1.Progress on mechanism of IL-32 in transformation process of gastric"inflammation to cancer"
Weijian ZHANG ; Yuqi WU ; Dishu ZHOU ; Shuya SONG ; Xinxin HONG ; Yifei XU ; Tiantian CAI ; Shaoju GUO ; Huafeng PAN ; Haiwen LI
Chinese Journal of Immunology 2025;41(9):2264-2271
IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.
2.Progress on mechanism of IL-32 in transformation process of gastric"inflammation to cancer"
Weijian ZHANG ; Yuqi WU ; Dishu ZHOU ; Shuya SONG ; Xinxin HONG ; Yifei XU ; Tiantian CAI ; Shaoju GUO ; Huafeng PAN ; Haiwen LI
Chinese Journal of Immunology 2025;41(9):2264-2271
IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.
3.Effect of heptamethoxyflavone on proliferation,migration and invasion of human colorectal cancer cells and its mechanism
Shiqi XU ; Yingtong CHEN ; Man ZHUANG ; Gengxin YU ; Xiaoyan WANG ; Yi CAI ; Shaoju GU
Chinese Journal of Pathophysiology 2024;40(8):1392-1398
AIM:This study is aimed to investigate the impact of 3,5,6,7,8,3',4'-heptamethoxyflavone(HMF)on the proliferation,invasion,and migration of human colorectal cancer(CRC)cell lines(SW480 and HCT116)and preliminarily explore the underlying molecular mechanisms.METHODS:Human colorectal cancer cells(SW480 and HCT116)cultured in vitro were subjected to various concentrations of HMF(0,12.5,25 and 50 μmol/L)for 48 h.Proliferation levels were assessed using the CCK-8 assay,invasion abilities were examined via the Transwell assay,migra-tion rates were measured using the scratch assay,and oxidative stress levels were determined by the DCF-DA reactive oxy-genation assay.The mRNA expression levels of heme oxygenase-1(HO-1)mRNA and NAD(P)H:quinone oxidoreduc-tase-1(NQO-1)were quantified using RT-qPCR.RESULTS:Treatment with varying concentrations of HMF resulted in a significant reduction in the proliferative capacity of SW480 and HCT116 cancer cells,as was indicated by CCK-8 experi-ments(P<0.05).Transwell assays demonstrated a pronounced attenuation in the invasive potential of SW480 and HCT116 following HMF treatment(P<0.05).Scratch assays highlighted a notable constraint on the migratory capabilities of SW480 and HCT116 after HMF treatment(P<0.05).DCF-DA staining revealed a substantial increase in reactive oxy-gen species(ROS)levels within SW480 and HCT116 cells after HMF treatment(P<0.05).Furthermore,RT-qPCR ex-periments elucidated that HMF markedly suppressed the mRNA expression of antioxidant genes HO-1 and NQO-1.CON-CLUSION:HMF induces oxidative stress response in SW480 and HCT116 cells,consequently inhibiting their prolifera-tion,invasion and migration.
