1.Mechanism of Dihuangyin in Treatment of Mice with Atopic Dermatitis by Regulating JAK1/STAT3 Signaling Pathway
Xuening MA ; Juncheng ZHANG ; Teng YU ; Suqing YANG ; Xiaowen WEN ; Shulin JIA ; Suitian WANG ; Jielin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):11-19
ObjectiveTo investigate the effect and potential mechanism of Dihuangyin on 2, 4-dinitrochlorobenzene (DNCB) -induced model mice with atopic dermatitis (AD). MethodA mouse model with AD was established by repeatedly stimulating the back skin of mice with DNCB. After successful modeling, the mice were randomly divided into model group, Runzao group (0.78 g·kg-1), and high, medium, and low dose (40.30, 20.15, and 10.08 g·kg-1) groups of Dihuangyin, with 12 mice in each group, and the blank group consisted of 12 mice, 72 in total. The administration groups were given the corresponding liquid by dose, and the blank group and model group were given the same dose of pure water by intragastric administration, once a day. The skin lesions and scratching times of mice were observed after continuous administration for two weeks. The back skin lesions of mice were stained with hematoxylin-eosin (HE) and toluidine blue to observe the pathology. The contents of serum immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-6 (IL-6), and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of IFN-γ, IL-4, IL-6, Janus kinase 1 (JAK1), and transcriptional activator 3 (STAT3) in skin lesion tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expressions of JAK1, phosphorylation(p)-JAK1, STAT3, and p-STAT3 proteins in skin lesion tissue were detected by Western blot. ResultCompared with the blank group, the back skin of the model group showed large-scale scab, dryness, erosion, hypertrophy with scratching, epidermal hyperplasia with hyperkeratosis and parakeratosis, hyperacanthosis with edema, and a large number of mast cell infiltration in the dermis, some of which were degranulated. The contents of IgE, IL-4, IL-6, and IFN-γ in the serum of mice were significantly increased (P<0.01), and the protein expression levels of p-JAK1, STAT3, and p-STAT3 and mRNA expressions of IL-4, IL-6, IFN-γ, JAK1, and STAT3 in skin lesion tissue were significantly increased (P<0.01). Compared with the model group, only a small amount of dryness and desquamation were observed in the back skin of mice in each administration group, and cell edema was reduced. The inflammatory infiltration was significantly reduced, and the number of mast cell infiltration was significantly decreased. The serum IgE, IL-4, IL-6, and IFN-γ of mice were decreased to varying degrees (P<0.05, P<0.01). The protein expression levels of p-JAK1, STAT3, and p-STAT3 and mRNA expressions of IL-4, IL-6, IFN-γ, JAK1, and STAT3 in skin lesion tissue were significantly decreased, and the effect of high dose group of Dihuangyin was the best (P<0.01). ConclusionDihuangyin can improve skin lesions and pruritus in mice with AD, and its mechanism may be related to the effective regulation of cytokines on the helper T cells (Th1)/Th2 axis by interfering with the JAK1/STAT3 signaling pathway and affecting skin barrier function.
