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.A Health Economic Evaluation of an Artificial Intelligence-assisted Prescription Review System in a Real-world Setting in China.
Di WU ; Ying Peng QIU ; Li Wei SHI ; Ke Jun LIU ; Xue Qing TIAN ; Ping REN ; Mao YOU ; Jun Rui PEI ; Wen Qi FU ; Yue XIAO
Biomedical and Environmental Sciences 2025;38(3):385-388
3.TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children
Xi MING ; Liqun WU ; Ziwei WANG ; Bo WANG ; Jialin ZHENG ; Jingwei HUO ; Mei HAN ; Xiaochun FENG ; Baoqing ZHANG ; Xia ZHAO ; Mengqing WANG ; Zheng XUE ; Ke CHANG ; Youpeng WANG ; Yanhong QIN ; Bin YUAN ; Hua CHEN ; Lining WANG ; Xianqing REN ; Hua XU ; Liping SUN ; Zhenqi WU ; Yun ZHAO ; Xinmin LI ; Min LI ; Jian CHEN ; Junhong WANG ; Yonghong JIANG ; Yongbin YAN ; Hengmiao GAO ; Hongmin FU ; Yongkun HUANG ; Jinghui YANG ; Zhu CHEN ; Lei XIONG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(7):722-732
Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.
4.Genetic analysis of a pedigree affected with Intellectual disability due to variants of two different genes
Tingting SHI ; Zengguo REN ; Ke YANG ; Litao QIN ; Xingxing LEI ; Bing ZHANG ; Shixiu LIAO ; Li WANG
Chinese Journal of Medical Genetics 2024;41(11):1302-1307
Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.
5.Analysis of allergen-specific IgE in children with atopic dermatitis from 2021 to 2023 in a hospital of pediatric in Tianjin City
Ren NA ; Yuanmin SUN ; Ke LI ; Qinfeng LI ; Ying WANG ; Jiayi ZHANG ; Lisheng ZHENG ; Chaomeng FAN ; Qianqian XIN ; Xiaohui YANG ; Yongming SHEN
Chinese Journal of Preventive Medicine 2024;58(6):799-805
Objective:To explore the distribution of allergen-specific IgE (sIgE) for children with atopic dermatitis in Tianjin City and provide the evidences of clinical diagnosis and treatment.Methods:A retrospective cross-sectional study was conducted to analyze the children who were suspected of atopic dermatitis and tested for serum sIgE in the Tianjin Children′s Hospital from March 2021 to February 2023. Using first detection results only, a total of 1 841 serum samples were tested for twenty common allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children′s characteristics and factors such as different sexes, ages and seasons by the mass data.Results:Among the 1 841 cases, the results showed that 1 247 (67.73%) were sensitized to at least 1 allergen-sIgE, comprising to 49.86% (918/1 841) to food allergen-sIgE and 47.96% (883/1 841) to aeroallergen-sIgE. The top three food allergens-sIgE were egg 32.10% (591/1 841), milk 25.91% (477/1 841) and wheat flour 14.61% (269/1 841); the top three positive rates of aeroallergens-sIgE were house dust 24.33% (448/1 841), alternaria 20.59% (379/1 841) and dermatophagoides farinae 14.83% (273/1 841). The positive rates of food allergens-sIgE were the highest in the 1-3 years old group (64.11%, 434/677) ( χ2=122.854, P<0.001), while the positive rates of aeroallergens-sIgE were higher in the 11-14 years old group (71.26%, 62/87) ( χ2=134.968, P<0.001). No seasonal difference was revealed in the overall positive rate of food allergen-sIgE and aeroallergen-sIgE ( χ2=4.047, P=0.256; χ2=7.549, P=0.056). The positive rates of soybean-sIgE and milk-sIgE were the highest in summer ( χ2=11.329, P=0.010; χ2=28.720 , P<0.001), whereas alternaria-sIgE and mugwort-sIgE were the highest in summer and autumn, respectively ( χ2=8.462, P=0.037; χ2=10.641 , P=0.014). Among the 1 841 cases, 32.21% were sensitized to three or more allergens-sIgE. The sIgE concentration levels of egg, milk and house dust were mainly level 1 to 2, and the proportions of level 3 and above were all under 15%; although the positive rates of crab, shrimp, and peanut were low, the proportions of grade 3 and above were all beyond 30%. Children sensitized to alternaria, dermatophagoides farinae, mugwort, and cat dander had higher sIgE concentration levels, which were 68.07%, 49.45%, 56.57% and 47.83% respectively. Conclusions:This study can reflect the epidemic characteristics of allergen-sIgE in children with atopic dermatitis in Tianjin region to a certain extent. Allergen-sIgE positivity in patients differed by age, and there were seasonal differences and grade distribution differences in the positive rates of some allergens-sIgE. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of atopic dermatitis.
