Translator's note:
The translation team of "Pearl River Vision" of the Department of Anesthesiology of Zhujiang Hospital of Southern Medical University selects the high-quality SCI literature and research results published by domestic anesthesiology departments through the subject word search every month, from PubMed and Web of Science search engines, and conducts abstract introduction, and promotes it to colleagues across the country in the form of monthly good articles through the Pearl River Vision column of "New Youth Anesthesia Forum".
This issue of "Pearl River Vision - Monthly Good Articles" excerpts from some articles published from July 2023 to August 2024, from West China Hospital of Sichuan University, Peking University First Hospital, the Second Affiliated Hospital of Zhejiang University School of Medicine, Guangzhou Medical University Cancer Hospital, etc., covering sepsis treatment, postoperative pain management, dexmedetomidine and cognitive function (#为第一作者, * is the corresponding author).
Monthly good articles (2023.07-2023.08) above
1
1.YuJun Zhang#, Kun Shi#, Xi Yang, Wen Chen, TianHong Wang, Yi Kang, DeYing Gong, ZhiYong Qian*, WenSheng Zhang*. Sustained release of levobupivacaine from temperature-sensitive injectable hydrogel for long-term local anesthesia in postoperative pain management. Biomaterials, 2023 Aug. PMID: 37167892
【Topic】
Warm-sensitive injection of hydrogel extended-release levobupivacaine is used as a long-acting local anesthetic for postoperative pain management
【Corresponding Author】
Zhang Wensheng, Department of Anesthesiology, West China Hospital, Sichuan University; Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University; National and Local Joint Engineering Research Center for Translational Medicine of Anesthesiology;
Qian Zhiyong State Key Laboratory of Biotherapy, Sichuan University
【First Author】
YuJun Zhang Department of Anesthesiology, West China Hospital, Sichuan University, Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital of Sichuan University, National and Local Joint Engineering Research Center for Translational Medicine of Anesthesiology
Kun Shi State Key Laboratory of Biotherapy, Sichuan University
【Abstract】
Postoperative pain is a major complication for patients after surgery, and poor postoperative pain control can lead to a range of complications. Because local anesthetics can effectively control pain and have fewer side effects, they have become the treatment of choice for postoperative pain management. However, local anesthetics currently have a short duration of action and cannot meet the requirements for postoperative analgesia. In this study, a biodegradable poly-poly(D,L-lactide) injectable levobupivacaine (LB) loaded thermal hydrogel system was developed for long-acting local anesthesia in which the soluble charged cationic form of LB is partially alkalized to the poorly soluble base form (LB base). This mixed LB-loaded PLEL system (hLB/PLEL) is a free-flowing liquid at room temperature and transforms into a semi-solid hydrogel with physiological temperature changes once injected in vivo. Dissolved LB HCl is first released from the hydrogel, which contributes to rapid onset, while insoluble LB base gradually dissolves and is released with the decrease of pH during the biodegradation of PLEL hydrogel, resulting in local long-term release of LB. This project focuses on the in vitro and in vivo release behavior, pharmacokinetics and biocompatibility of heat-sensitive hLB/PLEL. The anesthesia effect of hLB/PLEL system was evaluated in rat sciatic nerve block, subcutaneous infiltration anesthesia and postoperative pain models. The hLB/PLEL system produced a significant long-lasting analgesia in rat models, with a duration of approximately 7 times that of 0.75% LB-HCl, and effectively relieved spontaneous pain for 3 days. Overall, the proposed hLB/PLEL system not only achieves rapid action, but also continuously releases LB to block nerves and significantly prolong the effect of local analgesia, suggesting that this drug may be an effective candidate for long-acting postoperative pain management therapy.
2
2. Chao Chen#, Yuhua Zuo#, Hongmei Hu, Yuting Shao, Si Dong, Junquan Zeng, Ling Huang , Ziyi Liu , Qinyuan Shen, Fasheng Liu, Xinjun Liao, Zigang Cao, Zilin Zhong, Huiqiang Lu*, Yanlong Bi* , Jianjun Chen*. Cysteamine hydrochloride affects ocular development and triggers associated inflammation in zebrafish. J Hazard Mater, 2023 Jul 27. PMID: 37517235
【Topic】
Cysteamine hydrochloride affects eye development and causes associated inflammation in zebrafish
【Corresponding Author】
Chen Jianjun, Department of Pediatrics, Shanghai Fourth People's Hospital, Tongji University School of Medicine; Clinical Research Center for Anesthesiology and Perioperative Medicine; Institute for Brain and Brain-like Intelligence Translation; Shanghai Key Laboratory of Anesthesia and Brain Function Regulation;
Bi Yanlong, Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine;
Lu Huiqiang Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases in Jiangxi Province; Jiangxi Provincial Key Laboratory of Organ Development Biology; Clinical Research Center, Affiliated Hospital of Jinggangshan University; College of Life Sciences, Jinggangshan University;
【First Author】
Chao Chen Department of Pediatrics, Shanghai Fourth People's Hospital, Tongji University School of Medicine; Key Laboratory of Anesthesia and Brain Function Regulation; Clinical Research Center for Anesthesia and Perioperative Medicine; Institute for Brain and Brain-like Intelligence Translation; Department of Medical Genetics, School of Medicine, Tongji University; Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine
Yuhua Zuo School of Optometry, Wenzhou Medical University;
【Abstract】
The increasing use of cosmetics has caused widespread concern about its ingredients. Cysteamine hydrochloride (CSH) is a newly discovered allergenic ingredient in cosmetics, and its potential toxicity needs to be further elucidated. Here, we used zebrafish models to investigate the in vivo toxic effects of CSH during eye development. CSH exposure is associated with smaller eyes, more fundus blood vessels, and reduced vessel diameter in zebrafish juveniles. In addition, CSH exposure accelerates the angiobudding process and enhances ocular endothelial cell proliferation. Through photo-visual motor response analysis and pathological examination, the weakened response of zebrafish juveniles to visual stimuli and damage to eye structures after CSH treatment were confirmed, respectively. Through transcription assays, transgenic fluorescence photography, and molecular docking analysis, we determined that CSH inhibits transcription of the Notch receptor, resulting in abnormal proliferation mediated by Vegf signaling mediated by endothelial cells in the eye. This process disrupts the homeostasis of the eye and induces an inflammatory response to neutrophil accumulation, in addition to producing high levels of reactive oxygen species, which in turn promotes the occurrence of apoptotic cells and ultimately impairs eye structure and visual function during zebrafish development.
