1.PDGF-C: an Emerging Target in The Treatment of Organ Fibrosis
Chao YANG ; Zi-Yi SONG ; Chang-Xin WANG ; Yuan-Yuan KUANG ; Yi-Jing CHENG ; Ke-Xin REN ; Xue LI ; Yan LIN
Progress in Biochemistry and Biophysics 2025;52(5):1059-1069
Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.
2.Application of extraocular muscle related indexes combined with serum Th1 cytokine levels in the diagnosis of thyroid associated ophthalmopathy
Jun DU ; Jiakai LIU ; Ke XU ; Jing LI ; Chunmei ZHOU ; Jin ZHU
International Eye Science 2025;25(12):2022-2027
AIM: To evaluate the diagnostic value of serum Th1-type cytokine levels and extraocular muscle-related parameters in thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective study was conducted on 45 patients diagnosed with TAO in our hospital from January 2023 to December 2024, and 20 normal volunteers during the same period as controls. Venous blood samples of the patients were collected to detect the concentrations of Th1-type cytokines [interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), and interleukin-12(IL-12)] in the serum. Additionally, the end diastolic velocity(Ved), velocity maximum(Vmax), resistance index(RI)of the central retinal artery, as well as the thickness and left-right diameter of the medial rectus muscle were measured. Logistic regression model was used to analyze the risk factors of TAO, and receiver operating characteristic curve(ROC)was adopted to evaluate the diagnostic efficacy of each index for the occurrence of TAO.RESULTS: The general information of the two groups was comparable. Compared with the normal control group, the serum concentrations of IFN-γ and TNF-α in TAO patients were significantly increased, Ved and Vmax were lower than those in the control group, and RI and the thickness of the medial rectus muscle were higher than those in the control group(all P<0.05). Logistic regression analysis showed that serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle were all risk factors for TAO. ROC curve analysis indicated that the AUCs of serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle for the diagnostic efficacy of TAO were 0.756, 0.769, 0.732, and 0.642, respectively. The combined detection of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle had an AUC of 0.840 and a Youden index of 0.59, which was superior to the detection of a single indicator.CONCLUSION: The levels of serum Th1-type cytokines and extraocular muscle-related ultrasound indicators have certain value in the diagnosis of TAO. The combination of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle has better diagnosis efficiency in TAO, which can provide a certain reference for the early diagnosis of TAO.
3.Research on the application of short video scenery teaching method in the teaching of cardiology interns
Ran JING ; Ying HUANG ; Yali OU ; Yixia ZHAO ; Lingfang LI ; Ke XIA
Chinese Journal of Medical Education Research 2024;23(5):667-670
Objective:To explore the application of short video situational teaching based on clinical pathway management cases in cardiology internship teaching.Methods:30 medical students who were interned in the Department of Cardiology of Xiangya Hospital of Central Souty University from June 2020 to May 2021 were selected as the control group, using traditional clinical teaching mode, and another 30 medical students from June 2021 to May 2022 were selected as the observation group. Short video situational teaching based on clinical pathway management cases was used to compare the performance evaluation results, satisfaction evaluation results, teaching effectiveness, improvement of critical thinking ability, and teaching method evaluation results of the two groups of students. Perform chi square test and t-test using SPSS 20.0. Results:The results showed that the performance of the observation group students in the entrance examination [theoretical: (88.25±5.14) vs. (80.23±5.34); operational: (90.36±5.23) vs. (86.58 ± 5.12)] was better than that of the control group, and the difference was statistically significant; The observation group showed statistically significant differences in teaching effectiveness compared to the control group ( P<0.05); The critical thinking ability score of the observation group students was better than that of the control group ( P<0.05); The observation group students rated the teaching methods higher ( P<0.05). Conclusions:The use of situational teaching in cardiology internships can enhance the critical thinking ability of medical students, meet clinical needs, and is worth promoting in diagnostic teaching.
