1.Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.
Wenzhen DANG ; Xiaomin WANG ; Huaying LI ; Yixuan XU ; Xinyu LI ; Siqi HUANG ; Hongru TAO ; Xiao LI ; Yulin YANG ; Lijiang XUAN ; Weilie XIAO ; Dean GUO ; Hao ZHANG ; Qiong WU ; Jie ZHENG ; Xiaoyan SHEN ; Kaixian CHEN ; Heng XU ; Yuanyuan ZHANG ; Cheng LUO
Acta Pharmaceutica Sinica B 2025;15(8):3997-4013
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.
2.Effects of lncRNA ZFAS1 on hippocampal neuron damage andcognitive function in diabetic encephalopathy mice
Huaying GUAN ; Mingxing ZHU ; Zhijing WU ; Huan WANG ; Weiwen CHEN ; Zhenqin WU ; Yanfang ZHENG ; Mingqing HUANG
Chinese Journal of Pathophysiology 2025;41(11):2081-2090
AIM:To investigate the expression profile and biological significance of long noncoding RNA(lncRNA)zinc finger antisense 1(ZFAS1)in the brains of mice with diabetic encephalopathy(DE).METHODS:Ten db/m mice served as the normal control group,while twenty 22-week-old db/db mice were used to establish the DE model and randomly divided into two subgroups:ten as the db/db model control and the remaining ten receiving ZFAS1 gene knockdown(db/db+sh-ZFAS1)via lentiviral transfection.Weekly measurements of body weight and blood glucose levels were performed.Brain tissues were collected for Nissl staining to evaluate neuronal damage,TUNEL assay to detect apop-tosis,and immunofluorescence staining to examine neural biomarker expression.Serum levels of tumor necrosis factor-α(TNF-α)and oxidative stress markers,including reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px),were determined.Western blot was conducted to quantify the protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),p38 mitogen-activated protein kinase and phosphorylated p38(p-p38)in brain tissues.The expression levels of ZFAS1 and caspase-3 mRNA were determined by RT-qPCR.RESULTS:Knockdown of ZFAS1 in db/db mice significantly improved cognitive function,alleviated hippocampal neuronal damage,and reduced body weight and blood glucose levels(P<0.01).More-over,oxidative stress was mitigated,as evidenced by decreased MDA and ROS levels(P<0.01)and increased activity of antioxidant enzymes,GSH-Px,SOD and CAT(P<0.01 or P<0.05).Meanwhile,ZFAS1 silencing down-regulated Bax and p-p38/p38 protein expression(P<0.01 or P<0.05)while up-regulating Bcl-2(P<0.01).Consistently,RT-qPCR confirmed significant down-regulation of ZFAS1 and caspase-3 mRNA levels(P<0.01).CONCLUSION:lncRNA ZFAS1 is highly expressed in the hippocampus of DE mice.Down-regulation of ZFAS1 expression enhances cognitive func-tion,suppresses oxidative stress,and inhibits neuronal apoptosis,thereby attenuating neural damage in DE.
