1.Three-dimensional classification and clinical treatment of posterior cruciate ligament tibial avulsion fracture based on CT.
Guang-Kai REN ; Yu-Hang TIAN ; Ming-Yu CUI ; Bao-Ming YUAN ; Yan-Bing WANG ; Chuan-Gang PENG ; Ming LI ; Dan-Kai WU
China Journal of Orthopaedics and Traumatology 2025;38(4):389-395
OBJECTIVE:
A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study.
METHODS:
From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test.
RESULTS:
A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency.
CONCLUSION
The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans
;
Male
;
Female
;
Posterior Cruciate Ligament/surgery*
;
Adult
;
Tibial Fractures/classification*
;
Tomography, X-Ray Computed
;
Middle Aged
;
Retrospective Studies
;
Fractures, Avulsion/classification*
;
Imaging, Three-Dimensional
;
Young Adult
2.Protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on a yorkshire model of brain injury after traumatic blood loss.
Xiang-Yu SONG ; Yang-Hui DONG ; Zhi-Bo JIA ; Lei-Jia CHEN ; Meng-Yi CUI ; Yan-Jun GUAN ; Bo-Yao YANG ; Si-Ce WANG ; Sheng-Feng CHEN ; Peng-Kai LI ; Heng CHEN ; Hao-Chen ZUO ; Zhan-Cheng YANG ; Wen-Jing XU ; Ya-Qun ZHAO ; Jiang PENG
Chinese Journal of Traumatology 2025;28(6):469-476
PURPOSE:
To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss.
METHODS:
This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA+, K+, and Ca2+ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance.
RESULTS:
The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA+ and K+ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca2+ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group.
CONCLUSIONS
Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals
;
Perfusion/methods*
;
Disease Models, Animal
;
Brain Injuries/etiology*
;
Swine
;
Male
;
Hypothermia, Induced/methods*
3.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: A resting-state functional magnetic resonance imaging study.
Xuan YIN ; Xiao-Ling ZENG ; Jing-Jing LIN ; Wen-Qing XU ; Kai-Yu CUI ; Xiu-Tian GUO ; Wei LI ; Shi-Fen XU
Journal of Integrative Medicine 2025;23(2):159-168
OBJECTIVE:
Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.
METHODS:
Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.
RESULTS:
Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.
CONCLUSION
EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals
;
Electroacupuncture
;
Male
;
Magnetic Resonance Imaging
;
Depression/diagnostic imaging*
;
Mice, Inbred C57BL
;
Brain/diagnostic imaging*
;
Disease Models, Animal
;
Mice
;
Pain/diagnostic imaging*
;
Acupuncture Points
4.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
5.Omalizumab facilitates oral desensitization after levothyroxine-induced anaphylactic shock: A case report
Ruizhi JIAJUE ; Miao YU ; Le CUI ; Lianglu WANG ; Rui TANG ; Lin LU ; Kai FENG ; Yuxiu LI
Chinese Journal of Endocrinology and Metabolism 2024;40(10):879-883
Levothyroxine anaphylaxis is a rare yet severe adverse reaction to exogenous levothyroxine. While levothyroxine desensitization is commonly employed, its direct application in patients with severe shock poses considerable risks. Omalizumab may offer a potential adjunctive approach to induce tolerance to levothyroxine. We reported a case of a 30-year-old female with a history of thyroid papillary carcinoma who developed anaphylactic shock following oral administration of 50 μg levothyroxine daily after surgery. High serum level of immunoglobulin E (IgE 99.2 kU/L) and positive intradermal tests to all brands of levothyroxine available in China confirm a type Ⅰ hypersensitivity reaction. Several reports have proven the role of omalizumab in desensitization protocol in IgE-mediated diseases; therefore, she was pretreated with three courses of omalizumab (150 mg intradermal injection every four weeks). She then successfully completed oral levothyroxine desensitization and tolerated treatment dose of levothyroxine without experiencing allergic symptoms along with normalization of thyroid function. Further research is warranted to assess its potential as a standard treatment in difficult-to-treat levothyroxine hypersensitivity.
6.The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy.
Jia Xin WANG ; Shu Juan YANG ; Xuan MA ; Shi Qin YU ; Zhi Xiang DONG ; Xiao Rui XIANG ; Zhu Xin WEI ; Chen CUI ; Kai YANG ; Xiu Yu CHEN ; Min Jie LU ; Shi Hua ZHAO
Chinese Journal of Cardiology 2023;51(6):619-625
Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0
Humans
;
Female
;
Adult
;
Middle Aged
;
Male
;
Contrast Media
;
Retrospective Studies
;
Stroke Volume
;
Gadolinium
;
Ventricular Function, Left
;
Magnetic Resonance Imaging
;
Cardiomyopathy, Hypertrophic/diagnostic imaging*
;
Death, Sudden, Cardiac
;
Risk Assessment
7.Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression.
