最新刊期
卷 49 ， 期 10 ， 2024
- “在围手术期神经认知功能障碍领域，专家探讨了睡眠紊乱的作用及干预策略，为改善患者预后提供指导。”摘要：Perioperative neurocognitive disorder (PND) significantly threatens brain health, leading to prolonged hospitalization, increased patient mortality risk, and poor long-term prognosis. Sleep disorder may substantially elevate the risk of neurocognitive dysfunction. However, the specific role of sleep in PND development remains to be elucidated. In addition, controversy exists over whether interventions for perioperative sleep disorder can effectively prevent PND. Therefore, this review aims to explore the basic function and regulatory principles of sleep, the clinical characteristics of perioperative sleep disorder, its role and potential mechanisms in PND development. Furthermore, we also provide new evidence on the potential therapeutic strategies to modulate sleep disorder for PND management, to improve patient's neurocognitive prognosis and long-term outcomes.关键词：sleep disorders;general anesthesia;perioperative neurocognitive disorder;sleep modulation
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发布时间：2024-11-07 - “瑞马唑仑作为GABA受体激动剂，在脑、心、肝、肺等器官保护方面取得研究进展，为临床应用提供理论基础。”摘要：Remazolam is a γ-aminobutyric acid (GABA) receptor agonist. It is a short-acting benzodiazepine drug that has just been launched in China in recent years. Its mechanism of action is to enhance inhibitory neurotransmitters of GABA in the central nervous system. It has been widely used in clinical practice for sedation, hypnosis, anti anxiety, and the treatment of insomnia. Meanwhile, remazolam is mainly used for induction and maintenance of general anesthesia during the perioperative period, with a fast onset time and a brief duration of action. Recent studies have shown that remazolam can protect important organs and alleviate organ damage by reducing inflammatory responses and oxidative stress, regulating cell apoptosis, and other pathways. This article summarizes the protective effects and mechanisms of remazolam on the brain, heart, liver, and lung, providing a theoretical basis for the clinical application of remazolam.关键词：remazolam;organ protection;organ damage;inflammation response
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发布时间：2024-11-07 - “据最新研究，心脏外科手术患者术后谵妄发生率为31.6%，手术时间、ICU入住时间、机械通气时间、VAS评分是独立可干预危险因素。”摘要：ObjectiveTo investigate incidence and modifiable risk factors of postoperative delirium (POD) in patients undergoing cardiac surgery.MethodsA prospective observational research method was conducted on 880 cardiac surgery patients admitted to the Department of Cardiovascular Surgery, at the First Affiliated Hospital of Chongqing Medical University from January 2022 to June 2023. Patients' general and clinical data were collected. POD was assessed twice daily from the second day in the ICU using the Confusion Assessment Method of Intensive Care Unit(CAM-ICU) until discharge or transfer from ICU. The patients were divided into two groups based on the presence of POD, and the incidence rate was calculated. Subsequently, a 1:1 propensity score matching (PSM) was applied between the two groups. The differences in general information and clinical characteristics between the two groups of patients before and after PSM were compared. Logistic regression analysis was used to evaluate the modifiable risk factors for POD in patients undergoing cardiac surgery after PSM.ResultsOf the 880 patients, 278 experienced POD during their stay in the ICU, with an incidence rate of 31.6%. POD occurred between the 2nd and 12th day following ICU admission, with 91.4%(254 patients) experiencing it between the 2nd and 6th day. Univariate analysis identified preoperative factors of POD including gender, age, history of hypertension, history of diabetes, and smoking history; Intraoperative factors were ASA anesthesia grade, operation duration, extracorporeal circulation time, and aortic occlusion time; Postoperative factors included ICU length of stay, mechanical ventilation duration, and VAS score, all of which were statistically significant (P<0.05). After PSM, the distribution of three immutable demographic factors including gender, age, and blood type tended to be consistent among groups (P>0.05). Further multivariate logistic regression analysis showed that surgical time, ICU stay time, mechanical ventilation time, and VAS score were independent modifiable risk factors for POD in cardiac surgery patients (P<0.05), with corresponding OR values of 1.003, 3.117, 1.385, and 1.590, respectively.ConclusionsSurgical time, ICU stay time, mechanical ventilation time, and VAS score are independent modifiable risk factors for the occurrence of POD in patients undergoing cardiac surgery. In clinical work, early intervention should be carried out based on the characteristics of the patient's condition and risk factors to further reduce the occurrence of POD.关键词：cardiac surgery;postoperative delirium;modifiable risk factors;propensity score matching