4.Mechanism of Intestinal Metaplasia of Gastric Mucosa and Prediction of Traditional Chinese Medicine Based on M2 Polarization of Macrophages
Weijian ZHANG ; Junyi LI ; Shiting LI ; Dishu ZHOU ; Xinxin HONG ; Yifei XU ; Tiantian CAI ; Huafeng PAN ; Haiwen LI ; Shaoju GUO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(9):2333-2345
Objective To explore the effect of M2 polarization of macrophages on intestinal metaplasia(IM)of gastric mucosa and its therapeutic target,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The data sets related to IM and macrophage M2 polarization were downloaded from the public database,and the correlation between IM and macrophage M2 polarization was further expounded by immune infiltration analysis,gene correlation analysis,functional enrichment analysis,protein interaction network and experimental verification.Finally,the obtained hub genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and treatment of IM.Results Immunoinfiltration and immunofluorescence analysis showed that the expression of macrophage M2 polarization markers CD68+CD163+(P=0.0394)and CD68+CD206+(P=0.002)in IM group was significantly higher than that in normal group,and the infiltration level of M2 macrophages in IM group was significantly higher than that in normal group(P<0.05).IM related marker genes(CDX1,MUC2,TFF3)were positively correlated with macrophage M2 polarization markers(CD209,ARG1,MSR1,STAT3,IL32,SELENOP)(P<0.05).Functional enrichment analysis showed that the differential genes co-expressed by IM and macrophage M2 polarization were closely related to molecular biological functions such as carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.Finally,7 pivotal differential genes co-expressed by IM and macrophage M2 were screened,which were TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA,respectively.According to the prediction of traditional Chinese medicine,23 kinds of traditional Chinese medicine for IM were predicted,which could be classified into 14 categories according to their efficacy,among which heat-clearing antidote appeared most frequently,followed by drugs for tonifying qi and painkillers for promoting blood circulation drugs.Conclusion Macrophage M2 polarization may be involved in the pathogenesis and development of IM through exocrine pathway.IM and seven hub genes co-expressed by macrophage M2 polarization(TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA)and IM specific molecules CDX1,MUC2 and TFF3 may be associated with each other and participate in the progression of IM.The therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM in traditional Chinese medicine.Starting from the M2 polarization of macrophages,it is expected to become a new direction and breakthrough in clinical prevention and treatment of IM.
5.Mechanism of Intestinal Metaplasia of Gastric Mucosa and Prediction of Traditional Chinese Medicine Based on M2 Polarization of Macrophages
Weijian ZHANG ; Junyi LI ; Shiting LI ; Dishu ZHOU ; Xinxin HONG ; Yifei XU ; Tiantian CAI ; Huafeng PAN ; Haiwen LI ; Shaoju GUO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(9):2333-2345
Objective To explore the effect of M2 polarization of macrophages on intestinal metaplasia(IM)of gastric mucosa and its therapeutic target,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The data sets related to IM and macrophage M2 polarization were downloaded from the public database,and the correlation between IM and macrophage M2 polarization was further expounded by immune infiltration analysis,gene correlation analysis,functional enrichment analysis,protein interaction network and experimental verification.Finally,the obtained hub genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and treatment of IM.Results Immunoinfiltration and immunofluorescence analysis showed that the expression of macrophage M2 polarization markers CD68+CD163+(P=0.0394)and CD68+CD206+(P=0.002)in IM group was significantly higher than that in normal group,and the infiltration level of M2 macrophages in IM group was significantly higher than that in normal group(P<0.05).IM related marker genes(CDX1,MUC2,TFF3)were positively correlated with macrophage M2 polarization markers(CD209,ARG1,MSR1,STAT3,IL32,SELENOP)(P<0.05).Functional enrichment analysis showed that the differential genes co-expressed by IM and macrophage M2 polarization were closely related to molecular biological functions such as carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.Finally,7 pivotal differential genes co-expressed by IM and macrophage M2 were screened,which were TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA,respectively.According to the prediction of traditional Chinese medicine,23 kinds of traditional Chinese medicine for IM were predicted,which could be classified into 14 categories according to their efficacy,among which heat-clearing antidote appeared most frequently,followed by drugs for tonifying qi and painkillers for promoting blood circulation drugs.Conclusion Macrophage M2 polarization may be involved in the pathogenesis and development of IM through exocrine pathway.IM and seven hub genes co-expressed by macrophage M2 polarization(TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA)and IM specific molecules CDX1,MUC2 and TFF3 may be associated with each other and participate in the progression of IM.The therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM in traditional Chinese medicine.Starting from the M2 polarization of macrophages,it is expected to become a new direction and breakthrough in clinical prevention and treatment of IM.
