1.Exploring mechanism of occurrence and treatment of acute lung injury in mice based on GEO database and in vivo experiments
Yonghu CHEN ; Xilin WU ; Zhe JIANG ; Xuezheng LI
Chinese Journal of Immunology 2025;41(11):2561-2566
Objective:To identify key genes involved in LPS-induced acute lung injury(ALI)using GEO database,to eluci-date its pathogenesis and discover potential therapeutic drugs.Methods:Gene expression data from LPS-induced ALI was collected by GEO database,and microbiotics online analysis platform was employed to identify differential expression genes,from which core genes were obtained.Metascape and DAVID were used for GO and KEGG enrichment analysis of these core genes to identify pathways associated with ALI.GSEA and protein interaction analysis were performed for these pathways for identification of core targets.Poten-tial therapeutic drug,kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside(KAE)was validated by animal experiments.Results:Two GEO datasets were incorporated and 261 core genes with differential expression were identified.Data visualization indicated that LPS-induced ALI predominantly involved inflammatory pathways,such as TNF and NF-κB.In vivo validation was conducted in mice on two core targets within this pathway:NF-κB and NLRP3,potential therapeutic drug KAE was administered,which was found to mitigate LPS-induced lung tissue damage.Further investigations demonstrated that KAE could effectively improve ALI by reducing expressions of p-NF-κB,NLRP3 and other proteins.Conclusion:This study markes screening of LPS-induced ALI model within GEO database.Above findings reveal predominant involvement of NF-κB and NLRP3 within TNF and NF-κB signaling pathways in LPS-in-duced ALI.KAE has potential for ALI treatment by down-regulating expressions of p-NF-κB,NLRP3 and other proteins,expecting to be a candidate drug for ALI treatment.
2.Exploring mechanism of occurrence and treatment of acute lung injury in mice based on GEO database and in vivo experiments
Yonghu CHEN ; Xilin WU ; Zhe JIANG ; Xuezheng LI
Chinese Journal of Immunology 2025;41(11):2561-2566
Objective:To identify key genes involved in LPS-induced acute lung injury(ALI)using GEO database,to eluci-date its pathogenesis and discover potential therapeutic drugs.Methods:Gene expression data from LPS-induced ALI was collected by GEO database,and microbiotics online analysis platform was employed to identify differential expression genes,from which core genes were obtained.Metascape and DAVID were used for GO and KEGG enrichment analysis of these core genes to identify pathways associated with ALI.GSEA and protein interaction analysis were performed for these pathways for identification of core targets.Poten-tial therapeutic drug,kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside(KAE)was validated by animal experiments.Results:Two GEO datasets were incorporated and 261 core genes with differential expression were identified.Data visualization indicated that LPS-induced ALI predominantly involved inflammatory pathways,such as TNF and NF-κB.In vivo validation was conducted in mice on two core targets within this pathway:NF-κB and NLRP3,potential therapeutic drug KAE was administered,which was found to mitigate LPS-induced lung tissue damage.Further investigations demonstrated that KAE could effectively improve ALI by reducing expressions of p-NF-κB,NLRP3 and other proteins.Conclusion:This study markes screening of LPS-induced ALI model within GEO database.Above findings reveal predominant involvement of NF-κB and NLRP3 within TNF and NF-κB signaling pathways in LPS-in-duced ALI.KAE has potential for ALI treatment by down-regulating expressions of p-NF-κB,NLRP3 and other proteins,expecting to be a candidate drug for ALI treatment.
