1.Magnolol inhibits appetite and causes visceral fat loss through Growth/differentiation factor-15 (GDF-15) by activating transcription factor 4-CCAAT enhancer binding protein γ-mediated endoplasmic reticulum stress responses.
Keru CHENG ; Yanyun ZHOU ; Yilong HAO ; Shengyun WU ; Nanping WANG ; Peng ZHANG ; Yinfang WANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(3):334-345
Magnolol, a compound extracted from Magnolia officinalis, demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases. Its biological activities encompass anti-inflammatory, antioxidant, anticoagulant, and anti-diabetic effects. Growth/differentiation factor-15 (GDF-15), a member of the transforming growth factor β superfamily, is considered a potential therapeutic target for metabolic disorders. This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism. The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo, and determined the involvement of endoplasmic reticulum (ER) stress signaling in this process. Luciferase reporter assays, chromatin immunoprecipitation, and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4 (ATF4), CCAAT enhancer binding protein γ (CEBPG), and CCCTC-binding factor (CTCF). The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene, as well as the influence of single nucleotide polymorphisms (SNPs) on magnolol and ATF4-induced transcription activity. Results demonstrated that magnolol triggers GDF-15 production in endothelial cells (ECs), hepatoma cell line G2 (HepG2) and hepatoma cell line 3B (Hep3B) cell lines, and primary mouse hepatocytes. The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene. SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15. In high-fat diet ApoE-/- mice, administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15. These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity, indicating its potential as a drug for the treatment of metabolic disorders.
Lignans/pharmacology*
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Growth Differentiation Factor 15/metabolism*
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Animals
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Biphenyl Compounds/pharmacology*
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Endoplasmic Reticulum Stress/drug effects*
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Activating Transcription Factor 4/genetics*
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Mice
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Humans
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Male
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Magnolia/chemistry*
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CCAAT-Enhancer-Binding Proteins/genetics*
;
Mice, Inbred C57BL
2.Clinical significance of cytokeratin 19 fragment in anti-melanoma differentiation-associated protein-5 antibody positive patients
Wenjuan GUAN ; Lijun LIU ; Panpan ZHANG ; Cong WANG ; Xin ZHANG ; Lijuan ZHANG ; Lishuai HAN ; Yinli ZHANG ; Yujie HE ; Shengyun LIU
Chinese Journal of Rheumatology 2025;29(3):189-196
Objective:To investigate the clinical significance of elevated cytokeratin 19 fragment (CYFRA21-1) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:142 consecutive cases with newly onset anti-MDA5(+) (MADEDM)-DM admitted to the first affiliated hospital of Zhengzhou University from June 2018 to October 2021 were enrolled. They were divided into two groups, the low serum CYFRA21-1 group (CYFRA21-1≤4 ng/ml) and the high serum CYFRA21-1 group (CYFRA21-1>4 ng/ml). The clinical manifestations, laboratory tests results, imaging examinations treatment and outcome were collected for statistical analysis. Enumeration data