1.Inhibitory effect of hydroxy safflower yellow A on neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment
Zeqian WANG ; Yanzhe DUAN ; Yige WU ; Dong MA ; Jianjun HUANG ; Yuqing YAN ; Lijuan SONG
Chinese Journal of Tissue Engineering Research 2025;29(19):4044-4051
BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.
2.Evaluation of colistin sulfate administration regimen based on PK/PD theory and Monte Carlo simulation
Yingchao MA ; Xia WU ; Yongjing WANG ; Jianjun GU ; Xiuling YANG
China Pharmacy 2025;36(4):459-463
OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics (PK)/pharmacodynamics (PD) theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration (MIC) data of colistin sulfate against Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC (fAUC0-24 h/MIC) ≥15 as the target value, the probabilities of target attainment (PTA) of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC; and the expected population PTA, specifically the cumulative fraction of response (CFR), for each regimen within a specific bacterial population was further calculated, to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL, PTA of all colistin sulfate regimens (500 000 IU, q12 h; 500 000 IU, q8 h; 750 000 IU, q12 h; 750 000 IU, q8 h; 1 000 000 IU, q12 h) were all more than 90%. When bacterial MIC=1 µg/mL, PTA for regimen (750 000 IU, q8 h) against A. baumannii, K. pneumoniae, P. aeruginosa, E. coli and E. cloacae, and for regimen (1 000 000 IU, q12 h) against the other four bacterial species (excluding P. aeruginosa) remained above 90%. When bacterial MIC≥2 µg/mL, PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli, the CFR of only colistin sulfate regimen (500 000 IU, q12 h) was less than 90%; for K. pneumoniae, the CFR of only colistin sulfate regimen (750 000 IU, q8 h and 1 000 000 IU, q12 h) was greater than 90%; for the other three bacteria, CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL, colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL, an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.
3.Significance of precise classification of sacral meningeal cysts by multiple dimensions radiographic reconstruction MRI in guiding operative strategy and rehabilitation.
Jianjun SUN ; Qianquan MA ; Xiaoliang YIN ; Chenlong YANG ; Jia ZHANG ; Suhua CHEN ; Chao WU ; Jingcheng XIE ; Yunfeng HAN ; Guozhong LIN ; Yu SI ; Jun YANG ; Haibo WU ; Qiang ZHAO
Journal of Peking University(Health Sciences) 2025;57(2):303-308
OBJECTIVE:
To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI.
METHODS:
From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients.
RESULTS:
Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation.
CONCLUSION
Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans
;
Magnetic Resonance Imaging/methods*
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Male
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Female
;
Sacrum/surgery*
;
Adult
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Middle Aged
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Imaging, Three-Dimensional/methods*
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Cysts/rehabilitation*
;
Aged
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Adolescent
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Young Adult
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Spinal Nerve Roots/diagnostic imaging*
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Minimally Invasive Surgical Procedures
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Neurosurgical Procedures/methods*
5.Clinical characteristics and potential predisposing factors of the external cervical resorption
Yanxia LI ; Keqiang MA ; Miao LIU ; Jianjun TANG ; Ying DENG ; Cuifen HE ; Qingshan DONG
Journal of Practical Stomatology 2024;40(4):520-524
Objective:To investigate the clinical characteristics and potential predisposing factors of the external cervical resorption(ECR).Methods:22 ECR cases with 38 affected teeth from 2016 to 2022 were retrospectively reviwed.Descriptive analysis combined with single factor analysis was used to study the clinical characteristics and influencing factors of ECR.Results:Maxillary anterior teeth(34.2%)were the most affected by ECR.Univariate analysis showed that ECR was more commonly noted in teeth without percussion pain and palpation pain,the probing depth of the periodontal pocket was greater than 3mm,with pulp activity reaction,without forma-tion of abscess and/or sinus tract,and without periapical lesions.There were statistically significant differences in percussion tender-ness,palpation tenderness and probing depth among the different Heithersary stages(P<0.05).In the advanced cases,deep periodon-tal pockets and abscess formation were observed.The most common related dental factors of ECR were orthodontic treatment(15.87%)and dental traumatic injury(28.57%).Conclusion:ECR affected teeth often lack of clinical signs and symptoms.Radiology is the key to early diagnosis.