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发布时间：2024-11-07 - “在非心脏非神经外科手术领域，研究揭示了围手术期缺血性卒中的发病率、危险因素及预防措施，为降低卒中风险提供科学依据。”摘要：ObjectiveTo explore the incidence and risk factors of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgeries and its correlation with preoperative risk assessment of cerebrovascular events, so as to guide perioperative risk management.MethodsA retrospective study was conducted on 40 patients aged ≥18 years who underwent non-cardiac and non-neurosurgical surgeries and experienced perioperative ischemic stroke in the First Affiliated Hospital of Henan University of Science and Technology from January 2015 to January 2022, forming the stroke group. A control group of 160 patients without perioperative ischemic stroke was selected in a 1:4 case-control ratio, matched for gender, age, date of operation, and the surgeon. Clinical data and preoperative risk assessment of cerebrovascular events (including the single or combined application of head CT/MRI, transcranial Doppler ultrasound, carotid ultrasound, and neurological consultation) of the two groups of patients were collected and statistically analyzed. Multiple logistic regression analysis was used to identify risk factors associated with perioperative ischemic stroke.ResultsThe incidence of perioperative ischemic stroke was 0.042%. Multiple logistic analysis results showed that hypertension (OR=7.858, 95%CI 2.175-28.388, P=0.002), hyperlipidemia (OR=4.457, 95%CI 1.320-15.049, P=0.016), renal insufficiency (OR=8.277, 95%CI 1.480-46.282, P=0.016), and intraoperative hypotension (OR=3.862, 95%CI 1.211-12.317, P=0.022) were independent risk factors for perioperative ischemic stroke in non-cardiac and non-neurological surgeries; preoperative cerebrovascular risk assessment (OR=0.130, 95%CI 0.031-0.542, P=0.005) was a protective factor against it.ConclusionsThe incidence of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgery is low but has a poor prognosis. Hypertension, hyperlipidemia, renal insufficiency, and postoperative hypotension are risk factors for perioperative ischemic stroke, while preoperative cerebrovascular event risk assessment is beneficial to reducing its incidence.关键词：non-cardiac, non-neurological surgery;perioperative;ischemic stroke;risk factor;risk assessment
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发布时间：2024-11-07 - “在体外循环后脑损伤领域，研究者探究了尿酸代谢与脑损伤的关系，发现CPB过程中尿酸代谢改变可能是导致脑损伤的关键机制。”
摘要：ObjectiveTo investigate the relationship between uric acid metabolism and brain injury following cardiopulmonary bypass (CPB) in rats.MethodsHealthy male SD rats were randomly assigned to either a Sham group or a CPB group, each comprising 12 rats. The Sham group only underwent vascular puncture and did not perform CPB conversion, while the CPB group was subjected to a CPB procedure with a perfusion duration of 110 min, and the brain tissue was collected post-procedure. Microdialysate was collected 1 h before and after CPB initiation. Apoptosis in the paraventricular nucleus (PVN) was assessed using TUNEL staining, and the expression of Bax mRNA in cerebral cortex and hypothalamus was determined via real-time quantitative PCR. Apoptosis-related protein expression was analyzed by Western blotting. Differentially expressed genes (DEGs) were identified through RNA-sequencing between brain tissues of two groups, and Gene Ontology (GO) analysis was performed to identify enriched pathways among the DEGs. Protein-protein interaction (PPI) networks were constructed using String and Cytoscape softwares to identify key genes. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to analyze differential metabolites in the PVN before and after CPB, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis constructed subsequently. Uric acid levels in the hypothalamus was measured using a uric acid assay kit, and the expression of key enzymes of uric acid metabolism [xanthine reductase (XDH), adenosine deaminase (ADA)] and uric acid transporter [organic anion transporter family protein 1 (OAT1), organic anion transporter family protein 3 (OAT3), ATP-binding cassette transporter subfamily G member 2 (ABCG2), glucose transporter 9 (GLUT9)] genes in the hypothalamus was evaluated by real-time quantitative PCR.ResultsReal-time quantitative PCR revealed a significant upregulation of Bax mRNA in the cerebral cortex and hypothalamus of CPB group compared to Sham group (P<0.05). TUNEL staining indicated a significantly higher apoptosis rate of cells in PVN region in CPB group than that in Sham group (19.0%±5.0% vs. 7.6%±0.8%, P=0.01). Western blotting showed a significantly increased Bcl-2/Bax ratio in the hypothalamus of CPB group compared to Sham group (P<0.05). A total of 2829 DEGs were identified between Sham group and CPB group, with 1374 upregulated genes and 1455 downregulated genes. Uric acid metabolism-related pathways were predominantly enriched in purine nucleoside metabolism and biosynthesis, purine nucleoside monophosphate metabolism, purine nucleoside triphosphate metabolism, purine ribonucleotide metabolism and biosynthesis, purine ribonucleoside monophosphate metabolism and biosynthesis, purine ribonucleoside triphosphate metabolism and biosynthesis, and reaction to purine compounds. Eighteen differential metabolites were identified in the microdialysate, with 13 upregulated and 5 downregulated metabolites. KEGG enrichment analysis identified 7 significantly enriched metabolic pathways, among which the nicotinate and nicotinamide metabolism pathways were closely related to uric acid metabolism. Both RNA-sequencing and LC-MS/MS analysis suggested alterations in uric acid metabolism in CPB groups. Post-CPB, uric acid concentration in the hypothalamic tissue significantly increased (P<0.01), and the expression of XDH and ADA mRNA in the hypothalamus were significantly increased (P<0.05), while the expression of ABCG2, OAT1, OAT3 and GLUT9 mRNA significantly decreased (P<0.001).ConclusionUric acid metabolism in brain is altered during CPB, which may be an important mechanism for brain injury following CPB.关键词：cardiopulmonary bypass;cerebral injury;uric acid;metabolomics;transcriptomics- 5
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发布时间：2024-11-07
Special Issue on Mechanisms and Protective Strategies of Perioperative Organ Injury Ⅱ
- “最新研究显示，术前HBV-DNA阴性的HBV相关性肝内胆管细胞癌患者预后优于非HBV相关性患者。”
摘要：ObjectiveTo investigate the prognosis of patients with hepatitis B virus (HBV)‑related intrahepatic cholangiocarcinoma (ICC) whose HBV DNA was negative before surgical.MethodsA retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017. All patients were divided into HBV-related ICC (HBV-ICC) group (n=62) and non-HBV-related ICC (Con-ICC) group (n=35). HBV-ICC group included 34 patients with HBV core antigen positive (HBcAb+) and HBV surface antigen positive (HBsAg+), and 28 patients with HBcAb positive and HBsAg negative. Kaplan-Meier analysis was used to plot survival curves and compare the overall survival (OS) and postoperative recurrence-free survival (RFS) among patients in Con-ICC, ICC patients with HBsAg+/HBcAb+, and ICC patients with HBsAg-/HBcAb+. Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS, RFS and early postoperative recurrence among gender, age, pathogenic factor, liver cirrhosis, Child-Pugh grade, carbohydrate antigen 19-9 (CA199), alpha-fetoprotein (AFP), glutamine transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), American Joint Committee on Cancer (AJCC) stage, tumor size, tumor number, tumor differentiation, microvascular invasion, lymph node metastasis, hepatectomy procedure, cholecystectomy, and follow-up treatment.ResultsOf the 97 patients, the median age was 56 years, and 79 (81.4%) of them were male. The median follow-up time was 92.2 months. Eighty-eight (90.7%) patients presented with tumor recurrence and 73 (75.3%) died. In multivariate analyses, HBV-ICC and CA199>37 kU/L were independent predictors of OS (HR=0.45, 95%CI 0.26-0.77, P=0.003; HR=2.10, 95%CI 1.24-3.57, P=0.006), RFS (HR=0.43, 95%CI 0.27-0.68, P<0.001; HR=1.78, 95%CI 1.12-2.81, P=0.014), and postoperative early recurrence (HR=0.42, 95%CI 0.26-0.70, P=0.001; HR=2.02, 95%CI 1.20-3.39, P=0.008). AJCC stage Ⅲ was an independent risk factor for postoperative RFS (HR=1.81, 95%CI 1.04-3.14, P=0.037). Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence (HR=1.73, 95%CI 1.07-2.77, P=0.024; HR=1.90, 95%CI 1.12-3.24, P=0.017). There was no statistically significant difference in OS, RFS, and early recurrence between HBV-ICC patients with HBsAg-/HBcAb+ and Con-ICC patients (P<0.05), whereas HBsAg+/HBcAb+ was a significant factor affecting postoperative OS (HR=0.32, 95%CI 0.16-0.62, P=0.001), RFS (HR=0.32, 95%CI 0.18-0.55, P<0.001), and early recurrence (HR=0.29, 95%CI 0.15-0.54, P<0.001) in ICC patients.ConclusionsThe prognosis of HBV-ICC patients with preoperative HBV-DNA- is better than that of Con-ICC patients. The prognosis of HBV-ICC patients with HBcAb+/HBsAg- is worse than that of HBV-ICC patients with HBcAb+/HBsAg+, but similar to Con-ICC patients. Therefore, the postoperative stratified management of HBV-ICC patients should be emphasized.关键词：intrahepatic cholangiocarcinoma;hepatitis B virus;early recurrence;prognosis- 12