were expressed as the number of cases and percentage (%). Normally distributed parameters were tested by t-test. Parameters with skewed distribution were tested by Mann-Whitney Wilcoxon analysis. Categorical variables were compared by the Chi-square test or Fisher′s exact test. Risk factor analysis was performed using Logistic regression. Cumulative survivals were described by Kaplan-Meier curves. Results:The age of onset in the high CYFRA21-1 group [(56±9)years vs. (50±10) years, t=-3.50, P=0.001] was higher than that in the low CYFRA21-1 group. Fever [63.3% (38/60) vs. 40.2% (33/82), χ2=7.39, P=0.007] was more common in the high CYFRA21-1 group, and arthritis [41.7% (25/60) vs. 69.5%(57/82), χ2=11.01, P=0.001] was less common. Myalgia, myasthenia, rashes, Raynaud′s phenomenon and skin ulcers had no significant difference between the two groups. The WBC count [5.2(4.1, 6.9)×10 9/L vs. 4.3(3.2, 6.2)×10 9/L, Z=-2.57, P=0.010], neutrophil count [4.0(2.9, 5.5)×10 9/L vs. 2.9(2.1, 4.5)×10 9/L, Z=-3.25, P=0.001] and neutrophil/lymphocyte ratio [5.75(3.50, 9.20) vs. 3.55(2.64, 5.41), Z=-3.77, P<0.001] in high CYFRA21-1 group were significantly higher than those in low CYFRA21-1 group. At the same time, LDH [384(302, 519)U/L vs. 318(260, 405)U/L, Z=-2.98, P=0.003], ferritin [1 204(677, 2 039)ng/ml vs. 570(229, 846)ng/ml, Z=-4.78, P<0.001], KL-6 [995(658, 1 491)U/ml vs. 750(563, 1 197)U/ml, Z=-2.49, P=0.013], ESR [36(22, 61)mm/1 h vs. 28(15, 46)mm/1 h, Z=-2.18, P=0.029] and CRP [9.2(4.7, 31.5)mg/L vs. 3.1(1.1, 11.6)mg/L, Z=-3.53, P<0.001] were significantly increased in the high level of CYFRA21-1 group, while serum albumin[(32±5)g/L vs. (35±5)g/L, t=3.92, P<0.001] was significantly decreased. There was no significant difference in the titers of serum anti-MDA5 antibodies between the two groups. The positive rate of anti-RO52 antibody [44(74.6%) vs. 44(53.7%), χ2=6.40, P=0.011] in high CYFRA21-1 group was higher than that in low CYFRA21-1 group. The ground glass opacity (GGO) score [1.75(1.33, 2.42) vs. 1.09(0.67, 1.67), Z=-4.60, P<0.001] based on high resolution CT (HRCT) was also significantly increased in the CYFRA21-1 high level group. Compared with the low CYFRA21-1 group, the high CYFRA21-1 group had a higher probability of RP-ILD [48.3%(29/60) vs. 23.2%(19/82), χ2=9.80, P=0.002] and a higher 6-month mortality rate[48.3%(29/60) vs.13.4%(11/82), χ2=19.70, P<0.001]. Logistic regression analysis showed that age ≥53 years old [ OR(95% CI)=5.197(1.781, 15.165), P=0.003], duration < 2 months [ OR(95% CI)=3.314 (1.058, 10.378), P=0.040], NE/LYMP >5 [ OR(95% CI)=3.443(1.120, 10.586), P=0.031], CRP>5 mg/L[ OR(95% CI)=6.271(1.749, 22.480), P=0.005], CA125>14 U/ml[ OR(95% CI)=7.500 (2.409, 23.345), P=0.001] and CYFRA21-1>4 ng/ml[ OR(95% CI)=3.665(1.258, 10.676), P=0.017] were independent risk factors for death within 6 months in MDA5-DM patients. Kaplan-Meier survival curve showed that the survival rate of the high CYFRA21-1 group was significantly lower than that of the low CYFRA21-1 group( P<0.001). Conclusion:Elevated CYFRA21-1 is an independent risk factor for early mortality in MDA5-DM patients and can serve as a novel serological marker for risk stratification in these patients.
3.Clinical significance of cytokeratin 19 fragment in anti-melanoma differentiation-associated protein-5 antibody positive patients
Wenjuan GUAN ; Lijun LIU ; Panpan ZHANG ; Cong WANG ; Xin ZHANG ; Lijuan ZHANG ; Lishuai HAN ; Yinli ZHANG ; Yujie HE ; Shengyun LIU
Chinese Journal of Rheumatology 2025;29(3):189-196