6.Diagnostic value of serum sFlt-1 and sCD14 for stroke-associated pneumonia
Ruixue MA ; Jianhua JIAO ; Honghong GU ; Xiuli CAO ; Youxiang LI ; Jianjun LI
International Journal of Laboratory Medicine 2024;45(11):1338-1342,1347
Objective To investigate the diagnostic value of serum soluble fms-like tyrosine kinase 1(sFlt-1)and soluble differentiation cluster 14(sCD14)in stroke-associated pneumonia(SAP).Methods A total of 67 SAP patients admitted to the hospital from March 2022 to January 2023 were selected as the study group,and 50 stroke patients without pneumonia during the same period were selected as the control group.Enzyme-linked immunosorbent assay was used to measure serum sFlt-1 and sCD14 levels.Pearson correlation analysis was used to analyze the correlation between serum sFlt-1,sCD14 levels and clinical data.Multivariate Logistic regression was used to analyze the influencing factors of SAP in patients with stroke.Receiver operating char-acteristic(ROC)curve was used to analyze the diagnostic value of serum sFlt-1 and sCD14 levels in predicting SAP in patients with stroke.Results The serum levels of sFlt-1 and sCD14 in SAP patients were higher than those in stroke patients without pneumonia and stroke patients with pneumonia alone(P<0.05).SAP in stroke patients was associated with age,atrial fibrillation,heart failure,aspiration,dysphagia,brain stem stroke,proton pump inhibitor use,fever,cough,dyspnea,low-density lipoprotein cholesterol,procalcitonin(PCT),C-reactive protein,white blood cell count,national institutes of health stroke scale(NIHSS)score,clinical pulmonary infection(CPIS)score(P<0.05).Correlation analysis showed that serum sFlt-1 level was positively correlated with sCD14(r=0.439,P<0.001),and serum sFlt-1 and sCD14 levels were positively correlated with NIHSS score and CPIS score(P<0.05).Multivariate Logistic regression analysis showed that sFlt-1,sCD14,proton pump inhibitor use,PCT,dysphagia,and age were the influencing factors of SAP in stroke patients(P<0.05).ROC curve results showed that the area under the curve of serum sFlt-1 and sCD14 combined to evaluate SAP in stroke patients was higher than that of single detection(ZsFlt-1-combined=2.194,P=0.028,ZscD14-combined=2.310,P=0.002).Conclusion The serum levels of sFlt-1 and sCD14 are in-creased in SAP patients,and the combination of the two has a good diagnostic value for predicting the occur-rence of SAP.
7.Interventional precision shunting for portal hypertension
Jingqin MA ; Jianjun LUO ; Zhiping YAN
Journal of Interventional Radiology 2024;33(10):1045-1048
Portal hypertension is a pathological elevation of portal pressure gradient(PPG),often leading to severe complications.Interventional shunting such as transjugular intrahepatic portosystemic shunt(TIPS)has gradually become an important means of treatment,but the postoperative hemodynamic changes are uncertain,therefore,individualized treatment scheme with precision shunting is needed.The purpose of precision shunting is to balance the amount of shunting blood with the amount of blood perfusion in the liver tissue,which can minimize the incidence of complications while relieving symptoms.The determination of hemodynamic goals after interventional shunting is influenced by various factors,and the procedural differences and individual variances should be taken into consideration when making reasonable postoperative hemodynamic targets(optimal PPG).The preliminary results of clinical practice of precision shunting indicates that accurate measurement of preoperative portal pressure and effective monitoring of postoperative hemodynamic status should be emphasized.Future studies should further improve the interventional shunting technique to achieve a more individualized precision treatment.
8.Efficacy of acupuncture in the trentment of postoperative gastroparesis syndrome:a meta analysis
Li MA ; Liping CHEN ; Ziqing XU ; Jianjun XUE
The Journal of Clinical Anesthesiology 2024;40(10):1073-1078
Objective To systematically review the efficacy of acupuncture in the treatment of post-operative gastroparesis syndrome.Methods Computer searches were conducted on PubMed,Embase,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,and Chinese biomedical literature database.The ran-domized controlled trial(RCT)on postoperative gastroparesis syndrome after acupuncture treatment was in-cluded.The retrieval time was from the establishment of the database to May 2023.Meta-analysis was per-formed using RevMan 5.3 software.Results Fifteen RCTs involving 1 072 patients were included,545 pa-tients in the acupuncture group and 527 patients in the control group.Compared with the control group,the effective rate of treatment in the acupuncture group was significantly increased(RR=1.08,95%CI 1.09 to 1.27,P<0.01),the levels of gastrin(SMD=1.86,95%CI 1.40 to 2.32,P<0.01)and motilin(SMD=1.53,95%CI 0.99 to 2.06,P<0.01)after operation were significantly increased,the recovery time of postoperative gastrointestinal function was significantly shortened(MD=-4.53 d,95%CI-6.51 to-2.55 d,P<0.01).Conclusion Acupuncture can improve the effective rate of PGS treatment,in-crease the levels of Gastrin and motilin after operation,and promote the recovery of gastric motility after op-eration.
9.Research Progress on the Role of HMGB1 in Regulating the Function of Osteoarthritis Chondrocytes
Xin QI ; Xiaogang ZHANG ; Haiyang YU ; Xin CHEN ; Wenbo AN ; Zhipeng WANG ; Duoxian WANG ; Pengfei LUO ; Yixin CHEN ; Jiaojiao MA ; Wei QI ; Ziyang HU ; Jianjun LIU
Medical Journal of Peking Union Medical College Hospital 2024;15(1):141-146
Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.
10.Hydroxysafflor yellow A intervenes astrocyte lipocalin 2 expression after cerebral ischemia/reperfusion injury
Kexin LIU ; Lijuan SONG ; Yige WU ; Guangyuan HAN ; Zhuyue MIAO ; Ruheng WEI ; Baoguo XIAO ; Cungen MA ; Jianjun HUANG
Chinese Journal of Tissue Engineering Research 2024;28(7):1063-1069
BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.

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