3
3. Jia-Hui Ma#, Ning-Hao Huang, Tao Huang*, Dong-Liang Mu*. 25-hydroxyvitamin D concentrations and risk of incident dementia, mild cognitive impairment, and delirium in 443,427 UK Biobank participants. Psychiatry Res, 2023, 327: 115369.PMID:37523888
【Topic】
25-hydroxyvitamin D concentrations in 443427 participants in the UK Biobank were associated with the risk of developing dementia, mild cognitive impairment and delirium
【Corresponding Author】
Mu Dongliang Department of Anesthesiology, Peking University First Hospital
HUANG Tao, Laboratory of Major Disease Epidemiology, Ministry of Education (Peking University)
【First Author】
Jia-Hui Ma Department of Anesthesiology, Peking University First Hospital
【Abstract】
To investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and dementia, mild cognitive impairment (MCI), and delirium. Participants were from the UK Biobank and had complete information on serum 25(OH)D concentration. Dementia, mild cognitive impairment, and delirium were defined using the UK Biobank algorithm. 443427 participants with a mean (standard deviation) age of 56.8 (8.0) years were enrolled in this study. Based on the Cox regression model, serum 25(OH)D concentrations were dose-dependently negatively correlated with the risk of dementia, MCI, and delirium after demographic adjustment (P trend< 0.001), and participants with the highest 25(OH)D levels (i.e., >64.4 nmol/L) developed dementia (hazard ratio [HR]: 0.58, 95% confidence interval [CI] 0.49-0.69, P<0.001), MCI (HR: 0.55, 95% CI 0.37-0.84, P=0.005), and delirium (HR: 0.63, 95% CI 0.51-0.79, P=0.001) were the lowest risk. These results were consistent with sensitivity analyses, which excluded participants who had events within the first two years of follow-up. This study found that lower serum 25(OH)D concentrations were significantly associated with a higher risk of dementia (including Alzheimer's disease and vascular dementia), mild cognitive impairment, and delirium.
4
4. Shu-Shan Hua#, Jin-Jun Ding, Tian-Cheng Sun#, Chen Guo#, Ying Zhang, Zi-Hui Yu, Yi-Qing Cao, Lin-Hong Zhong, Yu Wu, Lu-Ying Guo, Jian-Hong Luo, Yi-Hui Cui*, Shuang Qiu*. NMDAR-dependent synaptic potentiation via APPL1 signaling is required for the accessibility of a prefrontal neuronal assembly in retrieving fear extinction. Biological Psychiatry, 2023 Aug 1. PMID:36842495
【Topic】
NMDAR-dependent synaptic enhancement via the APPL1 signaling pathway is required to restore prefrontal neuronal assembly with fear resolution
【Corresponding Author】
Qiu Shuang, Department of Neurobiology and Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine;
Cui Yihui Department of Neurobiology and Neurology, Run Run Shaw Hospital, Zhejiang University School of Medicine
【First Author】
HUA Shushan, DING Jinjun, SUN Tiancheng, Department of Neurobiology and Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine;
Shen Guo Department of Neurobiology and Neurology, Run Run Shaw Hospital, Zhejiang University School of Medicine
【Abstract】
Background: The ventromedial prefrontal cortex (vmPFC) is thought to be a place for storing and recalling extinct memories. However, the synaptic and cellular mechanisms behind this process remain unclear.
Research Methods: We combined transgenic mice, electrophysiological recordings, activity-dependent cell markers, and chemogenetic manipulation to analyze the effect of the linker protein APPL1 on fear regression extraction in vmPFC.
Results: This study found that both routine and conditional APPL1 knockout reduces NMDA receptor function in vmPFCs and impairs fear regression extraction. In addition, during extinction extraction, APPL1 undergoes nuclear transposition. Blocking the APPL1 nucleoplasmic transposition reduces NMDA receptor current and interferes with fear resolution extraction. A cluster of prefrontal neurons was further identified as a prerequisite for storing extinct memories. In this cluster, inducible knockout of the APPL1 gene disrupts NMDA receptor-dependent synaptic enhancement and interferes with fear regression extraction, while chemogenetic activation of the cluster salvages impaired behavior.
Conclusion: The results show that clusters of prefrontal neurons store extinction memories, and APPL1 signaling supports these neurons to cancel regression memories by controlling NMDA receptor-dependent enhancement.
