1.Mechanism of Huayu jiedu formula in alleviating inflammatory injury in chronic kidney disease based on AIM2 pyroptosis pathway
Jinhuan XUE ; Ziwen WU ; Fan YANG ; Yunyun LOU ; Yingjun DING ; Yupeng XIAO ; Xianhui LIU ; Wenjie LIANG
China Pharmacy 2025;36(21):2638-2644
OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease (CKD). METHODS Fifty male SD rats were randomly divided into a sham surgery group (10 rats) and a modeling group (40 rats). The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling, the rats were randomly divided into model group, esaxerenone group (positive control), and TCM low- and high-dose groups, with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone, while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively, the sham surgery group and model group were given an equal volume of physiological saline, all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea (SUr), serum creatinine (SCr), malondialdehyde (MDA), and superoxide dismutase (SOD) levels; enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α(TNF-α); immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) , mitochondrial transcription factor A (TFAM), absent in melanoma 2(AIM2), caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in renal tissue; real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group, the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction, severe tubular dilation, and increased deposition of blue fibrin; the levels of SUr, SCr, MDA, IL-1β, IL-6, TNF-α,the protein expression of AIM2, GSDMD, caspase-1, IL-1β, IL-18 , and the mRNA expression of AIM2 were significantly increased or up-regulated (P<0.01); the levels of SOD, the protein expression of PGC-1α, TFAM were significantly reduced or down-regulated (P<0.01). Compared with the model group, all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function, alleviate renal inflammatory damage and pyroptosis, and exert renal protective effects by regulating the AIM2 pyroptosis pathway.
2.Life's Essential 8 scores, socioeconomic deprivation, genetic susceptibility, and new-onset chronic kidney diseases.
Panpan HE ; Huan LI ; Mengyi LIU ; Ziliang YE ; Chun ZHOU ; Yanjun ZHANG ; Sisi YANG ; Yuanyuan ZHANG ; Xianhui QIN
Chinese Medical Journal 2025;138(15):1835-1842
BACKGROUND:
The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association.
METHODS:
A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD.
RESULTS:
During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs. most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs. high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05).
CONCLUSION
Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans
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Renal Insufficiency, Chronic/epidemiology*
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Male
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Female
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Middle Aged
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Genetic Predisposition to Disease/genetics*
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Aged
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Risk Factors
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Adult
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Proportional Hazards Models
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Socioeconomic Factors
3.Early endovascular treatment for cerebral infarction caused by intracranial atherosclerosis or cardioembolism:a comparative study
Youqing XU ; Haichen SHEN ; Xiangjun XU ; Junfeng XU ; Ke YANG ; Xianhui DING ; Xianjun HUANG
Journal of Interventional Radiology 2025;34(9):931-934
Objective To compare the clinical efficacy and safety of early endovascular treatment(EVT)for the stroke patients caused by large vessel occlusion(LVO)due to intracranial atherosclerosis(ICAS)or due to cardioembolism(CE).Methods The clinical data of 488 patients with acute anterior circulation LVO stroke,who received early endovascular treatment at the Yijishan Hospital of Wannan Medical College of China from October 2015 to December 2023,were retrospectively analyzed.According to the cause of disease,the patients were divided into ICAS group(n=108)and CE group(n=380).The clinical data,mainly including the proportion of patients having a good prognosis at 90 days after operation(modified Rankin Scale score ≤2 points),the incidence of symptomatic intracranial cerebral hemorrhage(sICH),and the mortality of patients at 90 days after operation.Multivariate logistic regression analysis was used to analyze the factors influencing patient's prognosis.Results Of the 488 patients,29(5.9%)developed postoperative sICH,242(49.6%)achieved a good prognosis at 90 days after the operation,and 91(18.6%)died.The above outcomes in the ICAS group were one,66,and 11 patients respectively,which in the CE group were 28,176,and 80 respectively,and the differences between the two groups were statistically significant(all P<0.05).Multivariate logistic regression analysis indicated that good prognosis at 90 days after the operation(OR=0.962,95%CI:0.404-2.288,P=0.930)and the postoperative 90-day mortality(OR=1.379,95%CI:0.436-4.362,P=0.584)were not the factors influencing prognosis,while the postoperative sICH(OR=19.132,95%CI:1.332-274.791,P=0.030)was the factor influencing prognosis.Conclusion In CE group,the incidence of sICH and the postoperative 90-day mortality are higher,while in ICAS group,the postoperative 90-day good prognosis rate is higher.The postoperative sICH is the factor influencing prognosis.