6.The Effect of Doctor-patient Relationship Perception on Work Performance among Medical Staff in Public Hospitals:A Moderated Mediation Model
Fan XU ; Jiquan ZHANG ; Shaoju XIE ; Lin LUO ; Wei QING ; Qiao LI ; Yunfeng NING ; Jinlei DU ; Peimin ZHUANG
Chinese Medical Ethics 2023;36(7):760-769
To explore the effect of doctor-patient relationship perception on work performance among medical staff in public hospitals and its mechanism. The convenient sampling method was used to select 380 medical staff working in four public tertiary hospitals in Sichuan Province, Zhejiang Province, and Fujian Province from August 2022 to October 2022 as the research objects, and the General Information Questionnaire, Doctor-Patient Relationship Scale, General Self-Efficacy Scale, Perceived Organizational Support Scale, Work Performance Questionnaire were used. This paper showed that the doctor-patient relationship perception of medical staff was negatively correlated with self-efficacy (r=-0.392, P<0.01) and work performance (r=-0.286, P<0.01), self-efficacy was positively correlated with perceived organizational support (r=0.538, P<0.01) and work performance (r=0.507, P<0.01), perceived organizational support was positively correlated with work performance (r=0.510, P<0.01). Self-efficacy played a partial mediating role between doctor-patient relationship perception and work performance, and its effect value was -0.241, accounting for 64.78% of the total effect. Perceived organizational support weakened the negative predictive effect of doctor-patient relationship perception on self-efficacy, which moderates the first half path of the mediating model that doctor-patient relationship perception affects work performance through self-efficacy. It indicated that the doctor-patient relationship perceived by medical staff in public hospitals is poor. Measures should be taken from the aspects of policy support, hospital and society levels to alleviate the doctor-patient relationship, play the mediating role of self-efficacy and the moderating role of organizational support, minimize the negative impact of doctor-patient relationship on the work performance among medical staff, and improve the work performance of medical staff, so as to improve the overall quality of medical services.
7.Effects of Gentiopicroside on the Apoptosis of Human Pancreatic Cancer Cells PANC- 1 and IL- 6/JAK2/STAT3 Signaling Pathway
Song MENG ; Yaozhu ZHOU ; Yongchao MA ; Songtao XU ; Shaoju JIN
China Pharmacy 2020;31(15):1836-1841
OBJECTIVE:To study the effects of gentiopicroside on the apo ptosis o f human pancreatic cancer cells PANC- 1,and to explore its mechanism from the perspective of IL- 6/JAK2/STAT3 signaling pathway. METHODS :Using PANC- 1 cells as model , the proliferation inhibition rate of cells was tested by MTT assay after treated with 0(negative contro ),2,4,8,16,32,64,128 mg/L gentiopicroside for 72 h and IC 50 were calculated. The cells were divided into negative control group ,gemcitabine group (positive control,4 mg/L)and gentiopicroside low-concentration ,medium-concentration and high-concentration groups (15,30,60 mg/L). After cultured for 1,3,5,7 d,Trypan blue exclusion staining was used to count the survival cell ,and the growth of cells was investigated. After cultured for 72 h,colony formation assay was used to observe colony formation rate of cells ;the apoptotic rate of cells was detected by Hoechst 33258 staining;the mRNA and protein expressions of IL- 6,JAK2,STAT3 in cells were detected by RT-PCR and Western blotting assay. RESULTS :4-28 mg/L gentiopicroside could inhibit the proliferation of cells (P<0.05 or P< 0.01),in concentration dependent trend ;IC50 was 9.54 mg/L. Compared with negative control group ,survival cell count (cultured from 3,5,7 d),mRNA and protein expressions of IL- 6,JAK2 and STAT 3 in cells were decreased significantly in gemcitabine group , gentiopicroside medium-concentration and high-concentration groups (P<0.05 or P<0.01),while the apoptotic rate was increased significantly (P<0.01). The colony formation rate of cellswere decreased significantly in gemcitabine group and gentiopicroside high-concentration group (P<0.01). mail:hb.gz@163.com Compared with gemcitabine group ,there was no statistical significance in above indexes of gentiopicroside high- 6716008。 concentration group (P>0.05). CONC LUSIONS:30,60 mg/L gentiopicroside could inhibit the proliferation and induce apoptosis of PANC- 1 cells,and 60 mg/L gentiopicroside is similar to gemcitabine in the effects. Its mechanism may be related to inhibiting the activation of IL- 6/JAK2/STAT3 signaling pathway.