3.Bedside ultrasound monitoring of optic nerve sheath diameter is a predictive factor for 28-day coma, delirium and death in etiologically diverse critically ill patients
Haijun ZHI ; Xiaoya CUI ; Fengwei ZHANG ; Shujuan WANG ; Xuezheng LIANG ; Bo WANG ; Jie CUI ; Yong LI
Chinese Critical Care Medicine 2024;36(10):1088-1094
Objective:To explore whether the optic nerve sheath diameter (ONSD) within 24 hours of intensive care unit (ICU) admission is the predictor of 28-day delirium or coma and death in etiologically diverse critically ill patients.Methods:A prospective, observational study was conducted. The critically ill patients admitted to the emergency ICU of Cangzhou Central Hospital from January 2021 to October 2022 were enrolled. Bedside ultrasound monitoring ONSD was performed within 24 hours of ICU admission. The consciousness status was assessed daily during ICU hospitalization. Coma was defined as Glasgow coma scale (GCS) score < 8 or Richmond agitation-sedation scale (RASS) score -4 or -5. Delirium was defined as responsiveness to verbal stimulation and with a positive confusion assessment method-intensive care unit (CAM-ICU). A positive result of CAM-ICU was defined as acute change or fluctuating course of mental status+inattention+altered level of consciousness or disorganized thinking. X-tile software analysis was used to visualize the best cut-off value for creating divisions in predicting 28-day coma or delirium and death, and then Kaplan-Meier curves were plotted. ONSD≥the optimal cut-off value from X-tile analysis was defined as ONSD broadening. ONSD broadening and related indicators were enrolled, and multivariate Cox regression analysis was used to analyze the risk factors of 28-day coma or delirium and 28-day death in etiologically diverse critically ill patients.Results:A total of 321 critically ill patients were enrolled. Of them, 49 had primary brain injury, 54 had hypoxic ischemic brain injury (HIBI) after cardiac arrest, 70 had acute heart failure, 73 had sepsis, and 75 had other causes. Coma affected 184 patients (57.3%), and delirium affected 173 patients (53.9%). At 28 days of follow-up, 100 patients died, 16 patients remained comatose and 20 patients remained delirious. In all patients, as the GCS score decreased upon admission to the ICU, there was a gradually increasing trend in ONSD [GCS score 15 group: 5.20 (4.93, 5.43) mm, GCS score 10-14 group: 5.30 (4.90, 5.65) mm, GCS score 6-9 group: 5.40 (5.10, 5.80) mm, GCS score < 6 group: 5.70 (5.20, 5.96) mm, P < 0.05]. X-tile software analysis showed that in all patients and five etiological subgroups, ONSD broadening was a predictor for 28-day coma or delirium, and the optimal cut-off value was obtained (5.60 mm for all patients, 4.90 mm for primary brain injury, 5.75 mm for HIBI after cardiac arrest, 5.40 mm for acute heart failure, 5.90 mm for sepsis, and 5.75 mm for other causes). The Kaplan-Meier curves were plotted according to the optimal cut-off values, and the results showed that the higher the ONSD, the higher the incidence and duration of coma or delirium within 28 days in above patient population. X-tile software analysis showed that in all patients, and HIBI after cardiac arrest, sepsis and other causes patients, ONSD was a predictor for 28-day death, and the optimal cut-off value was obtained (6.20 mm for all patients, 5.85 mm for HIBI after cardiac arrest, 5.35 mm for sepsis, and 6.10 mm for other causes). The Kaplan-Meier curves were plotted according to the optimal cut-off values, and the results showed that the higher the ONSD, the higher the 28-day survival rate and the shorter survival duration in above patient population. Multivariate Cox regression analysis showed that ONSD broadening was an independent risk factor for 28-day coma or delirium in all patients [hazard ratio ( HR) = 1.513, 95% confidence interval (95% CI) was 1.093-2.095, P = 0.013] and patients with primary brain injury ( HR = 5.739, 95% CI was 2.112-15.590, P = 0.001). However, ONSD broadening was not independently associated with 28-day death in all patients or in the five etiological subgroups. Conclusions:ONSD within 24 hours of ICU admission is an independent risk factor for 28-day coma or delirium in etiologically diverse critically ill patients. It serves as a predictor for 28-day coma or delirium in 5 subgroups of etiology including primary brain injury, HIBI after cardiac arrest, acute heart failure, sepsis, and other causes, but not for 28-day death.