2.Ran-binding protein 9 targets transforming growth factor-β1 expression and induces cell apoptosis in colorectal cancer Colo320 cells
Rubo BAN ; Jielin YANG ; Xiaoyuan WANG ; Xueliang WU ; Yonggang LU
Chinese Journal of Comparative Medicine 2024;34(7):39-47
Objective To investigate the targeting of transforming growth factor β1(TGF-β1)expression by Ran-binding protein 9(RANBP9)and its effect on colorectal cancer Colo320 cell apoptosis.Methods Gene expression levels of RANBP9 were analyzed in 625 colon cancer tissues and 20 normal colon tissues in The Cancer Genome Atlas database.The relationship between RANBP9 expression and survival time of patients with colon cancer was analyzed using KMPLOT.The expression of TGF-β1 in normal colon tissues and colon cancer tissues was analyzed using the human protein immunohistochemistry database and the relationship between TGF-β1 expression and the survival of patients with colon cancer was analyzed using the UALCAN database.The relationship between RANBP9 and TGF-β1 was analyzed by dual luciferase experiments.Colo320 cells were transfected with pcDNA3.1-GFP-RANBP9 and control pcDNA3.1-GFP-RANBP9-NC plasmids,respectively,and normal control cells were established without transfection.The cells were cultured and the growth viability of each group of cells was detected by the iazolyl blue tetrazolium bromide method,apoptosis was detected by flow cytometry,the mitochondrial membrane potential was detected by JC-1 staining,and RANBP9 and TGF-β1 protein expression were detected by Western blot.Results RANBP9 expression was significantly reduced in colon cancer tissues.Compared with patients with low RANBP9 expression,patients with high RANBP9 expression had a higher survival curve and significantly higher expression of TGF-β1 in colon cancer tissue.Compared with patients with high TGF-β1 expression,patients with low TGF-β1 expression had a significantly higher survival curve(P<0.05).RANBP9 targeted the expression of TGF-β1 in colon cancer.Compared with the normal group,cell growth,mitochondrial membrane potential,and TGF-β1 expression were all significantly down-regulated and the apoptosis rate and RANBP9 expression were significantly increased in the experiment group(P<0.05).Conclusions RANBP9 can target the expression of TGF-β1,promote the growth of Colo320 colon cancer cells,decrease the mitochondrial membrane potential,and induce apoptosis.
3.Impacts of TXNIP and KLF9 expressions in colorectal cancer on the clinical characteristics and prognosis of patients
Jielin YANG ; Xiaoyuan WANG ; Xueliang WU
Journal of China Medical University 2024;53(11):1005-1011
Objective To investigate TXNIP and KLF9 expressions in the tissues of colorectal cancer(CRC)and their impact on clini-cal characteristics and prognosis.Methods This study included 90 CRC patients who were admitted to our hospital between January 2017 and December 2020.The cancer tissue and paired adjacent tissues removed surgically were collected.We performed detection and analysis of TXNIP and KLF9 protein expression levels in cancer and adjacent tissues and their correlation with clinical characteristics and overall survival rate of patients.Results GEPIA database analysis showed that TXNIP and KLF9 mRNA expression levels in READ tissues were significantly lower than those in normal tissues(P<0.05).The positive expression rates of TXNIP and KLF9 in CRC tissues were 32.22%and 37.78%,respectively,which were lower than those in adjacent tissues(73.33%and 76.67%,respectively;P<0.05).TXNIP and KLF9 expressions were positively correlated(r=0.519,P<0.05),and GEPIA database retrieval showed a positive correlation between TXNIP and KLF9 expressions(P<0.05).TXNIP and KLF9 expressions in patients with clinical stage Ⅲ and lymph node metas-tasis were lower than those in patients with stage Ⅰ/Ⅱ and non-lymph node metastasis(P<0.05).The overall survival rate of patients with TXNIP and KLF9 expressions was higher than that of patients without TXNIP and KLF9 expressions.Negative expression of TXNIP and KLF9 in TNM stage Ⅲ was a prognostic risk factor(P<0.05).Conclusion TXNIP and KLF9 expression levels are low in CRC tissues and associated with TNM stage,lymph node metastasis,and poor survival.
4.Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis.
Xia XU ; Haiwen LU ; Jianxiong LI ; Jielin DUAN ; Zhongwei WANG ; Jiawei YANG ; Shuyi GU ; Rongguang LUO ; Shuo LIANG ; Wei TANG ; Fengying ZHANG ; Jingqing HANG ; Juan GE ; Xin LIN ; Jieming QU ; Xinming JIA ; Jinfu XU
Chinese Medical Journal 2023;136(16):1949-1958
BACKGROUND:
Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.
METHODS:
A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.
RESULTS:
The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.
