1.Role of NLRP3 inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice
Hu CHENG ; Xiao CHENG ; Xueyan LI ; Yasen YALI ; Jianjiang WU ; Long YANG ; Wenbin YU ; Kuo ZHU ; Jiang WANG
Chinese Journal of Anesthesiology 2025;45(7):827-833
Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice.Methods:Fifty-two SPF healthy male wild-type C57BL/6 mice and 52 NLRP3 -/- mice, aged 8-10 weeks, were divided into 4 groups ( n=26 each) using a random number table method: wild type sham operation group (W-S group), wild type myocardial ischemia-reperfusion group (W-IR group), NLRP3 -/- sham operation group (NLRP3 -/--S group), and NLRP3 -/- myocardial ischemia-reperfusion group (NLRP3 -/--IR group). The myocardial ischemia-reperfusion-induced brain injury model was established by ligating the left anterior descending coronary artery for 45 min followed by 24 h of reperfusion in anesthetized mice. The cognitive function was evaluated using the modified Morris water maze test at 24 h of reperfusion. The mice were sacrificed after blood specimens were collected, and brain tissues were obtained for measurement of the blood-brain barrier permeability and water content, for microscopic examination of the pathological changes of brain tissues, and for determination of serum S-100β protein and neuron-specific enolase (NSE) concentrations, contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in hippocampal tissues (by enzyme-linked immunosorbent assay), expression of NLRP3, apoptosis-associated speck-like protein (ASC), cleaved cysteine aspartate protease 1 (cleaved-caspase-1), gasdermin D (GSDMD), ionized calcium-binding adapter molecule 1 (Iba-1), and occludin in hippocampal tissues (by immunofluorescence and/or Western blot). The apoptosis rate of neurons and density of dendritic spine were calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, and the time spent in the target quadrant was shortened, the concentrations of serum S-100β protein and NSE were increased, the blood-brain barrier permeability and brain water content were increased, the dendritic spine density in the hippocampal CA1 area was decreased, the contents of IL-1β, IL-6 and TNF-α were increased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was up-regulated, and the expression of occludin was down-regulated ( P<0.05), and the pathological injury to brain tissues was found in ischemia-reperfusion group. Compared with W-IR group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the time spent in the target quadrant was prolonged, the concentrations of serum S-100β protein and NSE were decreased, the blood-brain barrier permeability and brain water content were decreased, the dendritic spine density in the hippocampal CA1 area was increased, the contents of IL-1β, IL-6 and TNF-α were decreased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was down-regulated, and the expression of occludin was up-regulated ( P<0.05), and the pathological injury to brain tissues was alleviated in NLRP3 -/--IR group. Conclusions:NLRP3 inflammasome-mediated microglia activation is involved in myocardial ischaemia-reperfusion-induced brain injury in mice.
2.Effect of Helicobacter pylori induced mitochondrial unfolded protein response on gastric cancer cell proliferation
Jili Chen ; Leilei Li ; Yuanjia Chen ; Yan Zhao ; Yuan Xie ; Jianjiang Zhou
Acta Universitatis Medicinalis Anhui 2025;60(2):300-306
Objective :
To explore the mechanism of proliferation of gastric cancer cells induced byHelicobacter pylori(Hp) from the perspective of the mitochondrial unfolded protein response(UPRMT).
Methods :
C57BL6/J mice, human gastric cancer cells AGS and SGC-7901 cells were infected with Hp, mitochondrial proteins were extracted, and the expressions of UPRMT, including activation of transcription factor 5(ATF5), heat shock protein 60(mtHSP60), heat shock protein 70(mtHSP70) and mitochondrial protease(ClpP), were detected by Western blot. Immunohistochemistry was used to locate the expression sites of 4 proteins in mouse gastric tissue. AGS and SGC-7901 cells were infected with Hp, and cell proliferation was detected by RTCA and CCK-8. Finally, the expression of four indexes in gastric cancer tissues was analyzed by TCGA samples in the UALCAN database.