3.Effects of lncRNA ZFAS1 on hippocampal neuron damage andcognitive function in diabetic encephalopathy mice
Huaying GUAN ; Mingxing ZHU ; Zhijing WU ; Huan WANG ; Weiwen CHEN ; Zhenqin WU ; Yanfang ZHENG ; Mingqing HUANG
Chinese Journal of Pathophysiology 2025;41(11):2081-2090
AIM:To investigate the expression profile and biological significance of long noncoding RNA(lncRNA)zinc finger antisense 1(ZFAS1)in the brains of mice with diabetic encephalopathy(DE).METHODS:Ten db/m mice served as the normal control group,while twenty 22-week-old db/db mice were used to establish the DE model and randomly divided into two subgroups:ten as the db/db model control and the remaining ten receiving ZFAS1 gene knockdown(db/db+sh-ZFAS1)via lentiviral transfection.Weekly measurements of body weight and blood glucose levels were performed.Brain tissues were collected for Nissl staining to evaluate neuronal damage,TUNEL assay to detect apop-tosis,and immunofluorescence staining to examine neural biomarker expression.Serum levels of tumor necrosis factor-α(TNF-α)and oxidative stress markers,including reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px),were determined.Western blot was conducted to quantify the protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),p38 mitogen-activated protein kinase and phosphorylated p38(p-p38)in brain tissues.The expression levels of ZFAS1 and caspase-3 mRNA were determined by RT-qPCR.RESULTS:Knockdown of ZFAS1 in db/db mice significantly improved cognitive function,alleviated hippocampal neuronal damage,and reduced body weight and blood glucose levels(P<0.01).More-over,oxidative stress was mitigated,as evidenced by decreased MDA and ROS levels(P<0.01)and increased activity of antioxidant enzymes,GSH-Px,SOD and CAT(P<0.01 or P<0.05).Meanwhile,ZFAS1 silencing down-regulated Bax and p-p38/p38 protein expression(P<0.01 or P<0.05)while up-regulating Bcl-2(P<0.01).Consistently,RT-qPCR confirmed significant down-regulation of ZFAS1 and caspase-3 mRNA levels(P<0.01).CONCLUSION:lncRNA ZFAS1 is highly expressed in the hippocampus of DE mice.Down-regulation of ZFAS1 expression enhances cognitive func-tion,suppresses oxidative stress,and inhibits neuronal apoptosis,thereby attenuating neural damage in DE.
4.Application of PDCA cycle method in internal error control management of intravenous drug dispen-sing center
Huaying HUANG ; Xiaojing YE ; Lixiu LIU ; Xiuzhen WEN ; Honglan ZHONG ; Guangyang XIE
Modern Hospital 2025;25(1):38-40
Objective This study aims to explore the application effectiveness of the PDCA cycle method in preventing and reducing internal errors in the intravenous drug dispensing center(PIVAS).Methods Internal error data from our hospital's PIVAS in 2020 and 2021 were collected.The data from 2020 represented the pre-implementation of the PDCA cycle,while the data from 2021 represented the post-implementation period.The changes in internal errors and error rates before and after imple-mentation were compared.Results After implementing the PDCA cycle management measures,the annual error rate decreased from 0.887%o in 2020 to 0.681‰ in 2021,a decrease of 23.22%.Conclusion The PDCA cycle method can effectively reduce the occurrence of internal errors,improve work accuracy,and ensure the safety of clinical drug use in PIVAS.
5.Application of PDCA cycle method in internal error control management of intravenous drug dispen-sing center
Huaying HUANG ; Xiaojing YE ; Lixiu LIU ; Xiuzhen WEN ; Honglan ZHONG ; Guangyang XIE
Modern Hospital 2025;25(1):38-40
Objective This study aims to explore the application effectiveness of the PDCA cycle method in preventing and reducing internal errors in the intravenous drug dispensing center(PIVAS).Methods Internal error data from our hospital's PIVAS in 2020 and 2021 were collected.The data from 2020 represented the pre-implementation of the PDCA cycle,while the data from 2021 represented the post-implementation period.The changes in internal errors and error rates before and after imple-mentation were compared.Results After implementing the PDCA cycle management measures,the annual error rate decreased from 0.887%o in 2020 to 0.681‰ in 2021,a decrease of 23.22%.Conclusion The PDCA cycle method can effectively reduce the occurrence of internal errors,improve work accuracy,and ensure the safety of clinical drug use in PIVAS.
