1.Protective Effect of Taohong Siwutang on Cerebral Ischemia-reperfusion Injury Based on A1/A2 Phenotype Transformation of Astrocytes Mediated by JAK2/STAT3 Pathway
Huifang WANG ; Xinru CHEN ; Mengyuan CHEN ; Xian ZHOU ; Lan HAN ; Weidong CHEN ; Zhaojie JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):25-34
ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion (CIRI) injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups: A sham operation group, a model group, Taohong Siwutang treatment groups (low dose, medium dose, and high dose), ligustrazine phosphate tablet (LPT) group, and AG490 group. All groups, except for the sham operation group, underwent middle cerebral artery occlusion/reperfusion (MCAO/R) modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 (C3), S100 calcium-binding protein A10 (S100A10), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3). Additionally, protein expression levels of vascular endothelial growth factor-A (VEGF-A) were assessed, and the mRNA expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were evaluated. Glial fibrillary acidic protein (GFAP) and C3, S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly, VEGF expression levels were measured using enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham operation group, the model group showed a significant increase in cerebral infarction volume and neurological impairment (P<0.01). C3 protein levels were elevated, while S100A10 levels were decreased. Pathway-related markers were significantly upregulated (P<0.05, P<0.01), and VEGF-A protein levels were significantly reduced (P<0.01). The mRNA expression of inflammatory factors was significantly upregulated (P<0.01). Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity (P<0.01) and greatly decreased GFAP and S100A10 fluorescence intensity (P<0.01). Additionally, VEGF content was significantly elevated (P<0.01). Compared with the model group, medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment (P<0.01). Groups treated with low, medium, and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels (P<0.01). In the high-dose Taohong Siwutang and AG490 groups, both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated (P<0.05, P<0.01), while S100A10 expression and VEGF-A protein levels were significantly increased (P<0.01). Additionally, the mRNA expression levels of inflammatory factors were significantly reduced (P<0.01). The co-localization fluorescence intensity of GFAP and C3 significantly decreased (P<0.01), while that of GFAP and S100A10 greatly increased (P<0.01). Furthermore, VEGF content exhibited a marked elevation (P<0.01). ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway, promotion of A2-type astrocyte polarization, reduction of inflammatory factor release, and enhancement of VEGF production.
2.Protective Effect of Taohong Siwutang on Cerebral Ischemia-reperfusion Injury Based on A1/A2 Phenotype Transformation of Astrocytes Mediated by JAK2/STAT3 Pathway
Huifang WANG ; Xinru CHEN ; Mengyuan CHEN ; Xian ZHOU ; Lan HAN ; Weidong CHEN ; Zhaojie JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):25-34
ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion (CIRI) injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups: A sham operation group, a model group, Taohong Siwutang treatment groups (low dose, medium dose, and high dose), ligustrazine phosphate tablet (LPT) group, and AG490 group. All groups, except for the sham operation group, underwent middle cerebral artery occlusion/reperfusion (MCAO/R) modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 (C3), S100 calcium-binding protein A10 (S100A10), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3). Additionally, protein expression levels of vascular endothelial growth factor-A (VEGF-A) were assessed, and the mRNA expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were evaluated. Glial fibrillary acidic protein (GFAP) and C3, S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly, VEGF expression levels were measured using enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham operation group, the model group showed a significant increase in cerebral infarction volume and neurological impairment (P<0.01). C3 protein levels were elevated, while S100A10 levels were decreased. Pathway-related markers were significantly upregulated (P<0.05, P<0.01), and VEGF-A protein levels were significantly reduced (P<0.01). The mRNA expression of inflammatory factors was significantly upregulated (P<0.01). Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity (P<0.01) and greatly decreased GFAP and S100A10 fluorescence intensity (P<0.01). Additionally, VEGF content was significantly elevated (P<0.01). Compared with the model group, medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment (P<0.01). Groups treated with low, medium, and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels (P<0.01). In the high-dose Taohong Siwutang and AG490 groups, both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated (P<0.05, P<0.01), while S100A10 expression and VEGF-A protein levels were significantly increased (P<0.01). Additionally, the mRNA expression levels of inflammatory factors were significantly reduced (P<0.01). The co-localization fluorescence intensity of GFAP and C3 significantly decreased (P<0.01), while that of GFAP and S100A10 greatly increased (P<0.01). Furthermore, VEGF content exhibited a marked elevation (P<0.01). ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway, promotion of A2-type astrocyte polarization, reduction of inflammatory factor release, and enhancement of VEGF production.
