1.Mechanism of action and potential value of the IRE1α/TRAF2/JNK pathway in the progression of acute liver failure
Haimei GUAN ; Kan ZHANG ; Weiyu CHEN ; Guobao LI ; Yangling ZENG ; Riyun ZHANG ; Tianwen WANG ; Baohua XIE ; Dewen MAO
Journal of Clinical Hepatology 2024;40(6):1281-1288
Acute liver failure(ALF)is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people.Due to its high morbidity and mortality rates,unclear pathogenesis,and limited treatment methods,ALF has become a major problem that needs to be solved urgently in the field of liver diseases.In recent years,more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF,and the IRE1α/TRAF2/JNK pathway,as a part of endoplasmic reticulum stress signaling,plays a role in amplifying inflammatory response,promoting hepatocyte apoptosis,and inhibiting liver regeneration ability during the progression of diseases.As a traditional treasure of China,traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs.This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway,such as salidroside,Fructus Broussonetiae,Fructus Psoraleae+Schisandra chinensis,baicalein,genipin,kaempferol,resveratrol,sea buckthorn polysaccharide extract,and luteol,in order to provide a reference for further research and clinical practice of ALF.
2.Effect of Depression on Bacterial Infection Based on Chronic Unpredictable Mild Stress Model
Lei XU ; Runping ZHAO ; Jieyun CHEN ; Yanxian YANG ; Xilong GUO ; Min DAI ; Guobao TIAN ; Lina QIN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(4):567-581
[Objective]Depression is a common mental illness with a profound impact on physical health.Depression has been associated with a higher risk of bacterial infection;however,whether this relationship is causal and how depression affects infection remains unclear.Therefore,we aimed to investigate the effects of depressive phenotype in infected mice by constructing a chronic unpredictable mild stress(CUMS)model.[Methods]Mice were induced with CUMS for 4 weeks.The depressive phenotype was evaluated using behavioral tests.Subsequently,the mice were intraperitoneally injected with Klebsiella pneumoniae to establish bacterial infection.Serum and abdominal tissues were collected 48 h after infection.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the tissues,and enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of inflammatory factors.In addition,the fecal samples collected before infection were analyzed for 16S rDNA gene of gut microbiota,and the expression levels of NF-κB/NLRP3 signaling pathway in colon tissues of uninfected mice were detected.[Results]Behavioral tests showed that compared with the control mice,CUMS mice had significantly lower body weight(P<0.0001,t=5.426),lower sucrose preference rate(P<0.001,t=4.937),increased swimming stationary time(P<0.001,t=16.37),and decreased time spent in the central area of the open field(P<0.01,t=3.575).Survival analysis showed that compared with the control mice,the survival rate of CUMS mice significantly decreased after infection(P<0.05).Additionally,histochemical staining showed that tissue damage in the liver(P<0.05,t=4.025),kidney(P<0.05,t=2.828),and mesentery(P<0.01,t=5.367)significantly increased.Furthermore,ELISA results showed that the levels of the inflammatory cytokines IL-6(P<0.01,t=3.365),IL-1β(P<0.01,t=4.061),TNF-α(P<0.01,t=4.460)and LPS(P<0.0001,t=27.24)were elevated.The difference was statistically significant.According to 16S rDNA sequencing,CUMS-induced changes in the intestinal bacterial community structure of mice,making them significantly different from the control mice.Compared with the control mice,the expression levels of NF-κB(P<0.01,t=6.825)and NLRP3(P<0.001,t=9.561)were upregulated in CUMS mice.[Conclusion]The CUMS model was successfully constructed and CUMS mice developed more severe bacterial infection.Gut microbiota was dysregulated and the expression of NF-κB/NLRP3 signaling pathway was up-regulated in CUMS mice,which was related to the susceptibility to bacterial infection.
