1.Molecular mechanisms of hyperlipidemic acute pancreatitis comorbid with fatty liver disease
Shuo DONG ; Ying WANG ; Xiwang WANG ; Jingjing JIN ; Kai WEI ; Xiao WANG
Journal of Clinical Hepatology 2026;42(3):739-744
Both hyperlipidemic acute pancreatitis and fatty liver disease are associated with lipid metabolism disorders and are commonly comorbid with each other in clinical practice. The pathogenesis of such comorbidity involves the interaction between multiple factors such as hypertriglyceridemia, metabolic syndrome, obesity, and insulin resistance, and these factors may form a vicious cycle and jointly promote disease progression. In clinical practice, hyperlipidemic acute pancreatitis is characterized by severe disease conditions, a high incidence rate of complications, a high mortality rate, and a tendency for recurrence, and it can easily lead to multi-organ damage and even multiple organ failure without timely treatment, posing a serious threat to the life of patients. Starting from the various signaling pathways associated with hyperlipidemic acute pancreatitis comorbid with fatty liver disease, this article discusses the potential molecular mechanisms of synergistic pathogenesis between hyperlipidemic acute pancreatitis and fatty liver disease, so as to provide a reference for the early prevention and treatment of such comorbidity.
2.Salidroside alleviates progression of Parkinson's disease by modulating inflammatory responses
Xiao-lin DONG ; Gang WU ; Yan-ping LI ; Li-juan ZHANG ; Fu-rong JIN ; Rui LI ; Hong-mei LI ; Xiao-xiao ZHANG ; Qing-yun LI
Chinese Pharmacological Bulletin 2025;41(7):1340-1345
Aim To explore the neuroprotective effects of salidroside on Parkinson's disease(PD)through modulation of inflammatory responses and the underly-ing mechanisms.Methods Mice were divided into five groups:healthy control group,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)disease group,low-dose Rhodioloside intervention group,medium-dose salidroside intervention group,and high-dose salidro-side intervention group.MPTP-induced PD mouse model was established,and salidroside intervention was administered.Behavioral changes,inflammatory cyto-kine levels,autophagy-related protein expression,and neurons were observed through histological analysis and immunohistochemical staining.Results After MPTP treatment,mice exhibited significant behavioral chan-ges,increased pro-inflammatory cytokines,decreased anti-inflammatory cytokines,reduced autophagy-related proteins,and evident pyroptosis.Salidroside interven-tion alleviated these changes in a dose-dependent man-ner.Conclusions Salidroside exerts neuroprotective effects on PD by alleviating inflammatory responses and promoting autophagy,thereby protecting neurons.
3.Mechanism of ultrafine garlic powder in improving mouse atherosclerosis and dyslipidemia
Ning-ning SHAO ; Jian-ming YANG ; Yao-guang WANG ; Tao ZHANG ; Xiao-ming ZHAO ; Jin-rui DONG
Chinese Pharmacological Bulletin 2025;41(7):1376-1381
Aim To investigate the mechanism of ultra-fine garlic powder(UGP)in ameliorating dyslipidemia and aortic inflammation and fibrosis in atherosclerotic(AS)mice.Methods A 10-week ApoE-/-mouse AS model was constructed,cardiac index was meas-ured,and aortic histopathological changes were ob-served by oil red O staining.Serum inflammatory factor levels were detected by ELISA,and the expression of JNK,NF-κB,ERK and their phosphorylated proteins were detected by Western blot.Results Cardiac in-dex and other indicators as well as aortic lesions were worsened in the AS group,as compared with the normal control group.Compared with the AS group,the UGP treatment group and the traditional garlic grinding pow-der(TGP)treatment group significantly decreased total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),atherosclerosis index(AI1,AI2),and coronary cardiac index and restored high-density lipoprotein cholesterol(HDL-C)levels,and the area of aortic lesions,inflammation and fibrosis were significantly improved,and at the same time,sig-nificantly inhibited the expression of TNF-α,IL-1β,and IL-6,as well as the expression of p-JNK,p-NF-κB and p-ERK proteins.The therapeutic effect of the UGP group was superior to that of the TGP group.Conclu-sion UGP can significantly inhibit the formation of aortic endothelial AS plaques,reduce the levels of in-flammation and fibrosis,and regulate blood lipids in a-orta of AS mice.