Xiyue SHEN ; Kai LUO ; Juntao YUAN ; Junling GAO ; Bingqing CUI ; Zhuoran YU ; Zhongbing LU
Acta Pharmaceutica Sinica B 2023;13(8):3352-3364
Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1f/f), Ddah1HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.
8.Clinical and 18F-FDG PET/CT imaging features of hilar tumor pulmonary infarction
Kai CUI ; Yaru WANG ; Jingsong ZHENG ; Yong CUI ; Yu JI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(2):75-78
Objective:To investigate the clinical manifestations and 18F-FDG PET/CT imaging features of hilar tumor pulmonary infarction. Methods:From July 2016 to June 2021, 49 patients (40 males, 9 females; age 32-81 years) with hilar tumor pulmonary infarction who underwent PET/CT and enhanced CT in the second Hospital of Shandong University and Shandong Cancer Hospital and Institute, Shandong First Medical University were retrospectively enrolled. All patients were diagnosed by imaging follow-up or pathology. Clinical features and 18F-FDG PET/CT imaging features were analyzed. Results:A total of 108 infarcts were found in 49 patients by 18F-FDG PET/CT. Small cell carcinoma was the most common hilar tumor (67.35%, 33/49). The most common clinical manifestations of hilar tumor pulmonary infarction were cough (69.39%, 34/49) and hemoptysis (34.69%, 17/49). Pulmonary infarction was mainly multiple (69.39%, 34/49), and multiple lung lobes might be involved. The CT morphology of infarcts was wedge-shaped (46.30%, 50/108) or patchy (53.70%, 58/108), and the density was mainly bubble consolidation (61.11%, 66/108). There were 91 (84.26%, 91/108) infarcts showing FDG hypermetabolism, with the SUV max of 1.48-6.62, and the hypermetabolism mode was rim sign (36.11%, 39/108) or heterogeneous hypermetabolism (48.15%, 52/108). Nineteen patients (38.78%, 19/49) were complicated with pulmonary vein involvement, and 26 patients (53.06%, 26/49) had ipsilateral pleural effusion. Conclusions:Hilar tumor pulmonary infarction is characterized by cough. It is helpful for the diagnosis of hilar tumor pulmonary infarction in patients with hilar tumor when wedge-shaped, bubble consolidation, rim sign and heterogeneous hypermetabolism lesions are found in 18F-FDG PET/CT images.
9.Role of NLRP3 in sepsis-associated encephalopathy and the relationship with pyroptosis in microglia of mice
Cui LI ; Shu′an DONG ; Kai SONG ; Xiangyun LI ; Shihan DU ; Jianbo YU
Chinese Journal of Anesthesiology 2023;43(2):206-209
Objective:To evaluate the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in sepsis-associated encephalopathy (SAE) and the relationship with pyroptosis in microglia of mice.Methods:Twenty-four SPF healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SAE group and SAE plus an NLRP3 inhibitor MCC950 group (SAE+ MCC950 group). The mouse model of SAE was prepared by cecal ligation and puncture after anesthesia. MCC950 20 mg/kg was intraperitoneally injected at 1 h after developing the model in SAE+ MCC950 group, and the equal volume of normal saline was given instead in the other groups. Open field tests were conducted at 1 day after developing the model to record the number of rearing and time spent in the central area. Novel object recognition tests were conducted at 2-3 days after developing the model to record the recognition index. After the behavioral experiment on 3 day after developing the model, mice were sacrificed and hippocampal tissues were collected for determination of the expression of NLRP3 (by Western blot), count of cells co-expressing NLRP3 and microglia-specific ionized calcium-binding adaptor molecule 1 (Iba-1) (by immunofluorescence), activity of caspase-1, and contents of interleukin-1beta(IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Compared with Sham group, the number of rearing was significantly reduced, the time spent in the central area was shortened, the recognition index was decreased, the expression of NLRP3 was up-regulated, the count of NLRP3 + -Iba-1 + cells was increased, and the activity of caspase-1 and contents of IL-1β and IL-18 were increased in SAE and SAE+ MCC950 groups ( P<0.05). Compared with SAE group, the number of rearing was significantly increased, the time spent in the central area was prolonged, the recognition index was increased, the expression of NLRP3 was down-regulated, the count of NLRP3 + -Iba-1 + cells was decreased, and the activity of caspase-1 and contents of IL-1β and IL-18 were decreased in SAE+ MCC950 group ( P<0.05). Conclusions:NLRP3 is involved in the development of SAE, which may be related to the mediation in microglial pyroptosis in mice.
10.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
;
Female
;
Humans
;
Aged
;
Natriuretic Peptide, Brain
;
Simendan/therapeutic use*
;
Non-ST Elevated Myocardial Infarction
;
Heart Failure/drug therapy*
;
Peptide Fragments
;
Arrhythmias, Cardiac
;
Biomarkers
;
Prognosis

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