3.Model of "One Core, Multiple Elements" emergency blood donation volunteer team: a case study of Nanjing city
Shangyun YING ; Yudong DAI ; Yilun ZHAO ; Shijie ZHOU ; Huifang ZHOU
Chinese Journal of Blood Transfusion 2024;37(1):84-90
【Objective】 To explore the model of "One Core, Multiple Elements" emergency blood donation volunteer team (referred to as the Model) . 【Methods】 The Nanjing City Voluntary Blood Donation Joint Meeting serves as the core, with diverse entities including party committees, government departments, district governments, social organizations, enterprises, blood donors, etc. Following the principles of "emergency response in emergencies, wartime readiness, combining regular and wartime efforts," and adhering to the framework of the Model, the emergency blood donation volunteer team system in Nanjing was constructed. 【Results】 1) After the construction of the Model (2018—2022), the total number of emergency blood donation volunteers in Nanjing City increased by 191% compared to the pre-construction period (2013—2017), with an average annual blood donation of 20 929, showing significant differences (P<0.05). 2) After the construction of the Model, the number of emergency blood donation during the winter and summer increased by 206% and 185%, respectively, compared to the pre-construction period, demonstrating significant differences (P< 0.05) .3) Prior to the construction of the Model, Nanjing lacked a relatively stable emergency volunteer team. After the construction, Nanjing established a total of 5 relatively stable volunteer teams, with the district-level government and township personnel accounting for the highest proportion (52.96%), followed by medical personnel (23.95%), enterprise team (11.10%), State-owned Assets Supervision and Administration Commission team (7%), and Nanjing municipal government team (4.98%). 4) Following the Model, during the COVID-19 pandemic, Nanjing successfully initiated two Level Ⅱ blood emergency responses, with emergency blood donations reaching 23 041. 【Conclusion】 The Model can effectively ensure the blood supply in Nanjing region during emergencies.
4.Mechanism of differential involvement of muscle groups in the retrobulbar tissue of thyroid eye disease
Shihan SONG ; Caoxu ZHANG ; Runchuan LI ; Yue ZHANG ; Fengyao WU ; Huaidong SONG ; Qin SHEN ; Huifang ZHOU
Chinese Journal of Endocrinology and Metabolism 2024;40(3):242-247
Objective:The degree of involvement of extraocular muscles varies across different regions of retrobulbar tissue in patients with thyroid eye disease, but the mechanism is unclear. This study aims to explore the relationship between differential expression of thyroid-stimulating hormone receptor(TSHR) in different parts of the extraocular muscles and the varying degrees of muscle involvement.Methods:The medial, lateral, superior, and inferior rectus muscle were separated from the retrobulbar tissue of rats, and the expression level of TSHR in four extraocular muscles was detected by immunofluorescence and qPCR. Extraocular muscle tissue of patients with strabismus was collected to detect the expression of TSHR and the cell types expressed by fluorescence.Results:The results of qPCR showed that the expression of TSHR in the medial rectus muscle was significantly higher than that in the lateral, superior, and inferior rectus muscle(medial rectus vs lateral rectus, P=0.012; medial rectus vs superior rectus, P=0.015; medial rectus vs inferior rectus, P=0.013), but there was no difference in insulin-like growth factor 1(IGF-1R) expression. Immunofluorescence showed that TSHR was co-expressed with PAX7, a molecular marker of muscle satellite cells, and the expression level in the medial rectus muscle of rats and humans was significantly higher than those in the other three extraocular muscles. Conclusion:The high specific expression of TSHR in the satellite cells of the medial rectus muscle may be the reason why the medial rectus muscle is most susceptible to involvement in thyroid eye disease.
