1.Baicalein mitigates ferroptosis of neurons after subarachnoid hemorrhage
Ting ZHU ; Tingting YUE ; Yue CUI ; Yue LU ; Wei LI ; Chunhua HANG
Chinese Journal of Tissue Engineering Research 2025;29(1):52-57
BACKGROUND:Ferroptosis is a mode of programmed cell death distinct from apoptosis,necrosis,and other novel cellular deaths,which occurs mainly due to accumulated lipid peroxidation.Ferroptosis has been shown to be involved in the pathological process following subarachnoid hemorrhage.Baicalein,serving as an adept sequestered of iron,evinces its prowess by quelling lipid peroxidative cascades.Nonetheless,the enigma lingers as to whether baicalein possesses the capacity to ameliorate neuronal ferroptosis,elicited in the wake of early brain injury after subarachnoid hemorrhage. OBJECTIVE:To investigate the effect and mechanism of baicalein on neuronal ferroptosis after subarachnoid hemorrhage. METHODS:Primary neuronal cells were extracted from C57BL/6L fetal mice at 16-17 days of gestation.Hemoglobin was used to stimulate primary neuronal cells to simulate an in vitro subarachnoid hemorrhage model.The viability of primary neuronal cells treated with baicalein at concentrations of 5,15,25,50,and 100 μmol/L for 24 hours was detected by CCK-8 assay to determine the optimal concentration of baicalein.Primary neuronal cells were divided into control group,hemoglobin group,and hemoglobin+baicalein group.The levels of reactive oxygen species and malondialdehyde in cells were detected by kits.The mRNA expressions of ferroptosis-related markers PTGS2,SLC7A11,and glutathione peroxidase 4 were detected by RT-PCR.The primary neuronal cells were further divided into control group,SLC7A11 inhibitor Erastin group,hemoglobin group,hemoglobin+baicalein group,and hemoglobin+baicalein+Erastin group.The expression of the ferroptosis related markers SLC7A11 and glutathione peroxidase 4 was detected by western blot assay. RESULTS AND CONCLUSION:(1)Baicalein(25 μmol/L)was selected as the following experimental concentration.(2)Compared with the hemoglobin group,the level of malondialdehyde and the level of reactive oxygen species were significantly decreased(P<0.05)in the hemoglobin+baicalein group.(3)Compared with the hemoglobin group,the mRNA expression of PTGS2 significantly decreased,and the mRNA expression of SLC7A11 and glutathione peroxidase 4 significantly increased(P<0.000 1)in the hemoglobin+baicalein group.(4)SLC7A11 inhibitor Erastin could reverse the baicalin-improved ferroptosis effect to a certain extent(P<0.05).(5)The results showed that baicalein could alleviate the ferroptosis of neuronal cells after subarachnoid hemorrhage through the SLC7A11/GPX4 pathway.
2.Mechanism of Qishen Yiqi Dropping Pills in regulating gut microbiota and ROS/TXNIP/NLRP3 signaling pathway to improve chronic heart failure in rats
Lifei LYU ; Tingting ZHU ; Fan DING ; Yingdong LU ; Xiangning CUI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):354-369
Objective:
This study explored the regulatory effects of QiShen Yiqi Dropping Pills (QSYQ) on chronic heart failure (CHF) in rats and their related mechanisms based on the gut microbiota and reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.