CONCLUSION
Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans
;
Aspergillosis, Allergic Bronchopulmonary/complications*
;
Aspergillus fumigatus/genetics*
;
Asthma/genetics*
;
Aspergillus
;
Mutation/genetics*
;
CARD Signaling Adaptor Proteins/genetics*
5.Clinical characteristics of adult Chinese patients with syncope: a multicenter clinical study
Fengjing YANG ; Xu LI ; Peng LIANG ; Zhongmei LIU ; Tong LIU ; Yun WU ; Shuanli XIN ; Gaoxing ZHANG ; Shilin YAN ; Lingping XU ; Lixin WANG ; Bo HU ; Wenwei YUE ; Jielin PU ; Zhichun HUANG ; Rui WANG ; Wen WEN ; Peihong LIN ; Li LI ; Zaixin YU ; Xiaodong WANG ; Xijiu LIU ; Jie ZHANG ; Xiufen QU ; Gary TSE ; Yikun PAN ; Kui HONG ; Jieming ZHU ; Lihua LI ; Wen PAN ; Yong WU ; Min WANG ; Changjun SONG ; Zengshuai WANG ; Jianting DONG ; Xinchun YANG ; Xitian HU ; Fujun WANG ; Wenling LIU
Chinese Journal of Cardiology 2022;50(10):1014-1020
Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.
6.Characteristics of high-resolution magnetic resonance vessel wall imaging of cervicocerebral artery dissection and the influential factors of vascular recanalization.
Jielin OU ; Weihua LIAO ; Shuai YANG
Journal of Central South University(Medical Sciences) 2021;46(5):467-474
OBJECTIVES:
Cervicocerebral artery dissection (CAD) is one of the important causes for ischemic stroke in young and middle-aged people. CAD is dangerous and untimely diagnosis and treatment are likely to result in severe disability. Early diagnosis and timely intervention can greatly improve the prognosis of patients. This study was to investigate the imaging features of CAD on high-resolution magnetic resonance vessel wall imaging (HRMR-VWI) and to analyze the influential factors of vascular recanalization.
METHODS:
A total of 19 CAD patients with both baseline HRMR-VWI and follow-up data of vascular imaging in the period from April 2017 to December 2019 in Department of Radiology, Xiangya Hospital, Central South University were retrospectively analyzed. The diseased vessels were divided into a recovery group and a unrecovered group. After treatment, diseased vessels with no residual arterial dissection and no residual stenosis in the lumen were included in the recovery group. Diseased vessels with stenosis, occlusion or residual dissection were included in the unrecovered group. Diseased vessels were divided into a ischemic stroke group and a non-ischemic stroke group according to the presence or absence of ischemic stroke in the area supplied by the diseased vessels. Differences in clinical data and HRMR-VWI imaging findings were compared between the groups.
RESULTS:
A total of 26 vessels were involved, including 14 (53.8%) internal carotid artery extracranial segment, 8 (30.8%) vertebral artery extracranial segment, 3 (11.5%) vertebral artery intracranial segment, and 1 (3.9%) basilar artery. Ischemic stroke occurred in 16 diseased vascular supply areas. Intramural hematoma was all observed in the baseline HMR-VWI of the affected vessels. There were 18 vessels (69.2%) in the recovery group and 8 vessels (30.8%) in the unrecovered group. Compared with the vessels in the recovery group, the vessels in the unrecovered group were mostly found in the intracranial segment (
CONCLUSIONS
Intramural hematoma is a common imaging manifestation of CAD and can be shown clearly and accurately on HRMR-VWI. Recanalization rate of CAD is high, and the recanalization of CAD in intracranial segment is slower than that of CAD in extracranial segment, which can prolong the review time.