5
5. Ni Ding#, Gangjian Luo, Huiting Li, Chengyuan Xing, Yuanji Gao, Wenjie Xi, Weijie Wu, Dan Wang, Lei Zheng, Yang Kang*, Xinjin Chi*. A Cyclodextrin-Based pH-Responsive MicroRNA Delivery Platform Targeting Polarization of M1 to M2 Macrophages for Sepsis Therapy. Advanced Healthcare Materials. 2023 July 18. PMID:37463303
【Topic】
Cyclodextrin-based pH-responsive microRNA delivery platform targets M1 to M2 macrophage polarization therapy for sepsis
【Corresponding Author】
Chi Xinjin, Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-sen University;
Yang Kang Scientific Research Center of the Seventh Affiliated Hospital of Sun Yat-sen University
【First Author】
Ni Ding, Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-sen University
【Abstract】
Although the diagnosis and treatment of sepsis with symptomatic and supportive care such as anti-infective therapy and fluid resuscitation has improved, mortality remains high. Nucleic acid drugs have therapeutic potential, but due to their poor stability and low delivery efficiency, their wide application is hindered. This study confirmed that miR-223 can polarize pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages. A pH-responsive nanodrug delivery system containing β-cyclodextrin-poly(2-isopropylaminoethyl methacrylate)/glycol glycol (β-CD-PDPA/DSPE-PEG) containing -cyclodextrin-poly(2-isopropylaminoethyl methacrylate)/glycol aclycing miR-223 into nanoparticles (NPs) was synthesized and a targeted M1 macrophage was developed to encapsulate miR-223 into nanoparticles (NPs) for sepsis treatment. NPs/miR-223 exhibited pH responsiveness in vitro, with good biological safety, stability and high delivery efficiency. In vivo studies have shown that NPs/miR-223 preferentially accumulates and retains at the site of inflammation, thereby reducing the inflammatory response and improving survival in mice with sepsis, while showing ideal biosafety. In terms of mechanism, NPs/miR-223 regulates macrophage polarization by targeting Pknox1 and inhibiting the activation of NF-κB signaling pathway, thereby achieving anti-inflammatory effects. In summary, miRNA delivery vectors provide a new approach for sepsis treatment and accelerate the progress of nucleic acid drug therapy.
6
6. Qian Zhai#, Ying Zhang#, Mao Ye, Shan Zhu, Jianyu Sun, Yue Wang, Bin Deng,Daqing Ma*, and Qiang Wang*. Reducing complement activation during sleep deprivation yields cognitive improvement by dexmedetomidine. British Journal of Anaesthesia. 2023 July 29. PMID:37517957
【Topic】
Dexmedetomidine reduces complement activation and improves cognitive function during sleep deprivation
【Corresponding Author】
Wang Qiang, Department of Anesthesiology and Brain Science Research Center, The First Affiliated Hospital of Xi'an Jiaotong University;
Ma Daqing, Department of Anesthesia, Pain Medicine and Intensive Care at Chelsea Westminster Hospital, Imperial College London, UK; Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health
【First Author】
ZHAI Qian, ZHANG Ying, Department of Anesthesiology and Brain Science Research Center, The First Affiliated Hospital of Xi'an Jiaotong University;
【Abstract】
Research background: Lack of sleep and its associated symptoms, such as cognitive impairment, impose a great burden on society, but the underlying mechanisms of these cognitive impairments remain unknown. This review assesses the effects of dexmedetomidine (DEX) on cognitive decline due to sleep deprivation.
Research methods: C57BL/6 mice were subjected to chronic sleep restriction (CSR) for 7 consecutive days for 20 h per day (5 pm to 1 pm the next day), followed by cognitive testing. At the same time, mice were also studied for intravenous DEX (100ug/kg, 1 pm and 3 pm daily), and their neural molecules and cell changes were also studied.
The results of the study: In the Y maze and new object recognition tests, the learning and memory ability of CSR mice decreased by 12% (P <0.05) and 18% (P <0.01), respectively. These changes were associated with microglial activation, CD68+ microglial phagostosome count, astrocyte-derived complement C3 secretion, and increased expression of microglial C3a receptors (all P < 0.05). Synaptic elimination is associated with the development of cognitive impairment, manifested by a 66% decrease in synaptophyseal expression (P = 0.0004) and a 45% decrease in postsynaptic density protein-95 expression (P = 0.0003). DEX activates astrocytes α2A adrenergic receptors and inhibits astrocytes complement C3 release, mitigating synaptic elimination through microglial phagocytosis. DEX restores synaptic connections and reverses cognitive impairment caused by CSR.
Conclusion: The results show that cognitive impairment related to sleep deprivation is related to synaptic elimination related complement pathway activation, and dexmedetomidine can prevent complement activation caused by sleep deprivation, which has the potential to prevent cognitive impairment associated with sleep deprivation, which deserves further study.
7
7. Shuang-Jie Cao#, Yue Zhang#, Yu-Xiu Zhang, Dong-Xin Wang*. Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial. Br J Anaesth, 2023 Aug;131(2):266-275. PMID: 37474242
【Topic】
Long-term survival of major cancer surgery under propofol or sevoflurane anesthesia in elderly patients: a follow-up study of a multicenter randomized trial
【Corresponding Author】
Dongxin Wang, Department of Anesthesiology, Peking University First Hospital, Cleveland Clinic, Ohio, USA
【First Author】
Shuang-Jie Cao, Yue Zhang, Department of Anesthesiology, Peking University First Hospital;
【Abstract】
Background: Previous animal experiments have found that intravenous anesthesia may reduce cancer recurrence compared with volatile inhalation anesthesia, but clinical information is observational only. Therefore, we examined the main hypothesis that propofol-based anaesthesia improves survival in cancer patients at 3 years or more after radical major surgery.
Methods: A long-term follow-up study of a multicenter randomized trial conducted in 14 tertiary hospitals in China. We recruited 1228 patients aged 65-90 who were planning major cancer surgery. They were randomly assigned to propofol intravenous anesthesia or sevoflurane inhalation anesthesia. The primary endpoint was overall survival after surgery, and secondary endpoints included recurrence-free survival and event-free survival.