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发布时间：2024-11-07 - “郑州大学第三附属医院研究揭示，脑瘫共患癫痫患儿在胎龄、窒息史、HIE史、癫痫首次发作年龄、MRICS分类及GMFCS分级方面存在差异。”摘要：ObjectiveTo explore the clinical characteristics of pediatric patients with cerebral palsy (CP) who also have comorbid epilepsy.MethodsA retrospective analysis was conducted on the clinical data of 155 pediatric patients with CP and comorbid epilepsy admitted to the Third Affiliated Hospital of Zhengzhou University from January 2019 to December 2022. Patients were divided into 4 groups based on CP subtype: spastic diplegia group (n=29), spastic hemiplegia group (n=33), spastic quadriplegia group (n=73), and non-spastic group (n=20). Differences in sex, season of birth, birth weight, gestational age, and the relationship between gestational age and weight were compared among the groups. Additionally, the relationships between perinatal risk factors, MRI classification system (MRICS), gross motor function classification system (GMFCS), and the age of the first onset of epilepsy with respect to CP subtype were analyzed.ResultsAmong the 155 patients, 101 were male and 54 were female. A lower proportion of patients with spastic hemiplegia was observed with a gestational age of 28-31+6 weeks compared with those with spastic diplegia and spastic quadriplegia (P=0.009). The proportion of patients with a history of asphyxia in spastic hemiplegia group was significantly lower than that in the other 3 groups, and the proportion of patients with hypoxic-ischemic encephalopathy (HIE) in spastic hemiplegia group was significantly lower than in that both spastic quadriplegia group and non-spastic group (P<0.05). The proportion of patients in spastic quadriplegia group who had their first seizure at an age of <1 year was significantly higher than that in spastic diplegic group (P=0.041). The spastic diplegia group exhibited a higher percentage of white matter damage compared with the other 3 groups, and had a lower percentage of gray matter damage compared with both spastic hemiplegic group and non-spastic group(P=0.001). The proportion of patients with GMFCS levels Ⅳ－Ⅴ in spastic quadriplegia group was higher than those in the other 3 groups (P<0.001), and the proportion of patients with levels Ⅰ－Ⅲ in spastic hemiplegia group was significantly higher than those in spastic quadriplegia group and non-spastic group (P<0.001).ConclusionSignificant differences were observed among pediatric patients with different subtypes of CP and comorbid epilepsy in factors such as gestational age, history of asphyxia, HIE history, age of first seizure, MRICS classification and GMFCS levels.关键词：cerebral palsy;epilepsy;gross motor function classification system;clinical classification;electroencephalogram
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发布时间：2024-11-07 - “北京大学人民医院重症医学科研究揭示脑出血患者术后延迟脱机的危险因素，并构建预测模型，有助于早期识别高风险患者，优化通气策略。”
摘要：ObjectiveTo identify the risk factors for postoperative delayed weaning in patients with intracerebral hemorrhage and to establish a predictive model.MethodsA retrospective study was conducted on 207 patients who underwent surgery for intracerebral hemorrhage at the intensive care unit (ICU) of Peking University People's Hospital from October 2014 to October 2021. Utilizing the 2007 European Respiratory Society consensus criteria, patients were divided into delayed weaning group (n=66) and non-delayed weaning group (n=141). The demographic and operation-related conditions of the two groups were compared. Multiple logistic regression analysis was employed to identify the risk factors for delayed weaning, and a risk assessment nomogram was constructed and validated.ResultsCompared with the non-delayed weaning group, the delayed weaning group exhibited a significantly higher proportion of comorbid cardiovascular and cerebrovascular diseases, a lower Glasgow coma scale (GCS) score on admission, a greater incidence of preoperative brain herniation, a higher proportion of patients undergoing emergency surgeries and decompression craniotomies, and higher postoperative APACHE