4.Effect of atractylenolide Ⅲ on stroke in spontaneously hypertensive rats and its mechanism
Jibo LI ; Yongwen FENG ; Wenfeng WU ; Xuezheng FAN ; Haixia LI
Journal of Clinical Medicine in Practice 2023;27(22):71-76
Objective To investigate the effect of atractylenolide Ⅲ(A Ⅲ)on stroke in spon-taneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.Methods The spontaneously hypertensive rats(SHR)were given 0.9%sodium chloride solution freely for 2 months,and then fed with 1%sodium chloride solution to establish the stroke model of SHR.The rat models were randomly grouped into Model group,A Ⅲ low-dose group(A Ⅲ-L group),A Ⅲ high-dose group(A Ⅲ-H group),positive drug nimodipine group(Nim group),miR-296-5p agonist group(miR-296-5p agomir group),agomir NC group,A Ⅲ-H+miR-296-5p agomir group,and A Ⅲ-H+agomir NC group,with 12 in each group.The changes in neurological symptom scores,av-erage arterial pressure,survival time,and platelet adhesion rate were detected and recorded;hema-toxylin and eosin(HE)staining was applied to detect pathological changes in the CA1 region of the rat hippocampus;quantitative reverse transcription polymerase chain reaction(qRT-PCR)was ap-plied to detect the expression of miR-296-5p in the hippocampal CA1 region.Results Compared with the NC group,the Model group showed increases in neurological symptom score,mean arterial pressure,platelet adhesion rate,miR-296-5p expression,shortened survival time,and severe pathological damage to the hippocampal CA1 area(P<0.05);compared with the Model group,the neurological symptom scores,mean arterial pressure,platelet adhesion rate,and miR-296-5p expression in the A Ⅲ-L,A Ⅲ-H,and Nim groups decreased,the survival time was prolonged,and the pathological damage in the CA1 area of the hippocampus was alleviated(P<0.05);compared with Model group and agomir NC group,neurological symptom score,mean arterial pressure,platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased,survival time was shortened,and pathological damage in hippocampal CA1 region was aggravated(P<0.05).compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group,the neurological symptom score,average arterial pressure,platelet adhesion rate and miR-296-5p expression of rats were in-creased,the survival time was shortened,and the pathological damage in hippocampal CA1 region was serious in the AⅢ-H+miR-296-5p agomir group(P<0.05).Conclusion A Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.
5.Effect of atractylenolide Ⅲ on stroke in spontaneously hypertensive rats and its mechanism
Jibo LI ; Yongwen FENG ; Wenfeng WU ; Xuezheng FAN ; Haixia LI
Journal of Clinical Medicine in Practice 2023;27(22):71-76
Objective To investigate the effect of atractylenolide Ⅲ(A Ⅲ)on stroke in spon-taneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.Methods The spontaneously hypertensive rats(SHR)were given 0.9%sodium chloride solution freely for 2 months,and then fed with 1%sodium chloride solution to establish the stroke model of SHR.The rat models were randomly grouped into Model group,A Ⅲ low-dose group(A Ⅲ-L group),A Ⅲ high-dose group(A Ⅲ-H group),positive drug nimodipine group(Nim group),miR-296-5p agonist group(miR-296-5p agomir group),agomir NC group,A Ⅲ-H+miR-296-5p agomir group,and A Ⅲ-H+agomir NC group,with 12 in each group.The changes in neurological symptom scores,av-erage arterial pressure,survival time,and platelet adhesion rate were detected and recorded;hema-toxylin and eosin(HE)staining was applied to detect pathological changes in the CA1 region of the rat hippocampus;quantitative reverse transcription polymerase chain reaction(qRT-PCR)was ap-plied to detect the expression of miR-296-5p in the hippocampal CA1 region.Results Compared with the NC group,the Model group showed increases in neurological symptom score,mean arterial pressure,platelet adhesion rate,miR-296-5p expression,shortened survival time,and severe pathological damage to the hippocampal CA1 area(P<0.05);compared with the Model group,the neurological symptom scores,mean arterial pressure,platelet adhesion rate,and miR-296-5p expression in the A Ⅲ-L,A Ⅲ-H,and Nim groups decreased,the survival time was prolonged,and the pathological damage in the CA1 area of the hippocampus was alleviated(P<0.05);compared with Model group and agomir NC group,neurological symptom score,mean arterial pressure,platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased,survival time was shortened,and pathological damage in hippocampal CA1 region was aggravated(P<0.05).compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group,the neurological symptom score,average arterial pressure,platelet adhesion rate and miR-296-5p expression of rats were in-creased,the survival time was shortened,and the pathological damage in hippocampal CA1 region was serious in the AⅢ-H+miR-296-5p agomir group(P<0.05).Conclusion A Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.
