1.A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement.
Jianbing WU ; Duorui JI ; Weijie JIAO ; Jian JIA ; Jiayi ZHU ; Taijun HANG ; Xijing CHEN ; Yang DING ; Yuwen XU ; Xinglong CHANG ; Liang LI ; Qiu LIU ; Yumei CAO ; Yan ZHONG ; Xia SUN ; Qingming GUO ; Tuanjie WANG ; Zhenzhong WANG ; Ya LING ; Wei XIAO ; Zhangjian HUANG ; Yihua ZHANG
Acta Pharmaceutica Sinica B 2025;15(2):1070-1083
Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.
2.Clinical analysis of 208 children with congenital coronary artery origin abnormalities
Zhen ZHEN ; Ziyan DONG ; Yihua SHAO ; Jia NA ; Qirui LI ; Xi CHEN ; Lu GAO ; Yue YUAN
Chinese Pediatric Emergency Medicine 2023;30(8):566-572
Objective:To describe the clinical features and prognosis of congenital anomalous origin of coronary artery(AOCA) in children to increase our understanding of the disease.Methods:This retrospective study included children diagnosed with AOCA using computed tomography coronary angiography(CTCA) admitted to the Department of Cardiology, Beijing Children′s Hospital, Capital Medical University, from January 1, 2014 to December 31, 2019.The clinical presentations, laboratory results, imaging analyses, treatments, and prognoses of these patients were analyzed.Results:A total of 208 children, including 105 boys and 103 girls, we evaluated the ages(9.03±4.18)years old with AOCA.Of these, 157 cases(75.5%) presented with cardiac symptoms, such as chest tightness, palpitations, dizziness, syncope, fatigue, and decreased endurance.Three cases(1.4%) had atypical symptoms of paroxysmal crying, dyspnoea and cyanosis, and 48 cases(23.1%) were asymptomatic.Levels of serological markers of myocardial injury were elevated in 59 cases(28.4%), and 140 cases(67.3%) had predominant ST-T abnormalities on electrocardiograms.Transthoracic echocardiography identified 27 cases (13%) with cardiac enlargement and ten cases(4.8%) with left ventricular systolic dysfunction.There were 126 cases(60.6%) with the anomalous origin of the left coronary artery revealed by CTCA, 50 cases(24.0%) with the anomalous origin of the right coronary artery and 32 cases(15.4%) with bilateral coronary arteries of anomalous origin.Five children underwent surgical treatment, and the remaining 203 children were treated conservatively with drugs.The whole group was successfully treated, and no death case was recorded during the follow-up period.Conclusion:AOCA may cause different degrees of myocardial ischemia.Diverse clinical presentations and diagnostic limitations of transthoracic echocardiography often lead to missed diagnosis or misdiagnosis.In contrast, CTCA has high diagnostic accuracy and can be used to identify the location and course of the coronary ostia.Hence, the management of AOCA should be tailored on a case-to-case basis, taking into consideration of the specific type of coronary origin, with surgical intervention being warranted if necessary.
3.Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells
Zhang CHEN ; Han XUESHUAI ; Liu JINGKUN ; Chen LEI ; Lei YING ; Chen KUNYING ; Si JIA ; Wang TIAN-YI ; Zhou HUI ; Zhao XIAOYUN ; Zhang XIAOHUI ; An YIHUA ; Li YUEYING ; Wang QIAN-FEI
Genomics, Proteomics & Bioinformatics 2022;20(1):70-86
Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodu-latory capacities.However,the exact characteristics of MSCs remain largely unknown.By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly,we revealed five distinct subpopulations.The developmental trajectory of these five MSC subpopulations was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2)bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondro-cytes.The stem-like APCs,expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES,uniquely exhibited strong proliferation and stemness signatures.Remarkably,the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to sup-press activated CD3+T cell proliferation in vitro,supporting the role of this population in immunoregulation.In summary,our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation.Our findings advance the definition of MSCs by identifying the specific functions of their heteroge-neous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.
4.Synthesis and protective effect of carboxymethylcysteine L-arginate in bronchial epithelial cells
Jian JIA ; Jianbing WU ; Yihua ZHANG ; Zhangjian HUANG
Journal of China Pharmaceutical University 2022;53(2):171-177
Carboxymethylcysteine (CMC) is a common drug for the clinical treatment of chronic obstructive pulmonary disease, yet its long-term use can cause severe irritation to the gastrointestinal tract.As the substrate of nitric oxide (NO) synthase (NOS), L-arginine can be converted in the body into NO beneficial to the cardiovascular system, the gastrointestinal tract and so on.As a basic amino acid, L-arginine can be salified with some compounds containing acidic groups to improve the water solubility of the parent drug and may enhance the activity and alleviate side effects due to NO release.In this study, we designed and synthesized carboxymethylcysteine L-arginate (CMCA), and tested its physico-chemical properties, and the abilities to scavenge reactive oxygen species (ROS), inhibit apoptosis and release NO in cigarette smoke-induced injury model of human bronchial epithelial cells.The results revealed that CMCA is superior to CMC or L-arginine in that it could capture ROS, release NO and suppress apoptosis, suggesting that CMCA is worthy of further research and development.