Ⅱ score, GCS score, incidence of atelectasis, weaning failure rate and mortality rate, and longer ICU stay and hospital stay (P<0.05). Multiple logistic regression analysis indicated that emergency surgery, low postoperative oxygenation index, low postoperative score of highest GCS before weaning, and incidence of atelectasis were independent risk factors for postoperative delayed weaning (P<0.05). A nomogram predictive model was established using these four predictors, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.855(95%CI 0.804-0.907), and the Hosmer-Lemeshow test showed good model fit (P=0.659).ConclusionsPostoperative delayed weaning is associated with extended durations of mechanical ventilation, ICU stay, and hospital stay, as well as an increased risk of weaning failure and in-hospital mortality rate. The nomogram model provides valuable insights for the early recognition of patients at high risk for postoperative delayed weaning, thereby facilitating timely adjustment in ventilation management strategies.关键词：intracerebral hemorrhage;prolong ventilation;risk factors;predictive model- 14
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发布时间：2024-11-07 - “在神经内科领域，开封市中心医院神经内科通过分析两例茎突-颈动脉综合征患者，揭示了该病的临床特点，为诊治提供了新思路。”
摘要：ObjectiveTo summarize the clinical characteristics of 2 cases of styloid-carotid syndrome(SCS) and review the literature to enhance understanding of the disease.MethodsA retrospective analysis was conducted on the clinical manifestations, auxiliary examinations, and diagnosis and treatment of 2 patients with SCS admitted to the Neurology Department of Kaifeng Central Hospital. Additionally, relevant literature was searched through domestic and foreign databases such as PubMed, WOS, Embase, CNKI and VIP. The clinical characteristics of SCS were summarized based on the literature results.ResultsThe 2 cases were diagnosed as transient cerebral ischemia (TIA) combined with SCS through head and neck CT angiography (CTA) and styloid process CT. Apart from the 2 cases treated in our hospital, a total of 11 cases of SCS have been reported in Chinese and English literature up to October 2023. Among the 13 cases, 11 cases (84.6%) started with episodic TIA symptoms, and 11 cases (84.6%) had obvious inducing factors related to specific head position changes. Common clinical manifestations included unilateral limb weakness with or without sensory disturbance (10 cases, 76.9%), slurred speech (7 cases, 53.8%), unilateral limb sensation disorder (4 cases, 30.7%), syncope (3 cases, 23.1%) and amaurosis (2 cases, 15.4%). All 13 cases underwent 64-row head and neck CTA examination, and 6 cases (46.2%) dynamically observed the changes in blood flow velocity through examinations such as transcranial Doppler ultrasound (TCD), cervical vascular ultrasound, and digital subtraction angiography (DSA). All patients were followed up for more than 3 months; and 10 cases (76.9%) achieved clinical cure after treatment, of which 8 cases underwent styloid process shortening surgery; 3 cases (23.1%) achieved clinical symptom improvement after treatment.ConclusionsFor patients with recurrent TIA and/or cerebral infarction, it is necessary to identify whether there are inducing factors related to specific body position changes. For patients highly suspected of SCS, routine examinations such as styloid process CT and 64-row head and neck CTA should be performed, and if necessary, whole brain DSA, dynamic TCD and/or carotid ultrasound should be conducted to guide the diagnosis and treatment. When non-surgical treatment is ineffective, radical styloid process truncation can be considered as a treatment option.关键词：styloid-carotid syndrome;elongated styloid process;stroke;dynamic ultrasonography;CT angiography- 10
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发布时间：2024-11-07
Clinical Research
- “最新研究发现，LETM1蛋白能促进骨肉瘤细胞增殖、迁移和成瘤，抑制细胞凋亡和成骨分化。”