4.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
5.Antibiotic bone cement covered reconstruction plate for infected anterior pelvic ring fractures
Meng LI ; Ke-Jing WANG ; Zhen-Yang GAO ; Yun-Fei XIE ; Tao GUO
China Journal of Orthopaedics and Traumatology 2024;37(5):451-457
Objective To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.Methods From January 2017 to March 2022,11 patients with infected ante-rior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 fe-males and the age ranged from 27 to 49 years old.The pelvic fractures were classified according to the Tile typology:4 cases of Cl type,4 cases of C2 type,and 3 cases of C3 type.Among them,2 cases of infected anterior ring were infected after internal fixation of anterior ring,and 9 patients were infected with infected anterior ring due to incomplete early debridement,which was classified as infected according to the injury severity score(ISS)for 24 to 38 scores.The anterior ring was internally fixed by extended debridement,irrigation,and antibiotic bone cement covered reconstruction plate,and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws.Results All 11 cases obtained follow-up from 13 to 20 months.A-mong them,2 patients had recurrence of postoperative infection,1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation,and 1 case had a milder infection without accumulation of the medullary cavity,and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting.Two cases developed incisional oozing,which healed after removal of the internal fixation three months postoperatively.All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period.All 11 cases eventually healed bony.At the final follow-up,according to the Matta score,the fracture reduction was excellent in 6 cases,good in 4,and possible in 1.According to the Majeed functional score,it was excellent in 6,good in 3,and possible in 2.Conclusion Antibiotic bone cement covered reconstruction plate is ef-fective in the treatment of infected anterior pelvic ring fracture,with high intraoperative safety and low recurrence rate of infec-tion,which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.
6.Calcium binding protein S100A4 inhibitor Niclosamide regulates inflammatory response of bronchial epithelial cells
Ke CHEN ; Shihui MO ; Shirong YAN ; Jing LI ; Tongqian WU ; Fang YU
Chinese Journal of Immunology 2024;40(11):2262-2266,2272
Objective:To investigate potential mechanisms of Niclosamide,a calcium-binding protein S100A4 inhibitor,in regulating inflammatory response of bronchial epithelial cells.Methods:Human bronchial epithelial cells BEAS-2B were cultured in vitro and stimulated by LPS or Niclosamide-pretreatment.Inflammatory cytokines and potential signaling molecules expressions were determined by RT-qPCR and Western blot.Intracellular ROS level was quantified by fluorescent probe.Results:Increased ROS level was observed in LPS-stimulated and Niclosamide-pretreatment cells(P<0.05).Compared with control group,mRNA and protein expressions of S100A4 were increased(P<0.05),TLR4/STAT3,MAPK1/3/SIRT1,NF-κB/IKKβ/p65 mRNA expressions were increased(P<0.05),inflammatory cytokines IL-1β and IL-6,tight junction Occludin and ZO-1 mRNA expressions were increased after LPS-treatment(P<0.05),whereas these genetic expressions were downregulated by Niclosamide-pretreatment(P<0.05),except for TLR4/MAPK1 and NF-κB/IKKβ/p65(P>0.05).Western blot showed that compared with control group,LPS-stimulation promoted protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while downregulated protein expression of Occludin.Compared with LPS group,niclosamide-pretreatment downregulated protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while restored protein expression of Occludin(P<0.05).Conclusion:Calcium-binding protein S100A4 inhibitor Niclosamide can alleviate S100A4 expression and inflammatory response of bronchial epithelial cells,which is poten-tially related to STAT3 or MAPK3/SIRT1 signaling.
7.Analysis of the efficacy of enteral nutrition combined with step-up drainage in the treatment of acute necrotizing pancreatitis complicated by duodenal fistula
Jingzhu ZHANG ; Gang LI ; Jing ZHOU ; Bo YE ; Lu KE ; Zhihui TONG ; Weiqin LI
Chinese Journal of General Surgery 2024;33(9):1473-1480
Background and Aims:The occurrence of duodenal fistula following infected pancreatic necrosis(IPN)in the later stage of treatment for acute necrotizing pancreatitis presents a significant clinical challenge.It often leads to severe complications such as difficulty in administering enteral nutrition,electrolyte imbalances,abdominal bleeding,and worsening infections.This study was performed to explore the efficacy of enteral nutrition combined with step-up drainage in treating IPN complicated by duodenal fistula and to share single-center experience. Methods:The clinical data of 66 patients with IPN complicated by duodenal fistula who underwent enteral nutrition combined with step-up drainage in the Severe Pancreatitis Treatment Center of the Nanjing Eastern Theater General Hospital between January 2018 and December 2020 were retrospectively analyzed. Results:Among the 66 patients,the median time from disease onset to the development of duodenal fistula was 53(32-75)d.In 46 cases(69.7%),suspicious digestive fluid-like discharge was observed from drainage tube or double-lumen tube.The diagnosis and location of the duodenal fistula were confirmed in 49 patients(74.2%)through fistulography,while the remaining cases were confirmed via surgical exploration or endoscopy.The duodenal fistulas were mainly located in the horizontal part(33.3%)or descending part(50.0%)of the duodenum.Nutritional access was safely established through nasojejunal tube in 61 patients(92.4%),while 5 patients(7.6%)required surgery to establish the access.Twenty patients(30.3%)experienced secondary abdominal bleeding,and 14 patients(21.2%)died.Among the 52 patients who recovered,49(94.2%)healed through step-up drainage,while 3(5.8%)required surgery due to delayed healing.Of the 49 patients who underwent non-surgical treatment,10(20.4%)achieved fistula closure through drainage tube,and 39(79.6%)achieved closure through continuous lavage drainage via double-lumen tube.The median healing time for duodenal fistula in non-surgically treated patients was 41(29-80)d. Conclusion:Patients with IPN complicated by duodenal fistula are in a critical condition.Enteral nutrition combined with step-up drainage is an effective treatment for these patients.
