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.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
3.Comparison of different laparoscopic treatments for upper urinary tract urothelial carcinoma
Meng ZHU ; Junfei GU ; Yuepeng LIU ; Zihao LI ; Chao MA ; Lixin REN
Journal of Modern Urology 2024;29(7):597-601
Objective To compare the clinical efficacy of peritoneolaparoscopic single position nephreteral total length resection(PSPNTLR)and posterior laparoscopic subabdominal incision technique(PLSIT)in the treatment of upper urothelial carcinoma(UTUC).Methods A total of 82 UTUC patients treated in our hospital during Jan.2018 and Feb.2021 were divided into the observation group(n=41,treated with PSPNTLR)and control group(n=41,treated with PLSIT)according to the random number table method.Perioperative indicators,pain degree,inflammatory factors,bladder recurrence and distant metastasis were compared between the two groups.Results The operation time[(122.15±15.14)min vs.(160.88±17.26)min],hospitalization time[(10.07±2.14)d vs.(12.22±3.13)d]and postoperative exhaust time[(1.46±0.57)d vs.(3.10±0.88)d]were significantly shorter,the intraoperative blood loss[(42.85±4.88)mL vs.(78.22±8.17)mL]and drainage volume[(53.61±9.74)mL vs.(81.56±11.06)mL]were significantly less in the observation group than in the control group(P<0.05).The visual analogue score(VAS)of the observation group at 6,12 and 24 h after operation was significantly lower than that of the control group(P<0.05).The levels of interleukin-6(IL-6)and C-reactive protein(CRP)were increased in both groups one day after surgery,but the indexes were increased more significantly in the control group(P<0.05).During the 2-year follow-up after surgery,there were no statistical difference in bladder recurrence(12.20%vs.14.63%)and distant metastasis(9.76%vs.4.88%)between the two groups(P>0.05).Conclusion Both PSPNTLR and PLSIT have good therapeutic safety,but PSPNTLR is more effective in improving perioperative indicators,reducing postoperative pain,and inhibiting inflammatory factors.
4.Prognostic and clinical value of circPRKCI expression in diverse human cancers
Zhongyue LIU ; Xiaolei REN ; Zhimin YANG ; Lin MEI ; Wenyi LI ; Chao TU ; Zhihong LI
Chinese Medical Journal 2024;137(2):152-161
Background::Highly expressed in various human cancers, circular RNA Protein Kinase C Iota (circPRKCI) has been reported to play an important role in cancer development and progression. Herein, we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.Methods::We searched the Pubmed, Web of Science, and the Cochrane Library databases from inception until May 16, 2021. The relationship between circPRKCI expression and cancer patients’ survival, including overall survival (OS) and disease-free survival (DFS), was assessed by pooled hazard ratios (HR) with corresponding 95% confidence interval (CI). The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios (OR) with corresponding 95% CI. The data were analyzed by STATA software (version 12.0) or Review Manager (RevMan 5.3).Results::A total of 15 studies with 1109 patients were incorporated into our meta-analysis. The results demonstrated that high circPRKCI expression was significantly related to poor OS (HR = 1.96, 95% CI: 1.61, 2.39, P <0.001) when compared with low circPRKCI expression in diverse human cancers. However, elevated circPRKCI expression was not associated with DFS (HR = 1.34, 95% CI: 0.93, 1.95, P = 0.121). Furthermore, the patient with a higher circPRKCI expression was prone to have a larger tumor size, advanced clinical stage, and lymph node metastasis, but it was not significantly correlated with age, gender, and distant metastasis. Conclusion::Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features, suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.
5.Quantitative detection of tiny amounts of tritium in hydrogen using the catalytic oxidation-liquid scintillation counting method
Chao WU ; Binyong ZHANG ; Ying REN ; Yan LIU ; Lebin LI
Chinese Journal of Radiological Health 2024;33(3):267-272
Objective To establish a method for quantitative analysis of tiny amounts of tritium in hydrogen below the detection limit of isotope ratio mass spectrometer. Methods Hydrogen was oxidized to produce water in a self-developed catalytic oxidation device filled with platinum hydrophobic catalyst. The effects of different experimental conditions on hydrogen conversion rate were investigated. The tritium concentration in the synthetic water was measured using a liquid scintillation counter. The tritium concentration in hydrogen was calculated according to the measurement of the synthetic water. Results When the flow rate of hydrogen was fixed, the conversion rate of hydrogen increased with the increase of the reaction temperature but increased and then decreased with the increase of the flow rate of oxygen. Hydrogen could be completely converted under optimal experimental conditions. The hydrogen samples with volumetric tritium concentrations in the range of 1 × 10−7 to 2 × 10−14 were converted to water at the reaction temperature of 110 ℃ and hydrogen/oxygen flow rate of 100 mL/min. The resulting water was measured using a liquid scintillation counter. The measurement accuracy was better than 2%. Conclusion This method can be used to measure hydrogen samples with tiny amounts of tritium below the detection limit of isotope ratio mass spectrometer. Our results provide data support for the calculation of the separation capacity of cryogenic distillation process.