Methods:
Sixty-five SPF-grade male SD rats were used to establish a CHF model through subcutaneous multiple injections of isoproterenol (ISO) combined with exhaustion and food control methods. The modeled rats were randomly divided into model, captopril (5.30 mg/kg), and QSYQ low-, medium-, and high-dose groups (0.08, 0.16, and 0.32 g/kg, respectively), with 11 rats per group, plus a blank group of seven rats. The medication groups were given corresponding drugs by gavage, whereas the blank and model groups were administered an equivalent volume of purified water continuously for four weeks. Rat heart function was assessed via transthoracic echocardiography, and myocardial tissue pathology changes were observed through hematoxylin and eosin staining. Serum levels of brain natriuretic peptide (BNP), lipopolysaccharide (LPS), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were measured using an enzyme-linked immunosorbent assay. Automated biochemical analyzers were used to determine creatine kinase (CK), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) content. Myocardial ROS levels were examined using flow cytometry; myocardial TXNIP and NLRP3 expression were detected using immunohistochemistry. Real-time qPCR and Western blotting were used to examine myocardial mRNA and protein expression of TXNIP, NLRP3, apoptosis-related spot-like protein (ASC), caspase-1, and IL-1β, as well as myocardial thioredoxin (Trx) and colonic tight junction proteins (zonula occludens-1, ZO-1), occludin, and claudin-5. Differences in the gut microbiota of the blank, model, and QSYQ high-dose groups were determined using high-throughput 16S rDNA sequencing.
Results:
Compared to the blank group, the model group exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01); increased serum BNP, LPS, IL-18, and IL-1β (P<0.01) levels; increased CK, LDH, and CK-MB (P<0.01) contents; visible myocardial tissue fibrous edema, wavy appearance, cytoplasmic loosening, round vacuolar degeneration, local tissue fibrous dissolution replaced by proliferative connective tissue, accompanied by inflammatory cell infiltration; significantly increased myocardial ROS levels (P<0.01); and significantly increased myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly increased (P<0.05, P<0.01, respectively), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly decreased (P<0.01). Compared to the model group, the QSYQ high-dose group showed the most significant changes (P<0.05, P<0.01), with significant increases in LVEF and LVFS (P<0.01); significant decreases in serum BNP, LPS, IL-18, and IL-1β levels (P<0.01); significant reductions in CK, LDH, and CK-MB content (P<0.01); improved myocardial tissue damage; significantly decreased myocardial ROS levels (P<0.01); and significantly reduced myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly decreased (P<0.05, P<0.01), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly increased (P<0.01). 16S rDNA sequencing results confirmed that the gut microbiota of rats changed after modeling and drug intervention, with significant differences in both α- and β-diversity. Compared to the blank group, at the family level, the abundance of Oscillospiraceae decreased (P<0.05), whereas the abundance of Lactobacillaceae increased. At the species level, the abundance of Segatella copri and Treponema succinifaciens increased, whereas the abundance of Kineothrix alysoides (P<0.05), Ruminococcus callidus, and Prevotellamassilia timonensis decreased. Compared to the model group, at the family level, the abundance of Oscillospiraceae increased (P<0.05) in the QSYQ high-dose group, whereas the abundance of Lactobacillaceae decreased. At the species level, the abundance of Segatella copri and Treponema succinifaciens decreased, whereas the abundance of Kineothrix alysoides increased (P<0.05).
Conclusion
QSYQ can regulate the relative abundance of symbiotic bacteria Kineothrix alysoides in the intestines, reduce serum LPS levels, inhibit the ROS/TXNIP/NLRP3 signaling pathway, and improve inflammatory responses, thereby exerting therapeutic effects on CHF.
3.Overview of Preparation Characteristics and Application of the Mofeng Ointment Formulation (摩风膏方) in the Dunhuang Manuscript Unnamed Treatise on the Pulse (《亡名氏脉经》)
Tingting DOU ; Yuting WEI ; Cui MA ; Xingke YAN
Journal of Traditional Chinese Medicine 2025;66(12):1300-1304
The Mofeng Ointment Formulation (MOF, 摩风膏方) is recorded in the Dunhuang manuscript Unnamed Treatise on the Pulse (《亡名氏脉经》) and stands as a representative ancient external therapeutic formula in traditional Chinese medicine (TCM). Known for dispelling wind, activating blood circulation, warming the meridians, and relieving pain, it is particularly effective in treating rheumatic arthralgia. Through literature research, this paper systematically reviews the composition, preparation techniques, and clinical application characteristics of MOF. In recent years, advancements in modern pharmaceutical technology have led to the development of various innovative ointment-based formulations derived from the traditional recipe, such as Dunhuang Xiaoding Ointment (敦煌消定膏), Dunhuang Xiaozhong and Zhentong Ointment (Patch) (敦煌消肿镇痛膏/贴), Xiaoding Ointment (消定膏) gel patch, and Xiaoding Ointment (消定膏) cataplasm. These innovations explore pathways for transforming classical prescriptions into modern applications, providing a theoretical basis for the external TCM treatment of pain-related and orthopedic conditions.