4.Efficacy and prognostic analysis of prothrombin complex concentrate in 349 patients with trauma-induced coagulopathy
Xianhui MA ; Yangbo KANG ; Qi YANG ; Hongbo DING ; Jiasheng SHEN ; Yong'an XU
Chinese Journal of Emergency Medicine 2025;34(1):70-77
Objective:Efficacy of prothrombin complex concentration (PCC) and analysis of prognostic factors in patients with traumatic trauma-induced coagulopathy (TIC).Methods:A retrospective study was conducted on patients with TIC admitted to 11 hospitals from January to December 2021. The data included baseline characteristics, injury information, blood product transfusions (including PCC treatment), laboratory examination at admission and 24 hour-after admission, treatment measure, pre-hospitalization time, and clinical outcomes (improvement at discharge, length of hospital stay). The patients were divided into a conventional group and a PCC group according to whether they were treated with PCC. Propensity score matching method was used to match the patients at a 1:1 ratio, and the differences in different indicators between the groups were compared. Univariate and multivariate logistic regression analyses were performed to identify prognostic factors for TIC patients.Results:After propensity score matching, 103 patients were identified in both the PCC and conventional groups. Univariate logistic regression analysis revealed no significant differences in age, gender, Glasgow Coma Scale (GCS) score, injury severity score, acute physiology and chronic health evaluation score, underlying diseases, pre-hospitalization time, injury type and site, and treatment measure (use of vasoactive drugs, calcium agents, tranexamic acid, and emergency surgery) between the two groups (all P>0.05). Compared with the conventional group, the PCC group exhibited lower 24-hour white blood cell counts, lactate level, prothrombin time, and international normalized ratio (INR) (all P<0.05), whereas hemoglobin level and pH value were higher (both P<0.05). The PCC group also had a shorter hospital stay (13 d vs. 15 d, P<0.05). However, there was no significant difference in the rate of improvement at discharge between the two groups ( P=0.308). Multivariate logistic regression revealed that age (>68 years), GCS score (<5 points), fibrinogen (FIB) level (after 24 h, <2.04 g/L), and INR (after 24 h, >1.455) were independent risk factors affecting the prognosis of TIC patients, and the AUCs were 0.632, 0.702, 0.733, and 0.752, respectively. Conclusions:Treatment with PCC in TIC patients can correct coagulation dysfunction and reduce hospital stay. Age, GCS score, FIB level and INR after 24 h affect the clinical prognosis of TIC patients, which requires special attention.
5.Prediction analysis of the number of pre-hospital emergency ambulance trips in Handan based on the LPro Ensemble Model
Feng TIAN ; Chengcheng BI ; Penghui LI ; Haifang ZHANG ; Tingting ZHAO ; Zhenjie YANG ; Xian WANG ; Jiaxuan GU ; Shitao ZHOU ; Zengjun JIN ; Zhen WANG ; Feifei ZHAO ; Xianhui SU ; Longqiang ZHANG ; Saicong LU
Chinese Journal of Emergency Medicine 2025;34(11):1530-1537
Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.
