middle Aged
;
Pedicle Screws
;
Printing, Three-Dimensional
9.Different effects of long-term and short-term repeated restraints on the hematopoietic stem cells in mice.
Chen-Ke MA ; Xian WU ; Zhe XU ; Jian LIU ; Ji-Yan ZHANG ; Tao-Xing SHI
Acta Physiologica Sinica 2020;72(2):167-174
Humans with chronic psychological stress are prone to develop multiple disorders of body function including impairment of immune system. Chronic psychological stress has been reported to have negative effects on body immune system. However, the underlying mechanisms have not been clearly demonstrated. All immune cells are derived from hematopoietic stem cells (HSC) in the bone marrow, including myeloid cells which comprise the innate immunity as a pivotal component. In this study, to explore the effects of chronic psychological stress on HSC and myeloid cells, different repeated restraint sessions were applied, including long-term mild restraint in which mice were individually subjected to a 2 h restraint session twice daily (morning and afternoon/between 9:00 and 17:00) for 4 weeks, and short-term vigorous restraint in which mice were individually subjected to a 16 h restraint session (from 17:00 to 9:00 next day) for 5 days. At the end of restraint, mice were sacrificed and the total cell numbers in the bone marrow and peripheral blood were measured by cell counting. The proportions and absolute numbers of HSC (LinCD117Sca1CD150CD48) and myeloid cells (CD11bLy6C) were detected by fluorescence activated cell sorting (FACS) analysis. Proliferation of HSC was measured by BrdU incorporation assay. The results indicated that the absolute number of HSC was increased upon long-term mild restraint, but was decreased upon short-term vigorous restraint with impaired proliferation. Both long-term mild restraint and short-term vigorous restraint led to the accumulation of CD11bLy6C cells in the bone marrow as well as in the peripheral blood, as indicated by the absolute cell numbers. Taken together, long-term chronic stress led to increased ratio and absolute number of HSC in mice, while short-term stress had opposite effects, which suggests that stress-induced accumulation of CD11bLy6C myeloid cells might not result from increased number of HSC.
Animals
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Antigens, Ly
;
metabolism
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Bone Marrow Cells
;
cytology
;
CD11b Antigen
;
metabolism
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Cell Proliferation
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Hematopoietic Stem Cells
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cytology
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Mice
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Mice, Inbred C57BL
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Restraint, Physical
;
Stress, Psychological
10.Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19.
Xiaoyan LIU ; Zhe LI ; Shuai LIU ; Jing SUN ; Zhanghua CHEN ; Min JIANG ; Qingling ZHANG ; Yinghua WEI ; Xin WANG ; Yi-You HUANG ; Yinyi SHI ; Yanhui XU ; Huifang XIAN ; Fan BAI ; Changxing OU ; Bei XIONG ; Andrew M LEW ; Jun CUI ; Rongli FANG ; Hui HUANG ; Jincun ZHAO ; Xuechuan HONG ; Yuxia ZHANG ; Fuling ZHOU ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2020;10(7):1205-1215
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

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