8.Efficacy and Safety of Lanqin Oral Liquid for Herpangina in Children :a Meta-analysis
Bin YUAN ; Yalei SUN ; Yiwen WU ; Shaoju XU
China Pharmacy 2019;30(12):1702-1706
OBJECTIVE: To systematically evaluate the efficacy and safety of Lanqin oral liquid in the treatment of herpangina in children. METHODS: Randomized controlled trials (RCTs) involving Lanqin oral liquid or routine symptomatic treatment combined with Lanqin oral liquid (trial group) versus routine treatment (control group) in the treatment of pediatric herpangina were retrieved from PubMed, Embase, CBM, CNKI, Wanfang database, VIP database, etc. Meta-analysis was performed by using Rev Man 5.3 software after literature screening, data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0. RESULTS: A total of 11 RCTs were included, involving 1 204 patients. Meta-analysis showed that total response rate [RR=1.17, 95%CI(1.10, 1.24), P<0.000 01], fade time of herpes [MD=-2.17, 95%CI(-2.63, -1.72), P<0.000 01] and fade time of fever [MD=-1.52, 95%CI(-1.72, -1.31), P<0.000 01] in trial group was significantly higher than in control group. There was no statistical significance in the incidence of ADR between 2 groups [RR=1.00, 95%CI(0.52, 1.93), P=1.00]. Subgroup analysis based on rehydration symptomatic treatment showed that without rehydration, fade time of herpes in trial group was significantly shorter than control group [MD=-1.64, 95%CI (-2.03, -1.26), P<0.000 01]; with rehydration, fade time of herpes in trial group was significantly shorter than control group [MD=-2.79, 95%CI(-2.97, -2.61),P<0.000 01]. CONCLUSIONS: Lanqin oral liquid can effectively improve therapeutic efficacy of herpangina patients, effectively shorten fade time of fever and herpes, without increasing the occurrence of ADR.
9.Effects of Analgesic and Anti-inflammatory of Sophocarpine and Related COX- 2/PGE2 Signaling Pathway
Congmin FU ; Min WANG ; Songtao XU ; Shaoju JIN
China Pharmacy 2019;30(13):1775-1780
OBJECTIVE: To study analgesic and anti-inflammatory effects of sophocarpine (SC) on inflammatory pain model mice and related COX-2/PGE2 signaling pathway. METHODS: (1)Analgesic experiment. Totally 50 mice were randomly divided into blank control group (normal saline), positive control group (aspirin, 100 mg/kg) and SC high-dose, medium-dose and low-dose groups (40, 20, 10 mg/kg), with 10 mice in each group. They were given relevant medicine once a day intragastrically for consecutive 5 d. 2 h after last medication, mice in each group was given glacial acetic acid solution intraperitoneal injection; writhing times of mice within 15 minutes were recorded. Other 50 mice were collected; they were grouped and given medicine as above. The response pain threshold (Tr) of mice was determined by intelligent hot plate instrument 15, 30, 60, 120 min after last administration. (2)Anti-inflammatory and mechanism experiment. Other 60 mice were randomly divided into blank control group (normal saline), model control group (normal saline), positive control group (aspirin, 100 mg/kg), SC high-dose, medium-dose and low-dose groups (40, 20, 10 mg/kg), with 10 mice in each group; they were given relevant medicine intragastrically, once a day, for consecutive 5 d. 60 min after last medication, except for blank control group, other groups were given 1% carrageenan to induce inflammation. 1, 3, 5 h after inducing inflammation, the degree of paw swelling were determined in each group. Other 30 mice were randomly divided into blank control group (normal saline), model control group (normal saline), SC group (40 mg/kg), with 10 mice in each group; they were given relevant medicine intragastrically once a day, for consecutive 5 d. 60 min after last medication, except for blank control group, other groups were given 1% carrageenan to induce inflammation in other groups. 