4.Total triterpenoids from Hovenia dulcis increase sensitivity of A549/DDP to cisplatin by inducing Nrf2-mediated ferroptosis
Xiao-lan KUANG ; Dong-ning SHEN ; Ting FU ; Fan WU ; Jian-zhan YANG ; Jin-lang ZHONG ; Bo LIU ; Fang-fang XU
Chinese Pharmacological Bulletin 2025;41(11):2128-2134
Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.
5.Correlation between serum MIF,25(OH)D and cognitive function in patients with vestibular migraine
Xiao JIN ; Yanhong WANG ; Lianqi YANG ; Dong ZHANG ; Yong LI ; Zhihua REN ; Caihong WANG
Tianjin Medical Journal 2025;53(11):1175-1179
Objective To explore the correlation between serum macrophage migration inhibitory factor(MIF),25-hydroxyvitamin D[25(OH)D]and cognitive function in patients with vestibular migraine(VM).Methods A total of 200 patients with VM were selected and used as the VM group.Based on the Montreal Cognitive Assessment(MoCA)criteria,patients were divided into the cognitively normal group(128 cases)and the cognitively impaired group(72 cases).Additionally,200 healthy individuals undergoing routine health examination were selected as the control group.Serum MIF and 25(OH)D levels were measured using enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze influencing factors of cognitive impairment in VM patients.The value of serum MIF and 25(OH)D levels in diagnosing cognitive impairment in patients with VM was analyzed by using the receiver operating characteristic(ROC)curve.Results The serum MIF was higher in the VM group than that of the control group,and serum 25(OH)D was lower in the VM group(P<0.05).The serum MIF was higher in the cognitive impairment group than that of the cognitive normal group,while the serum 25(OH)D was lower in the cognitive impairment group than that of the cognitive normal group(P<0.05).Multivariate Logistic regression found that increased serum MIF level and decreased 25(OH)D level were independent risk factors for cognitive impairment in VM patients(P<0.05).ROC curve analysis showed that the AUC(95%CI)of the combined diagnosis of cognitive impairment in VM patients using serum MIF and 25(OH)D levels was 0.900(0.850-0.938),which was higher than that of MIF diagnosed alone[0.797(0.735-0.851)]and 25(OH)D alone[0.817(0.756-0.868),P<0.05].Conclusion VM patients with cognitive impairment have elevated serum MIF levels and decreased 25(OH)D levels.The combined diagnostic value of the two markers has a relatively high value for VM patients with cognitive impairment.
6.Establishment and evaluation of a lipopolysaccharide-induced acute respiratory distress syndrome model in minipigs
Chuang-Ye WANG ; Ran WANG ; Jian ZHANG ; Ling-Xiao QIU ; Bin QING ; Heng YOU ; Jin-Cheng LIU ; Bin WANG ; Nan-Bo WANG ; Jia-Yu LI ; Xing LIU ; Shuang WANG ; Jin HU ; Jian WEN ; Quan LI ; Xiao-Ou HUANG ; Kun ZHAO ; Shuang-Lin LIU ; Gang LIU ; Mei-Ju WANG ; Qing XIANG ; Hong-Mei WU ; Xiao-Rong SUN ; Tao GU ; Dong ZHANG ; Qi LI ; Zhi XU
Medical Journal of Chinese People's Liberation Army 2025;50(9):1154-1161
Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.
7.Total triterpenoids from Hovenia dulcis increase sensitivity of A549/DDP to cisplatin by inducing Nrf2-mediated ferroptosis
Xiao-lan KUANG ; Dong-ning SHEN ; Ting FU ; Fan WU ; Jian-zhan YANG ; Jin-lang ZHONG ; Bo LIU ; Fang-fang XU
Chinese Pharmacological Bulletin 2025;41(11):2128-2134
Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.
