1.Comparison of anti-inflammatory, antibacterial and analgesic activities of formulated granules versus traditional decoction of Yinqiao Powder.
Zhuolin GUO ; Zhiheng ZHANG ; Xindeng GUO ; Weiwei YANG ; Zhiqing LIANG ; Jinying OU ; Huihui CAO ; Zibin LU ; Linzhong YU ; Junshan LIU
Journal of Southern Medical University 2025;45(5):1003-1012
OBJECTIVES:
To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction.
METHODS:
We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg.
RESULTS:
Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models.
CONCLUSIONS
The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals
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Mice
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Drugs, Chinese Herbal/pharmacology*
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Anti-Inflammatory Agents/pharmacology*
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Analgesics/pharmacology*
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RAW 264.7 Cells
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Zebrafish
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Anti-Bacterial Agents/pharmacology*
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Powders
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Tumor Necrosis Factor-alpha/metabolism*
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Acute Lung Injury/drug therapy*
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Interleukin-6/metabolism*
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Lipopolysaccharides
2.Exploring the mechanism of Xiaoaiping Injection inhibiting autophagy in prostate cancer based on proteomics.
Qiuping ZHANG ; Qiuju HUANG ; Zhiping CHENG ; Wei XUE ; Shoushi LIU ; Yunnuo LIAO ; Xiaolan LI ; Xin CHEN ; Yaoyao HAN ; Dan ZHU ; Zhiheng SU ; Xin YANG ; Zhuo LUO ; Hongwei GUO
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):64-76
Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male
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Humans
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Prostatic Neoplasms/physiopathology*
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Autophagy/drug effects*
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Animals
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Drugs, Chinese Herbal/pharmacology*
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Proteomics
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Mice
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Apoptosis/drug effects*
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Cell Line, Tumor
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Cell Proliferation/drug effects*
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Forkhead Box Protein O3/genetics*
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Xenograft Model Antitumor Assays
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Mice, Nude
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Mice, Inbred BALB C
3.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
4.Application of 3D printing accurate osteotomy guide combined with the revision of anterior cruciate ligament with abnormally increased posterior slope of tibial plateau
Zhiheng WEI ; Tianmin GUAN ; Qing LIU ; Jue GONG ; Xianxiang XIANG
Chinese Journal of Tissue Engineering Research 2025;29(33):7130-7136
BACKGROUND:For patients with anterior cruciate ligament re-rupture after reconstruction with abnormally increased posterior slope of the tibial plateau,anterior cruciate ligament reconstruction combined with anterior closing-wedge high tibial osteotomy was performed.However,there is a lack of precise tools for osteotomy.OBJECTIVE:To investigate the effectiveness of three-dimensional(3D)printed accurate osteotomy template in anterior cruciate ligament revision for patients with excessive posterior slope.METHODS:The medical records of 30 patients who underwent anterior cruciate ligament revision combined with anterior closing-wedge high tibial osteotomy were retrospectively collected and divided into two groups according to the operation method.The trial group(n=15)was assisted by 3D printing osteotomy guide plate.The control group(n=15)was conventional surgery.The osteotomy time,fluoroscopy times,intraoperative and 24 hours postoperative blood loss,preoperative and 3 months postoperative tibiofemoral anatomical angle,medial proximal tibial anatomical angle,posterior slope,the difference between planned posterior slope correction angle and actual correction angle,and KT-2000 side-to-side difference before operation,3 and 24 months after operation were compared between the two groups.Lachman test and Pivot shift test were performed before operation,immediately after operation,and 24 months after operation.International Knee Documentation Committee score and Lysholm score were performed before operation,3 and 24 months after operation.RESULTS AND CONCLUSION:(1)The osteotomy time,fluoroscopy times,and blood loss during operation and 24 hours after operation in the trial group were significantly less than those in the control group(P<0.05).(2)The posterior slope of the two groups decreased significantly after operation.There was no significant change in tibiofemoral anatomical angle and medial proximal tibial anatomical angle after operation.The difference between preoperative planned and postoperative actual posterior slope degree in the trial group(0.64±0.41)° was smaller than that in the control group(2.18±0.54)°,and the difference was statistically significant(P<0.001).(3)The KT-2000 side-to-side difference was significantly reduced in both groups after surgery(P<0.05).At 3 and 24 months after operation,there was no significant difference in KT-2000 side-to-side difference between the two groups(P>0.05).The Lachman test and Pivot shift test of the two groups were negative immediately after operation,3 and 24 months after operation.(4)The International Knee Documentation Committee and Lysholm scores of the two groups increased significantly after surgery(P<0.05).At 3 months after operation,the International Knee Documentation Committee score and Lysholm score of the trial group were significantly higher than those of the control group(P<0.05).At 24 months after operation,there was no significant difference in International Knee Documentation Committee score and Lysholm score between the two groups(P>0.05).(5)In conclusion,with the assistance of 3D printing accurate osteotomy guide plate,anterior cruciate ligament reconstruction combined with anterior closing-wedge high tibial osteotomy is easier to operate,with shorter operation time,fewer fluoroscopy times,less intraoperative and postoperative blood loss,and faster recovery of knee joint function after operation,which has high clinical application value.