6.Influencing factor of acute multivessel occlusion and its impact on prognosis of acute large vessel occlusion stroke patients after successful recanalization of endovascular treatment
Yuepei GAO ; Chenglei WANG ; Yapeng GUO ; Junfeng XU ; Xianhui DING ; Xiangjun XU ; Ke YANG ; Qian YANG ; Xianjun HUANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2024;21(11):767-777
Objective To investigate the influencing factors for acute multiple vessels occlusion(MVO)and its impact on the prognosis of patients with anterior circulation acute large vessel occlusion stroke(ALVOS)who achieved successful recanalization after endovascular treatment(EVT).Methods Patients with anterior circulation ALVOS who received successful EVT at the Yijishan Hospital of Wannan Medical College between July 2015 and April 2023 were retrospectively analyzed.Baseline data,including age,sex,onset-to-puncture time(OTP),onset-to-recanalization time(OTR),medical history(including atrial fibrillation,diabetes,hypertension),alcohol and smoking history,admission blood pressure(systolic and diastolic),Alberta stroke program early CT score(ASPECTS),National Institutes of Health stroke scale(NIHSS)score,trial of Org 10172 in acute stroke treatment(TOAST)classification(atherosclerotic type,cardioembolic type,and other etiology types),and 90-day modified Rankin scale(mRS)score were collected.Collateral circulation was assessed based on the degree of contrast agent reflux observed in the occluded arterial supply area during delayed DSA,and patients were classified into poor and good collateral circulation groups.Malignant cerebral edema was defined as a midline shift of ≥5 mm on the follow-up CT scan performed on day 3 post-surgery.The primary endpoint(efficacy indicator)was the 90-day mRS score,with mRS score≤ 2 considered as a good prognosis and mRS score>2 considered as a poor prognosis.The secondary endpoint(safety indicator)was the 90-day mortality rate.All patients were divided into MVO and non-MVO groups based on whether they had single or multiple intracranial vessel occlusions.Acute MVO was defined as the detection of acute occlusion of other large or medium vessels,in addition to the main vessels(internal carotid artery or M1/M2 segments of the middle crebral artery[MCA]),in CT angiography,MR angiography,or DSA,resulting in ischemia in brain regions distinct from the main occlusion area.Factors that showed statistically significant differences in univariate analysis were further analyzed using multivariate Logistic regression to identify the risk factors for the occurrence of acute MVO and the factors associated with the prognosis of ALVOS patients.Results A total of 846 patients with ALVOS were included,with ages ranging from 26 to 94 years(mean age[69±11]years).The proportion of male patients was 57.2%(484/846).The median admission ASPECTS was 8(7,9)and the median admission NIHSS score was 14(12,18).The incidence of malignant cerebral edema at 3 days post-surgery was 13.4%(112/835),and the 90-day mortality rate was 19.1%(162/846).(1)Among the 846 ALVOS patients,810(95.7%)were in the non-MVO group and 36(4.3%)were in the MVO group.Univariate analysis showed significant differences between the MVO and non-MVO groups in terms of atrial fibrillation,malignant cerebral edema,admission ASPECTS,admission NIHSS scores,TOAST classification,collateral circulation,rate of complete recanalization,and 90-day poor prognosis rate(all P<0.05).However,there was no statistically significant difference in 90-day mortality between the two groups(P=0.193).Multivariate Logistic regression analysis showed that TOAST classification of cardioembolic type(OR,16.089,95%CI 1.835-141.061,P=0.012)and other etiology types(OR,9.768,95%CI 1.078-88.540,P=0.043)were associated with the occurrence of MVO.(2)Among the 846 ALVOS patients,445 had a good prognosis at 90days,and 401 had a poor prognosis.Univariate analysis showed that,compared to the good prognosis group,the poor prognosis group had a lower proportion of males and smokers,and a higher proportion of patients with older age,higher baseline systolic blood pressure,hypertension,diabetes,and atrial fibrillation(all P<0.01).Additionally,the poor prognosis group had higher admission NIHSS scores(P<0.01),lower admission ASPECTS,lower rates of good collateral circulation and complete recanalization,higher rates of malignant cerebral edema and MVO,and statistically significant differences in TOAST classification distribution(all P<0.01).Multivariate Logistic regression analysis showed that MVO was associated with poor 90-day prognosis in ALVOS patients after EVT(OR,3.368,95%CI 1.149-9.878,P=0.027).Furthermore,older age(OR,1.045,95%CI 1.025-1.066),diabetes(OR,1.719,95%CI 1.080-2.734),higher baseline systolic blood pressure(OR,1.012,95%CI 1.004-1.019),lower admission ASPECTS(OR,0.746,95%CI 0.674-0.826),higher admission NIHSS score(OR,1.115,95%CI 1.070-1.162),without immediate postoperative complete recanalization(OR,0.413,95%CI 0.290-0.592),poor collateral circulation(OR,0.594,95%CI 0.415-0.851),and malignant cerebral edema(OR,6.191,95%CI 3.026-12.670)were all associated with poor 90-day prognosis after EVT in ALVOS patients(all P<0.05).Conclusions The TOAST classification of cardioembolic type and other etiology types is associated with MVO.MVO is a risk factor for poor outcomes after successful EVT in ALVOS patients.
7.Pioglitazone's Therapeutic Effect and Electrophysiological Mechanism on Rat Ventricular Arrhythmias Induced by β1-adrenergic Receptor Autoantibodies
Linqiang XI ; Huaxin SUN ; Luxiang SHANG ; Qianhui WANG ; Jie SONG ; Na YANG ; Xing ZHANG ; Taiwaikuli DILARE ; Rejiepu MANZEREMU ; Ling ZHANG ; Baopeng TANG ; Xianhui ZHOU
Chinese Circulation Journal 2024;39(7):716-724
Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P<0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P<0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P<0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P<0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P<0.05.Mitochondrial morphology abnormalities and network damage did not recover(P<0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.
