1.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.
2.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.
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.Predictive value of preoperative combined detection of NLR and PTAR for early abdominal infection after liver transplantation
Huabin PENG ; Ying LIU ; Fei HOU ; Shuang ZHAO ; Yizhi ZHANG ; Tingting CUI ; Zhiying HE ; Jingyi LIU ; Haofeng XIONG ; Liying SUN
Organ Transplantation 2025;16(6):931-943
Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.
6.Design and implementation of epidemiological survey on dementia in community residents in Tongliao City
Yuanyuan LI ; Linfeng ZHANG ; Guangming XU ; Xiaoyi TIAN ; Hongjun SUN ; Tingting ZHANG ; Hongmei YU ; Peilin XU ; Wujisiguleng ; Jiana MUHAI ; Ying CUI ; Junjie HUANG ; Muren ; Guifang LEI ; Yueqin HUANG ; Zhaorui LIU
Chinese Mental Health Journal 2024;38(9):752-758
Objective:To describe the detail sampling design,weighting,instruments,filed procedures and quality control methods of the epidemiological survey on dementia among community residents in Tongliao City.Methods:A three-stage disproportionate probability sampling design was used to investigate the inhabitants aged 65 years and over in Tongliao City,Inner Mongolia Autonomous Region.The 10/66 Dementia Research Group(10/66 DRG)assessment instruments were used to diagnose dementia,using computer-assisted personal interview mode in the selected older people.Comprehensive quality control methods were implemented throughout the field-work.Results:A total of 166 villages or communities were sampled from nine counties or districts in Tongliao Cit-y.Totally 4 345 older people were interviewed with 96.2%response rate.By calculating sampling design weights,non-response adjustment weights and post-stratification adjustment weights,these weights were multiplied and per-formed trimming adjustment and standardization adjustment to generate final weights.The 171 interviewers were well-trained and qualified to carry out filed interview.Quality control methods included computer data check,audio record check,and telephone check in order to ensure the quality of the survey.Conclusion:This survey is imple-mented using a rigorous sampling design and timely quality control methods,and uses the 10/66 DRG assessment instruments with satisfactory international validity and reliability as survey instruments,which has international cross-cultural comparability.It provides a valid and feasible methodology of epidemiological survey on dementia for further studies in different regions in China.
7.Effect of milrinone-induced controlled low central venous pressure on intraoperative cerebral blood flow in patients undergoing laparoscopic hepatectomy
Yushuo DONG ; Jiali CUI ; Ju GAO ; Tingting ZHANG ; Lin LI ; Yali GE
Chinese Journal of Anesthesiology 2024;44(5):553-557
Objective:To evaluate the effect of controlled low central venous pressure (CLCVP) induced by milrinone on intraoperative cerebral blood flow in the patients undergoing laparoscopic hepatectomy.Methods:Eighty American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, regardless of gender, scheduled for elective laparoscopic hepatectomy, with body mass index of 18-30 kg/m 2, aged 18-64 yr, were divided into 2 groups ( n=40 each) by a random number table method: nitroglycerin group (X group) and milrinone group (M group). After the start of surgery, milrinone 0.5 μg·kg -1·min -1 was continuously infused in group M and nitroglycerin 0.5-1.5 μg·kg -1·min -1 was continuously infused in group X to maintain central venous pressure (CVP)<5 cmH 2O. Norepinephrine 0.01-0.10 μg·kg -1·min -1 was intravenously injected during operation to maintain mean arterial pressure at 60-90 mmHg. Norepinephrine 8-16 μg was intravenously injected when necessary. At 10 min after tracheal intubation (T 1), after establishment of pneumoperitoneum (T 2), at 5 and 30 min after CVP reached the target value (T 3, T 4), at 5 min after CVP returned to normal value (T 5) and at the end of surgery (T 6), the internal carotid artery mean blood flow velocity, internal carotid artery blood flow, cardiac output, and cardiac index were recorded. The surgical field score, consumption of intraoperative norepinephrine, fluid input and output, and occurrence of adverse reactions at 7 days after operation were recorded. Results:Compared with group X, the cardiac output, cardiac index, internal carotid artery mean blood flow velocity and internal carotid artery blood flow were significantly increased, the consumption of intraoperative norepinephrine was decreased, and the surgical field score was increased at T 3-5 in group M ( P<0.05). There was no significant difference in the intraoperative fluid intake and output and incidence of postoperative adverse reactions at each time point between the 2 groups ( P>0.05). Conclusions:Compared with nitroglycerin-induced CLCVP, milrinone-induced CLCVP can improve the reduction in intraoperative cerebral blood flow in the patients undergoing laparoscopic hepatectomy to some extent.