Results :
Hp infection could significantly promote the expression of ATF5, mtHSP60, mtHSP70 and ClpP in the mitochondria of gastric epithelial cells of C57BL6/J mice, AGS and SGC-7901 cells, and promote the proliferation of gastric cancer cells. When compared to normal gastric tissues in TCGA samples, ATF5, mtHSP60, mtHSP70, and ClpP were highly expressed in gastric cancer tissues, with statistically significant difference(allP<0.01).
Conclusion
Hp infection can induce UPRMTin gastric epithelial cells and gastric cancer cells, which in turn promotes cell proliferation.
3.Role of NLRP3 inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice
Hu CHENG ; Xiao CHENG ; Xueyan LI ; Yasen YALI ; Jianjiang WU ; Long YANG ; Wenbin YU ; Kuo ZHU ; Jiang WANG
Chinese Journal of Anesthesiology 2025;45(7):827-833
Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice.Methods:Fifty-two SPF healthy male wild-type C57BL/6 mice and 52 NLRP3 -/- mice, aged 8-10 weeks, were divided into 4 groups ( n=26 each) using a random number table method: wild type sham operation group (W-S group), wild type myocardial ischemia-reperfusion group (W-IR group), NLRP3 -/- sham operation group (NLRP3 -/--S group), and NLRP3 -/- myocardial ischemia-reperfusion group (NLRP3 -/--IR group). The myocardial ischemia-reperfusion-induced brain injury model was established by ligating the left anterior descending coronary artery for 45 min followed by 24 h of reperfusion in anesthetized mice. The cognitive function was evaluated using the modified Morris water maze test at 24 h of reperfusion. The mice were sacrificed after blood specimens were collected, and brain tissues were obtained for measurement of the blood-brain barrier permeability and water content, for microscopic examination of the pathological changes of brain tissues, and for determination of serum S-100β protein and neuron-specific enolase (NSE) concentrations, contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in hippocampal tissues (by enzyme-linked immunosorbent assay), expression of NLRP3, apoptosis-associated speck-like protein (ASC), cleaved cysteine aspartate protease 1 (cleaved-caspase-1), gasdermin D (GSDMD), ionized calcium-binding adapter molecule 1 (Iba-1), and occludin in hippocampal tissues (by immunofluorescence and/or Western blot). The apoptosis rate of neurons and density of dendritic spine were calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, and the time spent in the target quadrant was shortened, the concentrations of serum S-100β protein and NSE were increased, the blood-brain barrier permeability and brain water content were increased, the dendritic spine density in the hippocampal CA1 area was decreased, the contents of IL-1β, IL-6 and TNF-α were increased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was up-regulated, and the expression of occludin was down-regulated ( P<0.05), and the pathological injury to brain tissues was found in ischemia-reperfusion group. Compared with W-IR group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the time spent in the target quadrant was prolonged, the concentrations of serum S-100β protein and NSE were decreased, the blood-brain barrier permeability and brain water content were decreased, the dendritic spine density in the hippocampal CA1 area was increased, the contents of IL-1β, IL-6 and TNF-α were decreased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was down-regulated, and the expression of occludin was up-regulated ( P<0.05), and the pathological injury to brain tissues was alleviated in NLRP3 -/--IR group. Conclusions:NLRP3 inflammasome-mediated microglia activation is involved in myocardial ischaemia-reperfusion-induced brain injury in mice.
