1.Astrocyte FGF7/FGFR2 autocrine signaling mediates neuroinflammation and promotes MPTP-induced degeneration of dopaminergic neurons.
Xin SUN ; Yueping WANG ; Yajie ZHANG ; Ruixue HAN ; Min WANG ; Jing ZHANG ; Ting SUN ; Yang LIU ; Gang HU ; Lei CAO ; Ming LU
Acta Pharmaceutica Sinica B 2025;15(9):4730-4750
Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.
2.Strengthening research on prevention and treatment of chronic skin diseases — population medicine research program
Yan HAN ; Peng XU ; Zhi XIANG ; Tingting JIANG ; Fengqin GE ; Yueping YIN ; Xiangsheng CHEN
Chinese Journal of Dermatology 2024;57(6):567-569
Chronic skin diseases have complex pathogeneses and prolonged courses, and have long adverse impacts on the physical and mental health, as well as the normal life of patients. It is necessary to develop evidence-based strategies and measures for effective prevention and control of chronic skin diseases. However, related studies are limited in China. This article proposes a population medicine research plan for health promotion and equity, and disease prevention, diagnosis, control, treatment, and rehabilitation to establish a collaborative platform for strengthening research on the prevention and treatment of chronic skin diseases in China.
3.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.
4.Prognostic significance of systemic immune inflammation index in patients with pancreatic cancer based on propensity score matching analysis
Rongshuang HAN ; Zibin TIAN ; Yueping JIANG ; Xiaowei WANG ; Xuechun LIU ; Shenghua BI ; Xue JING
Chinese Journal of Pancreatology 2022;22(5):359-364
Objective:To investigate the predictive value of systemic immune inflammation index (SII) for the overall survival of patients with pancreatic cancer by propensity score matching analysis.Methods:The clinical data of 457 patients with pancreatic cancer admitted to the Affiliated Hospital of Qingdao University from August 2000 to December 2019 were retrospectively analyzed. The age, gender, presence of jaundice, pancreatitis and diabetes, serum CA19-9, total bilirubin level, neutrophil count, platelet count, lymphocyte count in blood, presence of radical surgery, tumor TNM stage, tumor location and the like were recorded. The cut-off value of SII was determined by Youden index. The patients were divided into high and low SII groups accroding to the cut-off value. The propensity score matching was applied to reduce the selection bias of patients. Patients were 1∶2 matched and the caliper value was 0.1. The difference on overall survival between the two groups was compared. The prognostic factors were analyzed by univariate and multivariate Cox regression analysis. Kaplan-Meier was used to draw the overall survival curve to calculate the cumulative survival rate, and the differences between the curves were analyzed by Log-Rank test.Results:The cut-off value of SII was 765. There were statistically significant differences between the high SII group ( n=125) and the low SII group ( n=332) on the presence or absence of pancreatitis, the level of total bilirubin in blood, radical surgery, and TNM stage before the propensity score matching (all P value <0.05). After propensity score matching, there was no statistically significant difference between the high SII group ( n=113) and the low SII group ( n=182) on all the clinical parameters mentioned above except for CA19-9, indicating that the two groups were comparable. Univariate analysis showed that the level of CA19-9, SII, radical surgery and different TNM stage were all related to the overall survival of pancreatic cancer patients. Multivariate analysis showed that high CA19-9 level, high SII, no radical surgery, and worse TNM stage were independent risk factors for short overall survival, and high SII ( HR=1.882, 95% CI 1.446-2.450, P<0.001) was significantly associated with poor prognosis. The overall survival of patients with high SII was obviously shorter than the low SII group ( P<0.001), and the average survival time of patients with high and low SII were 8.86 and 11.38 months, respectively. Conclusions:SII is of great value in evaluating the overall survival of pancreatic cancer patients. Higher SII is associated with shorter overall survival.
5. Consistency of ALK Ventana-D5F3 immunohistochemistry interpretation in lung adenocarcinoma among Chinese histopathologists
Lin LI ; Liping ZHANG ; Yuchen HAN ; Weiya WANG ; Yan JIN ; Qingxin XIA ; Yueping LIU ; Jin XIANG ; Chao LIU ; Shanshan LU ; Wei WU ; Zhen CHEN ; Juan PANG ; Yanfeng XI ; Yushuang ZHENG ; Dongmei GU ; Jun FAN ; Xiaona CHANG ; Weiwei WANG ; Liang WANG ; Zhihong ZHANG ; Xiaochu YAN ; Yi SUN ; Ji LI ; Feng HOU ; Jingyuan ZHANG ; Rongfang HUANG ; Jianping LU ; Zheng WANG ; Yongbin HU ; Hongtu YUAN ; Yujie DONG ; Lu WANG ; Zhenyu KE ; Jingshu GENG ; Lei GUO ; Jing ZHANG ; Jianming YING
Chinese Journal of Pathology 2019;48(12):921-927
Objective:
To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy.
Methods:
This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS.
Results:
There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109).