Objective:To investigate the clinical significance of elevated cytokeratin 19 fragment (CYFRA21-1) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:142 consecutive cases with newly onset anti-MDA5(+) (MADEDM)-DM admitted to the first affiliated hospital of Zhengzhou University from June 2018 to October 2021 were enrolled. They were divided into two groups, the low serum CYFRA21-1 group (CYFRA21-1≤4 ng/ml) and the high serum CYFRA21-1 group (CYFRA21-1>4 ng/ml). The clinical manifestations, laboratory tests results, imaging examinations treatment and outcome were collected for statistical analysis. Enumeration data were expressed as the number of cases and percentage (%). Normally distributed parameters were tested by t-test. Parameters with skewed distribution were tested by Mann-Whitney Wilcoxon analysis. Categorical variables were compared by the Chi-square test or Fisher′s exact test. Risk factor analysis was performed using Logistic regression. Cumulative survivals were described by Kaplan-Meier curves. Results:The age of onset in the high CYFRA21-1 group [(56±9)years vs. (50±10) years, t=-3.50, P=0.001] was higher than that in the low CYFRA21-1 group. Fever [63.3% (38/60) vs. 40.2% (33/82), χ2=7.39, P=0.007] was more common in the high CYFRA21-1 group, and arthritis [41.7% (25/60) vs. 69.5%(57/82), χ2=11.01, P=0.001] was less common. Myalgia, myasthenia, rashes, Raynaud′s phenomenon and skin ulcers had no significant difference between the two groups. The WBC count [5.2(4.1, 6.9)×10 9/L vs. 4.3(3.2, 6.2)×10 9/L, Z=-2.57, P=0.010], neutrophil count [4.0(2.9, 5.5)×10 9/L vs. 2.9(2.1, 4.5)×10 9/L, Z=-3.25, P=0.001] and neutrophil/lymphocyte ratio [5.75(3.50, 9.20) vs. 3.55(2.64, 5.41), Z=-3.77, P<0.001] in high CYFRA21-1 group were significantly higher than those in low CYFRA21-1 group. At the same time, LDH [384(302, 519)U/L vs. 318(260, 405)U/L, Z=-2.98, P=0.003], ferritin [1 204(677, 2 039)ng/ml vs. 570(229, 846)ng/ml, Z=-4.78, P<0.001], KL-6 [995(658, 1 491)U/ml vs. 750(563, 1 197)U/ml, Z=-2.49, P=0.013], ESR [36(22, 61)mm/1 h vs. 28(15, 46)mm/1 h, Z=-2.18, P=0.029] and CRP [9.2(4.7, 31.5)mg/L vs. 3.1(1.1, 11.6)mg/L, Z=-3.53, P<0.001] were significantly increased in the high level of CYFRA21-1 group, while serum albumin[(32±5)g/L vs. (35±5)g/L, t=3.92, P<0.001] was significantly decreased. There was no significant difference in the titers of serum anti-MDA5 antibodies between the two groups. The positive rate of anti-RO52 antibody [44(74.6%) vs. 44(53.7%), χ2=6.40, P=0.011] in high CYFRA21-1 group was higher than that in low CYFRA21-1 group. The ground glass opacity (GGO) score [1.75(1.33, 2.42) vs. 1.09(0.67, 1.67), Z=-4.60, P<0.001] based on high resolution CT (HRCT) was also significantly increased in the CYFRA21-1 high level group. Compared with the low CYFRA21-1 group, the high CYFRA21-1 group had a higher probability of RP-ILD [48.3%(29/60) vs. 23.2%(19/82), χ2=9.80, P=0.002] and a higher 6-month mortality rate[48.3%(29/60) vs.13.4%(11/82), χ2=19.70, P<0.001]. Logistic regression analysis showed that age ≥53 years old [ OR(95% CI)=5.197(1.781, 15.165), P=0.003], duration < 2 months [ OR(95% CI)=3.314 (1.058, 10.378), P=0.040], NE/LYMP >5 [ OR(95% CI)=3.443(1.120, 10.586), P=0.031], CRP>5 mg/L[ OR(95% CI)=6.271(1.749, 22.480), P=0.005], CA125>14 U/ml[ OR(95% CI)=7.500 (2.409, 23.345), P=0.001] and CYFRA21-1>4 ng/ml[ OR(95% CI)=3.665(1.258, 10.676), P=0.017] were independent risk factors for death within 6 months in MDA5-DM patients. Kaplan-Meier survival curve showed that the survival rate of the high CYFRA21-1 group was significantly lower than that of the low CYFRA21-1 group( P<0.001). Conclusion:Elevated CYFRA21-1 is an independent risk factor for early mortality in MDA5-DM patients and can serve as a novel serological marker for risk stratification in these patients.