Results: Of the randomized participants, 1195 patients (mean age 72 years; 773 [65%] males) were included in the intention-to-treat modified analysis. At the end of follow-up (median follow-up 43 months), 188 of the 598 patients who received propofol anaesthesia died (31%) compared with 175 of the 597 patients who received sevoflurane anaesthesia (29%); The adjusted hazard ratio was 1.02, and the 95% confidence interval (CI) was 0.83-1.26, P=0.834. The recurrence-free survival rate was 223/598 (37%) in patients receiving propofol anesthesia and 206/597 (35%) in patients receiving sevoflurane anesthesia; The adjusted hazard ratio was 1.07, with a 95% confidence interval (CI) of 0.89 to 1.30, and P=0.465. Event-free survival was 294/598 (49%) in patients receiving propofol anesthesia and 274/597 (46%) in patients receiving sevoflurane anesthesia; The adjusted hazard ratio was 1.09, with a 95% confidence interval (CI) of 0.93 to 1.29, and P=0.298.
Conclusion: There is no significant difference in the long-term survival rate of cancer patients after major surgery between intravenous anesthesia and volatile inhalation anesthesia. Propofol-based intravenous anaesthesia should not be used to expect to improve overall survival or cancer-specific survival in cancer patients.
8
8. Changliang Liu#, Jiahui Wu#, Ming Li, Rui Gao, Xueying Zhang, Shixin Ye-Lehmann, Jiangning Song, Tao Zhu*, Chan Chen*. Smad7 in the hippocampus contributes to memory impairment in aged mice after anesthesia and surgery. J Neuroinflammation, 2023 Jul 28;20(1):175. PMID: 37507781
【Topic】
Smad7 in the hippocampus impairs memory impairment after anesthesia and surgery in aged mice
【Corresponding Author】
ZHU Tao,CHEN Chan, Department of Anesthesiology, West China Hospital, Sichuan University Institute of Anesthesia and Critical Care Medicine, West China Hospital, Sichuan University;
【First Author】
Changliang Liu, Jiahui Wu Department of Anesthesiology, West China Hospital, Sichuan University Institute of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University;
【Abstract】
Background: Postoperative cognitive dysfunction (POCD) is a common neurological complication after anesthesia and surgery. There is growing evidence that neuroinflammation caused by the perioperative systemic inflammatory response is a key factor in the development of POCD. In addition, SMAD family member 7 (Smad7) has been shown to play an important role in the pathogenesis and treatment of inflammatory diseases such as inflammatory bowel disease. However, whether Smad7 is involved in the regulatory processes of neuroinflammation and apoptosis during POCD development remains unknown.
Methods: In this study, a mouse model of POCD was constructed by unilateral nephrectomy under anesthesia, and the cognitive function of mice was evaluated using fear conditioning experiment and open field experiment. The expression of Smad7 at the level of Smad7 in the hippocampus 3 days after surgery was detected by qRT-PCR, Western blot, and immunofluorescence analysis. In addition, to determine whether the elevation of Smad7 in the hippocampus after unilateral nephrectomy leads to cognitive impairment, Smad7 expression in the CA1 region of the hippocampus was downregulated by hybridization or stereotactic injection of shRNA-Smad7 in Smad7fl/fl-conditioned mutant mice and CaMKIIα-Cre T29-1 transgenic mice. Inflammation and apoptosis in hippocampal tissues were assessed by measuring mRNA levels of typical inflammatory cytokines including TNF-α, IL-1β, IL-6, CCL2, CXCL1, and CXCL2 and protein levels of apoptotic proteins, including Bax and Bcl2. In addition, apoptosis in hippocampal tissues after surgery was studied by terminal deoxynucleotidyl transferase dUTP terminal labeling (TUNEL) staining experiments. Finally, Western blotting was used to investigate the mechanism by which Smad7 mediates inflammation and apoptosis after surgery.
Results: The results clearly showed that elevated Smad7 in the CA1 region of the hippocampus significantly inhibited TGF-β signaling by blocking the phosphorylation of Smad2/3, thereby enhancing neuroinflammation and apoptosis in hippocampal tissues and further impairing learning and memory impairment after surgery.
Conclusion: Our results suggest that Smad7 promotes postoperative cognitive dysfunction by enhancing neuroinflammation and apoptosis in the hippocampus, and may be a potential therapeutic target for the treatment of cognitive dysfunction after anesthesia surgery.
9
9. Wang LY#, Wang XP#, Lv JM, Shan YD, Jia SY, Yu ZF, Miao HT, Xin Y, Zhang DX, Zhang LM*. NLRP3-GABA signaling pathway contributes to the pathogenesis of impulsive-like behaviors and cognitive deficits in aged mice. J Neuroinflammation. 2023 Jul 11;20(1): 162. PMID: 37434240.
【Topic】
The NLRP3-GABA signaling pathway is involved in the pathogenesis of impulsive-like behavior and cognitive impairment in aged mice
【Corresponding Author】
Zhang Limin, Department of Anesthesiology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Hebei Province
【First Author】
Lu-Ying Wang, Laboratory of Anesthesia and Trauma Stress, Department of Anesthesiology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Hebei Province
Xu-Peng Wang, Department of Anesthesiology, Third Hospital of Hebei Medical University
【Abstract】
Background: Neurocognitive impairment (PND) is a common perioperative complication in older patients, mainly including delirium and cognitive dysfunction. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is abnormally synthesized by reactive astrocytes following inflammatory stimuli and is associated with the pathophysiology of neurodegenerative diseases. In addition, the activation of the inflammasome of NOD-like receptor protein 3 (NLRP3) is also involved in the development of PND. Here, we aimed to investigate whether the NLRP3-GABA signaling pathway is involved in the pathogenesis of PND in aging mice.