8.Functional gastrointestinal disorders, mental health, genetic susceptibility, and incident chronic kidney disease
Mengyi LIU ; Panpan HE ; Ziliang YE ; Sisi YANG ; Yanjun ZHANG ; Qimeng WU ; Chun ZHOU ; Yuanyuan ZHANG ; Fan Fan HOU ; Xianhui QIN
Chinese Medical Journal 2024;137(9):1088-1094
Background::Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods::About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.Results::At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion::Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.
9.Implication of Qidi Tangshen Prescription (QDTS) on Podocyte Pyroptosis in Diabetes Nephropathy by Regulating MAPK14/RELA/Caspase-8 Signaling Pathway
Fei GAO ; Borui YU ; Huidi XIE ; Ying ZHOU ; Yang SHI ; Xianhui ZHANG ; Hongfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):67-75
ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription (QDTS) in regulating podocyte pyroptosis in diabetes nephropathy (DN). MethodThrough in vivo experiment, db/db mice were divided into the model group, QDTS group (3.34 g·kg-1), valsartan capsule group (10.29 mg·kg-1), with db/m mice serving as the normal control. Each group consisted of 8 mice, and they underwent continuous intervention for 8 weeks. After the last administration, mice were euthanized, and kidney pathological changes were observed. Additionally, the expression levels of pyroptosis-related indicators, including NOD-like receptor protein 3 (NLRP3), Gasdermin D protein (GSDMD), and interleukin-1β (IL-1β) protein, were examined. Through in vitro experiment, mouse podocytes were divided into the normal glucose group (5.5 mmol·L-1 glucose), high glucose group (35 mmol·L-1 glucose), DMSO group (35 mmol·L-1 glucose+200 mg·L-1 DMSO), and QDTS group (35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder). After 48 hours of intervention, the expression levels of NLRP3, GSDMD, and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed, and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group, glomerular hyperplasia and glomerular basement membrane thickening were observed in model group, and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3, GSDMD and IL-1β in mouse kidney were increased, the protein expressions of mitogen-activated protein kinase 14 (MAPK14), V-Rel reticuloendotheliosis virus oncogene homology A (RELA) and Caspase-8 in mouse kidney were increased (P<0.05). Compared with model group, kidney pathological injury of mice in QDTS group was significantly reduced, and the expressions of NLRP3, GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased (P<0.05). The protein expressions of MAPK14, RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased (P<0.05). Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath, among which MAPK14, RELA and Caspase-8 were the key targets. Compared with normal glucose group, the protein expressions of NLRP3, GSDMD and IL-1β in high glucose group were increased (P<0.05), and the protein expressions of MAPK14, RELA and Caspase-8 in mouse podocytes were increased (P<0.05). Compared with high glucose group, the expressions of NLRP3, GSDMD and IL-1β in podocytes of mice in QDTS group were decreased (P<0.05), and the expressions of MAPK14, RELA and Caspase-8 in podocytes of mice in QDTS group were decreased (P<0.05). ConclusionQDTS reduces damage to DN podocytes, which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.