3.Association of frailty with anxiety and depression in patients on maintenance hemodialysis
Hongmei LIU ; Huahong ZHOU ; Xiangjiu CHEN ; Guobao HONG ; Xiongbin WU ; Yanjuan LIANG ; Chunting LI ; Meidi ZHENG ; Yueqin LAI ; Fanna LIU
The Journal of Practical Medicine 2024;40(18):2612-2617
Objective To investigate the current status of frailty in patients on maintenance hemodialysis(MHD),and explore the correlation of frailty with anxiety and depression.Methods General information,clinical data and blood biochemical data of 101 cases who underwent MHD in Department of Nephrology,Shunde Hospital Affiliated to Jinan University from January 2023 to January 2024 were collected.FRAIL scale was applied to evaluate the frailty of the patients,and they were accordingly classified into frailty group and non-frailty group(including pre-frail and non-frail participants).Anxiety and depression were evaluated by GAD-7 and PHQ-9 scale.Univariate analysis and logistic regression were used to explore the association of frailty with anxiety,depression and other possible influencing factors.Results Among the 101 cases,29 cases(28.71%)were includedin frailty group and 72 cases(71.29%)in non-frailty group.There were 42 patients with depression(41.58%)and 25 with anxiety(24.75%).In the frailty group,the prevalence of depression was 65.52%and that of anxiety 55.17%.There were significant differences in age,grip strength,exercise,stroke and coronary heart disease,anxiety and depression,ferritin and CRP between the two groups(P<0.01).Multivariate regression analysis showed that depression,anxi-ety,no exercise,stroke and high ferritin concentration were independent risk factors for frailty in MHD patients(P<0.05).Conclusion In patients on MHD,frailty is closely associated with depression,anxiety,and lack of exercise,and stroke as well as high ferritin concentration are independent risk factors for frailty.
4.Efficacy and prognostic analysis of rituximab in the treatment of M-type phospholipase A2 receptor-associated idiopathic membranous nephropathy
Jia CHEN ; Haofei HU ; Yuan CHENG ; Dongli QI ; Mijie GUAN ; Guobao WANG ; Qijun WAN
Chinese Journal of Nephrology 2024;40(8):628-636
Objective:To investigate the efficacy and prognosis of rituximab (RTX) in the treatment of M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The clinical data of PLA2R-associated IMN patients who received RTX treatment in the Shenzhen Second People's Hospital from September 2018 to March 2023 were collected. According to remission status of proteinuria, the patients were divided into proteinuria remission group (24-hour urinary protein quantity < 3.5 g) and non-proteinuria remission group (24-hour urinary protein quantity ≥ 3.5 g), and the clinical data between the two groups were compared. According to baseline 24-hour urinary protein quantity and estimated glomerular filtration rate (eGFR), the patients were divided into high-risk disease progression group [24-hour urinary protein quantity ≥ 8 g or eGFR < 60 ml·min -1·(1.73 m 2) -1] and non-high-risk disease progression group [24-hour urinary protein quantity < 8 g or eGFR ≥ 60 ml·min -1·(1.73 m 2) -1]. Kaplan-Meier survival curve was utilized to compare the differences of proteinuria remission rates and renal composite endpoint event survival rates between the two groups. Multivariate Cox regression analysis was utilized to identify the influencing factors of proteinuria remission and renal composite endpoint event. Results:This study included 46 PLA2R-associated IMN patients, with 31 males (67.4%). The baseline eGFR was (78.4±34.1) ml·min -1·(1.73 m 2) -1. The 24-hour urinary protein quantity was 8.33 (6.04, 12.85) g. After 14.95 (7.44, 22.15) months of follow-up, 29 patients (63.0%) achieved proteinuria remission, with remission time of 6.0 (5.0, 9.0) months. Six (20.7%) patients relapsed, with relapsed time of 17.25 (11.75, 18.28) months. CD20 in the proteinuria remission group was lower than that in the non-proteinuria remission group ( Z=2.270, P=0.023). Eleven (23.9%) patients experienced renal composite endpoint events wtih occurrence time of 16.07 (7.87, 29.63) months. Kaplan-Meier survival curve analysis indicated that there was no statistically significant difference in proteinuria remission rates (log-rank χ2=0.26, P=0.612) and renal composite endpoint event survival rates (log-rank χ2=0.25, P=0.619) between baseline 24-hour urinary protein quantity ≥ 8 g and < 8 g groups. There was no statistically significant difference in proteinuria remission rates after RTX treatment (log-rank χ2=0.77, P=0.381) and renal composite endpoint event survival rates (log-rank χ2=1.41, P=0.236) between eGFR ≥ 60 ml·min -1·(1.73 m 2) -1 and < 60 ml·min -1·(1.73 m 2) -1 groups. Multivariate Cox regression analysis showed that hypertension history ( HR=0.16, 95% CI 0.05-0.55), immunosuppressive therapy history ( HR=0.08, 95% CI 0.01-0.50), baseline eGFR < 60 ml·min -1·(1.73 m 2) -1 ( HR=0.21, 95% CI 0.05-0.92), baseline PLA2R antibody titer ≥ 100 RU/ml ( HR=0.20, 95% CI 0.06-0.69), long time between treatment and first diagnosis ( HR=1.33, 95% CI 1.12-1.57), high baseline triglyceride ( HR=1.46, 95% CI 1.02-2.08), and baseline 24-hour urinary protein quantity ≥ 8 g ( HR=8.54, 95% CI 2.08-35.12) were independent influencing factors of proteinuria remission after RTX treatment. The baseline PLA2R antibody titer ≥ 100 RU/ml was an independent influencing factor of reaching the renal composite endpoint event ( HR=7.31, 95% CI 1.23-43.62). Conclusions:The proteinuria remission rate after RTX treatment of PLA2R-associated IMN is 63.0% and the recurrence rate is 20.7%. The incidence rate of renal composite endpoint event is 23.9%. The hypertension history, immunosuppressant medication history, baseline eGFR < 60 ml·min -1·(1.73 m 2) -1, baseline PLA2R antibody titer ≥ 100 RU/ml, long time between treatment and first diagnosis, high baseline triglyceride, and baseline 24-hour urinary protein quantity ≥ 8 g are independent influencing factors of proteinuria remission, and baseline PLA2R antibody titer ≥ 100 RU/ml is an independent risk factor of renal poor prognosis in PLA2R-associated IMN patients.