8.Application of 18F-AlF-P16-093 PET combined with multiparametric MRI in the diagnosis of primary prostate cancer lesions: a head-to-head comparative study based on needle biopsy pathology
Miao KE ; Jinhui LIU ; Shaonan ZHONG ; Jing ZHANG ; Mingzhao LI ; Di GU ; Ruiyue ZHAO ; Xinlu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(9):533-538
Objective:To evaluate the diagnostic efficacy of the novel prostate specific membrane antigen (PSMA)-targeted PET imaging agent 18F-AlF-P16-093 in combination with multiparametric MRI (mpMRI) for prostate cancer (PCa), and to explore its application in guiding transperineal puncture biopsy. Methods:A retrospective analysis was conducted on the clinical and pathological data of 36 patients diagnosed as PCa (age: 68-76 years) who underwent 18F-AlF-P16-093 PET/CT and mpMRI examinations at the First Affiliated Hospital of Guangzhou Medical University from August 2023 to March 2024. The entire prostate was divided into 12 regions based on biopsy localization. Imaging evaluations were performed using PET/CT and mpMRI at the lesion level, with biopsy pathology as the gold standard. The correlations between mpMRI scores, PET/CT scores and pathological diagnosis results were evaluated by Phi coefficient analysis. Diagnostic efficacy was assessed by ROC curve analysis. Logistic regression was used to determine the impact of bleeding on image interpretation. Results:18F-AlF-P16-093 PET/CT showed a moderate positive correlation with pathological diagnosis result ( Phi=0.415, P<0.001), which was superior to mpMRI ( Phi=0.338, P<0.001). The diagnostic efficacy of PET single-modality model was superior to mpMRI in all indicators. The combination of 18F-AlF-P16-093 PET/CT with mpMRI significantly improved diagnostic specificity and positive predictive value, with the diagnostic specificity of the PET+ T 2 weighted imaging (WI)+ diffusion WI (DWI) and PET+ T 2WI+ DWI+ apparent diffusion coefficient (ADC) combinations exceeding 90%, and the positive predictive value exceeding 80%. Bleeding did not significantly affect the diagnosis of PCa by mpMRI and PET/CT (odds ratio ( OR): 0.463-0.785, all P>0.05). Conclusion:18F-AlF-P16-093 PET/CT is superior to mpMRI in the detection and diagnostic efficacy of PCa lesions, and the combination of 18F-AlF-P16-093 PET with mpMRI can further improve diagnostic specificity and positive predictive value, which is of guiding significance for targeted prostate biopsy.
9.Clinical and immunoserological characteristics of 26 cases of linear IgA bullous dermatosis: a retrospective analysis
Ke JING ; Suo LI ; Suying FENG
Chinese Journal of Dermatology 2024;57(6):503-509
Objective:To investigate clinical, immunoserological, and therapeutic characteristics of patients with linear IgA bullous dermatosis (LABD) .Methods:Clinical data were collected from patients with LABD in Hospital of Dermatology, Chinese Academy of Medical Sciences from 2016 to 2023, and their clinical, immunoserological, and therapeutic characteristics were retrospectively analyzed.Results:Twenty-six patients were included, comprising 12 males and 14 females, with a median age ( Q1, Q3) of 32 (11, 48) years. Among the 26 patients, 12 (46.2%) presented with annular erythema and blisters, while 14 (53.8%) with atypical lesions (erythema and blisters not in an annular arrangement). Direct immunofluorescence assay yielded positive results in 14 out of 19 patients (73.7%). Indirect immunofluorescence on salt-split skin showed IgA with or without IgG deposited in the epidermis of the salt-split skin in 53.8% (14/26) of the patients. The positive rate of IgA antibody detected by Western blot analysis was 88.5% (23/26). Western blot analysis with epidermal extracts as substrates showed that 18 patients (69.2%) had serum IgA recognizing the linear IgA bullous dermatosis autoantigen LAD-1 with a relative molecular weight of 120 000, of whom 4 (15.4%) also had IgA recognizing BP180; in 1 case (3.8%), the serum IgA could recognize a protein with a relative molecular weight of about 170 000 in the epidermal extracts; another 1 (3.8%) had IgA recognizing BP230 and a protein with a relative molecular weight of 140 000 in the epidermal extracts at the same time; additionally, the serum IgA recognizing type Ⅶ collagen with a relative molecular weight of 290 000 in the dermal extracts was detected in 1 case (3.8%). Among 23 patients receiving dapsone treatment, 21 well responded, 1 showed poor response, and 1 was intolerant; in addition, the latter two patients could not achieve complete remission by tofacitinib. Minocycline, colchicine, and sulfasalazine were effective in another 3 patients. Conclusions:In this study, LABD mainly occurred in middle-age individuals, and LAD-1 was determined to be a major autoantigen. Western blot analysis showed an increased positive rate of IgA antibody compared with immunofluorescence assay, and could be an important means of differential diagnosis. Although the LABD patients responded well to dapsone, it is still necessary to explore other safe and effective medications.