4.Application of the defect situational objective structured clinical examination in the training of specialized nurses in the operating room
Yu WANG ; Zengmei ZHANG ; Shengyun LI ; Wei WEI
Chinese Journal of Practical Nursing 2024;40(20):1521-1527
Objective:To evaluate the effects of the defect situational objective structured clinical examination (OSCE) in the training of specialized nurses in the operating room, and provide a new idea for the training of specialized nurses in the operating room.Methods:A quasi experimental study was used in this study. A total of 78 nurses who participated in the training of the operating room specialized nurses in Henan Province in 2022 and 2023 which were organized by the First Affiliated Hospital of Zhengzhou University were selected by cluster sampling method. The nurses who participated in the training in 2022 and 2023 were assigned to the control group (38 participants) and the experimental group (40 participants), respectively. Nurses in the experimental group received defect situational OSCE, while nurses in the control group received conventional teaching. After the training, the effect of the two teaching methods was evaluated by skill operation assessment results and Clinical Thinking Ability Assessment Scale.Results:There were 4 males and 34 females in the control group, aged (30.03 ± 4.33) years old, and 3 males and 37 females in the experimental group, aged (29.93 ± 3.95) years old. The scores of the verification and handover of surgical patients, surgical position placement and the occupational exposure protection were (91.80 ± 2.95), (90.38 ± 3.66), (91.10 ± 3.26) points in the experimental group and were (89.08 ± 3.21), (87.84 ± 3.49), (88.39 ± 4.21) points in the control group, the differences between the two groups were statistically significant ( t = 3.91, 3.13, 3.18, all P<0.05). The total score of clinical thinking ability in the experimental group was (80.66 ± 1.85) points, which was higher than (77.77 ± 1.62) points in the control group, the difference between the two groups was statistically significant ( t = 7.31, P<0.05). The evaluation of the teaching effect in the experimental group was better, and the satisfaction rate was 92.5%(37/40)-100.0%(40/40). Conclusions:The application of defect situational OSCE teaching method in the training of operating room nurses could better improve the operational ability and help to improve the clinical thinking ability of nurses. The training effect is superior to the conventional teaching method, and it is worthy of clinical application.
5.Construction of a competency evaluation indicator system for infection prevention and control nurses in Operating Rooms
Liqun SUN ; Zengmei ZHANG ; Haiyun ZHAO ; Ying ZHANG ; Zi JIN ; Yunfei NIE ; Wei WEI ; Yu WANG ; Shengyun LI ; Ruifang HUA
Chinese Journal of Modern Nursing 2024;30(13):1698-1705
Objective:To construct a competency evaluation indicator system for infection prevention and control nurses in Operating Rooms (hereinafter referred to as "IPC") and provide an objective basis for the management of IPC nurses.Methods:From June to November 2022, an initial competency evaluation indicator system for IPC nurses was developed through literature review and semi-structured interviews. The Delphi method was employed to consult 20 experts from 11 provinces and municipalities across the country. Analytical Hierarchy Process (AHP) and mean distribution method were applied to quantify and determine the weight of each level of indicators within the system.Results:Nineteen experts were finally included, with two rounds of questionnaire recovery rates of 95.00% (19/20) and 100.00% (19/19), respectively. The authority coefficients of the experts were 0.858 and 0.861, familiarity coefficients were 0.850 and 0.853, and coefficients of judgment basis were 0.865 and 0.868, respectively. The Kendall's W coefficient of concordance for the two rounds of inquiries were 0.139 and 0.202 ( P<0.05), respectively. The final IPC nurse competency evaluation indicator system included six primary indicators, 22 secondary indicators, and 66 tertiary indicators. Conclusions:The constructed IPC nurse competency evaluation indicator system is scientific, reasonable, objective, and comprehensive, providing a valuable reference for the capability training, assessment, entry standards, and qualification certification of IPC nurses.