5.Effectiveness of the three-line relaxation-based group intervention on mental stress management among nursing students
ZHAO Xiuhe, SUN Jinhai, JIA Shoumei, CHEN Yu, PENG Yihua
Chinese Journal of School Health 2019;40(7):1040-1042
Objective:
To investigate the feasibility and efficiency of three-line relaxation-based group intervention on mental stress management among nursing students.
Methods:
A total of 224 nursing students were randomly divided into the intervention group in which three-line relaxation training for 12 weeks were delivered together with psychological health education (PHE), and the control group which only delivered PHE. The SelfRating Anxiety Scale (SAS) and the Self Rating Depression Scale (SDS) were used before and after intervention. T-test was used to compare inter-group difference.
Results:
After 4-week intervention, there’s no significant difference in the score of SAS and SDS between the two groups(P>0.05). After 12-week intervention, average SAS and SDS score of intervention group was significantly decreased compared with before intervention (both P<0.01). After 12-week intervention, no significant changes were observed in the score of SAS and SDS in the control group (both P>0.05). After 4-and 12-week intervention, average score in SAS and SDS of intervention group was significantly lower than that of the control group(P<0.05).
Conclusion
Three-line relaxation is effective in relieving mental stress of nursing students.
6. Natural sideburn reconstruction with retroauricular expanded flap with original hairline
Tiran ZHANG ; Yihua CHEN ; Liqiang LIU ; Jincai FAN ; Cheng GAN ; Jia TIAN ; Zengjie YANG ; Hu JIAO ; Hua ZHANG ; Hongbo CHEN
Chinese Journal of Plastic Surgery 2019;35(5):425-429
Objective:
To introduce a reconstruction procedure of natural sideburn, with combined expanded retroauricular flap and scalp flap.
Methods:
A retrospective study was produced in Plastic Surgery Hospital, PUMC, from January 2014 to December 2017. Twenty patients (21 sides) underwent sideburn reconstruction with combined expanded retroauricular flap and scalp flap (double pedicled flap,
7. Combination of orbicularis oculi muscular myolemma release and orbital septum reset to create double eyelid
Liqiang LIU ; Jincai FAN ; Leren HE ; Tao YANG ; Hu JIAO ; Zengjie YANG ; Cheng GAN ; Jia TIAN ; Tiran ZHANG ; Yihua CHEN ; Hongbo CHEN
Chinese Journal of Plastic Surgery 2019;35(6):533-537
Objective:
To explore a surgical method for the reconstruction of naturally dynamic double eyelid by fully reserving orbicularis oculi muscle.
Methods:
Incisional double eyelid blepharoplasty were performed on 352 patients. Orbicularis oculi muscle in incisional and pretarsal area were completely preserved. Muscle was elevated from plate by resecting deep muscular myolemma and muscles to form pretarsal myocutaneous flap. Thereafter, the orbital septum was completely exposed. The free end of muscle flap was fixed to a higher position of the levator aponeurosis. The orbital septum was repaired at the same time.
Results:
From June 2009 to December 2017, 352 patients were performed double eyelid blepharoplasty using above technique. They are 337 females and 15 males. Fifty-two patients were followed up for 6-60 months, with the mean time of 27 months. All the incisions were uneventfully healed. The new double eyelid presented smooth appearance, and the so-called " sausage" phenomena were not noticed. There was no concave groove or step-like deformity when eyes closed. Forty-five patients were satisfied with the outcomes. Two patients had shallower supratarsal folds on one side, and 1 patient underwent secondary repair. Two patients complained about asymmetry. Two patients suffered from mild unilateral eyelash eversion (without need of reparation).
Conclusions
The combined application of deep and superficial myolemma release of the orbicularis oculi muscle, and orbital septum reset, could create a double eyelid with natural and dynamic appearance.