Methods: A mouse model of PND was established by tibial fracture surgery in 24-month-old C57BL/6 male mice with astrocytes-specific knockout of NLRP3. Postoperative intraperitoneal injection of the monoamine oxidase-B (MAOB) inhibitor selegiline (1 mg/kg) once a day for 7 days. PND includes impulsivity-like behavior and cognitive impairment, which are assessed by open-field testing, elevated cross mazes, and fear experiments. Western blots and immunofluorescence are used to detect degenerative pathological changes in nerves.
Results: Selegiline significantly improved the impulsive-like behavior induced by tibial plateau fracture and reduced the overproduction of GABA in reactive hippocampal astrocytes. In addition, astrocytes-specific knockout NLRP3 mice reversed impulsive-like behavioral and cognitive impairment induced by tibial plateau fractures, reduced GABA levels in reactive astrocytes, improved early NLRP3-related inflammatory responses, and restored hippocampal neuronal degeneration.
Conclusion: Neuroinflammation and cognitive dysfunction caused by anesthesia and surgery in aged mice may be related to the activation of NLRP3-GABA in the hippocampus.
10
10. Sun Z#, Chen A#, Fang H#, Sun D, Huang M, Cheng E, Luo M, Zhang X*, Fang H*, Qian G*. B cell-derived IL-10 promotes the resolution of lipopolysaccharide-induced acute lung injury. Cell Death Dis. 2023 Jul 13;14(7):418. PMID: 37443161
【Topic】
B-cell-derived IL-10 promotes recovery from lipopolysaccharide-induced acute lung injury
【Corresponding Author】
Qian Guojun, Cancer Hospital and Cancer Institute Affiliated to Guangzhou Medical University;
Fang Hao, Department of Anesthesiology, Zhongshan Hospital, Fudan University;
Zhang Xiaoren, Cancer Hospital and Cancer Institute of Guangzhou Medical University;
【First Author】
Sun Z,Chen A Guangzhou Medical University Cancer Hospital and Cancer Institute;
Fang H, Department of Anesthesiology, Zhongshan Hospital, Fudan University;
【Abstract】
Resolution of inflammation is essential for recovery from acute lung injury (ALI). Interleukin(IL)-10 is a potent anti-inflammatory factor. However, its role in the ALI recovery process is unclear. We investigated the effects of IL-10 during ALI recovery in a mouse lipopolysaccharide (LPS)-induced ALI model. Blocking the IL-10 signaling axis exacerbates LPS-induced lung injury, manifested by increased production of pro-inflammatory factors and increased recruitment of neutrophils to the lung. Afterwards, we used IL-10 GFP reporter mice to identify the source cells of IL-10 during ALI. We found that IL-10 is mainly produced by B cells during ALI recovery. Furthermore, we use IL-10 in specifically missing B cells to further elucidate the effect of B cell-derived IL-10 on the ALI recovery process. Specific deletion of IL-10 in B cells leads to increased expression of inflammatory factors, persistent leukocyte infiltration, and prolonged alveolar barrier damage. In terms of mechanism, B cell-derived IL-10 inhibited the activation and recruitment of macrophages, reduced the production of chemokine KC and lung recruitment of neutrophils. Moreover, we found that the loss of IL-10 in B cells led to alterations in the cGMP-PKG signaling pathway. In addition, exogenous IL-10 promotes LPS-induced recovery of ALI, and IL-10-secreting B cells are present in sepsis-associated ARDS. The study highlights that B-cell-derived IL-10 is critical for LPS-induced recovery of ALI and may be a potential therapeutic target for ALI.
11
11. Chin-Tsang Yang#, Yun Guan, Chih-Cheng Chen, Wei-Tso Lin, Kuo-Hsiang Lu, Chung-Ren Lin, Bai-Chuang Shyu*, Yeong-Ray Wen*. Novel Pulsed-Ultrahigh-Frequency Spinal Cord Stimulation Inhibits Mechanical Hypersensitivity and Brain Neuronal Activity in Rats after Nerve Injury. Anesthesiology.2023, Jul 10. PMID: 37428715.
【Topic】
Novel pulsed UHF spinal cord electrical stimulation inhibits mechanical hypersensitivity and brain neuronal activity after nerve injury in rats
【Corresponding Author】
Yeong-Ray Wen Department of Anesthesiology, Affiliated Hospital of China Medical University, Pain Management Research Center
Bai-Chuang Shyu Institute of Biomedical Research, Academia Sinica (Taiwan)
【First Author】
Chin-Tsang Yang, Institute of Biomedical Research, Academia Sinica (Taiwan)
【Abstract】
Background: Electrical spinal cord stimulation (SCS) is an important pain treatment modality. We hypothesize that a novel pulsed ultra-high frequency SCS (pUHF-SCS) can safely and effectively inhibit neuropathic pain caused by nerve injury in rats.
Methods: Implant an epidural pUHF-SCS (± 3V, 2Hz pulse, including a 500kHz biphasic sine wave) in the thoracic spine (T9-T11). Record local brain potentials after hindpaw electrical stimulation. Analgesic efficacy was assessed by Von-Frey-induced hyperalgesia and acetone-induced cold hypersensitivity.
Results: The threshold of mechanical stimulation foot shrinkage of injured claw was 0.91±0.28 g lower than that of the sham surgery group (24.9±1.2 g). When pUHF-SCS was administered 5, 10, or 20 minutes every two days, the shrinkage thresholds increased significantly to 13.3± 6.5, 18.5± 3.6, and 21.0±2.8 g, respectively (p=0.0002, <0.0001 and). <0.0001; n=6/group), the next day increased to 6.1±2.5, 8.2±2.7, and 14.3±5.9 g (p = 0.123, 0.013, and < 0.0001), and the number of acetone-induced foot shrinkage responses decreased from 1 hour before (41±12) and 28±10 times before SCS 1 h and 5 h after three rounds of 20 min pUHF-SCS ±(p=0.006 and 0.027; n=9). The area under the curve for evoked potential C components of the left primary somatosensory cortex and anterior cingulate cortex decreased significantly from before spinal cord stimulation (101.3±58.3 and 86.9±25.5, respectively) to 39.7±40.3 and 36.3±20.7 60 minutes after spinal cord stimulation (p=0.021 and 0.003; n=5). The intensity threshold at which pUHF-SCS results in brain and sciatic nerve activation is much higher than that of traditional low-frequency SCS.