6.Correlation analysis between renal ectopic fat deposition and early diabetic kidney disease
Jianjun HUA ; Wenting YANG ; Huaying HUANG ; Yonghao PAN ; Sisi WANG ; Mingliang YING
Chinese Journal of Diabetes 2024;32(5):352-356
Objective To investigate the value of iterative decomposition of water and fat with echo asymmetry and least-squares(IDEAL-IQ)sequence in evaluating the correlation between renal ectopic fat deposition and early diabetic kidney disease(DKD)in patients with diabetes mellitus(DM).Methods A total of 51 patients with T1DM or T2DM were enrolled in this study from the Endocrinology and Metabolism Department in Affiliated Jinhua Hospital,Zhejiang University School of Medicine during January 2022 to July 2023.All the patients were divided into two groups according to the results of urine albumin creatinine ratio(UACR):normal or slightly increased urinary micro albumin group(NAU,UACR<30 mg/g,n=27)and diabetic kidney disease group(DKD,UACR 30~300 mg/g,n=24).Meanwhile,55 healthy subjects in health examination were selected as control group(NC).Pearson correlation analysis was used to analyze the correlation between renal FF and other indicators.Logistic regression analysis was used to analyze the influencing factors of early DKD,and the diagnostic efficiency of renal FF for early DKD was analyzed by the ROC curve.Results Serum creatinine(Scr)and renal fat fraction(FF)value were higher in DKD group than in NC and NAU groups(P<0.05).Pearson correlation analysis showed that kidney FF were positively correlated with UACR and Hcy(P<0.05).Logistic regression analysis showed that after adjusting for confounding factors,renal FF was a contributing factor to early DKD.The ROC curve revealed that model 2 had the highest diagnostic efficiency,with AUC=0.801,sensitivity of 66.7%,specificity of 85.2%,accuracy of 80.0%,and a renal FF cut-off value was 2.46%.Conclusion IDEAL-IQ could non-invasively measure the renal fat content in DM patients,and the renal FF were significantly associated with DKD in early stage.
7.Correlation analysis of fragmented QRS on electrocardiogram and microalbuminuria and serum uric acid in patients with type 2 diabetes mellitus
Lili WANG ; Lifang BAO ; Linjun ZHENG ; Jiayu HU ; Huaying HUANG ; Jun JIANG
Chinese Journal of Diabetes 2024;32(9):652-656
Objective To analyze the relationship between fragmented QRS(fQRS)and microalbuminuria(MAU)and serum uric acid(SUA)in patients with type 2 diabetes mellitus(T2DM).Methods From October 2022 to June 2023,245 T2DM patients diagnosed by The Department of Endocrinology,Jinhua Hospital Affiliated to Zhejiang University School of Medicine were selected and divided into fQRS group(fQRS,n=111)and T2DM group(n=134)according to ECG results.The general data,biochemical indexes,left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),interventricular septum(IVS),left ventricular posterior wall(LVPW),left ventricular ejection fraction(LVEF),left atrial diameter(LAd),peak value ratio of mitral orifice blood flow velocity in early and late diastole(E/A)and mitral orifice blood flow velocity in early diastole were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between fQRS wave and other indexes in T2DM patients,and Logistic regression analysis was used to analyze the influencing factors of fQRS.Results The prevalence rates of UACR,SUA,HbA1c and MAU in fQRS group were higher than in T2DM group(P<0.05 or P<0.01).LVEDd,LAd,E,E/e'and E/A>1.5 in QRS group were higher than in T2DM group(P<0.05 or P<0.01).Pearson correlation analysis showed that fQRS wave was positively correlated with smoking history,BMI,HbA1c,UACR,MAU,SUA,LVEDd,LAd,E/A and E/e'(P<0.05).Logistic regression analysis showed that MAU was the influencing factor of fQRS wave in T2DM patients.Conclusions The fQRS in ECG in patients with T2DM is associated with MAU and SUA and may be an important evidence of myocardial fibrosis associated with subclinical cardiac diastolic dysfunction.
8.Investigation of symptom clusters and sentinel symptoms in early postoperative breast cancer patients
Lizhen WANG ; Cuiwei LAI ; Ni QIU ; Huaying HUANG ; Junfeng SONG ; Shiqi WEN ; Yuting ZENG ; Danna ZENG ; Tai XU ; Tianli LAI
Journal of Clinical Medicine in Practice 2024;28(20):23-26
Objective To investigate the composition of symptom clusters in early postoperative breast cancer patients and analyze the sentinel symptoms of each cluster of symptoms. Methods A total of 309 patients who underwent mastectomy were conveniently sampled and surveyed using the Chinese version of the Anderson Symptom Inventory. Principal component analysis and varimax orthogonal rotation were employed to analyze the symptom clusters, and their associations were analyzed using the Apriori algorithm model to identify the sentinel symptoms of each cluster of symptoms. Results Three symptom clusters were identified in early postoperative breast cancer patients: neuro-sleep symptom cluster [fatigue (weakness)-distress-pain-sleepiness-restless sleep], sensory-perception symptom cluster (numbness-forgetfulness-shortness of breath-sadness-dry mouth), and digestive system symptom cluster (nausea-vomiting-loss of appetite). Fatigue was the sentinel symptom of the neuro-sleep symptom cluster, numbness was the sentinel symptom of the sensory-perception symptom cluster, and nausea was the sentinel symptom of the digestive system symptom cluster. Conclusion Early postoperative breast cancer patients experience multiple symptom clusters, with sentinel symptoms existing in each cluster. Healthcare staff should develop intervention measures based on sentinel symptoms to improve the efficiency of symptom management and reduce the degree of symptom distress for patients.