8.Expression of miRNA-203 in psoriasis vulgaris skin lesions and its effect on the proliferation of HaCaT cells
Yinghong LIANG ; Ming WEI ; Jia LIU ; Yanjie GONG ; Ling TU ; Yihua ZHANG
Chinese Journal of Dermatology 2017;50(10):719-723
Objective To investigate the expression of miRNA-203 in skin lesions of patients with psoriasis vulgaris,and to explore its effect on the proliferation of a human keratinocyte cell line HaCaT.Methods Lesional skin and adjacent non-lesional skin tissues were obtained from 23 patients with psoriasis vulgaris from 2014 to 2016.Fluorescence-based quantitative PCR was performed to determine the expression of miRNA-203 in these skin tissues.Targeted miRNA in skin tissues was in situ hybridized by using 5'and 3'digoxigenin-labelled probes,so as to localize the expression of miRNA-203 in skin tissues.Cultured HaCaT cells were divided into 3 groups:miRNA-203 mimic group and negative control group transfected with miRNA-203 mimics and negative control miRNA-203 respectively,and blank control group receiving no treatment.Methyl thiazolyl tetrazolium (MTT) assay,flow cytometry and Western blot analysis were performed to investigate changes in cellular proliferative activity,cell cycle and its related proteins Cyclin D1 and Cyclin B1 in HaCaT cells respectively.Results MiRNA-203 was specifically expressed in epidermal keratinocytes.Besides the cell nuclei,it could be expressed in the cytoplasm.In the patients with psoriasis vulgaris,the expression of miRNA-203 was significantly higher in lesional skin tissues than in non-lesional skin tissues (1.35 ± 0.28 vs.0.52 ± 0.09,t =6.76,P =0.012).The transfection with miRNA-203 mimics could significantly inhibit the proliferation of HaCaT cells (F =9.36,P =0.007).Additionally,the blank control group,negative control group and miRNA-203 mimic group all showed a gradual increase in proliferative activity of HaCaT cells over time (F =18.68,P < 0.001).HaCaT cells were arrested in G2/M phase in the miRNA-203 mimic group with the percentage of cells in G2/M phase being 31.33% ± 4.56%,compared to 17.02% ± 3.53% in the negative control group (P < 0.05) and 16.67% ± 3.32% in the blank control group (P < 0.05).Moreover,the miRNA-203 mimic group showed significantly higher protein expression of Cyclin D1 (1.15 ± 0.13),but significantly lower protein expression of Cyclin B1 (0.43 ± 0.08),compared with the negative control group (0.52 ± 0.05,0.93 ± 0.16,respectively,both P < 0.05) and blank control group (0.56 ± 0.07,0.91 ± 0.0.15,respectively,both P < 0.05).Conclusion MiRNA-203 may participate in the occurrence and development of psoriasis vulgaris.
9.Teaching practice and thinking of diagnostic pathology for postgraduates of pathology and patho-physiology
Juan LI ; Yihua CHEN ; Xinlian LIU ; Lushun ZHANG ; Jing SUN ; Cui JIA ; Shurong LI
Chinese Journal of Medical Education Research 2017;16(9):892-895
Some problems are arisen in teaching diagnostic pathology in our college for postgradu-ates of Pathology and Pathophysiology, the students' basic knowledge is weak, the cycle is short, the teaching team and resources are relatively insufficient. To promote the cultivation of graduate students, we should carry out the CBL teaching method, add the clinical practice and training, strengthen the teaching staff, and apply digital section and network platform.
10.Value of early-phase enhancement ratio combined with peripheral vascular diameter in the differential diagnosis of benign and malignant breast lesions under dynamic contrast enhanced ;MRI
Meihong SHENG ; Weixia TANG ; Yihua LU ; Hongbiao JIANG ; Haitao CHEN ; Shenchu GONG ; Jia WU
Chinese Journal of Radiology 2016;50(5):324-328
Objective To investigate the value of early?phase enhancement ratio combined with peripheral vascular diameter in the differential diagnosis of benign and malignant breast lesions using 3.0 T dynamic contrast?enhanced magnetic resonance imaging (DCE?MRI). Methods Sixty seven cases of patients (35 with malignant lesions and 32 with benign lesions in the breasts) were retrospectively analyzed. Their diagnoses were confirmed by surgery and pathology and all the patients underwent breast MRI plain scan and DCE?MRI in the two weeks before surgery. Lesion ROIs were drawn and time?signal intensity curves in the DCE?MRI were generated. Early?phase enhancement rate, time to peak, early?phase enhancement ratio, numbers of tumor vessel within 3 cm of the lesion and diameter of the largest vessel were recorded. Mann?Whitney U test was used to compare the difference of DCE?MRI between benign and malignant lesions, and the ROC curve was used to evaluate the efficiency of early?phase enhancement rate, early?phase enhancement ratio and vascular diameter in differentiating benign and malignant lesions. Results With breast malignant lesions, the medians of time to peak, early?phase enhancement rate, early?phase enhancement ratio, numbers of tumor vessel and vascular diameter were 2.2 s, 176.0%, 100.0%, 4 and 2.96 mm respectively, while with benign lesions of these parameters were 4.7 s, 113.3%, 81.9%, 0 and 0.00 mm respectively, and the differences were statistically significant (all P<0.05).When early?phase enhancement rate was used for differential diagnosis of breast benign and malignant lesions, the area under the ROC curve was 0.702 and the sensitivity and specificity were 82.86%and 56.25%with a threshold of 120.0%. When early?phase enhancement ratio was used, the area under the ROC curve was 0.854 and the sensitivity and specificity were 94.29% and 68.75% with a threshold of 86.0%. When peripheral vascular diameter was used, the area under the ROC curve was 0.896 and the sensitivity and specificity were 74.29%and 84.38% with a threshold of 2.78 mm. When early?phase enhancement ratio was combined with peripheral vascular diameter, the area was 0.925 and the sensitivity and specificity were 97.14% and 62.50%. Conclusion In the differential diagnosis of benign and malignant breast lesions under DCE?MRI, early?phase enhancement ratio combining with peripheral vascular diameter has improved sensitivity.


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