6.Results analysis of unexpected antibody screening for blood donors and cost comparison of two detection modes
Liqin HUANG ; Lifeng WU ; Tong LI ; Ran LI ; Heng LIU ; Dandan DU ; Yunlong CHEN ; Xuezheng ZENG ; Jinfeng ZENG
Chinese Journal of Blood Transfusion 2022;35(3):324-327
【Objective】 To establish a routine screening method for unexpected antibodies of blood donors, analyze the results of centralized screening for unexpected antibody of blood donors in the blood center, and compare the cost of centralized and decentralized screening modes. 【Methods】 A total of 35 591 blood donors were screened for unexpected antibodies from March 31, 2021 to July 31, 2021, using microcolumn gel method. Unexpected antibody screening reactive samples were further confirmed by the Transfusion Research Institute of Shenzhen Blood Center, and the demographic characteristics were further determined through the analysis of unexpected antibody positive population. The direct cost and indirect cost of centralized and decentralized unexpected antibody screening mode were compared. 【Results】 Forty unexpected antibody positive samples were confirmed in Shenzhen, with the positive rate at 0.11%(40/35 591), among which MNS, Rh and Lewis system accounted for 35% (14/40), 32.5% (13/40) and 17.5% (7/40), respectively. Males and females accounted for 45% (18/40) and 55% (22/40), respectively (P<0.01). No significant difference was noticed by age and repeated-donor or not (P>0.05). Unexpected antibody screening in a centralized way saved about 1.16 million yuan per year. 【Conclusion】 It is necessary to carry out unexpected antibody screening for all blood donors, and centralized screening is more economical than decentralized screening.
7. Effect of esketamine and butorphanol on morphine-induced pruritus after cesarean section: A randomized controlled clinical study
Yan FENG ; Gaowei LI ; Qiqi JIN ; Weicha CAI ; Jun LI ; Yan FENG ; Gaowei LI ; Xuezheng LIN
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(12):1425-1430
AIM: To evaluation the effects of esketamine and butorphanol on postoperative pruritus induced by epidural morphine injection in cesarean delivery parturients. METHODS: A total of 162 parturients who underwent elective cesarean section under continuous epidural anesthesia in Taizhou Central Hospital (Taizhou University Hospital), were selected and randomly divided into esketamine group (group K), butorphanol group (group B) and blank control group (group C). 5min after umbilicus amputation, parturients in group K was injected with 3 mg morphine diluent through epidural catheter, and esketamine 0.2 mg/kg intravenously. Parturients in groups B and C were given the same dose of morphine,and butorphanol 10 μg/kg or the same volume of normal saline, respectively. The incidence of postoperative pruritus at different times, the degree of pruritus and incidence of other adverse reactions were compared among three groups. RESULTS: The highest incidence of pruritus occurred within 4 hours after operation. The incidence of postoperative pruritus at 4 hours in group K and B was significantly lower than that in group C (3.7% vs. 3.7% vs. 29.6%, P < 0.05), the total incidence of postoperative pruritus within 48 hours was also significantly lower than that in group C (13.0% vs. 11.1% vs. 40.7%, P < 0.05), and the incidence of moderate to severe pruritus was also significantly lower than that of group C (5.6% vs. 3.7% vs. 31.5%, P < 0.05). There was no significant difference between group K and group B (all P > 0.05). There were no significant differences in the incidence of postoperative nausea, vomiting, dizziness and postoperative pain scores among three groups (P > 0.05). CONCLUSION: Both esketamine and butorphanol can reduce the incidence and degree of pruritus caused by epidural morphine injection in parturients, without affecting the analgesic effect of morphine and without increasing the incidence of adverse reactions. Esketamine is as effective and safe as butorphanol in preventing pruritus after cesarean section.
8. The efficacy of gradeⅡ glioma with postoperative intensity modulated radiotherapy
Shan LI ; Xuezheng WANG ; Yanbin CHEN ; Zanyi WU ; Hairong ZHANG ; Jiang ZENG ; Chuanshu CAI ; Weijian ZHANG ; Li SU ; Jinsheng HONG
Chinese Journal of Radiological Medicine and Protection 2020;40(2):112-115
Objective:
To retrospectively analyze the efficacy and prognostic factors of postoperative intensity modulated radiotherapy for grade Ⅱ gliomas.
Methods:
Retrospective analysis was conducted on patients with postoperative grade Ⅱ glioma in our hospital from Jan. 2010 to Dec. 2018. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival. Correlative analyses of prognosis by age, gender, initial resection status, the maximum diameter of the lesions, bi-hemisphere, astrocytoma, chemoradiation, adjuvant chemotherapy were conducted.