5.Analysis and summary of clinical characteristics of 289 patients with paroxysmal nocturnal hemoglobinuria in Zhejiang Province
Gaixiang XU ; Weimei JIN ; Baodong YE ; Songfu JIANG ; Chao HU ; Xin HUANG ; Bingshou XIE ; Huifang JIANG ; Lili CHEN ; Rongxin YAO ; Ying LU ; Linjie LI ; Jin ZHANG ; Guifang OUYANG ; Yongwei HONG ; Hongwei KONG ; Zhejun QIU ; Wenji LUO ; Binbin CHU ; Huiqi ZHANG ; Hui ZENG ; Xiujie ZHOU ; Pengfei SHI ; Ying XU ; Jie JIN ; Hongyan TONG
Chinese Journal of Hematology 2024;45(6):549-555
Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.
6.Long-term hypomethylating agents in patients with myelodysplastic syndromes: a multi-center retrospective study
Xiaozhen LIU ; Shujuan ZHOU ; Jian HUANG ; Caifang ZHAO ; Lingxu JIANG ; Yudi ZHANG ; Chen MEI ; Liya MA ; Xinping ZHOU ; Yanping SHAO ; Gongqiang WU ; Xibin XIAO ; Rongxin YAO ; Xiaohong DU ; Tonglin HU ; Shenxian QIAN ; Yuan LI ; Xuefen YAN ; Li HUANG ; Manling WANG ; Jiaping FU ; Lihong SHOU ; Wenhua JIANG ; Weimei JIN ; Linjie LI ; Jing LE ; Wenji LUO ; Yun ZHANG ; Xiujie ZHOU ; Hao ZHANG ; Xianghua LANG ; Mei ZHOU ; Jie JIN ; Huifang JIANG ; Jin ZHANG ; Guifang OUYANG ; Hongyan TONG
Chinese Journal of Hematology 2024;45(8):738-747
Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.
7.The Effect of Bushen Zhuyun Decoction on Treg,Th17 and Their Related Factors in Luteal Phase Defect Infertility Rats
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(2):129-136
OBJECTIVE To investigate the effects of Bushen Zhuyun Decoction(BSZYD)on regulatory T cells(Treg),helper T cell 17(Th17)and related factors in rat with luteal phase defect(LPD)infertility.METHODS Rats were administered mifepris-tone mixture(10 mL·kg-1)to construct the LPD-induced infertility model.The positive drug dydrogesterone mixture(0.02 g·kg-1)and low(4.5 g·kg-1),medium(9 g·kg-1),and high(18 g·kg-1)doses of BSZYD were given for intervention.Uterine tissue morphology of the rat was evaluated by HE staining;the ratio of Treg and Th17 and related factor contents in rat peripheral blood were detected by flow cytometry and ELISA;the protein and mRNA expression levels of Treg and Th17 cell tran-scription factors were detected by Western blot and qPCR.RESULTS Compared with the blank group,the endometrial thickness of the model group significantly decreased(P<0.01),the proportion of Treg and the content of the anti-inflammatory factor interleukin-10(IL-10)reduced significantly(P<0.01),the percentage of Th17 cells and the inflammatory factor interleukin-17A(IL-17A)were significantly increased(P<0.01),the protein and mRNA expression levels of FOXP3 were inhibited(P<0.05,P<0.001),the RORγT protein and mRNA levels were higher(P<0.01,P<0.001).Compared with the model group,the dydrogesterone and mid-dle-and high-dose BSZYD could increase endometrial thickness(P<0.05,P<0.01),promoting the proliferation and development of endometrial glands;the percentage of Treg cells and IL-10 content increased significantly(P<0.01,P<0.001),the percentage of Th17 cells decreased significantly(P<0.01,P<0.001),and FOXP3 protein expression was increased(P<0.01,P<0.001);IL-17A content and RORγT protein expression were decreased in the middle and high-dose BSZYD groups(P<0.05,P<0.01);the FOXP3 mRNA levels in the dydrogesterone group and the high-dose BSZYD group were significantly increased(P<0.01,P<0.001),and the expression of RORγT mRNA was down-regulated(P<0.001).CONCLUSION BSZYD can regulate the immune balance of Treg and Th17 cells in LPD-infertility rats and improve endometrial receptivity.