8.Feasibility of wavelet index in monitoring depth of sedation with propofol in pediatric patients
Tingting ZI ; Jianmin ZHANG ; Xiaoxia PENG ; Lijing LI ; Jie YU ; Muyang TIAN ; Xiaohuan CUI ; Fang WANG
Chinese Journal of Anesthesiology 2024;44(8):1000-1005
Objective:To assess the feasibility of wavelet index (WLI) in monitoring the depth of sedation with propofol in pediatric patients.Methods:This was a prospective observational trial. One hundred and sixty-five pediatric patients, aged >1-12 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective surgery requiring general anesthesia with endotracheal intubation or laryngeal mask airway from July to December 2016 in our hospital, were divided into 11 age groups ( n=15 each): >1-2 yr group, >2-3 yr group, >3-4 yr group, >4-5 yr group, >5-6 yr group, >6-7 yr group, >7-8 yr group, >8-9 yr group, >9-10 yr group, >10-11 yr group, and >11-12 yr group. General anesthesia was induced by injection of propofol 3 mg/kg for more than 30 s. WLI and BIS values were recorded immediately before administration and at 30, 40, 50, 60, 90, 120, 180 and 240 s after the end of administration. If there were differences among age groups, age groups with no statistically significant differences were combined and re-grouped. Pearson linear correlation analysis and Bland-Altman consistency analysis were performed. Results:A total of 149 pediatric patients were actually included. There were no significant differences in BIS values between 4 groups aged > 1-5 yr and between 7 groups aged > 5-12 yr ( P>0.05). Regrouping was performed based on the aforementioned results, 4 groups of children aged > 1-5 yr were divided into > 1-5 yr group ( n=60), and 7 groups of children aged > 5-12 yr were divided into > 5-12 yr group ( n=89). WLI values and BIS values were significantly decreased at each time point after administration compared with immediately before administration in group aged > 1-5 yr and in group aged >5-12 yr ( P<0.05). The BIS values were the lowest at 60 s after the end of the administration, and the WLI values were the lowest at 120 and 180 s after the end of the administration in two groups ( P<0.05). There were no statistically significant differences between WLI values and BIS values at 90 s and 240 s after the end of the administration ( P>0.05), and there was statistically significant difference at the other time points in group aged > 1-5 yr ( P<0.05). There was no significant difference between WLI values and BIS values at 180 s and 240 s after the end of the administration ( P>0.05), but there were significant differences at the other time points in group aged > 5-12 yr ( P<0.05). The Pearson correlation coefficients between WLI values and BIS values were 0.61 and 0.56 in group aged > 1-5 yr and group aged > 5-12 yr, respectively ( P<0.001). Bland-Altman agreement analysis: In group aged > 1-5 yr and group aged > 5-12 yr, the 95% agreement limits were -0.484-0.621 and -0.551-1.015, respectively, and there were 4.6% (23/504) and 5.1% (40/777) of the points outside the 95% agreement limits, respectively, and both limits exceeded the clinically acceptable range. Conclusions:WLI is feasible for monitoring the depth of sedation with propofol in pediatric patients aged > 1-12 yr, but the accuracy is lower than BIS.
9.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.
10.Dosimetric effects of flatten filter on hippocampal-avoidance whole brain non-uniform intensity-modulated radiotherapy
Zhiqiang CUI ; Tingting DONG ; Tongyou SUN ; Yanjie ZHENG ; Junli DAI
China Medical Equipment 2024;21(8):23-28
Objective:To study the dosimetric differences of hippocampal-avoidance whole brain radiotherapy(HA-WBRT)between non-uniform 9-fields intensity-modulated radiotherapy-flatten filter(9F-IMRT-FF)and 9-fields intensity-modulated radiotherapy-flatten filter-free(9F-IMRT-FFF)mode.Methods:From January to December 2023,the simulated images of computed tomography(CT)location of 20 patients with intracranial metastases who had completed whole-brain radiotherapy at the Department of Radiotherapy of Chengde Central Hospital were selected.The radiotherapy plans of two kinds of modes of brand-new 9F-IMRT-FF and 9F-IMRT-FFF were redesigned in the planning system.The differences of dosimetric parameters of the two kinds of mode plans were compared,as well as the differences of irradiation efficiency of accelerator.Results:The exposure dose(D2%)of 2%volume of target region of planned target volume(PTV)of 9F-IMRT-FFF mode was significantly lower than that of 9F-IMRT-FF mode(t=-2.496,P<0.05).The exposure dose(D100%)of 100%volume of target region,the maximum dose(Dmax)and the mean dose(Dmean)of the left side of hippocampus of 9F-IMRT-FFF mode plan were significantly lower than those of 9F-IMRT-FF mode plan,with statistically significant(Z=-3.179,-3.018,-2.145,P<0.05),respectively.The D100%and Dmax of the right side of hippocampus of 9F-IMRT-FFF mode plan were significantly lower than those of 9F-IMRT-FF mode plan,with statistically significant(Z=-3.099,-3.260,P<0.05),respectively.The monitor unit(MU)value of 9F-IMRT-FFF mode plan increased by 25%than that of 9F-IMRT-FF mode plan,while the treatment time of 9F-IMRT-FFF mode plan shortened 38%than that of 9F-IMRT-FF mode plan,with statistically significant(t=-9.664,-13.312,P<0.05),respectively.Conclusion:Both the non-uniform 9F-IMRT-FF and the 9F-IMRT-FFF can meet the clinically requirement.The 9F-IMRT-FFF has better modulation capabilities in beams,which has more advantages in reducing the dose of radiotherapy for hippocampus,and reducing treatment time,and increasing treatment efficiency.


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