10.Clinical and immunoserological features of 35 cases of anti-p200 pemphigoid: a retrospective analysis
Suo LI ; Ke JING ; Yuan WANG ; Zhiliang LI ; Chenjing ZHAO ; Hanmei ZHANG ; Guirong LIANG ; Suying FENG
Chinese Journal of Dermatology 2024;57(10):897-903
Objective:To analyze clinical, immunoserological, and therapeutic features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to February 2024. Their clinical, immunoserological, and therapeutic characteristics were retrospectively analyzed.Results:A total of 35 patients were included, with a male-to-female ratio of 2.5∶1 (25 males and 10 females) and ages of 57.74 ± 17.12 years. Two (5.71%) patients were accompanied by psoriasis. In these patients, anti-p200 pemphigoid exhibited heterogeneous clinical phenotypes, mimicking classic bullous pemphigoid (20 cases, 57.14%), linear IgA bullous dermatosis (8 cases, 22.86%), or eczema (4 cases, 11.43%). The positive rates of direct immunofluorescence (DIF), indirect immunofluorescence on salt-split skin (ss-IIF), Western blot analysis with dermal extracts as substrates, and Western blot analysis with laminin γ1 C-terminal region (Lnγ1C) as substrates were 100% (24/24), 82.86% (29/35), 100% (35/35), and 80.64% (25/31), respectively. Among the 35 patients, treatment and follow-up information was available for analysis in 33. Six patients (18.18%) received non-glucocorticoid systemic therapy and topical glucocorticoid therapy, with a follow-up period ( M [ Q1, Q3]) of 19.50 (6.50, 69.25) months, and 1 withdrew the drugs. Sixteen patients received systemic glucocorticoids combined with traditional anti-inflammatory drugs, with a follow-up period of 13.50 (4.25, 18.00) months, the initial dose of glucocorticoids was equivalent to 0.30 - 0.50 mg·kg -1·d -1 of prednisone, and the time to disease control was 15.31 ± 5.23 days; among the 16 patients, 3 experienced fluctuations in disease condition which were alleviated by adding dapsone, and 1 discontinued glucocorticoids. Five patients (15.15%) received systemic glucocorticoids combined with immunosuppressants, with a follow-up period of 26.00 (14.00, 90.00) months, the initial dose of glucocorticoids was equivalent to 0.50 - 0.75 mg·kg -1·d -1 of prednisone, and the time to disease control was 10.20 ± 3.27 days; among the 5 patients, 2 received maintenance treatment with glucocorticoids (5 - 10 mg/d prednisone), 2 withdrew the drugs, and 1 relapsed after discontinuing glucocorticoids. One patient (3.03%) received systemic glucocorticoids combined with rituximab therapy, with a follow-up period of 53 months, and discontinued glucocorticoids thereafter. One patient (3.03%) received systemic glucocorticoids combined with dupilumab therapy, which proved to be effective. Four patients (12.12%) received systemic glucocorticoids combined with Janus kinase inhibitors, and 3 responded well. Conclusions:Anti-p200 pemphigoid presented a heterogeneous clinical profile in this series of patients, but scarring and milia were rare. Some patients showed negative results in Western blot analysis with Lnγ1C as substrates. The prognosis of anti-p200 pemphigoid was usually favorable, and most patients could achieve complete remission and ultimately discontinue medication.

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