4.SHI Zaixiang's Clinical Experience in Using Chaihu Guizhi Ganjiang Decoction (柴胡桂枝干姜汤) to Treat High Fever in Sepsis
Tingting ZHU ; Yingying LIU ; Hailan CUI ; Zhiying REN ; Mingjing SHAO ; Yan BIAN ; Liyan WANG ; Zhenjie CHEN ; Yuan LIU ;
Journal of Traditional Chinese Medicine 2025;66(16):1645-1648
This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction (柴胡桂枝干姜汤). He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever, chills, and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile, soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice, treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids, using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect, particularly in cases where multiple anti-infective treatments have failed.
5.Clinical significance of determining the level of biliary calprotectin in patients with cholangiocarcinoma or choledocholithiasis
Tingting JI ; Bingqing BAI ; Yufang CUI ; Shaofei WANG ; Jianglong HONG ; Yang LI ; Junjun BAO ; Qiao MEI
Journal of Clinical Hepatology 2024;40(3):568-572
ObjectiveTo investigate the difference in the level of biliary calprotectin between patients with cholangiocarcinoma and those with choledocholithiasis. MethodsClinical data and bile samples were collected from 34 patients with cholangiocarcinoma and 78 patients with choledocholithiasis who were diagnosed and treated with endoscopic retrograde cholangiopancreatography in The First Affiliated Hospital of Anhui Medical University from May 2021 to September 2022. Fluorescence lateral flow immunoassay was used to measure the levels of calprotectin, hemoglobin, and lactoferrin in bile. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Spearman correlation test was used for correlation analysis; the DeLong test was used for comparison of the area under the ROC curve (AUC). ResultsCompared with the choledocholithiasis group, the cholangiocarcinoma group had significant increases in the levels of calprotectin [4 795.50 (2 286.79 — 20 179.73) ng/mL vs 411.16 (67.03 — 1 991.88) ng/mL, Z=5.572, P<0.001] and fluoride [115.70 (109.10 — 125.50) mmol/L vs 106.60 (98.60 — 114.40) mmol/L, Z=2.702, P=0.007]. The patients with cholangiocarcinoma were further divided into high cholangiocarcinoma group and low cholangiocarcinoma group, and there was no significant difference between the two groups in the level of calprotectin [3 867.71 (2 235.66 — 26 407.40) ng/mL vs 4 795.50 (2 361.15 — 13 070.53) ng/mL, Z=0.129, P>0.05]. Biliary calprotectin level was correlated with white blood cell count, hemoglobin concentration, and lactoferrin concentration in bile (r=0.316, 0.353, and 0.464, all P<0.05). The ROC curve analysis showed that biliary calprotectin (with a sensitivity of 79.4% and a specificity of 75.6%), blood CA19-9 (with a sensitivity of 82.4% and a specificity of 78.2%), and their combination (with a sensitivity of 88.2% and a specificity of 73.1%) had good sensitivity and specificity in the diagnosis of cholangiocarcinoma. ConclusionThere is an increase in the level of biliary calprotectin in patients with cholangiocarcinoma, and therefore, it might become a biomarker for the diagnosis of cholangiocarcinoma.
6.Predictive value of renal venous Doppler waveform pattern for 28-day renal dysfunction in critically ill patients
Haijun ZHI ; Jie CUI ; Mengwei YUAN ; Yaning ZHAO ; Xingwen ZHAO ; Tingting ZHU ; Chunmei JIA ; Yong LI
Chinese Journal of Emergency Medicine 2024;33(3):324-331
Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.