6.Expert consensus on cryoablation therapy of oral mucosal melanoma
Guoxin REN ; Moyi SUN ; Zhangui TANG ; Longjiang LI ; Jian MENG ; Zhijun SUN ; Shaoyan LIU ; Yue HE ; Wei SHANG ; Gang LI ; Jie ZHNAG ; Heming WU ; Yi LI ; Shaohui HUANG ; Shizhou ZHANG ; Zhongcheng GONG ; Jun WANG ; Anxun WANG ; Zhiyong LI ; Zhiquan HUNAG ; Tong SU ; Jichen LI ; Kai YANG ; Weizhong LI ; Weihong XIE ; Qing XI ; Ke ZHAO ; Yunze XUAN ; Li HUANG ; Chuanzheng SUN ; Bing HAN ; Yanping CHEN ; Wenge CHEN ; Yunteng WU ; Dongliang WEI ; Wei GUO
Journal of Practical Stomatology 2024;40(2):149-155
Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.
7.Analysis of allergen-specific IgE in children with atopic dermatitis from 2021 to 2023 in a hospital of pediatric in Tianjin City
Ren NA ; Yuanmin SUN ; Ke LI ; Qinfeng LI ; Ying WANG ; Jiayi ZHANG ; Lisheng ZHENG ; Chaomeng FAN ; Qianqian XIN ; Xiaohui YANG ; Yongming SHEN
Chinese Journal of Preventive Medicine 2024;58(6):799-805
Objective:To explore the distribution of allergen-specific IgE (sIgE) for children with atopic dermatitis in Tianjin City and provide the evidences of clinical diagnosis and treatment.Methods:A retrospective cross-sectional study was conducted to analyze the children who were suspected of atopic dermatitis and tested for serum sIgE in the Tianjin Children′s Hospital from March 2021 to February 2023. Using first detection results only, a total of 1 841 serum samples were tested for twenty common allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children′s characteristics and factors such as different sexes, ages and seasons by the mass data.Results:Among the 1 841 cases, the results showed that 1 247 (67.73%) were sensitized to at least 1 allergen-sIgE, comprising to 49.86% (918/1 841) to food allergen-sIgE and 47.96% (883/1 841) to aeroallergen-sIgE. The top three food allergens-sIgE were egg 32.10% (591/1 841), milk 25.91% (477/1 841) and wheat flour 14.61% (269/1 841); the top three positive rates of aeroallergens-sIgE were house dust 24.33% (448/1 841), alternaria 20.59% (379/1 841) and dermatophagoides farinae 14.83% (273/1 841). The positive rates of food allergens-sIgE were the highest in the 1-3 years old group (64.11%, 434/677) ( χ2=122.854, P<0.001), while the positive rates of aeroallergens-sIgE were higher in the 11-14 years old group (71.26%, 62/87) ( χ2=134.968, P<0.001). No seasonal difference was revealed in the overall positive rate of food allergen-sIgE and aeroallergen-sIgE ( χ2=4.047, P=0.256; χ2=7.549, P=0.056). The positive rates of soybean-sIgE and milk-sIgE were the highest in summer ( χ2=11.329, P=0.010; χ2=28.720 , P<0.001), whereas alternaria-sIgE and mugwort-sIgE were the highest in summer and autumn, respectively ( χ2=8.462, P=0.037; χ2=10.641 , P=0.014). Among the 1 841 cases, 32.21% were sensitized to three or more allergens-sIgE. The sIgE concentration levels of egg, milk and house dust were mainly level 1 to 2, and the proportions of level 3 and above were all under 15%; although the positive rates of crab, shrimp, and peanut were low, the proportions of grade 3 and above were all beyond 30%. Children sensitized to alternaria, dermatophagoides farinae, mugwort, and cat dander had higher sIgE concentration levels, which were 68.07%, 49.45%, 56.57% and 47.83% respectively. Conclusions:This study can reflect the epidemic characteristics of allergen-sIgE in children with atopic dermatitis in Tianjin region to a certain extent. Allergen-sIgE positivity in patients differed by age, and there were seasonal differences and grade distribution differences in the positive rates of some allergens-sIgE. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of atopic dermatitis.