Conclusion: pUHF-SCS inhibits neuropathic pain-related behaviors and foot contraction stimulation-induced brain activation by a mechanism different from low-frequency SCS.
12
12. Jia-wen Xu#, Xin Deng#, Ai-hong Gu#, Yu-qun Cai#, Yun-yun Huang, Wen Zhang, Yi-qing Zhang, Wen-yu Wen*, Yun-li Xie*. Ccdc85c-Par3 condensates couple cell polarity with Notch to control neural progenitor proliferation. Cell Rep, 2023, 42(7): 112677. PMID: 37352102.
【Topic】
CCDC85c-Par3 aggregates couple cell polarity to Notch to regulate neural progenitor cell proliferation
【Corresponding Author】
Xie Yunli, Wen Wenyu Department of Anesthesiology, Zhongshan Hospital, Fudan University, Center for Frontier Science in Brain Science/State Key Laboratory of Medical Neurobiology
【First Author】
Jia-wen Xu, Xin Deng, Ai-hong Gu, Yu-qun Cai, Department of Anesthesiology, Zhongshan Hospital, Fudan University, Center for Frontier Science of Brain Science/State Key Laboratory of Medical Neurobiology
【Abstract】
Polar proteins regulate the proliferation and differentiation of neural progenitor cells through a variety of signaling pathways, producing neurons during brain development. However, how cell polarity conjugates signaling pathways remains unclear. Here, we found that the coiled spiral domain protein 85c (Ccdc85c) interacts with the polar protein Par3 to regulate the proliferation of radial glial cells (RGCs) through phase separation coupling osmosis (PSCP). We found that the interaction with Ccdc85c alleviated the self-inhibition within the Par3 molecule, resulting in the PSCP of Par3. The down-regulation of CCDC85c can lead to RGC differentiation. Importantly, the open conformation of Par3 promotes the recruitment of the Notch regulator Numb to Par3 aggregates, which may prevent the weakening of Notch activity to maintain RGC proliferation. In addition, ectopic activation of the Notch signal salvages RGC proliferation defects caused by Ccdc85c downregulation. These results suggest that Ccdc85c-mediated PSCP of Par3 regulates Notch signaling during brain development to control RGC proliferation.
13
13. Xiang Li#, He Liu#, Jun Wang, Zhi-Lin Ni, Zhong-Xiao Liu, Jia-Li Jiao, Yuan Han, and Jun-Li Cao*. Individualized Positive End-expiratory Pressure on Postoperative Atelectasis in Patients with Obesity: A Randomized Controlled Clinical Trial. Anesthesiology, 2023, 139(3):262-273. PMID: 37440205
【Topic】
Effect of personalized positive end-expiratory pressure on postoperative atelectasis in obese patients: a randomized controlled clinical trial
【Corresponding Author】
Cao Junli, School of Anesthesiology, Xuzhou Medical University;
【First Author】
Xiang Li# Department of Anesthesiology, Eye, Ear, Nose and Throat Hospital, Fudan University; Jiangsu Provincial Key Laboratory of Anesthesiology, China; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University;
He Liu# Department of Anesthesiology, Huzhou Central Hospital;
【Abstract】
Background: Personalized positive end-expiratory pressure (PEEP) guided by dynamic compliance improves oxygenation and reduces postoperative atelectasis in non-obese patients. We hypothesized that PEEP guided by dynamic compliance also reduced postoperative atelectasis in bariatric surgery patients.
Methods: Patients who were scheduled to undergo laparoscopic bariatric surgery were eligible. All patients were treated with decreasing PEEP modulation guided by dynamic compliance. Recruitment manoeuvres were performed before and after the adjustment (PEEP from 10 cm H2O to 25 cm H2O, 5 cm H2O increments every 30 seconds, driving pressure to 15 cm H2O). Patients are then randomized (1:1) to either the AD-guided PEEP group (PEEP plus 2 cm H2O plus 2 cm H2O when ambulatory compliance is maximized) or the PEEP group with 8 cm H2O. The main result is postoperative atelectasis, which is evaluated by computed tomography (CT) within 60~90 minutes after extubation, and is expressed as a percentage of the volume of lung tissue to the total amount of lung tissue at the time of measurement. Secondary outcomes included arterial partial pressure of oxygen (PaO2)/ratio of inspired oxygen (FiO2), i.e. oxygenation index, and postoperative pulmonary complications.
Results: Forty patients were enrolled in the study (mean plus minus standard deviation; 28±7 years old; 25 women; The average body mass index was 41.0 ± 4.7 kg/m2. In all 40 patients, the median PEEP at the time of maximum dynamic compliance during tuning was 15 cm H2O (interquartile range 13~17; range 8~19). Taking postoperative atelectasis as the primary outcome (19 patients in each group), 13.1 ± 5.3% and 9.5 ± 4.3% in the PEEP group with PEEP of 8 cm H2O and dynamic compliance guidance were 13.1 5.3% and 9.5 4.3%, respectively (the within-group difference was 3.7%; 95% CI，0.5~6.8%； P=0.025）。 One hour after pneumoperitoneum, the oxygenation index was higher in the PEEP group guided by ambulatory compliance (397 vs. 337 mmHg; The difference between groups was 60; 95% CI, 9~111; P=0.017), but 30 minutes after extubation, there was no difference between the two groups (359 vs. 375 mmHg; The between-group difference was -17; 95% CI，-53 ~ 21；P=0.183）。 The incidence of postoperative pulmonary complications was 4/20 in both groups.