Basilar Artery
;
Dissection
;
Humans
;
Magnetic Resonance Angiography
;
Magnetic Resonance Imaging
;
Magnetic Resonance Spectroscopy
;
Middle Aged
;
Retrospective Studies
;
Stroke
7.Virulence-associated gene detection and analysis of Staphylococcus aureus isolates from pediatric patients′ feces
Xiaolan AI ; Yan LONG ; Bingshao LIANG ; Shuwen YAO ; Yunfeng LIU ; Fei GAO ; Jialiang MAI ; Zhile XIONG ; Zhuwei LIANG ; Jielin WANG ; Xiantang CHEN ; Min YANG ; Sitang GONG ; Zhenwen ZHOU
Chinese Journal of Laboratory Medicine 2021;44(4):291-297
Objective:To investigate the multilocus sequence typing feature of the virulence-associated genes of Staphylococcus aureus(S. aureus) separated from the clinical specimens of a multi-center cohort children in Guangzhou area. Methods:A total number of 412 Staphylococcus aureus strains isolated from 2 059 non-repeated fecal specimens of children by three groups′ researchers in Guangzhou Women and Children′s Medical Center from August 2018 to November 2018. While collecting specimens, patient clinical information is also properly collected and preserved. After extracting the DNA of the strain, the virulence-associated genes were detected by polymerase chain reaction (PCR), including the staphylococcal enterotoxin (SE) genes ( sea, seb, sec, sed, see) and the Panton-Valentine leucocidin-encoding gene ( pvl).The multi-locus sequence typing (MLST) method was performed to reveal the MLST feature of these genes and the statistical difference were examined by the the χ 2 test. Results:Among the 412 isolates of S. aureus, 256 strains (256/412, 62.1%) contains at least one SE gene. Among the enterotoxin gens, the sec (125/412, 30.3%), seb(98/412, 23.8%)and sea (66/412, 16.0%)genes were the three most prevalent members of SEs. The frequency of pvl gene in Staphylococcus aureus was 18.7%(77/412).Among them, the frequency of Staphylococcus aureus sea gene isolated from patients with gastroenteritis (58/319, 18.2%) was significantly higher than that from the non-gastroenteritis group (8/93, 8.6%)(χ2=4.912, P=0.027). The frequency of Staphylococcus aureus pvl gene isolated from the patients with pneumonia (8/21, 38.1%) was greater than that from the non-pneumonia group (6/47, 12.8%)(χ2=4.252, P=0.039). In addition, the virulence-associated gene of S. aureus was closely related to the specific ST type, 82.4% (28/34) of ST6 carried sea gene, all ST338 and ST59 carried seb gene, 96% (48/50) ST45 carried sec gene, and the pvl gene carrying rate of ST338 was 5/5. Conclusions:The SEA toxin produced by ST6 Staphylococcus aureus may be closely related to the diagnosis of gastroenteritis in children. The frequency of pvl virulence gene in Staphylococcus aureus in children with community-acquired pneumonia was higher than that in the non-pneumonia group, and closely related to the CC59.
8.Relationship between the Red Cell Volume Distribution Width in Patients with Gestational Diabetes and Insulin Resistance
Fei GAO ; Hongling YANG ; Jielin WANG ; Xiurong GAO ; Yan LONG ; Hao ZHENG ; Xiaojuan CHEN
Journal of Modern Laboratory Medicine 2017;32(1):66-68
Objective To explore the relationship between the red cell volume distribution width (RDW)in patients with ges-tational diabetes and insulin resistance(IR).Methods A total number of 160 pregnancies performed in Guangzhou Women and Children’s Medical Center from January to October 2016.Matching 80 patients with gestational diabetes (the GDM Group)with 80 healthy pregnancies according to their age,gestational weeks and times.Their inflammatory parameters (hs-CRP,neutrophil-to-lymphocyte ratio,RDW)were respectively examined.HOMA-IR was calculated by testing the level of FBG and FIns.The association of the red cell volume distribution width with insulin resistance was analyzed.Results The level of four inflammatory parameters (hs-CRP,WBC,neutrophil-to-lymphocyte ratio,RDW)were significantly higher than that the control group (t=5.695,5.232,3.337,7.814,all P<0.01).Pearson correlated analysis suggested that RDW had positive correlation with HOMA-IR (r=0.58,P<0.01).Conclusion The RDW level were elevated in the GDM patients and had positive correlation with HOMA-IR,which indicated that IR was associated with inflammation and provided proof to research mechanism of GDM.