Conclusion
There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.
6. Analysis of the situation of school bullying and related factors in junior high school students in China 2016
Yueping SONG ; Xiao HAN ; Jingwen ZHANG
Chinese Journal of Preventive Medicine 2019;53(10):1032-1037
Objective:
To analyze the current situation of school bullying and related factors in junior high school students in China 2016.
Methods:
Junior high school students were selected from the 2016 China Education Panel Survey. A total of 6 750 students with completed records of suffering from school bulling, individual characteristics, family environment, and school conditions were selected. Multivariate logistic regression models were used to analyze the related factors of being bullied.
Results:
A total of 57.29% (3 867/6 750) of students in the past year had suffered from at least one type of school bullying. The proportions of students who suffered from verbal bullying, social bullying, physical bullying and cyber bullying were 49.12% (3 298/6 714), 37.87% (2551/6736), 18.18% (1226/6743), and 13.51% (910/6 735), respectively. According to the logistic regression model, students who were boys, came from ethnic minorities, lived with their mothers only, had frequent quarreling parents, boarded and had experience of school transfer in primary education were more vulnerable to school bullying compared with those who were girls, came from Han nationality, lived with parents, had parents who seldom quarrel, commute to school daily and had no school transfer experience in primary education. The corresponding
7.Effect of peer education based on information technology on self-management behavior of patients after anus-preserving surgery for rectal cancer
Yanfei YIN ; Lin CAO ; Yueya HAN ; Qiwei WANG ; Yueping LIU
Chinese Journal of Modern Nursing 2019;25(26):3386-3389
Objective? To explore the effect of peer education based on information technology on self-management behavior of rectal cancer patients after anus-preserving surgery. Methods? Using convenience sampling method, from January to October 2018, patients with rectal cancer who were hospitalized in General Surgery Department of a Class Ⅲ Grade A hospital in Harbin were selected as the research objects. According to the time of admission, 34 patients from January to May 2018 were taken as control group and 37 patients from June to October 2018 were taken as observation group. Patients in the control group received routine discharge guidance, while patients in the observation group received peer education based on information technology. The effect of intervention was evaluated by Self-management Behavior Questionnaire for Intestinal Symptoms of Rectal Cancer Patients after Anus-preserving Operation and Self-rating Anxiety Scale(SAS). Results? After intervention, the total scores of Self-management Behavior Questionnaire for Intestinal Symptoms of Rectal Cancer Patients after Anus-preserving Operation, "treatment management", "perianal skin management","seeking help from others", "self-emotion adjustment" and "social management" in the observation group were higher than those in the control group with statistically difference (P< 0.05), and there was no statistically significant difference in the dimensional scores of "dietary management" between the two groups (P> 0.05). After the intervention, the SAS score of the observation group was lower than that of the control group, and the difference was statistically significant (P < 0.05). Conclusions? Information technology-based peer education can improve the self-management behavior of patients with rectal cancer after anus-preserving operation and reduce the anxiety level of patients. It is worthy of popularization and application.
8.Analysis of the situation of school bullying and related factors in junior high school students in China 2016
Yueping SONG ; Xiao HAN ; Jingwen ZHANG
Chinese Journal of Preventive Medicine 2019;53(10):1032-1037
Objective To analyze the current situation of school bullying and related factors in junior high school students in China 2016. Methods Junior high school students were selected from the 2016 China Education Panel Survey. A total of 6 750 students with completed records of suffering from school bulling, individual characteristics, family environment, and school conditions were selected. Multivariate logistic regression models were used to analyze the related factors of being bullied. Results A total of 57.29% (3 867/6 750) of students in the past year had suffered from at least one type of school bullying. The proportions of students who suffered from verbal bullying, social bullying, physical bullying and cyber bullying were 49.12% (3 298/6 714), 37.87% (2551/6736), 18.18% (1226/6743), and 13.51% (910/6 735), respectively. According to the logistic regression model, students who were boys, came from ethnic minorities, lived with their mothers only, had frequent quarreling parents, boarded and had experience of school transfer in primary education were more vulnerable to school bullying compared with those who were girls, came from Han nationality, lived with parents, had parents who seldom quarrel, commute to school daily and had no school transfer experience in primary education. The corresponding OR (95%CI) values were 1.86 (1.66-2.08), 1.27 (1.02-1.57), 1.35 (1.13-1.61), 1.49 (1.23-1.81), 1.65 (1.33-2.04), and 1.21 (1.08-1.36), respectively. Students who were the only child, had relatively good health, had mothers with middle school, high school or secondary specialized school education level, had medium or good family economic conditions, had good academic performance, served as class cadres and had good relations with head teachers were less vulnerable to school bullying compared with those who were not the only child, had relatively bad health, had mothers with primary school or below education level, had poor family economic conditions, had poor academic performance, had never been class cadres and had bad relations with head teachers. The corresponding OR (95%CI) values were 0.80 (0.72-0.90), 0.60 (0.48-0.75), 0.74 (0.64-0.85), 0.75 (0.61-0.91), 0.70 (0.69-0.82), 0.64 (0.52-0.79), 0.85 (0.74-0.99), 0.88 (0.79-0.99), and 0.62 (0.55-0.69), respectively. Conclusion The situation of suffering from school bullying among junior high school students in China is not optimistic. Individual characteristics, family environment and school conditions were all related to school bullying.