5.Effects of short-term insemination and early rescue ICSI on pregnancy and neonatal outcomes
Hui WANG ; Zhiheng CHEN ; Li YANG ; Yunhao LIANG ; Huijiao WU ; Yu JIANG ; Shuai LIU
The Journal of Practical Medicine 2025;41(2):202-207
Objective This study aims to explore the impacts of short-term insemination and early rescue intracytoplasmic sperm injection (E-RICSI) on clinical and neonatal outcomes for IVF patients. Methods A retrospective analysis was conducted on the clinical data from the patients who underwent fresh embryo transfer at the Reproductive Center from January 2019 to December 2023. Patients were divided into four groups based on fertilization method:short-term IVF group (n=204),conventional IVF group (n=208),E-RICSI group (n=13) and conventional ICSI group (n=92). The fertilization rates,embryo development,pregnancy outcomes,and neonatal outcomes were compared between the short-term IVF and conventional IVF groups,and between the E-RICSI and conventional ICSI groups. Results There were no statistically significant differences in embryo development,clinical pregnancy,miscarriage,ectopic pregnancy,live birth rates,neonatal sex,and birth weight between the short-term IVF group and conventional IVF group. Similarly,no significant differences were observed in the E-RICSI group compared to the conventional ICSI group (P>0.05). However,the fertilization rate (79.11% vs. 84.39%,P<0.001) and the rate of 2PN zygotes (63.98% vs. 70.83%,P<0.001) were significantly lower in the short-term IVF group compared to the conventional IVF group;The fertilization rate (65.49% vs. 91.68%,P<0.001) and the rate of 2PN zygotes (57.75% vs. 88.35%,P<0.001) were significantly lower in the E-RICSI group compared to the conventional ICSI group. Conclusions Although the fertilization rate of short-term insemination and E-RICSI is lower than that of conventional IVF and ICSI,it has no effect on embryonic development,preg-nancy outcome and neonatal outcome. Short-term insemination combined with early rescue ICSI is an effective and safe technology to prevent complete fertilization failure.
6.Efficacy analysis of cefoperazone-sulbactam and ulinastatin combined treatment for stroke-associated pneumonia in patients with acute large vessel occlusion stroke undergoing endovascular treatment
Wenlong MA ; Zhiheng LI ; Fude LIU ; Xiangning HAN ; Jia YU ; Jianfeng HAN ; Yawen CHENG
Chinese Journal of Cerebrovascular Diseases 2025;22(4):225-234
Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7%)and 30 females(30.3%),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P>0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1%[41/46]vs.69.8%[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P>0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P<0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P<0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P<0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5%(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5%(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P>0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5%[43/46]vs.77.4%[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P>0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5%[3/46]vs.20.8%[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.
7.Risk factors for stroke-associated pneumonia after endovascular therapy in patients with acute anterior circulation large vessel occlusion stroke
Zhiheng LI ; Yawen CHENG ; Xiangning HAN ; Jiahao LI ; Wenlong MA ; Jia YU ; Guogang LUO ; Fude LIU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(2):203-208
Objective To investigate the risk factors for stroke-associated pneumonia(SAP)in patients with acute anterior circulation large-vessel occlusion stroke after endovascular treatment(EVT).Methods A total of 115 patients with acute anterior circulation large-vessel occlusion stroke who received EVT in the Department of Neurology,The First Affiliated Hospital of Xi'an Jiaotong University,from March 2022 to May 2023 were continuously included.Their clinical data were retrospectively collected.The patients were divided into SAP group(55 cases)and non-SAP group(60 cases)according to the occurrence of SAP after the operation.Differences in baseline data,surgical and perioperative indicators were compared between the two groups,and the risk factors for SAP after EVT were analyzed using the multivariate Logistic regression analysis.Results Univariate analysis showed there were significant differences in the Glasgow Coma Scale(GCS)score and the National Institute of Health Stroke Scale(NIHSS)score at admission,incidence of dysphagia,duration of the surgery,proportion of general anesthesia,rate of unsuccessful vascular recanalization and the rate of immediate CT high-density sign between SAP group and non-SAP group(all P<0.05).Multivariate Logistic regression analysis of the above indicators showed that duration of the surgery(OR=1.014,95%CI:1.001-1.028,P<0.05),dysphagia(OR=6.137,95%CI:1.694-22.232,P<0.01)and unsuccessful vascular recanalization(OR=6.043,95%CI:1.062-34.382,P<0.05)were independent risk factors for SAP after EVT.Conclusion Long duration of EVT,dysphagia and unsuccessful vascular recanalization are directly related to the occurrence of SAP after EVT in patients with acute anterior circulation large-vessel occlusive infarction.Therefore,targeted measures should be taken as soon as possible to reduce the incidence of SAP after EVT and thus improve the clinical prognosis of these patients.