6.Establishment and validation of a dose-response curve for semi-automatic analysis of dicentric chromosomes
Qianqian MENG ; Zhongxin ZHANG ; Yue REN ; Xiaozhen LI ; Zeyu MIAO ; Chao WANG ; Hongyan LIU ; Ruifeng ZHANG
China Occupational Medicine 2024;51(1):70-74
ObjectiveTo establish a dose-effect curve for semi-automatic analysis of dicentric chromosomes(DC) based on an automatic chromosome analysis system. Methods A total of three healthy volunteers were recruited as the study subjects, and their peripheral blood was collected and stimulated by X-ray at doses of 0.00, 0.10, 0.25, 0.50, 0.75, 1.00, 2.00, 3.00, 4.00, and 5.00 Gy, with the absorbed dose rate of 1.0 Gy/min. Images of DC in the mid-stage of cell division were collected using a high-throughput automatic chromosome analysis system. The DCScore software was used to automatically analyze DC aberrations, and a dose-effect curve for semi-automatic analysis of DC was fitted after manual confirmation. The fitted dose-effect curve for semi-automatic analysis of DC was validated for accuracy using three proficiency test samples from the national quality assessment of biological dose. Results The incidence of DC increased with increasing irradiation doses in the range of 0.00-5.00 Gy (P<0.01). The dose-effect curve for the fitted semi-automatic analysis of DC was ŷ =0.000 8 (±0.000 2) +0.009 2(±0.000 9) D+0.014 2(±0.000 4) D2 (R2= 0.999 8). The relative deviation between the estimated dose and the actual dose of the three test samples was about 20.00%, indicating curve applicability for biological dose estimation. Moreover, excluding the time spent on manual analysis, the semi-automatic analysis method increased the analysis efficiency by 26.0 times. Conclusion The semi-automatic analysis dose-effect curve for DC stimulated by X-ray is constructed for biological dose estimation, which can reduce the manual analysis time, and holds great potential for application in nuclear emergency response to large-scale radiation accidents.
7.Research progress on the intervention of traditional Chinese medicine in renal interstitial fibrosis based on PI3K/Akt signaling pathway
Xue LI ; Yunlong ZHANG ; Ziyi SONG ; Zhujiang ZHANG ; Chao YANG ; Tianjiao REN ; Linzhen JIA
China Pharmacy 2024;35(14):1795-1800
Renal interstitial fibrosis(RIF) is the main pathological manifestation of chronic kidney disease. Due to the complexity of the mechanism, there is no specific treatment for RIF in clinical practice. The abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt) signaling pathway and the activation of downstream target genes are key drivers of RIF induction and progression. Traditional Chinese medicine has the characteristics of precise efficacy and minimal toxic side effects, and the occurrence and development of RIF can be regulated by multiple targets and mutual coordination. This review focuses on the PI3K/Akt signaling pathway and summarizes the potential targets and regulatory mechanisms of traditional Chinese medicine in the treatment of RIF. It is found that various effective ingredients (such as sinomenine, mangiferin, coumarin derivates from Hydrangea paniculata, etc.) and formulas (such as Fushengong decoction, Qi-Bang-Yi-Shen formula, etc.) of traditional Chinese medicine can inhibit fibroblast proliferation, improve inflammation and oxidative stress, maintain mitochondrial stability, and slow down ferroptosis through this pathway, thereby delaying the occurrence and progression of RIF.
8.New Advances in the Use of 18F-FET PET in the Diagnosis and Management of Adult High-Grade Gliomas
Qingqing HAN ; Tuo LI ; Haiqun XING ; Chao REN ; Jiahui LIU ; Yu WANG ; Wenbin MA ; Xin CHENG ; Li HUO
JOURNAL OF RARE DISEASES 2024;3(1):102-107
Gliomas are the most common primary intracranial tumors in adults, among which high-grade glioma patients are characterized by short survival and poor prognosis. The diagnosis, treatment, evaluation of effective treatments, and prognosis prediction of high-grade gliomas are of great significance for improving patient survival. Conventional enhanced magnetic resonance imaging has deficiencies in delineating tumor extent, identifying tumor progression and treatment-related changes. Therefore, there is a broad consensus to incorporate amino acid PET, and 18F-FET PET inparticular, into the diagnostic and therapeutic process of high-grade gliomas. In this article, we review the new research progress of 18F-FET PET in the diagnosis and treatment of adult high-grade glioma in recent years.