8.Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China: Findings from real-world data
Ruoxi HE ; Xiaoxia REN ; Ke HUANG ; Jieping LEI ; Hongtao NIU ; Wei LI ; Fen DONG ; Baicun LI ; Ye WANG ; Ting YANG ; Chen WANG
Chinese Medical Journal 2024;137(10):1179-1189
Background::Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.Methods::Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared.Results::Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34%-3.10%), 2.09% (95% CI: 1.76%-2.43%), and 1.25% (95% CI: 0.99%-1.51%), respectively. In multivariable models, age ≥60 years (60-69 years, odds ratio [OR]: 1.90, 95% CI: 1.11-3.25; ≥80 years, OR: 2.00, 95% CI: 1.06-3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96-13.21), urban residence (OR: 1.69, 95% CI: 1.07-2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21-2.58; senior high school or above, OR: 2.61, 95% CI: 1.69-4.03), former smoking (OR: 1.79, 95% CI: 1.15-2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29-4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45-0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment.Conclusions::Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.
9.Evaluation of conjunctival sac culture findings prior to intravitreal injection
Xinjun REN ; Yifeng KE ; Liangzhang TAN ; Eric Emmanuel PAZO ; Yongtao LI ; Xiaorong LI
Chinese Journal of Ocular Fundus Diseases 2024;40(9):687-692
Objective:To observe the differences in the positive rate of conjunctival sac microbial culture after different methods of preventing infection before intravitreal injection (IVI).Methods:A prospective case-control study. A total of 1 200 participants with fundus diseases who received IVI injection at Tianjin Medical University Eye Hospital from July 2021 to December 2023 were included. Patients were randomly divided into 6 groups according to eye spot with antibiotic solution 3, 1 and 0 days before IVI and local eye disinfection with povidone-iodine (PVI) 3 min and 30 s before IVI: the first 3 days of antibiotics+3 min PVI group, the first 1 day of antibiotics+3 min PVI group, the first 0 days of antibiotics+3 min PVI group, the first 3 days of antibiotics+30 s PVI group, the first 1 day of antibiotics+30 s PVI group, the first 0 days of antibiotics+30 s PVI group, there were 200 cases in each group. Microbial sampling and cultivation of conjunctival sac were conducted before IVI to compare the differences in positive rates among different groups. Multiple group comparisons were conducted using one-way analysis of variance. The comparison of count data is conducted using χ2 test. Results:Among the 1 200 patients, there were 566 males and 634 females. Age (62.59±13.44) years old. There were 397 cases of diabetes and 482 cases of hypertension. IVI frequency (2.35±2.34). 64 cases were positive for conjunctival sac culture before IVI. The age ( F=1.468), sex composition ratio ( χ2=2.876), diabetes ( χ2=10.002), hypertension ( χ2=6.019), times of IVI ( χ2=4.507), and positive rate of conjunctival sac bacterial culture ( χ2 =6.272) of patients in each group had no statistical significance ( P>0.05). Using the duration of antibiotic application before IVI as a stratified factor, there was no statistically significant difference in the positive rate of conjunctival sac culture between groups with different durations of antibiotic application before IVI [ χ2=0.414, P=0.52, combined odds ratio ( OR)=0.819, 95% confidence interval ( CI) 0.493-1.360]. Using the duration of PVI application as a stratified factor, there was no statistically significant difference in the positive rate of conjunctival sac culture between different PVI disinfection times [ χ2=0.000, P=1.000, combined OR=1.00, 95% CI 0.503-1.988]. Conclusions:Pre IVI treatment with 0.5% PVI for 30 s can inhibit the growth of microbial colonies in the conjunctival sac. The application of local antibiotic eye fluid in the anterior eye of IVI cannot reduce the positive rate of conjunctival sac bacteria.
10.Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract improves radiation-induced pulmonary fibrosis in rats by regulating NLRP3/caspase-1/GSDMD pyroptosis pathway
Chun-Zhen REN ; Jian-Fang YUAN ; Chun-Ling WANG ; Xiao-Dong ZHI ; Qi-Li ZHANG ; Qi-Lin CHEN ; Xin-Fang LYU ; Xiang GAO ; Xue WU ; Xin-Ke ZHAO ; Ying-Dong LI
Chinese Pharmacological Bulletin 2024;40(11):2124-2131
Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P<0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P<0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P<0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P<0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

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