摘要：ObjectiveTo investigate the effect and mechanism of leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) on proliferation, migration, apoptosis, osteogenic differentiation, and tumorigenesis in vivo of human osteosarcoma MG63 and 143B cells.MethodsThe osteosarcoma MG63 and 143B cells were divided into blank control group (without adenovirus infection), negative control group (sh-NC group, infected with RNAi negative control virus), and LETM1 knockdown group (sh-LETM1 group, infected with sh-LETM1 adenovirus). Western blotting was performed to detect LETM1 expression in normal human osteoblasts hFOB1.19 and osteosarcoma cells, and to verify the knockdown effect of adenovirus; cell clone formation assays and CCK-8 method were used to detect the proliferation of MG63 and 143B cells; wound-healing assay and Transwell assay were used to test cell migration; DAPI staining and Annexin V-APC/7-AAD flow cytometry double staining were used to detect the apoptosis of MG63 and 143B cells; alkaline phosphatase (ALP) staining and Alizarin Red S staining were used to evaluate early and late osteogenic differentiation of MG63 and 143B cells. Ten nude mice were divided into sh-NC group (n=5, injected subcutaneously into nude mice with 143B cells infected with RNAi negative control virus) and sh-LETM1 group (n=5, injected subcutaneously into nude mice with 143B cells infected with sh-LETM1 adenovirus), and nude mice subcutaneous tumorformation assay was used to examine the in vivo tumor-forming ability of 143B cells in each group.ResultsWestern blotting showed that the expression of LETM1 protein in osteosarcoma MG63 and 143B cells was significantly higher than that in human normal osteoblasts hFOB1.19 (P<0.05), and that the expression of LETM1 protein was markedly reduced after injection with sh-LETM1 adenovirus in MG63 and 143B cells. The results of cell clone formation assay and CCK-8 assay indicated that in MG63 and 143B osteosarcoma cells, the clone formation ability and proliferation ability were significantly reduced in sh-LETM1 group compared with sh-NC group and blank control group (P<0.01). The results of wound-healing assay and Transwell assay demonstrated that in MG63 and 143B osteosarcoma cells, the cell migration rate in sh-LETM1 group was significantly lower than that in sh-NC group and blank control group (P<0.01). DAPI staining and flow cytometry results revealed that the apoptosis rate in sh-LETM1 group was significantly higher than those in MG63 and 143B osteosarcoma cells in sh-NC group (P<0.01). Alkaline phosphatase staining and Alizarin red S staining experiments showed more stained areas and calcium salt nodules in MG63 and 143B osteosarcoma cells in sh-LETM1 group than those in sh-NC group and blank control group. The results of the subcutaneous tumor formation assay in nude mice indicated that subcutaneous tumor formation ability was reduced in 143B sh-LETM1 group compared with 143B sh-NC group.ConclusionLETM1 promotes the proliferation, migration and in vivo tumor formation of MG63 and 143B osteosarcoma cells and the mechanism may be related to the inhibition of apoptosis and osteogenic differentiation.关键词：osteosarcoma cell;leucine zipper-EF-hand-containing transmembrane protein 1;cell proliferation;cell migration;apoptosis;cell differentiation- 5
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发布时间：2024-11-07 - “最新研究发现，毛蕊花糖苷通过抑制MAPK、Rap1和PI3K/Akt信号通路发挥抗急性肺损伤作用，为治疗急性肺损伤提供新思路。”
摘要：ObjectiveTo investigate the molecular mechanism of verbascoside against acute lung injury (ALI) by network pharmacology and molecular docking methods, and to validate the findings experimentally.MethodsThe 2D structure of verbascoside was obtained from the Pubchem database. Active ingredient targets of verbascoside were acquired from Pharmmapper database and Swiss Target Prediction database. Active component targets of ALI were acquired from datebase such as Gene Cards, OMIM, and DisGeNET. Common targets between verbascoside and ALI were determined by overlapping these sets. PPI network for potential targets was constructed using String database and Cytoscape software. The intersection targets were imported into the DAVID database for enrichment analysis of GO biological processes, KEGG signaling pathway and the pathway target genes. Molecular docking between verbascoside and core targets was performed using Autodock vina software. The mRNA expression level of core genes was validated using real-time quantitative PCR (RT-qPCR), and the expression of related proteins was detected using Western blotting.ResultsA total of 150 target genes of verbascoside against ALI were screened, and the key targets of verbascoside against ALI mainly involve pathways such as Rap1 signaling pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Verbascoside docked well with the core target molecules. RT-qPCR results showed that, compared with the control group, the mRNA expression levels of HSP90AA1, ALB, TP53, TNF, INS, and HRAS were significantly decreased in cells after the effect of verbascoside (P<0.05); Western blotting indicated that, compared with the model group, verbascoside treatment significantly reduced the expression of p-Akt, p-p38, and p-ERK proteins (P<0.05).ConclusionVerbascoside could inhibit MAPK, Rap1 and PI3K/Akt signaling pathways to exert its anti-ALI effects.关键词：acteoside;acute lung injury;network pharmacology;molecular docking;molecular mechanism- 2