6.Efficacy of AngioJet thrombectomy combined with iliac vein stenting in the treatment of lower extremity deep vein thrombosis with iliac vein compression
Haijun QIU ; Shengyun WAN ; Lisheng PAN ; Canjun FANG ; Zongjie NIE ; Wenrui WANG ; Xia BAI
Chinese Journal of General Surgery 2024;33(12):2023-2029
Background and Aims:Iliac vein compression syndrome (IVCS) is a major cause of acute lower extremity deep vein thrombosis (DVT). Without timely treatment,it can lead to thrombus detachment,resulting in pulmonary embolism and increased mortality risk. Percutaneous mechanical thrombectomy,particularly using the AngioJet thrombectomy system,is a widely used thrombectomy method. The combination of AngioJet thrombectomy with iliac vein stent placement provides a novel treatment option for DVT associated with IVCS. This study was performed to evaluate the efficacy and safety of AngioJet thrombectomy combined with iliac vein stent placement in treating DVT with IVCS.Methods:The clinical data of 120 patients with DVT and IVCS treated between April 2019 and October 2022 were retrospectively analyzed. Sixty patients underwent AngioJet thrombectomy combined with iliac vein stent placement (observation group),while another 60 patients received catheter-directed thrombolysis (CDT) combined with stent placement (control group). The clinical efficacy,outcomes (thrombus clearance grade,thrombolysis duration,venous patency score,hospitalization duration,urokinase dosage,thigh circumference difference,and calf circumference difference),Villalta scores at various time points before and after treatment,and adverse events (chest tightness,mild pulmonary embolism,bleeding at the catheter insertion site,and mild renal function impairment) were compared between the two groups.Results:The overall efficacy rate in the observation group was significantly higher than that in the control group (98.33% vs. 86.67%,P=0.015). While there was no significant difference in thrombus clearance grade between the two groups (P>0.05),the observation group had significantly shorter thrombolysis duration,lower urokinase dosage,and shorter hospitalization time compared to the control group (all P<0.05). Before treatment,there were no significant differences in thigh circumference difference,calf circumference difference,or venous patency score between the two groups (all P>0.05). After treatment,the observation group had significantly better venous patency score and smaller thigh and calf circumference differences than the control group (all P<0.05). There was no significant difference in Villalta score between the two groups before treatment (P>0.05). Post-treatment Villalta scores showed a significant decreasing trend over time in both groups compared to pre-treatment scores (all P<0.05),but there were no statistically significant differences in Villalta scores between the two groups at 1,6,and 12 months after treatment (all P>0.05). The total incidence of adverse events was not significantly different between the two groups (10.00% vs. 3.33%,P=0.143).Conclusion:The use of AngioJet thrombectomy combined with iliac vein stent placement for the treatment of lower extremity DVT with IVCS can shorten thrombolysis and hospitalization duration,reduce thrombolytic drug dosage,and achieve better and safer outcomes,making it worthy of clinical application.
7.Efficacy of AngioJet thrombectomy combined with iliac vein stenting in the treatment of lower extremity deep vein thrombosis with iliac vein compression
Haijun QIU ; Shengyun WAN ; Lisheng PAN ; Canjun FANG ; Zongjie NIE ; Wenrui WANG ; Xia BAI
Chinese Journal of General Surgery 2024;33(12):2023-2029
Background and Aims:Iliac vein compression syndrome (IVCS) is a major cause of acute lower extremity deep vein thrombosis (DVT). Without timely treatment,it can lead to thrombus detachment,resulting in pulmonary embolism and increased mortality risk. Percutaneous mechanical thrombectomy,particularly using the AngioJet thrombectomy system,is a widely used thrombectomy method. The combination of AngioJet thrombectomy with iliac vein stent placement provides a novel treatment option for DVT associated with IVCS. This study was performed to evaluate the efficacy and safety of AngioJet thrombectomy combined with iliac vein stent placement in treating DVT with IVCS.Methods:The clinical data of 120 patients with DVT and IVCS treated between April 2019 and October 2022 were retrospectively analyzed. Sixty patients underwent AngioJet thrombectomy combined with iliac vein stent placement (observation group),while another 60 patients received catheter-directed thrombolysis (CDT) combined with stent placement (control group). The clinical efficacy,outcomes (thrombus clearance grade,thrombolysis duration,venous patency score,hospitalization duration,urokinase dosage,thigh circumference difference,and calf circumference difference),Villalta scores at various time points before and after treatment,and adverse events (chest tightness,mild pulmonary embolism,bleeding at the catheter insertion site,and mild renal function impairment) were compared between the two groups.Results:The overall efficacy rate in the observation group was significantly higher than that in the control group (98.33% vs. 86.67%,P=0.015). While there was no significant difference in thrombus clearance grade between the two groups (P>0.05),the observation group had significantly shorter thrombolysis duration,lower urokinase dosage,and shorter hospitalization time compared to the control group (all P<0.05). Before treatment,there were no significant differences in thigh circumference difference,calf circumference difference,or venous patency score between the two groups (all P>0.05). After treatment,the observation group had significantly better venous patency score and smaller thigh and calf circumference differences than the control group (all P<0.05). There was no significant difference in Villalta score between the two groups before treatment (P>0.05). Post-treatment Villalta scores showed a significant decreasing trend over time in both groups compared to pre-treatment scores (all P<0.05),but there were no statistically significant differences in Villalta scores between the two groups at 1,6,and 12 months after treatment (all P>0.05). The total incidence of adverse events was not significantly different between the two groups (10.00% vs. 3.33%,P=0.143).Conclusion:The use of AngioJet thrombectomy combined with iliac vein stent placement for the treatment of lower extremity DVT with IVCS can shorten thrombolysis and hospitalization duration,reduce thrombolytic drug dosage,and achieve better and safer outcomes,making it worthy of clinical application.