7.Association between intraoperative hypotension and postoperative acute kidney injury in patients un-dergoing brain tumor resection
Qianyu CUI ; Jiaxin LI ; Tingting MA ; Xingyue ZHANG ; Shu LI ; Min ZENG ; Yuming PENG
The Journal of Clinical Anesthesiology 2024;40(2):160-164
Objective To investigate the association between intraoperative hypotension and post-operative acute kidney injury(AKI)in patients undergoing brain tumor resections.Methods A total of 428 patients undergoing elective craniotomy for tumor resection were selected,276 males and 152 females,aged≥18 years,BMI 15-36 kg/m2,ASA physical statusⅡ orⅢ.Based on postoperative occurrence of AKI,the patients were divided into two groups:the AKI group and the control group.This study defined three thresholds for hypotension,including MAP during surgery below 65 mmHg,60 mmHg,and 55 mmHg.Multivariate logistic regression was used to analyze the correlation between intraoperative hypotension and postoperative AKI under three thresholds.Results A total of 107 patients had postoperative AKI.The re-sults of multivariable regression analysis indicated that intraoperative MAP<65 mmHg(OR = 1.11,95%CI 1.03-1.20,P = 0.010)and intraoperative MAP<60 mmHg(OR = 1.12,95%CI 1.02-1.23,P = 0.017)were associated with postoperative AKI.Conclusion Intraoperative MAP<65 mmHg or 60 mmHg is associated with postoperative AKI in patients undergoing brain tumor resection.
8.Effect of stage Ⅰ comprehensive cardiac rehabilitation in patients with acute ST elevation myocardial infarctionafter emergency percutaneous coronary intervention
Yue REN ; Ting TIAN ; Guangsheng WEI ; Ming ZHANG ; Hong YU ; Jie LI ; Tingting DONG ; Yinmei FENG ; Hongchao CUI ; Jiao ZHANG
The Journal of Practical Medicine 2024;40(5):682-687
Objective This study aimed to investigate the effect of stage Ⅰ comprehensive cardiac rehabili-tation in patients with acute ST elevation myocardial infarction(STEMI)after emergency percutaneous coronary intervention(PCI).Methods A total of 72 patients with acute ST-segment elevation myocardial infarction combined with PCI admitted to the Department of Cardiovascular Medicine of Beijing Electric Power Hospital of State Grid Corporation from June 2021 to June 2022,which were selected as the research objectsand divided into control group and observation group randomly(36 cases in each group).The control group was treated with routine nursing and health education,and the observation group with stage Ⅰ comprehensive cardiac rehabilitation,including initial assessment(cardiovascular comprehensive assessment),exercise training(exercise training and breathing train-ing),daily activity suggestions and health education,discharge assessment(six-minute walking test and Barthel index assessment).The score of Barthel index(BI)at discharge,the 6-minute walking test distance(6MWD)at discharge,the incidence of major adverse cardiovascular event(MACE)during hospitalization and within one month of discharge,and the length of stay were compared between the two groups.Results After intervention,the six-minute walking test distance(6MWD)and Barthel index(BI)score in the observation group were better than those in the control group,the difference was statistically significant(P<0.05).The incidence of major adverse cardiovascular events(MACE)during hospitalization and one month after discharge was lower in the observation group than in the control group,and the difference was statistically significant(P<0.05).The length of hospital-ization in observation group was lower than that in control groupbut there was no statistical difference(P>0.05).Conclusion The application of phase Ⅰ comprehensive cardiac rehabilitation training in patients with acute ST-segment elevation myocardial infarction combined with emergency PCI could improve the patients'exercise ability,improve their ability of daily activity,reduce the incidence of major adverse cardiovascular events(MACE)in the early stage of the disease,facilitate the patients to return to their families and society as soon as possible,and improve their quality of life.It has high clinical application value.