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发布时间：2024-11-07 - “最新研究发现，环状RNA circ_100284通过miR-217/MAPK1通路影响食管癌侵袭和化疗敏感性，为食管癌治疗提供新思路。”
摘要：ObjectiveTo explore the effects of circ_100284 in affecting the invasion of esophageal squamous cell carcinoma (ESCC) cells and their sensitivity to 5-fluorouracil (5-FU) chemotherapy via regulating miR-217/mitogen-activated protein kinase 1 (MAPK1) acting as a competing endogenous RNA (ceRNA).MethodsThe bioinformatics approach was used to analyze the differentially expressed circRNAs in ESCC. qRT-PCR was used to detect the expression of circ_100284 in ESCC tissues and cells. The 5-FU-resistant KYSE450 cell line (KYSE45-R) was established by increasing concentrations of 5-FU. The IC50 of 5-FU in KYSE450 and KYSE450-R cells was determined through MTT assay. qRT-PCR was used to detect the expression of circ_100284, miR-217, and MAPK1 mRNA in KYSE450 and KYSE450-R cells, while Western blotting detecting the protein expression of MAPK1. In the experiments with KYSE450-R cells, we set up the following groups: (1) blank group (without treatment), si-NC group (transfected with si-NC), si-circ_100284 group (transfected with si-circ_100284), pc-Control group (transfected with pc-Control), pc-circ_100284 group (transfected with pc-circ_100284), pc-circ_100284+mimic NC group (transfected with pc-circ_100284 and mimic NC), and pc-circ_100284+miR-217 mimic group (transfected with pc-circ_100284 and miR-217 mimic). These groups were subjected to MTT assay to detect cell viability, Transwell assay to detect cell invasion, and flow cytometry to detect cell apoptosis. (2) Blank group (without treatment), si-NC group (transfected with si-MAPK1 negative control), si-MAPK1 group (transfected with si-MAPK1), si-MAPK1+inhibitor NC group (transfected with si-MAPK1 and inhibitor NC), and si-MAPK1+miR-217 inhibitor group (transfected with si-MAPK1 and miR-217 inhibitor). We detected the mRNA and protein expression of MAPK1 using qRT-PCR and Western blotting. We evaluated cell viability using MTT assay, invasion with Transwell assay, and apoptosis by flow cytometry. circ_100284-WT or circ_100284-MUT reporter plasmids, as well as MAPK1-WT or MAPK1-MUT reporter plasmids, were co-transfected with miR-NC or miR-217 mimic into KYSE450-R cells for 48 h, and dual luciferase reporter assay was used to measure luciferase activity.ResultsThe bioinformatics analysis revealed significant upregulation of circ_100284 in ESCC. Compared with adjacent normal tissues, the expression of circ_100284 in ESCC tissues is enhanced (P<0.05); compared with the HECC cells, the TE-11, ECA109 and KYSE450 ESCC cell lines showed enhanced expression of circ_100284 (P<0.05). Compared with the KYSE450 cells, KYSE450-R cells demonstrated increased IC50 with enhanced expression of circ_100284 and MAPK1 but suppressed expression of miR-217 (P<0.05). Compared with the si-NC group, the si-circ_100284 group demonstrated inhibited invasion and proliferation of cells with increased apoptosis (P<0.05). Compared with pc-Control group, the invasion and proliferation of cells in the pc-circ_100284 group are increased, and cell apoptosis is decreased (P<0.05). Over-expression of miR-217 reversed the malignant biological behavior of ESCC cells induced by pc-circ_100284 (P<0.05). Compared with si-NC group, in the si-MAPK1 group, we observed decreased cell invasion and proliferation, and increased apoptosis (P<0.05), but miR-217 inhibitor reversed the effect of si-MAPK1 on the biological behavior of ESCC cells (P<0.05). The targeting relationship of circ_100284 and miR-217, miR-217 and MAPK1 is confirmed.Conclusioncirc_100284 promotes ESCC cell invasion by regulating miR-217/MAPK1, inhibits the chemosensitivity of ESCC cells to 5-FU, and acts as a tumor-promoting factor in ESCC.关键词：circ_100284;miR-217;mitogen-activated protein kinase 1;esophageal cancer;chemosensitivity- 9
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发布时间：2024-11-07
Basic Research