4.Dexmedetomidine protects myocardium from ischemia/reperfusion injury by down regulating expression of Dectin-1 and inhibiting immune cells infiltration
Siyu CHEN ; Jianjiang WU ; Aimei LI ; Li DENG ; Zhenfei HU ; Jiang WANG
Chinese Journal of Immunology 2024;40(9):1843-1849
Objective:To explore the molecular mechanism of dexmedetomidine(Dex)protecting ischemia/reperfusion(I/R)myocardium.Methods:Wild type mice were grouped into control(Control)group,sham operation(Sham)group,WT I/R group,WT Dex group,and Dectin-1 knock out mice were grouped into KO I/R group and KO Dex group in the in vivo study(n=6).TTC stain-ing was used to determine the myocardial infarction area(%)of the above six groups of mice.HE staining and pathological analyze was used to determine the myocardial injury.Serum TNF-α,IL-6 and IL-10 levels in mice were detected by ELISA.Flow cytometry(FCM)was used to count and sort of infiltrating M2 macrophages and neutrophils in myocardium.qPCR assay was used to determine the Dectin-1 mRNA expression in the above sorted cells.Results:TTC results showed that there was no myocardial infarction in the mice of Control group and Sham group.Compared with the WT I/R group,the infarct volume was significantly lower in WT Dex group,KO I/R group and KO Dex group(P<0.05).Compared with the KO I/R group,the infarct volume was reduced in KO Dex group(P<0.05).The results of HE staining showed that the myocardial fibers of the WT I/R group of mice were disorderly arranged,with a large number of broken myocardial fibers,while the myocardial fibers of the WT Dex group,KO I/R group and KO Dex group of mice had a little breakage,the structural damage was not significant,and the myocardial arrangement was relatively neat.The degree of myocardi-al injury of mice in KO Dex group were less than that in KO I/R group mice.ELISA results showed that compared with Sham group,the serum TNF-α and IL-6 levels of the mice in WT I/R group were significantly increased,and the IL-10 level was significantly de-creased.Compared with WT I/R group,serum TNF-α and IL-6 levels of the mice in WT Dex group and KO I/R group were significant-ly decreased,and IL-10 level was significantly increased.Compared with KO I/R group,the serum TNF-α and IL-6 levels of the mice in KO Dex group were significantly decreased,and the IL-10 level was significantly increased(P<0.05).FCM cell counting results showed that compared with Sham group,a large number of M2 macrophages and neutrophils were infiltrated in the myocardium of WT I/R group of mice(P<0.05).Compared with WT I/R group,the M2 macrophages and neutrophils infiltrated in the myocardium were significantly decreased in WT Dex group,KO I/R group and KO Dex group of mice(P<0.05).While there was no significant differ-ence between the KO I/R group and the KO Dex group mice(P>0.05).qPCR results showed that compared with Sham group,the ex-pression level of Dectin-1 mRNA in the myocardial infiltrated M2 macrophages and neutrophils were significantly up-regulated in WT I/R group of mice(P<0.05).While compared with WT I/R group,the expression level of Dectin-1 mRNA in Dex group of mice was sig-nificantly lower(P<0.05).Mice in KO I/R group and KO Dex group did not express Dectin-1.Conclusion:The protective mecha-nisms of Dex preconditioning on I/R injured myocardium involves reducing the infiltrating number of M2 macrophages and neutrophils in myocardium after I/R injury,which may be achieved by inhibiting the expression of Dectin-1.
5.Efficacy of different concentrations of ZKY001 eyedrops in the treatment of corneal epithelial defect after primary pterygium excision
Hua GAO ; Lei ZHU ; Jianjiang XU ; Liming TAO ; Yanling DONG ; Luxia CHEN ; Xiuming JIN ; Guigang LI ; Huping WU ; Ping ZHAO ; Wei CHEN ; Xiaoyi LI ; Weiyun SHI
International Eye Science 2024;24(12):1888-1894
AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.
6.Practice and thinking of designated hospital medical emergency support for the 19th Hangzhou Asian Games
Jianjiang QI ; Huiquan JIANG ; Haiqing XIANG ; Yijun YUAN ; Yue ZHAN ; Yue YANG ; Jian PAN ; Li ZHU ; Zeyang ZHAO ; Lin LYU ; Xinwei JIANG ; Zhen JIANG ; Ganying HUANG
Chinese Journal of Emergency Medicine 2023;32(12):1617-1622
Objective:To analyze the construction and operation of the 19th Hangzhou Asian Games designated hospitals, and to discuss the medical emergency security work of large-scale sports events, so as to provide references for the planning of designated hospitals in future large-scale sports events.Methods:Retrospective analysis was made on the establishment principles, requirements, selection of medical support personnel, and training exercises of the designated hospitals, focusing on the key links such as organizational system, staffing, designated areas, and drug management.Results:Total of 40 designated hospitals have successfully completed the task of medical security by rebuilding the medical security area of the Asian Games, elevating the process, equipping facilities, and strengthening staff training. During the Asian Games, 349 people were transferred to designated hospitals by ambulance, 54 people were hospitalized, 19 people underwent surgery, and 1022 people went to designated hospitals by themselves.Conclusion:The construction of the designated hospitals during the 19th Hangzhou Asian Games was of high quality, efficient and smooth operation. It is suggested that efforts should be made in the reconstruction of the medical security area for the Asian Games to be "relatively independent". The treatment process of self-visiting patients should be fully considered and the flat urgent emergency response mechanism needs to be established.