5.Development of the Scientific, Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines.
Nan YANG ; Hui LIU ; Wei ZHAO ; Yang PAN ; Xiangzheng LYU ; Xiuyuan HAO ; Xiaoqing LIU ; Wen'an QI ; Tong CHEN ; Xiaoqin WANG ; Boheng ZHANG ; Weishe ZHANG ; Qiu LI ; Dong XU ; Xinghua GAO ; Yinghui JIN ; Feng SUN ; Wenbo MENG ; Guobao LI ; Qijun WU ; Ze CHEN ; Xu WANG ; Janne ESTILL ; Susan L NORRIS ; Liang DU ; Yaolong CHEN ; Junmin WEI
Chinese Medical Journal 2023;136(12):1430-1438
BACKGROUND:
This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability.
METHODS:
This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability.
RESULTS:
STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min.
CONCLUSION
The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results
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Surveys and Questionnaires
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Practice Guidelines as Topic
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Humans
6.Preparation and Performance of Three-Dimensional Silk FibroinScaffolds with Different Matrix Stiffness
Shiyun YIN ; Yaxin DENG ; Guobao CHEN
Journal of Medical Biomechanics 2023;38(1):E142-E148
Objective After hydrogen bonding between collagen ( COL) and silk fibroin ( SF ) at different concentrations, a composite scaffold with adjustable stiffness was prepared by combining with gel system, and its physical and chemical properties were characterized. Methods SF with different qualities was dissolved in sodium alginate (SA) solution, then COL solution at different concentration and calcium carbonate ( CaCO3 ) powder were added. The hydrogels of SC1, SC2, and SC3 groups were obtained by taking out the mixed solution and adding some gluconic acid lactone ( GDL) powder, and different SF scaffolds were obtained after freeze drying. Results The SF scaffolds with adjustable stiffness were successfully prepared. The compression moduli of SC1, SC2, and SC3 groups were (17. 31±2. 73), (24. 12±1. 81), (32. 54±1. 81) kPa, respectively. The innerstructure of the scaffolds was observed. From SC1 group to SC3 group, pores of the scaffolds were smaller and fewer, and hydrophilicity of the materials become better and better. Conclusions Three-dimensional ( 3D) porous scaffolds with different matrix stiffness can be prepared by changing the concentration of SF and COL solution. The concentration of SF and COL is proportional to the compression modulus, water absorption, water retention and swelling rate of SF scaffolds, while inversely proportional to porosity. The findings of this study are expected to provide theoretical guidance for construction of scaffolds with appropriate matrix stiffness for inducing osteogenic differentiation of mesenchymal stem cells
7.Study on the relationships between precollege sexual abuse experiences at different stages and adult attachment in college students
Liru CHEN ; Guobao ZHANG ; Guodie XIE ; Nuo XU ; Puyu SU
Chinese Journal of Preventive Medicine 2020;54(10):1098-1103
Objective:To explore the association between precollege sexual abuse experiences at different periods and adult attachment in college students.Methods:In October 2018,a total of 4 034 college students were selected from 4 colleges in Hefei City by using the stratified cluster sampling method. A self-designed questionnaire was used to investigate the demographic characteristics, sexual abuse experience, and attachment style of participants. Multivariate linear regression analysis was performed to analyze the association between different periods, types of precollege sexual abuse experiences and attachment style in college students.Results:The rate of total precollege sexual abuse, noncontact sexual abuse, and contact sexual abuse was 14.1% (569), 12.7% (512) and 5.4% (219), respectively. Multivariate linear regression analysis showed that secure attachment [β(95% CI)=-0.205 (-0.292, -0.117)] was negatively correlated with total precollege sexual abuse experiences, whereas anxiety attachment [β(95% CI)=0.211 (0.110, 0.310)], avoidant attachment [β(95% CI)=0.117 (0.020, 0.216)] were positively correlated with total precollege sexual abuse experiences. The number of periods of precollege noncontact sexual abuse was negatively correlated with secure attachment [β(95% CI)=-0.106(-0.171, -0.041)]and positively correlated with anxiety attachment [β(95% CI)=0.158 (0.084, 0.231)]and avoidant attachment [β(95% CI)=0.080 (0.008, 0.152)]. The noncontact [β(95% CI)=0.427 (0.018, 0.775)] and contact sexual abuse [β(95% CI)=0.468 (0.251, 0.687)] in high school were positively correlated with anxiety attachment ( P<0.05). Conclusion:Different periods, types of precollege sexual abuse experiences were all associated with adult attachment in college students.