9.Analysis of the situation of school bullying and related factors in junior high school students in China 2016
Yueping SONG ; Xiao HAN ; Jingwen ZHANG
Chinese Journal of Preventive Medicine 2019;53(10):1032-1037
Objective To analyze the current situation of school bullying and related factors in junior high school students in China 2016. Methods Junior high school students were selected from the 2016 China Education Panel Survey. A total of 6 750 students with completed records of suffering from school bulling, individual characteristics, family environment, and school conditions were selected. Multivariate logistic regression models were used to analyze the related factors of being bullied. Results A total of 57.29% (3 867/6 750) of students in the past year had suffered from at least one type of school bullying. The proportions of students who suffered from verbal bullying, social bullying, physical bullying and cyber bullying were 49.12% (3 298/6 714), 37.87% (2551/6736), 18.18% (1226/6743), and 13.51% (910/6 735), respectively. According to the logistic regression model, students who were boys, came from ethnic minorities, lived with their mothers only, had frequent quarreling parents, boarded and had experience of school transfer in primary education were more vulnerable to school bullying compared with those who were girls, came from Han nationality, lived with parents, had parents who seldom quarrel, commute to school daily and had no school transfer experience in primary education. The corresponding OR (95%CI) values were 1.86 (1.66-2.08), 1.27 (1.02-1.57), 1.35 (1.13-1.61), 1.49 (1.23-1.81), 1.65 (1.33-2.04), and 1.21 (1.08-1.36), respectively. Students who were the only child, had relatively good health, had mothers with middle school, high school or secondary specialized school education level, had medium or good family economic conditions, had good academic performance, served as class cadres and had good relations with head teachers were less vulnerable to school bullying compared with those who were not the only child, had relatively bad health, had mothers with primary school or below education level, had poor family economic conditions, had poor academic performance, had never been class cadres and had bad relations with head teachers. The corresponding OR (95%CI) values were 0.80 (0.72-0.90), 0.60 (0.48-0.75), 0.74 (0.64-0.85), 0.75 (0.61-0.91), 0.70 (0.69-0.82), 0.64 (0.52-0.79), 0.85 (0.74-0.99), 0.88 (0.79-0.99), and 0.62 (0.55-0.69), respectively. Conclusion The situation of suffering from school bullying among junior high school students in China is not optimistic. Individual characteristics, family environment and school conditions were all related to school bullying.
10.Evaluation of prototype IgA rapid test on diagnosis of early active syphilis
Yan HAN ; Wanhui WEI ; Yueping YIN ; Anderson DAVID ; Hongchun WANG ; Garcia L MARY ; Van HUY ; Xiaoyu ZHU ; Kai CHEN ; Xiangsheng CHEN
Chinese Journal of Dermatology 2018;51(5):372-375
Objective To evaluate the application of Burnet Institute-made prototype IgA rapid test,a kind of point-of-care (POC) testing,in the diagnosis of early syphilis.Methods Totally,455 stored serum samples in the Reference Laboratory of Sexually Transmitted Disease,the Institute of Dermatology were used to evaluate the application of the prototype IgA rapid test (IgA-POC) in the diagnosis of early syphilis.According to resluts of Treponema pallidum hemagglutination assay (TPHA),rapid plasma reagin card test (RPR),and enzyme-linked immunosorbent assay for IgM antibodies (IgM-ELISA),these stored samples were divided into 3 groups:uninfected group,previously infected group and early active syphilis group.IgA-POC test was performed in the 3 groups to evaluate its diagnostic performance for active syphilis,and researchers were blind to the group information.Results The prototype IgA-POC test had a sensitivity of 92.6% (147/163) for the early active syphilis group,a specificity of 72.22% (104/144) for the previously infected group,and a specificity of 97.97% (145/148) for the uninfected group.The total specificity of the prototype IgA-POC test was 85.27%,which met the minimum requirement of WHO for the POC test.The prototype IgA-POC test showed a significantly higher sensitivity for the diagnosis of early active syphilis compared with the IgM-ELISA (59.51%,Z =6.88,P < 0.05),but a significantly lower specificity for the diagnosis of previous syphilis infection compared with the IgM-ELISA (98.61%,Z =6.18,P < 0.05).Moreover,no significant difference in the specificity for the diagnosis of non-infection was observed between the prototype IgA-POC test and IgM-ELISA (Z =1.16,P =0.25).Conclusion The prototype IgA-POC test has better capacity for the diagnosis of early active syphilis compared with the IgM-ELISA,so it can be applied to the screening of early active syphilis.


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