8.Correlation between serum MIF,25(OH)D and cognitive function in patients with vestibular migraine
Xiao JIN ; Yanhong WANG ; Lianqi YANG ; Dong ZHANG ; Yong LI ; Zhihua REN ; Caihong WANG
Tianjin Medical Journal 2025;53(11):1175-1179
Objective To explore the correlation between serum macrophage migration inhibitory factor(MIF),25-hydroxyvitamin D[25(OH)D]and cognitive function in patients with vestibular migraine(VM).Methods A total of 200 patients with VM were selected and used as the VM group.Based on the Montreal Cognitive Assessment(MoCA)criteria,patients were divided into the cognitively normal group(128 cases)and the cognitively impaired group(72 cases).Additionally,200 healthy individuals undergoing routine health examination were selected as the control group.Serum MIF and 25(OH)D levels were measured using enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze influencing factors of cognitive impairment in VM patients.The value of serum MIF and 25(OH)D levels in diagnosing cognitive impairment in patients with VM was analyzed by using the receiver operating characteristic(ROC)curve.Results The serum MIF was higher in the VM group than that of the control group,and serum 25(OH)D was lower in the VM group(P<0.05).The serum MIF was higher in the cognitive impairment group than that of the cognitive normal group,while the serum 25(OH)D was lower in the cognitive impairment group than that of the cognitive normal group(P<0.05).Multivariate Logistic regression found that increased serum MIF level and decreased 25(OH)D level were independent risk factors for cognitive impairment in VM patients(P<0.05).ROC curve analysis showed that the AUC(95%CI)of the combined diagnosis of cognitive impairment in VM patients using serum MIF and 25(OH)D levels was 0.900(0.850-0.938),which was higher than that of MIF diagnosed alone[0.797(0.735-0.851)]and 25(OH)D alone[0.817(0.756-0.868),P<0.05].Conclusion VM patients with cognitive impairment have elevated serum MIF levels and decreased 25(OH)D levels.The combined diagnostic value of the two markers has a relatively high value for VM patients with cognitive impairment.
9.Clinical trail of vericiguat combined with sacubitril valsartan sodium in the treatment of patients with heart failure with reduced ejection fraction
Miao-jun WANG ; Shi-ping XU ; Xiao-jin PAN ; Zhi-dong YE ; Yu-fang LIAN ; Jun QIU ; Shao-tang LU ; Sheng-jie ZHOU
The Chinese Journal of Clinical Pharmacology 2025;41(1):6-10
Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34%(50 cases/53 cases)and 81.13%(43 cases/53 cases)with statistical significant difference(P<0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)%and(43.02±4.33)%,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66%and 13.21%,respectively;the differences were statistical significant between two groups(all P<0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21%and 7.55%,the incidences of major adverse cardiovascular events were 5.66%and 13.21%,respectively,without statistically significant differences(all P>0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.
10.Prognostic Value of Dynamic Monitoring of WT1 Expression Levels for Relapse and Overall Survival in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation During First Complete Remission
Xiao-Ya HE ; Han-Yun REN ; Yu-Jun DONG ; Li JI ; Qing-Yun WANG ; Yuan LI ; Yue YIN ; Ze-Yin LIANG ; Qian WANG ; Wei-Lin XU ; Jin-Ping OU ; Bing-Jie WANG ; Wei LIU
Journal of Experimental Hematology 2025;33(6):1790-1796
Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0%.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1%.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26%(range:0%-23.64%),with an upper quartile value of 0.74%.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels>0.74%at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P<0.001)compared to patients with WT1 levels ≤0.74%.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level>0.74%at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95%CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95%CI:0.749-16.100,P=0.037).Only WT1 level>0.74%at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95%CI:2.402-19.738,P<0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

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