8.Study on the relationships between precollege sexual abuse experiences at different stages and adult attachment in college students
Liru CHEN ; Guobao ZHANG ; Guodie XIE ; Nuo XU ; Puyu SU
Chinese Journal of Preventive Medicine 2020;54(10):1098-1103
Objective:To explore the association between precollege sexual abuse experiences at different periods and adult attachment in college students.Methods:In October 2018,a total of 4 034 college students were selected from 4 colleges in Hefei City by using the stratified cluster sampling method. A self-designed questionnaire was used to investigate the demographic characteristics, sexual abuse experience, and attachment style of participants. Multivariate linear regression analysis was performed to analyze the association between different periods, types of precollege sexual abuse experiences and attachment style in college students.Results:The rate of total precollege sexual abuse, noncontact sexual abuse, and contact sexual abuse was 14.1% (569), 12.7% (512) and 5.4% (219), respectively. Multivariate linear regression analysis showed that secure attachment [β(95% CI)=-0.205 (-0.292, -0.117)] was negatively correlated with total precollege sexual abuse experiences, whereas anxiety attachment [β(95% CI)=0.211 (0.110, 0.310)], avoidant attachment [β(95% CI)=0.117 (0.020, 0.216)] were positively correlated with total precollege sexual abuse experiences. The number of periods of precollege noncontact sexual abuse was negatively correlated with secure attachment [β(95% CI)=-0.106(-0.171, -0.041)]and positively correlated with anxiety attachment [β(95% CI)=0.158 (0.084, 0.231)]and avoidant attachment [β(95% CI)=0.080 (0.008, 0.152)]. The noncontact [β(95% CI)=0.427 (0.018, 0.775)] and contact sexual abuse [β(95% CI)=0.468 (0.251, 0.687)] in high school were positively correlated with anxiety attachment ( P<0.05). Conclusion:Different periods, types of precollege sexual abuse experiences were all associated with adult attachment in college students.
9. Association between suffering experiences from precollege peer bullying at different stages and the quality of health-related life among college students
Guobao ZHANG ; Nuo XU ; Azhu HAN ; Guodie XIE ; Liru CHEN ; Puyu SU
Chinese Journal of Epidemiology 2019;40(8):965-970
Objective:
To explore the effects of precollege peer bullying at different stages, on quality of life (QOL) among college students.
Methods:
A stratified cluster sampling method was used to select participants in October, 2018. Cluster sampling method was adopted to recruit a sample of 4 034 college students from four universities in Hefei city, Anhui province. Relations between peer bullying at different stages before entering college, and the quality of life, were investigated.
10.Mediating role of adult attachment in childhood abuse and borderline personality disorder in college students
Chinese Journal of School Health 2019;40(12):1838-1841
Objective:
To explore the relationship between childhood abuse, adult attachment and borderline personality disorder (BPD) in college students, and to provide reference for promoting the physical and mental health of college students.
Methods:
We selected undergraduate students from four colleges in Hefei, a total of 4 034 college students were surveyed by the childhood trauma questionnaire short form(CTQ-SF), the state adult attachment measure (SAAM) and the Personality Diagnostic Questionnaire(PDQ).
Results:
BPD was found in 4.2% of subjects, 4.5% of males and 3.7% of females. The score of BPD in non-single-parent families was lower than that in single-parent families, in families with average family economic status was lower than that in families with poor and good family economic status, and in families with medium father education level was lower than that in fathers with low and high education level(Z=-2.30, 29.25, 9.63, P<0.05). Childhood abuse, avoidant attachment and anxious attachment positively predicted BPD(β=0.21, 0.10, 0.23, P<0.01), secure attachment negatively predicted BPD(β=-0.15, P<0.01). Adult attachment played a partial mediating role in the effects of childhood abuse on BPD, with the mediating effect accounting for 16.7% of the total effect.
Conclusion
Adult attachment plays a mediating role in the effects of childhood abuse on BPD.


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