10.Association between the magnitude of systolic blood pressure reduction after successful endovascular thrombectomy with outcomes and post-procedure symptomatic intracranial hemorrhage in acute large vessel occlusion stroke patients
Xianjun HUANG ; Hao WANG ; Junfeng XU ; Xianhui DING ; Yapeng GUO ; Xiangjun XU ; Ke YANG ; Qian YANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2024;21(3):145-155
Objective To explore the association of the magnitude of systolic blood pressure reduction(SBPr)with post-procedure 24 h symptomatic intracranial hemorrhage(sICH)and 90-day clinical outcomes in patients with successful endovascular thrombectomy(EVT).Methods Consecutively registered patients with EVT caused by anterior circulation large vessel occlusion stroke(LVOS)in the First Affiliated Hospital of Wannan Medical College(Yijishan Hospital)between July 2015 and April 2023 and patients with successful reperfusion were analyzed.Demographic data,medical history(hypertension,diabetes),the trial of Org 10172 in acute stroke treatment(TOAST)classification,the baseline National Institutes of Health Stroke Scale(NIHSS)score and the baseline Alberta stroke early CT(ASPECT)score of patients were collected.And procedure related parameters(including time from onset to puncture,time from onset to reperfusion,occluded site[internal carotid artery,M1 segment of middle cerebral artery,M2 segment of middle cerebral artery],collateral circulation status[determined based on preoperative occluded angiography showing the range of collateral circulation in the occluded vessel area,defined as good collateral circulation with a reflux range of ≥ 50%and poor collateral circulation with a reflux range of<50%]),immediate postoperative reperfusion status(evaluated using the modified thrombolysis for cerebral infarction[mTICI]grading,successful reperfusion defined as mTICI grading of 2b-3),24 hours sICH,and 90 days clinical outcomes(evaluated using the modified Rankin scale score at 90days after EVT,with a score ≤ 2indicating a good prognosis and a score>2indicating a poor prognosis).SBPr was defined as(baseline SBP-mean SBP)/baseline SBP x 100%.According to the the magnitude of SBPr,SBPr is divided into 5 categories(<-10%,-10%-10%,>10%-20%,>20%-30%and>30%).Based on the clinical outcomes at 90 days and the occurrence of sICH at 24 hours after EVT,patients were divided into a good prognosis group and a poor prognosis group,as well as an sICH group and a non-sICH group.The relationship between SBPr and postoperative 90 days clinical prognosis or sICH was analyzed using a binary Logistic regression model.Subgroup analysis was conducted based on a history of hypertension(yes and no),continuous intravenous hypotensive therapy(yes and no),baseline ASPECT scores(3-5 and 6-10),and collateral circulation status(good and bad).Using a restricted cubic plot to depict the relationship between SBPr and sICH and clinical prognosis at 90days.Results(1)In total,731 patients were included.The median age was 71(62,77)years and 424(58.0%)were men.The median baseline NIHSS score was 14(12,18),the median baseline ASPECT was 9(7,10),405(55.4%)patients achieved 90-day modified Rankin scale score 0-2,and 35 patients(4.8%)developed sICH.(2)Multivariate analysis showed that the older age(OR,1.036,95%CI 1.017-1.056),the higher baseline NIHSS score(OR,1.095,95%CI1.049-1.144),the lower baseline ASPECT score(OR,0.704,95%CI 0.636-0.780),diabetes(OR,1.729,95%CI 1.084-2.758),bad collateral circulation(good collateral circulation vs.bad collateral circulation,OR,0.481,95%CI 0.332-0.696)and SBPr>30%(SBPr-10%-10%as a reference,OR,2.238,95%CI 1.230-4.071),the higher the risk of poor clinical outcomes at 90 days(all P<0.05).Continuous intravenous hypotensive therapy is a risk factor for postoperative 24 h sICH(OR,2.278,95%CI 1.047-4.953;P=0.038),while SBPr 20%-30%is associated with a lower risk of postoperative 24 h sICH(SBPr-10%-10%as a reference,OR,0.362,95%CI0.131-0.998;P=0.049).(3)The restrictive cube plot shows that there is a U-shaped relationship between SBPr after EVT and poor clinical outcomes at 90 days,while there is a nearly linear relationship with the occurrence of sICH.The more SBP reduction,the lower the incidence of sICH.(4)In the subgroup analyses,in the non-hypertension history and the good collateral circulation group,SBPr>30%has a higher risk of poor clinical outcomes compared to SBPr-10%-10%(OR and 95%CI were 2.921[1.000-8.528]and 2.363[1.078-5.183],respectively,with P=0.05 or P<0.05);After EVT,the group receiving continuous intravenous hypotensive therapy and the baseline ASPECT score 6-10 groups showed a significant correlation between SBPr>30%and poor clinical outcomes at 90 days(SBPr-10%-10%as a reference,OR and 95%CI were 2.646[1.168-5.993]and 2.481[1.360-4.527],respectively,with P<0.05).The correlation between SBPr and lower incidence of sICH was only found in the subgroup of poor collateral circulation(SBPr-10%-10%as a reference,SBPr>20%-30%:OR,0.133,95%CI 0.027-0.652;SBPr>30%:OR,0.104,95%CI 0.013-0.864;all P<0.05).Conclusions Among patients who achieved successful reperfusion with EVT,SBPr might be related to a worse functional outcome at 90 days and sICH 24 h after operation.However,the relationship may exhibit significant heterogeneity across different subgroups.Baseline ASPECT score,history of hypertension,collateral circulation,and the use of continuous venous hypertension after EVT have been highlighted in individualized blood pressure management after EVT.

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