9.Predictive Value of Electrocardiogram Abnormality on Prognosis of Chronic Heart Failure in Patients With Dilated Cardiomyopathy
Jie YANG ; Cuihong HOU ; Zhouying LIU ; Lan REN ; Xinggou SUN ; Jielin PU
Chinese Circulation Journal 2016;31(3):218-222
Objective: To study the predictive value of 12-lead electrocardiogram (ECG) abnormality on prognosis of chronic heart failure in patients with dilated cardiomyopathy (DCM-CHF).
Methods: A prospective, multicenter follow-up study in 787 DCM-CHF patients was conducted, and the endpoints were obtained by clinical visit, mail contact and telephone conversation. The independent predictors for all cause death were determined by Cox regression analysis, QRS duration > 120 ms was studied and the survival rates were investigated by Kaplan-Meier analysis.
Results: There were 203 patients died during the follow-up period. Cox regression analysis found that the following indexes were related to all cause death: atrial fibrillation (AF) (HR=2.064, 95% CI 1.102-3.864,P<0.05), non-sustained ventricular tachycardia (NSVT) (HR=3.887, 95% CI 1.554-9.724,P<0.05) and QRS duration (HR=1.010, 95% CI 1.002-1.018, P<0.05). Kaplan-Meier analysis revealed that the survival rates were different by each stratiifcation of QRS duration,P<0.05.
Conclusion: ECG indexes of AF, NSVT and QRS duration had the important impact on the survival rate in DCM-CHF patients; there were signiifcant differences between QRS durations and survival rates.
10.In vitro biocompatibility of polyhydroxybutyrate-co-volerate membrane with human bone marrow mesenchymal stem cells
Tao ZHANG ; Zhixu HE ; Chuan YE ; Jielin LIU ; Minxian MA ; Bo SUN ; Mei WANG ; Hua YANG
Chinese Journal of Tissue Engineering Research 2014;(12):1920-1925
BACKGROUND:Polyhydroxybutyrate-co-volerate (PHBV) is a noticeable tissue engineering material of polyhydroxyalkanoates family. It has the properties of low immune rejection response and good biocompatibility, and its degradation products are non-toxic.
OBJECTIVE:To investigate the biocompatibility of PHBV membrane material and human bone marrow mesenchymal stem cel s in vitro.
METHODS:Human bone marrow mesenchymal stem cel s at passage 3 were seeded upon PHBV membrane as experimental group and upon conventional culture plates as control group. Then we calculated the adherent cel number of two groups at 1, 2 and 4 hours and got the cel adherent rate. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay was used at days 2, 4, 6, 8 to observe the cel proliferation of two groups. Fluorimetric method with the fluorescent dye Hoechst 33258 was used to detect the DNA content of cel s at days 3, 6, 9 and 12 in both groups. After cel s were seeded upon PHBV membrane for 5 days, the cel growth upon the material was examined under a scanning electron microscope.
RESULTS AND CONCLUSION:When the cel s were cultured for 1 hour, the adherent rate in the experimental group was lower than that in the control group;but there were no significant differences between two groups at the other two periods. No difference was found in the cel proliferation and the DNA content between the two groups. Human bone marrow mesenchymal stem cel s seeded upon PHBV membrane for 5 days grew wel with spindle morphology and the intercel ular connections were tight and more extracel ular matrices were observed by scanning electron microscopy. Taken together, PHBV membrane material shows a good biocompatibility with human bone marrow mesenchymal stem cel s.

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