9.Effect of tiopronin on renal function during antituberculosis therapy
Lixiu LIU ; Guofeng LI ; Honglan ZHONG ; Huaying HUANG ; Xiuzhen WEN ; Xiang LI
The Journal of Practical Medicine 2024;40(23):3362-3366
Objective To investigate the effect of tiopronin on renal function during anti-tuberculosis liver protection therapy.Methods Clinical data of patients with initially treated sensitive tuberculosis treated in our hos-pital from September 2019 to September 2022 and whose anti-tuberculosis regimen was only isoniazid,rifampicin,pyrazinamide and ethambutol were retrospectively analyzed.The patients were divided into study group and control group according to whether tiopronin was used.The baseline data,blood creatinine(Scr),blood urea nitrogen(BUN),urine protein,creatinine clearance,drug combination and related adverse reactions of the two groups were compared.Results Patients obtained based on inclusion and exclusion criteria were divided into a study group(n=102)(antitubercular drugs+tiopronin)and a control group(n=105)(antitubercular drugs+glutathione).There were no statistically significant differences(P>0.05)in ALT,AST,DBIL,and TBIL levels between the two groups before treatment,at Middle and late treatment.At the later stage of treatment,serum Scr,BUN,creatinine clearance and urinary protein showed statistical differences between the study group and the control group(P<0.05).The abnormal rate of indicators and the incidence of adverse reactions in the study group were higher than those in the control group at the later stage of treatment(P<0.05).Conclusion For patients undergoing tuberculosis treatment,the efficacy of tiopronin and glutathione in protecting the liver is comparable.However,in terms of renal function,long-term use of tiopronin is associated with more pronounced damage.Due to the relatively low cost of tiopronin,for families with heavy economic burdens,short-term use of the drug can ensure safety,while long-term use requires close monitoring of renal function changes and timely adjustments to medication.
10.Effect of tiopronin on renal function during antituberculosis therapy
Lixiu LIU ; Guofeng LI ; Honglan ZHONG ; Huaying HUANG ; Xiuzhen WEN ; Xiang LI
The Journal of Practical Medicine 2024;40(23):3362-3366
Objective To investigate the effect of tiopronin on renal function during anti-tuberculosis liver protection therapy.Methods Clinical data of patients with initially treated sensitive tuberculosis treated in our hos-pital from September 2019 to September 2022 and whose anti-tuberculosis regimen was only isoniazid,rifampicin,pyrazinamide and ethambutol were retrospectively analyzed.The patients were divided into study group and control group according to whether tiopronin was used.The baseline data,blood creatinine(Scr),blood urea nitrogen(BUN),urine protein,creatinine clearance,drug combination and related adverse reactions of the two groups were compared.Results Patients obtained based on inclusion and exclusion criteria were divided into a study group(n=102)(antitubercular drugs+tiopronin)and a control group(n=105)(antitubercular drugs+glutathione).There were no statistically significant differences(P>0.05)in ALT,AST,DBIL,and TBIL levels between the two groups before treatment,at Middle and late treatment.At the later stage of treatment,serum Scr,BUN,creatinine clearance and urinary protein showed statistical differences between the study group and the control group(P<0.05).The abnormal rate of indicators and the incidence of adverse reactions in the study group were higher than those in the control group at the later stage of treatment(P<0.05).Conclusion For patients undergoing tuberculosis treatment,the efficacy of tiopronin and glutathione in protecting the liver is comparable.However,in terms of renal function,long-term use of tiopronin is associated with more pronounced damage.Due to the relatively low cost of tiopronin,for families with heavy economic burdens,short-term use of the drug can ensure safety,while long-term use requires close monitoring of renal function changes and timely adjustments to medication.


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