9.The impact of early enteral nutrition up to scratch on the prognosis of patients with veno-arterial extracorporeal membrane oxygenation
Yang YANG ; Zhen XU ; Jing SUN ; Tingting YANG ; Cui JIAO ; Jingjing ZHANG ; Zhenjie HU ; Jianchao LI
Chinese Journal of Emergency Medicine 2024;33(11):1546-1551
Objective:To determine the effects of early enteral nutrition (EEN) on the short-term prognosis of patients receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO).Methods:61 patients admitted to the Coronary Care Unit (CCU) of Henan Provincial Peoples' Hospital from February 2022 to March 2023 to receive VA-ECMO treatment were selected as the study objects according a retrospective survey. The patients were divided into an achievement group ( n=34) and a non-achievement group ( n=27) based on whether the feeding amount reached 70% or over of the target calories (25kcal/kg.d) on the 7th day of ECMO treatment. The general characteristics, disease information, complications, and prognosis between the two groups after ICU admission were recorded and compared. A multivariable Cox proportional hazards model was used to evaluate the impact of various factors on clinical outcomes. Kaplan-Meier analysis was used to draw survival curves for the two groups, and the predictive value of the ratio of actual EN intake to target energy was calculated by plotting the ROC curve. Results:A total of 61 patients were included, with an overall in-hospital mortality rate of 50.82% (31/61), with 32.35% (11/34) in the achievement group, and 70.37% (19/27) in the non-achievement group. Cox regression analysis revealed that the occurrence of hypoxic-ischemic encephalopathy (HR=0.341, 95% CI:0.119-0.975), ECOM weaning failure ( HR=0.269, 95% CI:0.111-0.651), and achieving EN targets on the 7th day of VA-ECMO treatment ( HR=10.891, 95% CI:1.178-100.718) were independent factors for patient mortality during hospitalization. The ROC curve for the percentage of EN achievement on the 7th day of VA-ECMO treatment and in-hospital mortality showed an area under the curve of 0.755, with a cutoff value of 0.73. Conclusion:The presence of ischemic hypoxic encephalopathy, ECOM weaning failure, and whether achieving EN targets or not is closely related to the prognosis of VA-ECMO patients. Patients who achieving EN targets of over 73% had the lowest in-hospital mortality rate. Therefore, more attention should be paid to the energy intake of VA-ECMO patients to reduce their risk of mortality.
10.Construction of rehabilitation nursing program for total knee arthroplasty patients with kinesiophobia based on capacity, opportuniy, motivation-behavior theoretical model
Zhou SU ; Qiyun ZHEN ; Huiwu QU ; Lili CUI ; Tingting DAI
Chinese Journal of Practical Nursing 2024;40(32):2513-2520
Objective:To construct a rehabilitation nursing program for total knee arthroplasty (TKA) patients with kinesiophobia based on capacity, opportuniy, motivation-behavior (COM-B) theoretical model, and to provide reference for clinical staff to implement rehabilitation treatment.Methods:From August to December 2023, literature analysis was used to construct a preliminary program, combined the COM-B theoretical model with the rehabilitation exercise guidelines and expert consensus. The rehabilitation nursing program for TKA patients with kinesiophobia was formed through 2 rounds of Delphi expert correspondence consultation, and the analytic hierarchy process was used to calculate the weight of each item.Results:A total of 15 experts were included, including 4 males and 11 females, aged (45.80 ± 5.72) years old. The effective recovery rate of the 2 rounds of expert correspondence questionnaires were 15/15, the expert authority coefficients were 0.860 and 0.875, and the Kendall coordination coefficients were 0.155 and 0.172, and the differences were statistically significant ( χ2 = 97.70, 105.91, both P<0.01). The final rehabilitation nursing program for TKA patients with kinesiophobia included 3 primary indexes, 8 secondary indexes and 25 tertiary indexes. Conclusions:The rehabilitation nursing program for TKA patients with kinesiophobia constructed based on COM-B theoretical model is scientific and practical, and can provide a practical basis for clinical staff.


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