- “血友病A发病机制研究取得进展，非编码RNA异常表达参与凝血因子Ⅷ调控，为理解血友病发病机制提供新方向。”摘要：Hemophilia, which includes different types such as hemophilia A and hemophilia B, is a hemorrhagic disorder with inherited blood clotting abnormalities. The main clinical manifestations are spontaneous bleeding of joints, muscles and deep tissues or repeated bleeding after trauma. It often starts at an early age and affects the whole life. The treatment of hemophilia patients is still dominated by alternative therapy, supplementing the corresponding clotting factors. In addition, non-factor drug therapy is adopted such as bispecific monoclonal antibodies and gene therapy. In recent years, the research on the pathogenesis of hemophilia A has made great progress, which is no longer limited to the mutation of the coding sequence of coagulation factor gene as the only cause of hemophilia. Many studies have found that abnormal expression of non-coding RNA (ncRNA) is involved in the regulation of coagulation factor Ⅷ (FⅧ) mRNA and protein, which not only explains why patients with normal FⅧ genotypes still present with hemophilia A, but also provides new directions for understanding the pathogenesis of other types of hemophilia. This paper reviews the research progress on the regulatory mechanism of ncRNA in hemophilia A.关键词：hemophilia;coagulation factors;miRNA;gene regulation
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发布时间：2024-11-07 -
Research progress on autophagy dysfunction of vascular cells in the pathogenesis of atherosclerosis AI导读
“最新研究发现，自噬功能失调在动脉粥样硬化形成与发展中起关键作用，为防治动脉粥样硬化提供新思路。”
摘要：Autophagy is an essential cellular metabolic process that involves clearance of damaged organelles and protein aggregates in cells through lysosomes, providing energy for cells, and maintaining cellular tissue homeostasis. Impaired autophagy is closely related to the pathophysiology of a variety of diseases. In the pathogenesis of atherosclerosis (AS), the dysfunction of autophagy of vascular cells plays a crucial role in the formation and progression of AS. The functional status, survival or death of vascular cells, including endothelial cells, vascular smooth muscle cells and macrophages, can influence the formation and stability of plaques, thereby affecting the progression of AS. This review summarizes the relationship between autophagy and AS, and details the impact of autophagy dysfunction on vascular cell function in the process of AS, as well as the role of mitophagy and inflammasome in the development of AS, aiming to provide novel insights for the prevention and treatment of AS.关键词：atherosclerosis;autophagy;cardiovascular diseases- 11
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发布时间：2024-11-07 - “在非酒精性脂肪性肝病治疗领域，运动疗法显示出良好应用前景，但患者依从性低和药物靶点寻找仍面临挑战。”摘要：Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by excess fat accumulation within liver cells. The main causes include obesity, diabetes, and hyperlipidemia. In recent years, NAFLD and other metabolic diseases have become global public health issues. Although some progress has been made in the drug treatment of NAFLD, the efficacy is limited and there are many adverse effects. As a treatment method with high safety and few adverse effects, exercise therapy has good application prospects in the treatment of NAFLD and other metabolic diseases. However, challenges remain in overcoming patients' low exercise compliance and in finding safe and effective exercise therapy drug targets. This article explores the mechanisms and application prospects of exercise therapy in the treatment of NAFLD and other metabolic diseases, summarizes the energy consumption, metabolic pathways, and inter-organ communication induced by exercise, aiming to provide useful references for clinical practitioners.关键词：non-alcoholic fatty liver disease;exercise;therapeutics
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发布时间：2024-11-07 - “肿瘤新抗原免疫治疗临床应用研究取得进展，为肿瘤诊断和治疗提供新思路。”摘要：Tumor neoantigens are antigens encoded by tumor-specific mutated genes, characterized by high specificity, significant exogenous origin, mutation randomness, clonal distribution and correlation with gene mutation. Because these antigens are not negatively screened by the thymus and recognized by T cells as "heterogeneous". They are less easily affected by the immune tolerance mechanism and exhibit strong immunogenicity, making them excellent targets for immunotherapy. Tumor neoantigens can be used to develop therapeutic vaccines, induce and cultivate T cells with stronger targeting capabilities, and are promising for predicting tumor survival prognosis and responses to immune checkpoint blockade therapies. This review summarizes the recent advances in clinical application of tumor neoantigen-based immunotherapy, and prospects for future research directions.关键词：neoantigen;tumor;immunotherapy;clinical trial
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发布时间：2024-11-07
Review
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