9.Effects of aging factors on biological characteristics of dental stem cells
Zhiguo XU ; Yanfei WU ; Zhenhui REN ; Xuwei YANG ; Yikun NIU ; Zhilong DONG ; Wei DU ; Wenling YANG ; Xin XU ; Yi ZHU ; Lefeng LIU ; Chao LIU
Chinese Journal of Tissue Engineering Research 2024;28(19):2996-3002
BACKGROUND:The research of dental stem cells in the fields of regenerative medicine and tissue engineering has been deepening,bringing hope for the repair of tooth-related tissues and the treatment of systemic diseases.However,there is a lack of systematic research and analysis on the biological characteristics of dental stem cells in different age groups. OBJECTIVE:To explore the biological characteristics of the human deciduous tooth and permanent tooth pulp stem cells cultured in umbilical cord blood platelet lysate to provide a reliable basis for human platelet lysates to replace fetal bovine serum. METHODS:The pulp tissues of deciduous teeth,juvenile permanent teeth and adult permanent teeth were taken out and cultured in DMEM/F-12 medium supplemented with 10%fetal bovine serum or different concentrations(5%,10%and 15%)of human platelet lysates.Cell proliferation in the four groups was detected by cytometry.The optimal concentration of human platelet lysates was selected for subsequent experiments.Under the optimal concentration of human platelet lysates,human deciduous tooth and juvenile and adult permanent tooth pulp stem cells were cultured in vitro.The cell growth status was observed under the microscope.The specific antigen on the cell surface was detected by flow cytometry.The cell proliferation ability was tested by the cell counting method and CCK-8 assay.The cell differentiation ability in vitro was observed by a three-line differentiation assay. RESULTS AND CONCLUSION:(1)The cell proliferation rate of the 10%human platelet lysate group was the highest.(2)In all three groups,fusiform fibrous cells grew and expanded from around the tissue block.There was no significant difference between deciduous teeth and juvenile permanent tooth cells,but the adult permanent tooth cells were larger than the deciduous and juvenile permanent tooth cells of the same generation.(3)The results of flow cytometry showed that deciduous teeth,juvenile permanent teeth and adult permanent teeth conformed to the phenotypic characteristics of mesenchymal stem cells.(4)The proliferative capacity of adult permanent dental pulp stem cells was significantly lower than those of deciduous teeth and juvenile permanent dental pulp stem cells(P<0.01).(5)mRNA expressions of osteoblast-related genes alkaline phosphatase and bone morphogenetic protein 2,lipoprotein lipase and peroxisome proliferator-activated receptor γ2,mRNA expressions of chondroblast related gene type II collagen α1 and cartilage oligomeric matrix protein in adult pulp stem cells of permanent teeth were significantly lower than those of deciduous teeth and juvenile permanent teeth pulp stem cells(P<0.01).(6)Compared with adult dental pulp stem cells,human deciduous teeth and juvenile permanent teeth dental pulp stem cells have the stronger proliferative capacity and multidirectional differentiation potential,and are more suitable for clinical research and disease treatment.
10.A case of toxic epidermal necrolysis caused by sorafenib and sintilimab
Lin DENG ; Chao REN ; Tao SUN ; Xi LI ; Shun GUO ; Ang ZHOU
Chinese Journal of Pharmacoepidemiology 2024;33(2):224-229
A 67-year-old female patient with postoperative recurrence of stage Ⅳright renal cell carcinoma and multiple intracranial metastases was treated with sorafenib and sintilimab.Within 2 weeks,the patient had a fever and red spotted rash in facial,back,buttocks and limb.After 2 days,the fever completely relieved,but subcutaneous exudation appeared on the skin of both elbow joints,buttocks,and outer thighs,followed by gradual epidermal lysis and detachment with skin ulceration.After 4 days,the patient's epidermolysis area was greater than 30%of the body surface area.The patient was diagnosed with toxic epidermal necrolysis(TEN).The adverse reaction correlation was assessed by ALDEN SCORE sheet.The adverse reaction of TEN was"likely"caused by sorafenib and sintilimab.After withdrawal and treatment,the TEN was cured.This paper explores the correlation between the TEN and the combination use of sorafenib and sintilimab and the management.This paper will provide reference for the early diagnosis and correct treatment of TEN.


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