Conclusion: Compared with the PEEP group with PEEP of 8 cm H2O, patients who underwent laparoscopic bariatric surgery had a lower chance of postoperative atelectasis in the PEEP group guided by dynamic compliance. There was no difference in postoperative oxygenation index between groups.
14
14. Ding Luo#, Xiaoyong Dai#, He Tian#, Chunlin Fan*, Huayan Xie, Nenghua Chen, Jinghao Wang, Laiqiang Huang, Hao Wang*, Guocai Wang*, and Yubo Zhang*. Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy. Phytomedicine, 2023, 116:154909. PMID: 37269775
【Topic】
A novel alkaloid extracted from Sophora radix A, Sophflarine A, can treat non-small cell lung cancer with ROS-mediated pyroptosis and autophagy
【Corresponding Author】
FAN Chunlin, Wang Guocai, Institute of Traditional Chinese Medicine and Natural Products, School of Pharmacy, Jinan University; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Pharmacodynamic Components and New Drug Research;
Wang Hao, Department of Anesthesiology, The First Affiliated Hospital of Jinan University;
Yubo Zhang, Institute of Traditional Chinese Medicine and Natural Products, School of Pharmacy, Jinan University; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Pharmacodynamic Components and New Drug Research; Guangdong Clinical Transformation Center of Targeted Drugs, Department of Pharmacology, School of Medicine, Jinan University;
【First Author】
Department of Anesthesiology, First Affiliated Hospital of Jinan University, Ding Luo; Institute of Traditional Chinese Medicine and Natural Products, School of Pharmacy, Jinan University; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Pharmacodynamic Components and New Drug Research; Guangdong Clinical Transformation Center of Targeted Drugs, Department of Pharmacology, School of Medicine, Jinan University;
Xiaoyong Dai Institute of Biomedicine and Health Engineering, Shenzhen International Graduate School, Tsinghua University; Shenzhen Key Laboratory of Gene and Antibody Therapeutics; State Key Laboratory of Chemical Oncology Genomics;
He Tian Department of Anesthesiology, The First Affiliated Hospital of Jinan University;
【Abstract】
Background: Treatment of non-small cell lung cancer (NSCLC) urgently requires novel compounds and more effective treatment options. Clinically, Sophora Sophora decoctions have been used to treat non-small cell lung cancer, and Sophorae Sophorae alkaloids are generally considered to be the key pharmacodynamic basis. But previous studies have shown that common radix-type alkaloids exhibit significant cytotoxicity only at concentrations close to millimolar (mM) levels. Key antitumor alkaloids in Sophora radix do not appear to have been revealed.
Objective: This study aimed to screen out water-soluble alkaloids with novel molecular framework and stronger activity from Sophora radix and reveal the pharmacological mechanism of NSCLC.
Research method: The alkaloids were extracted from Sophora radix by chromatographic separation. The structure of alkaloids was determined by spectroscopic analysis and single crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro in cell models was evaluated by MTT colorimetry, western blotting, cell migration and invasion assay, plate colony formation assay, angiogenesis assay, immunohistochemistry assay, hematoxylin and eosin staining. The anti-tumor efficacy of NSCLC was tested in vivo in the xenograft model.
Results: A novel water-soluble alkaloid with a 6/8/6/6 tetracyclic system was isolated from the root of Sophora radix and named Sophflarine A (SFA). Compared with common bitter ginseng-type alkaloids, SFA is significantly more cytotoxic with IC50 values of 11.3 μM for A549 cells and 11.5 μM for H820 cells over 48 hours. Mechanistically, SFA induces cell pyroptosis by activating the NLRP3/caspase-1/GSDMD signaling pathway, thereby promoting NSCLC cell death. By blocking the PI3K/AKT/mTOR signaling pathway, ROS production is increased to activate autophagy, thereby inhibiting cancer cell proliferation. In addition, SFA can inhibit the migration and invasion of NSCLC cells by inhibiting the EMT pathway, inhibiting cancer cell colony formation and the production of human umbilical vein endothelial cells. Consistent with the above results, SFA blocked tumor growth in an in situ mouse model grown with A549 cells.
Conclusion: This study reveals the potential therapeutic mechanism of a novel alkaloid SFA derived from Sophora radix, which not only reasonably explains the clinical application of Sophora radix, but also provides a potential candidate compound for the treatment of NSCLC.