8.Establishment and evaluation of a combination of disease and syndrome model of post-stroke depression based on the theory of"disease-syndrome-drug"
Zhiheng LIU ; Yuli CHEN ; Yu LIU ; Xin WANG ; Yu LIU ; Lin LIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):388-398
Objective To construct an animal model of post-stroke depression(PSD)based on the theory of"depression,stasis,phlegm",with the aim of developing and validating an objective assessment system.Methods Rats were divided randomly into five groups:control,depression,stroke,PSD,and Baishile decoction groups.A PSD syndrome-based animal model was established in rats using a combination of middle cerebral artery occlusion(MCAO)and chronic unpredictable mild stress(CUMS)."Depression,stasis,phlegm"were then evaluated in the model rats using the Morris water maze,open field,forced swimming,and sucrose preference tests,and by detection of neurotransmitter levels,brain tissue pathology,tongue and forepaw color RGB values,and blood rheology.Results PSD rats exhibited significantly shorter target quadrant dwelling times,platform crossings,and climbing and rearing frequencies,a significantly lower sucrose preference,and a significantly higher immobility time in the forced swim test compared with control rats.Hematoxylin and eosin and Nissl staining revealed brain tissue damage in PSD rats.Serum and cerebrospinal fluid levels of 5-hydroxytryptamine(5-HT)were significantly decreased,glutamate levels were significantly increased,and tongue and forepaw RGB values were all decreased.Blood rheology showed a hypercoagulable state and blood lipid metabolism-related indicators were significantly abnormal.Rats in the Baishile decoction group showed significant improvements compared with the PSD group,including increased target quadrant dwelling times,number of platform crossings,and climbing and rearing frequencies,increased sucrose preference,decreased immobility time in the forced swim test,improved brain tissue pathology,increased serum and cerebrospinal fluid levels of 5-HT,decreased glutamate levels,increased tongue and claw RGB values,and varying degrees of improvement in blood rheology and blood lipid metabolism-related indicators.Conclusions The combination of MCAO and CUMS successfully established a syndrome-based animal model of PSD exhibiting the characteristics of"depression,stasis,phlegm",with corresponding objective assessment criteria.
9.Efficacy analysis of cefoperazone-sulbactam and ulinastatin combined treatment for stroke-associated pneumonia in patients with acute large vessel occlusion stroke undergoing endovascular treatment
Wenlong MA ; Zhiheng LI ; Fude LIU ; Xiangning HAN ; Jia YU ; Jianfeng HAN ; Yawen CHENG
Chinese Journal of Cerebrovascular Diseases 2025;22(4):225-234
Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7%)and 30 females(30.3%),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P>0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1%[41/46]vs.69.8%[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P>0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P<0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P<0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P<0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5%(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5%(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P>0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5%[43/46]vs.77.4%[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P>0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5%[3/46]vs.20.8%[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.
10.Establishment and evaluation of a combination of disease and syndrome model of post-stroke depression based on the theory of"disease-syndrome-drug"
Zhiheng LIU ; Yuli CHEN ; Yu LIU ; Xin WANG ; Yu LIU ; Lin LIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):388-398
Objective To construct an animal model of post-stroke depression(PSD)based on the theory of"depression,stasis,phlegm",with the aim of developing and validating an objective assessment system.Methods Rats were divided randomly into five groups:control,depression,stroke,PSD,and Baishile decoction groups.A PSD syndrome-based animal model was established in rats using a combination of middle cerebral artery occlusion(MCAO)and chronic unpredictable mild stress(CUMS)."Depression,stasis,phlegm"were then evaluated in the model rats using the Morris water maze,open field,forced swimming,and sucrose preference tests,and by detection of neurotransmitter levels,brain tissue pathology,tongue and forepaw color RGB values,and blood rheology.Results PSD rats exhibited significantly shorter target quadrant dwelling times,platform crossings,and climbing and rearing frequencies,a significantly lower sucrose preference,and a significantly higher immobility time in the forced swim test compared with control rats.Hematoxylin and eosin and Nissl staining revealed brain tissue damage in PSD rats.Serum and cerebrospinal fluid levels of 5-hydroxytryptamine(5-HT)were significantly decreased,glutamate levels were significantly increased,and tongue and forepaw RGB values were all decreased.Blood rheology showed a hypercoagulable state and blood lipid metabolism-related indicators were significantly abnormal.Rats in the Baishile decoction group showed significant improvements compared with the PSD group,including increased target quadrant dwelling times,number of platform crossings,and climbing and rearing frequencies,increased sucrose preference,decreased immobility time in the forced swim test,improved brain tissue pathology,increased serum and cerebrospinal fluid levels of 5-HT,decreased glutamate levels,increased tongue and claw RGB values,and varying degrees of improvement in blood rheology and blood lipid metabolism-related indicators.Conclusions The combination of MCAO and CUMS successfully established a syndrome-based animal model of PSD exhibiting the characteristics of"depression,stasis,phlegm",with corresponding objective assessment criteria.

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