7.Effect of BiPAP ventilation on respiratory physiology in patients with stable COPD
Yunpeng LIU ; Xilong WANG ; Yuhe HU ; Kai WANG ; Yun LI ; Peng SHAO ; Jianjiang LI ; Haiyun ZHANG ; Xin CHEN
Chinese Journal of Health Management 2023;17(5):344-349
Objective:To observe the physiological effect of bi-level positive airway pressure (BiPAP) ventilation among stable chronic obstructive pulmonary disease (COPD) patients.Methods:This was a small sample size, exploratory, interventional study. A total of 10 outpatients with stable COPD were included from Department of Pulmonary and Critical Care Medicine of Zhujiang Hospital, Southern Medical University between January 2018 and December 2018. The BiPAP mode of noninvasive mechanical ventilation was adopted. The inspiratory positive airway pressure was gradually increased from 10 cmH 2O (1 cmH 2O=0.098 kPa) to 24 cmH 2O, and each time by 2 cmH 2O. The expiratory positive airway pressure remained unchanged at 4 cmH 2O. Baseline and test data were collected before and during the ventilation for comparison, including total respiratory cycle time (T tot), inspiratory time (T i), inspiratory time (T e), inspiratory tidal volume (V Ti); mouth pressure (P mo), esophageal pressure (P eso), transdiaphragmatic pressure (P di), esophageal pressure time product (PTP es), diaphragm pressure time product (PTP di), root mean square of electromyography of diaphragm (RMS), V e/RMS, inspiratory capacity (IC), the change in end-expiratory lung volume (ΔEELV) and dynamic PEEPi (PEEPi dyn). Results:All the 10 patients completed the trial. Compared to calm breathing, V Ti, V e, P mo, IC, ΔEELV score and V e/RMS increased significantly with increasing pressure levels (all P<0.05); T e only increased significantly at 20-22 cmH 2O pressure levels compared to calm breathing ( P<0.05). P di, PTP es, PTP di, RMS and RMS/RMS max decreased significantly with increasing levels (all P<0.05). PTP es and PTP di converged to 0 and no longer showed significant changes after the 18 cmH 2O pressure level. RMS and RMS/RMS max flattened out at pressure level greater than 16 cmH 2O. T i/T tot only significantly decreased at the 20 cmH 2O pressure level compared to calm breathing. PEEPi dyn showed a tendency to decrease and then increase with increasing pressure levels. Conclusion:BiPAP ventilation, at appropriate pressure levels, significantly relieves pulmonary ventilation disorders and reduces the load of respiratory muscle in patients with stable COPD.
8.Establishment of HPLC fingerprint and content determination of 8 components in Jianpi huayu decoction
Xiaokai CHEN ; Yong LI ; Wei TAN ; Rongjian YU ; Jianjiang HUANG ; Zhixin LIU ; Junze LIN ; Changjun WANG
China Pharmacy 2023;34(23):2874-2879
OBJECTIVE To establish the HPLC fingerprint of Jianpi huayu decoction, and to determine the contents of 8 components. METHODS Thermo Hypersil Gold C18 column was used with mobile phase consisted of methanol-0.05% phosphoric acid aqueous solution (gradient elution) at the flow rate of 1.0 mL/min. The column temperature was 30 ℃, the injection volume was 5 μL. The detection wavelength of matrine was 211 nm, and the other components’ detection wavelength was 283 nm. The similarity evaluation of HPLC fingerprints for 10 batches of Jianpi huayu decoction was performed by using the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine (2012 edition). The contents of chlorogenic acid, vanillic acid, p-coumaric acid, ferulic acid, hesperidin, quercetin, bergapten and matrine in the samples were determined by HPLC. RESULTS HPLC fingerprint of Jianpi huayu decoction was established. A total of 27 common peaks were identified, and 8 components were identified. The similarity between 10 batches of samples and the control map ranged from 0.942-0.999. RSDs of precision, repeatability and stability tests were less than 3% (n=6). The average recoveries of chlorogenic acid, vanillic acid, p-coumaric acid, ferulic acid, hesperidin, quercetin, bergapten and matrine were 99.48%, 101.32%, 101.18%, 100.79%, 101.12%, 99.19%, 99.81% and 102.46%, respectively; RSDs were 1.34%, 0.93%, 1.90%, 1.84%, 0.54%, 1.53%, 1.33% and 1.01%, respectively (n=6). The contents were 0.021-0.061, 0.025-0.034, 0.116-0.295, 0.006- 0.062, 0.014-0.053, 0.017-0.026, 0.014-0.027 and 14.05-24.11 mg/g, respectively. CONCLUSIONS The established fingerprint and content determination method can provide a reference for the quality control and subsequent preparation development for Jianpi huayu decoction.