15
15. Fei Huang#, Zhizhao Deng#, Qian Zhang#, Zheng Zhang, Xianlong Li, Weiqi Zeng, Yanling Wang*, Ziqing Hei*, and Dongdong Yuan*. Dual-regulation by Cx32 in hepatocyte to trigger and worsen liver graft injury. Transl Res, 2023, S1931-5244(23)00124-X. PMID: 37507007
【Topic】
The dual regulatory effect of CX32 in hepatocytes triggers and aggravates liver transplantation injury
【Corresponding Author】
Wang Yanling, Hei Ziqing, Yuan Dongdong, Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University;
【First Author】
Huang Fei, Zhizhao Deng, Qian Zhang Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University;
【Abstract】
Liver transplantation is the ultimate option for the treatment of end-stage liver failure. However, liver transplant injury remains a challenge. This study aims to investigate the role of gap junction protein 32 (Cx32) in liver transplantation injury and to elucidate its mechanism of action. By examining transplanted liver samples from 6 patients, we observed changes in Cx32 levels that coincided with liver transplant injury. Therefore, we established an autologous in situ liver transplantation (AOLT) model using Cx32 knockout mice and wild-type mice, and a hypoxia/reoxygenation (H/R) and lipopolysaccharide (LPS) pretreatment model using mouse normal hepatocytes (AML12) to explore the mechanism of action of Cx32 in liver transplantation injury. After in vivo and in vitro knockout of Cx32, by regulating PKC-α/NF-κB/NLRP3 and Nrf2/NOX4/ROS signaling pathways, oxidative stress and inflammatory responses were inhibited, thereby reducing apoptosis associated with Bak/Bax and improving liver transplant injury. When Cx32-based gap junctions (GJ) are blocked with 2-aminoethyldiphenyl borate (2-APB), ROS transfer between neighboring cells is attenuated, increased oxidative stress and inflammatory responses are prevented, and the degree of deterioration of liver transplant injury is reduced. These results highlight the dual regulatory mechanism of Cx32 in liver transplantation injury. By interacting with PKC-α, Cx32 regulates NF-κB/NLRP3 and Nrf2/NOX4/ROS signaling pathways, directly triggering oxidative stress and inflammatory responses. At the same time, the large amount of ROS produced is transferred to neighboring cells through the Cx32 channel, which indirectly exacerbates oxidative stress and inflammatory responses. Finally, apoptosis associated with Bak/Bax is activated, aggravating liver transplant injury. Our results suggest that Cx32 is a dual mechanistic factor that regulates apoptosis in oxidative stress and inflammatory signaling pathways in liver transplant injury, which provides a potential therapeutic target for liver transplant injury.
Searched: Luo Jiaming, Yin Mengyu
Translated by Hong Pu, Lin Zhiqiang
Proofreader: Lin Hongbin, Zhao Wei
Instructor Profile:
Mo Kai
Deputy Chief Physician of Department of Anesthesiology, Pearl River Hospital, Southern Medical University, Doctor of Medicine, Academic Master Supervisor
Professional expertise: engaged in chronic pain diagnosis and treatment and clinical anesthesiology teaching and research for nearly 16 years. In terms of pain diagnosis and treatment, he is good at the diagnosis and treatment of common and difficult chronic pain such as headache, trigeminal neuralgia, cervical spondylosis, lumbar disc herniation, bone and joint pain in the extremities, postherpetic neuralgia, various peripheral neuralgia, intractable cancer pain and chronic pain syndrome after surgery, proficient in ultrasound-guided nerve block, needle knife release, radiofrequency analgesia, ozone injection, internal heat needle and other visual precision treatment, trigeminal nerve radiofrequency/balloon compression, Various minimally invasive analgesic interventional procedures such as spinal cord electrical stimulation implantation and neuraxial drug perfusion system insertion. In terms of clinical anesthesia, he is good at the management of various surgical anesthesia, especially laparoscopic hepatectomy low central venous anesthesia technology, ultrasound-guided nerve block and vascular puncture technology, perioperative treatment and treatment of elderly critically ill patients. Presided over 3 new technologies and new businesses in the hospital.
Academic appointments: Member of the Youth Committee of the Pain Branch of Guangdong Medical Association, member of the Pain Branch of Guangdong Hospital Management Association, member of the Anesthesia Expert Committee of Guangdong Pharmaceutical Association, and member of the Perioperative Big Data Group of the Anesthesia Branch of Guangdong Medical Association. He studied at the Anesthesia and Pain Center of Rutgers University School of New Jersey for 2 years, presided over 3 Guangdong Provincial Natural Science Foundation, 1 Guangdong Province Health Appropriate Technology Promotion Project, participated in a number of national levels, and published 15 research papers in international first-class journals (such as Nature Communication, Journal of Neuroscience) and professional top journals (such as Pain, Anesthesiology). The pain research results won the second prize of the 2020 Military Science and Technology Progress Award.
【Pearl River Vision - Introduction to Translation Team】
Since its establishment in May 2020, the translation team of "Pearl River Vision" of the Department of Anesthesiology of Zhujiang Hospital of Southern Medical University has mainly carried out the translation and promotion of the latest progress in anesthesiology and related disciplines, and now launches the "Good Article of the Month" column to share the latest research progress of anesthesiology in mainland China with peers. The translation team searches the latest literature for the first time every month, organizes the graduate supervisor research group to translate and proofread, and after reviewing and collectively discussing the final draft through the division of labor of the group members, it is published in the "Pearl River Vision" column of the public account of the "New Youth Anesthesia Forum". So far, with the support and joint efforts of all the graduate tutors of the Department of Anesthesiology of Pearl River Hospital of Southern Medical University, the literature push column of "Pearl River Vision" has gone through more than 700 days and nights. In the future, we will continue to share academic achievements related to anesthesiology at home and abroad, and welcome constructive comments from colleagues at home and abroad on the content of this column.
"Pearl River Vision", focus on professionalism, the pursuit of excellence, and walk with the world!
Pearl River Vision | Professor Yan Min: Perioperative blood pressure management strategies for non-cardiac surgery patients Pearl River Vision | Good article of the month: Domestic Anesthesiology Abstracts 2023.07 (Part I) Pearl River Vision | Good article of the month: Domestic Anesthesiology Abstract2023.07 (Part II)
Pearl River Vision | Professor Hongwei Zhu: Anesthesia for esophageal surgery
Pearl River Vision | Good article of the month: Domestic Anesthesiology Digest 2023.06 (Part I)
Pearl River Vision | Good article of the month: Domestic Anesthesiology Abstracts 2023.06 (Part II)
Pearl River Vision | Professor Wu Jingxiang: How to do a good job in lung isolation technology
statement
The original or reprinted content published in this WeChat public account does not represent the views or positions of the New Youth Anesthesia Forum. The content of drug use, disease diagnosis and treatment mentioned in the article is for reference only.
▼ Click "