Results:
A total of 109 cases with grade Ⅱ glioma were enrolled. The follow-up rate was 91.75%, including 10 cases dead and 27 relapsed. There were 24 cases (88.9%) of in-field failure, and 3 cases (11.1%) of out-field failure. 14 cases of recurrence occurred in 81 cases of total resection group, accounting for 17.3%, and 13 in 28 cases of subtotal resection group, accounting for 46.4%. The recurrence rate in the subtotal resection group was significantly higher than that in the total resection group (
9.Research on the cardiovascular function evaluation system based on noninvasive detection indices.
Xiaorui SONG ; Gaoyang LI ; Xuezheng WANG ; Shigang WANG ; Xiangming FAN ; Yao YANG ; Aike QIAO
Journal of Biomedical Engineering 2019;36(4):649-656
Based on the noninvasive detection indeices and fuzzy mathematics method, this paper studied the noninvasive, convenient and economical cardiovascular health assessment system. The health evaluation index of cardiovascular function was built based on the internationally recognized risk factors of cardiovascular disease and the noninvasive detection index. The weight of 12 indexes was completed by the analytic hierarchy process, and the consistency test was passed. The membership function, evaluation matrix and evaluation model were built by fuzzy mathematics. The introducted methods enhanced the scientificity of the evaluation system. Through the Kappa consistency test, McNemer statistical results ( = 0.995 > 0.05) and Kappa values (Kappa = 0.616, < 0.001) suggest that the comprehensive evaluation results of model in this paper are relatively consistent with the clinical, which is of certain scientific significance for the early detection of cardiovascular diseases.
Cardiovascular Diseases
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diagnosis
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Cardiovascular System
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Fuzzy Logic
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Humans
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Models, Cardiovascular
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Research
10.Roles of nerve growth factor (NGF) in retinal synaptic plasticity in diabetic rats
Zheng LI ; Huimin LIANG ; Zhaowei LI ; Xuezheng LIU
Recent Advances in Ophthalmology 2017;37(9):816-818,823
Objective To investigate the effects of nerve growth factor (NGF) on retinal synaptic plasticity of diabetic mellitus rat and its underlying mechanisms.Methods A total of 24 clean SD male rats were randomly divided into three groups (n =8),and they were control group,diabetic group and treatment group.In the latter two groups,a model of diabetic rats was induced by streptozotocin,and then the rats of treatment group were injected intraperitoneally 800 U · kg-1 NGF once a day after the model was induced successfully.Both control group and diabetic group were given the same amount of normal saline.Twelve weeks later,MDA content and SOD activity were detected;meanwhile,the expression of retinal synaptophysin was detected by immunofluorescence,and the expressions of retina synaptophysin and Caspase-3 were detected by Western blot.Results The difference of MDA content in the three groups was statistically significant (F =85.46,P < 0.01);and the content of MDA in the diabetic group was significantly higher than that in the control group (P <0.01),while its content in the treatment group was significantly lower than that in the diabetic group (P <0.01).The difference of SOD activity in the three groups was statistically significant (F =17.76,P <0.01);and the SOD activity in the diabetic group was significantly lower than that in the control group (P <0.01),while its activity in the treatment group was significantly higher than that in the diabetic group (P <0.01).The difference of immunofluorescence intensity of synaptophysin in the three groups was statistically significant (F =395.42,P < 0.01);immunofluorescence intensity of synaptophysin in the diabetic group was attenuated compared with the control group (P <0.01),while the intensity in the treatment group was enhanced compared with the diabetic group(P <0.01).The difference of the relative expression of synaptophysin in the three groups was statistically significant (F =17.27,P < 0.01);and the expression of synaptophysin in the diabetic group was significantly downregulated compared with the control group (P < 0.01),while its expression in the treatment group was upregulated compared with the diabetic group (P < 0.01).The difference of relative expression of Caspase 3 protein in the three groups was statistically significant (F=217.13,P <0.01);and the expression level of Caspase 3 in the diabetic group was significantly higher than that in the control group (P <0.01),while its level in the treatment group was significantly lower than that in the diabetic group (P < 0.01).Conclusion NGF can help to inhibit the apoptosis of retinal cell,restore the number of retina synapse by reducing the oxidative stress in diabetic retina,which suggests that NGF may be involved in the changes of synaptic plasticity in diabetic retina via oxidative stress pathway.

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