8.Analysis of genetic etiology in a patient with 1p36 deletion syndrome in conjunct with Snijders Blok-Campeau syndrome
Huifang CHEN ; Chuan ZHANG ; Bingbo ZHOU ; Yupei WANG ; Xue CHEN ; Ling HUI
Chinese Journal of Medical Genetics 2024;41(3):363-367
Objective:To explore the genetic basis for a patient with unexplained developmental delay and special facial features.Methods:A male patient admitted to the Maternal and Child Health Care Hospital of Gansu Province on May 27, 2021 due to infertility was selected as the study subject. Clinical data of the patient was collected, and genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing.Results:The patient was found to harbor a 2.54 Mb deletion in 1p36.33p36.32 and a heterozygous c. 1123G>C (p.E375Q) variant of the CHD3 gene, neither of which was detected in his parents. Conclusion:The patient was diagnosed with Snijders Blok-Campeau syndrome in conjunct with 1p36 deletion syndrome, which has enabled genetic counseling for his family.
9.Focusing on clinical activity score of thyroid eye disease suitable for Chinese population
Chaoyu LEI ; Hui WANG ; Jing SUN ; Huifang ZHOU
Chinese Journal of Experimental Ophthalmology 2024;42(11):977-982
Thyroid eye disease (TED) is an orbital disease closely associated with thyroid disorders, with 25%-50% of patients with diffuse toxic goiter (Graves Disease) developing secondary TED, which can lead to blindness and disability and significantly impair patients' visual function and quality of life.Activity staging is a crucial assessment index for TED and is essential for clinical evaluation, treatment planning, and prognosis.The Clinical Activity Score (CAS) is currently the most widely used method for this purpose both domestically and internationally.To improve the accuracy and consistency of CAS evaluations, the European Group of Graves' Orbitopathy (EUGOGO) recommended the use of a CAS scoring atlas in the TED guidelines.However, existing atlases are primarily based on Caucasians.Considering the anatomical differences in the orbit between Chinese and Caucasians and the resulting divergent ocular characteristics, there is a need for a comprehensive interpretation of the CAS scoring details in the current guidelines.This should be followed by further refinement to tailor the CAS scoring criteria to Chinese patients with TED.Such measures will standardize the operational methods and judgment criteria of CAS scoring in China, thereby providing a reliable basis for the accurate diagnosis and treatment of the disease.
10.Meta-analysis of risk factors for perioperative malnutrition among aged fracture patients
Zhiqiang HE ; Wenbin WU ; Zihan LIN ; Jin LI ; Jing WANG ; Xiaoling ZHOU ; Huifang ZHANG
Chinese Journal of Modern Nursing 2024;30(20):2743-2750
Objective:To systematically evaluate the risk factors for perioperative malnutrition in aged fracture patients.Methods:A comprehensive search of databases including CNKI, WanFang, VIP, SinoMed, Web of Science, Embase, PubMed, and CINAHL was conducted to identify relevant studies on risk factors for perioperative malnutrition in aged fracture patients from inception to May 10, 2023. Additional grey literature was identified by snowball sampling and manual searches. Two postgraduate students trained in evidence-based nursing independently screened the literature, extracted data, and assessed the methodological quality of the studies. Meta-analysis was performed using RevMan 5.4 software.Results:Fourteen original studies were included, covering 46 risk factors for malnutrition. Meta-analysis of factors reported in at least two studies indicated that age≥ 70 years, low body mass index, low hemoglobin, preoperative hypoalbuminemia, female, physical inactivity, non-home residence, low self-care ability, intertrochanteric fracture, chronic obstructive pulmonary disease, chronic gastritis, dementia/cognitive decline, cancer, stroke, chronic heart failure, multiple chronic diseases, high Charlson Comorbidity Index, weight loss, depression, American Society of Anesthesiologists classification≥Ⅲ, taking multiple medications≥ 4 types, and longer hospital stays all increased the incidence of perioperative malnutrition in aged fracture patients ( P< 0.05) . Conclusions:The incidence of perioperative malnutrition in the aged fracture population is high and influenced by multiple factors. This highlights the need for healthcare providers to conduct dynamic and precise nutritional screenings for high-risk patients and to implement personalized perioperative nutritional management to prevent malnutrition and promote rapid recovery in aged fracture patients.

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