8.Recommendations of diagnosis and treatment of giant cell arteritis and polymyalgia rheumatic in China
Pei WANG ; Xuebing FENG ; Xingwang DUAN ; Shengyun LIU ; Yan ZHAO
Chinese Journal of Internal Medicine 2023;62(3):256-266
Polymyalgia rheumatica (PMR) is a syndrome characterized by pain and morning stiffness in the neck and shoulder and pelvic girdles, as well as raised acute-phase reactants, with or without systemic symptoms, such as fever. Giant cell arteritis (GCA) is a systemic vasculitis of unclear etiology that involves systemic arteries, principally affecting medium- and large-sized arteries with skipped, segmental alterations and granulomatous vasculitis seen on histopathology. In China, epidemiological data describing GCA are still limited; thus, the prevalence might be underestimated. The involvement of vessels in GCA can cause irreversible visual impairment or loss and stroke, which are serious complications. PMR is three times more prevalent than GCA, and other specific diseases should be excluded before the diagnosis is established. PMR symptoms can be present in 40%-60% of patients with GCA. Conversely, GCA can develop in 15% of patients with PMR. Chinese Rheumatology Association, based on the clinical diagnosis and treatment guidelines in 2005, utilizing the experience and guidelines of diagnosis and treatment at home and abroad, formulated this specification to standardize the diagnosis and treatment of GCA and PMR and improve the patient′s prognosis.
9.The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway
Zhiqi LI ; Qiqi FAN ; Meilin CHEN ; Ying DONG ; Farong LI ; Mingshuang WANG ; Yulin GU ; Simin GUO ; Xianwen YE ; Jiarui WU ; Shengyun DAI ; Ruichao LIN ; Chongjun ZHAO
Journal of Pharmaceutical Analysis 2023;13(1):39-54
Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.
10.Sex differences in systemic lupus erythematosus (SLE): an inception cohort of the Chinese SLE Treatment and Research Group (CSTAR) registry XVII.
Yinli GUI ; Wei BAI ; Jian XU ; Xinwang DUAN ; Feng ZHAN ; Chen ZHAO ; Zhenyu JIANG ; Zhijun LI ; Lijun WU ; Shengyun LIU ; Min YANG ; Wei WEI ; Ziqian WANG ; Jiuliang ZHAO ; Qian WANG ; Xiaomei LENG ; Xinping TIAN ; Mengtao LI ; Yan ZHAO ; Xiaofeng ZENG
Chinese Medical Journal 2022;135(18):2191-2199
BACKGROUND:
The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort.
METHODS:
Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex.
RESULTS:
In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P = 0.002), musculoskeletal damage (P = 0.023), cardiovascular impairment (P = 0.009), and CYC use (P = 0.001); while leukopenia (P = 0.017), arthritis (P = 0.014), and mycophenolate usage (P = 0.013) rates were lower.
CONCLUSIONS
Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.
Humans
;
Female
;
Male
;
Cross-Sectional Studies
;
Sex Characteristics
;
East Asian People
;
Severity of Illness Index
;
Lupus Erythematosus, Systemic/diagnosis*
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Lupus Nephritis/pathology*
;
Registries
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Cyclophosphamide/therapeutic use*
;
Thrombocytopenia
;
Leukopenia/drug therapy*
;
Arthritis

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