5 h later, the levels of SOD, MDA, GSH-Px and T-AOC in paw swelling tissue of mice were determined by biochemical method. The level of PGE2 in paw swelling tissue was determined by ELISA. The mRNA and protein expressions of COX-1 and COX-2 in paw swelling tissue of mice were detected by RT-PCR and Western blot method. RESULTS: In analgesic experiment, compared with blank control group, writhing times of mice were decreased significantly in administration groups (P<0.05 or P<0.01), Tr were increased significantly 30, 60, 120 min after last medication (P<0.05 or P<0.01). In anti-inflammatory and mechanism experiment, compared with blank control group, the degree of paw swelling were increased significantly in model control group 1, 3, 5 h after inducing inflammation (P<0.01); the levels of SOD, GSH-Px and T-AOC in paw swelling tissue were decreased significantly (P<0.01); the levels of MDA and PGE2 were increased significantly (P<0.01), and mRNA and protein expressions of COX-2 were increased significantly (P<0.01). Compared with model control group, the degree of paw swelling were decreased significantly in positive control group, SC high-dose and low-dose groups 3 and 5 h after inducing inflammation (P<0.05 or P<0.01). The levels of SOD, GSH-Px and T-AOC in paw swelling tissue were increased significantly in SC group (P<0.05 or P<0.01), while the levels of MDA and PGE2 were decreased significantly (P<0.01) as well as mRNA and protein expressions of COX-2 were decreased significantly (P<0.05). There was no statistical significance in other indexes (P>0.05). CONCLUSIONS: SC possesses good anti-inflammatory and analgesic effects, and its mechanism may be related to anti-oxidative stress and inhibition of COX-2/PGE2 signaling pathway.
10.Revision of the Theory of Mind Tests for Children with Autism Spectrum Disorder
Weiting SHAO ; Sheng XU ; Hua FENG ; Shaoju JIN ; Shuangshuang ZHU ; Dan LI ; Zhen ZHANG ; Qiao ZHOU ; Xianjin XU
Chinese Mental Health Journal 2017;31(2):144-149
Objective:To amendment a tool of theory of mind (TOM) tests that can be applied to children with autism spectrum disorder (ASD) in mainland China,and assess the ability of ToM of children with ASD.Methods:The items of the ToM tests were revised by observing and recording events of children's life.Totally 200 normal children were selected in line with the standard from kindergarten to Grade 6 for formal tes-ting.With 156 valid data,Pearson correlation coefficient and Cronbach α coefficient were established for the test.Three experts were invited to make sure the content validity.Researchers randomly selected 30 normal children for retest purpose after 2 months.Twenty five children with ASD were tested and compared with normal children's test scores.Results:The revised test included 39 entries,which was divided into three sub-tests,42 points in total.The correlation coefficient of three subtests of the tests was 0.54-0.77,the correlation coefficient between the test and the subtest was 0.62-0.93 (Ps < 0.01).The scores of three experts for the test were 114,108,and 105.The total scores and subtest scores were lower in children with ASD than in normal children (Ps <0.01).The Cronbach a coefficient of the test was 0.84,Cronbach a coefficients for three subtest were 0.83,0.80,and 0.78,respectively.The retest reliability was 0.84,and reliabilities for three subtest were 0.75,0.74,and 1.00.Conclusion:The revised Theory of Mind Tests for Children with Autism Spectrum Disorder are fulfilled mostly in line with psychometric testing requirement.It might be a selection to measure the ability of theory of mind of children with ASD in mainland China.

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