9.Effect of patent foramen ovale on perioperative complications and survival rate in pediatric patients undergoing living donor liver transplantation: a retrospective study
Yuli WU ; Yiqi WENG ; Yongle JING ; Tianying LI ; Jianjiang WU ; Mingwei SHENG ; Lili JIA ; Weihua LIU ; Wenli YU
Chinese Journal of Anesthesiology 2023;43(8):931-936
Objective:To evaluate the effect of patent foramen ovale (PFO) on the perioperative complications and survival rate in pediatric patients undergoing living donor liver transplantation.Methods:The medical records from pediatric patients of either sex with biliary atresia, aged<18 yr, who underwent living donor liver transplantation from January 2020 to January 2022, were retrospectively collected. The pediatric patients were divided into PFO group and non-PFO group according to the results of echocardiography before operation. The postreperfusion syndrome, acute lung injury, acute kidney injury, postoperative delirium and 1-year survival rate were recorded.Results:There was no significant difference in the incidence of postreperfusion syndrome, acute lung injury, acute kidney injury, postoperative delirium and one-year survival rate between PFO group and non-PFO group ( P>0.05). Conclusions:PFO has no obvious effect on the incidece of intraoperative and early postoperative complications and 1-year survival rate in pediatric patients undergoing living donor liver transplantation.
10.Comparison of clinical efficacy and sagittal parameters of two minimally invasive surgical methods in treating degenerative lumbar spondylolisthesis
Jianjiang LI ; Tao BAI ; Wei HU ; Yifei HUANG ; Nianrong HAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(1):105-110
【Objective】 To compare the clinical efficacy and sagittal parameters of oblique lateral interbody fusion (OLIF) combined with posterior percutaneous internal fixation and percutaneous transforaminal endoscope-assisted posterior lumbar interbody fusion (PT-Endo-TLIF) in treating degenerative lumbar spondylolisthesis. 【Methods】 A retrospective analysis was made on 43 patients with Meyerding Ⅰ and Ⅱ° degenerative lumbar spondylolisthesis treated in our hospital from September 2017 to January 2020. Among them 23 cases were treated by OLIF, and the other 20 cases were treated by PT-Endo-TLIF. We observed and recorded the operation time, average length of hospital stay, and intraoperative blood loss, and postoperative complications of the patients. The patients were followed up 3 day, 6 and 12 months after the operation. The lumbar sagittal parameters of the two groups were compared by X-ray, CT and MRI examinations. The patients’ lower back pain was recorded for visual analogue scale (VAS), and Oswestry disability index (ODI) was used to evaluate the clinical efficacy. 【Results】 Both groups of patients successfully completed the operation and follow-up, with the average follow-up time of 12 months. The average amount of intraoperative blood loss and operation time were significantly lower in OLIF group than in PT-Endo-TLIF group (P<0.05). Intervertebral height increased significantly in the two groups after operation compared with pre-operation (P<0.05). Compared with pre-operation, lumbar lordosis angle, lower lumbar lordosis angle and lumbar lordosis distribution index increased in both groups (P<0.05), with no significant difference between them (P>0.05). The inclination angle of L


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