最新刊期
卷 49 ， 期 8 ， 2024
- “最新研究揭示了三阴性乳腺癌新辅助化疗后病理完全缓解的影响因素，并构建了预测模型，为临床治疗提供新指导。”
摘要：ObjectiveTo analyze the factors affecting pathological complete response (pCR) of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy, and construct a nomogram to forecast the pCR rate.MethodsThe clinical and pathological data of 348 TNBC patients who received neoadjuvant chemotherapy in the Air Force Medical University-Affiliated Xijing Hospital from May 2018 to May 2021 were collected and set as modeling set. The clinical and pathological data of 69 TNBC patients who received neoadjuvant chemotherapy in the Xi'an No.3 Hospital from May 2018 to May 2021 were collected and set as validation set. The clinical and pathological characteristics were compared between the modeling set and the validation set. In the modeling set, the independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy were screened by LASSO regression model analysis, and the nomogram model was constructed. Internal validation of the model was conducted using Bootstrap method, and the discrimination of the model was assessed by receiver operating characteristic (ROC) curve. The accuracy of the model was evaluated by the calibration curve and the clinical benefits and application value of the model were evaluated by clinical decision curve analysis (DCA).ResultsThere were significant differences in surgical method and T stage between the patients in modeling set and validation set (P<0.05). The results of analysis of LASSO regression model showed that T stage, N stage, the use of platinum drugs and clinical efficacy evaluation were independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy (P<0.05). Based on the above variables, the nomogram models were constructed. In modeling set, area under curve (AUC) was 0.811 (95%CI 0.763-0.859); in validation set, AUC was 0.801 (95%CI 0.727-0.928). The Bootstrap method showed the C-index for internal validation was 0.79, indicating the model has good discrimination in both the modeling and validation sets. The calibration curve analysis showed that model predicted pCR rates had a good consistency with the actual observed values, and the DCA showed that model can bring clinical benefit.ConclusionThe nomogram can accurately predict the pCR rates of TNBC patients after neoadjuvant chemotherapy and provide scientific basis for clinical diagnosis and treatment.关键词：triple-negative breast cancer;neoadjuvant chemotherapy;pathological complete response;nomogram- 10
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发布时间：2024-09-12 - “在非小细胞肺癌治疗领域，郑州大学第一附属医院的专家团队通过回顾性研究，揭示了免疫检查点抑制剂相关性肺炎的潜在危险因素，为早期识别高危患者提供了科学依据。”
摘要：ObjectiveTo investigate the potential risk factors for immune checkpoint-related pneumonia (CIP) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), to identify high-risk patients with CIP at an early stage.MethodsA total of 728 NSCLC patients treated with ICIs at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were retrospectively selected, including 47 cases with CIP (CIP group), and 141 matched NSCLC patients without CIP (control group). Clinical data, laboratory tests, and CT images before the first immunotherapy were collected for all patients in two groups. The FACT medical imaging software was utilized for quantitative emphysema assessment in patients' CT scans. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with CIP. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of these factors for CIP occurrence in NSCLC patients.ResultsAmong the 47 CIP patients, 40(85.1%) were male, with 25(53.0%) aged between 41 and 65 years. Grade 3 pneumonia according to the Common Terminology Criteria for Adverse Events (CTCAE) was found in 28(59.6%) cases, characterized by a predominant reticular radiographic pattern. Multivariate logistic regression analysis showed that a low albumin level (OR=0.889, 95%CI 0.808-0.979, P=0.017), targeted therapy (OR=9.204, 95%CI 1.678-50.486, P=0.011), anti-angiogenic therapy (OR=0.056, 95%CI 0.020-0.161, P<0.001), and a high percentage of low attenuation area (LAA%) (OR=1.227, 95%CI 1.053-1.430, P=0.009) were significant factors influencing CIP occurrence. The combined predictive model using these four factors showed an area under the ROC curve of 0.888 (95%CI 0.838-0.939), with a sensitivity of 0.894 and a specificity of 0.801 for predicting CIP in NSCLC patients.ConclusionsLow serum albumin, first-line targeted therapy, and high LAA% are identified as risk factors for CIP occurrence, while anti-angiogenic therapy is a protective factor. The predictive model based on these four variables effectively predicts the risk of CIP in NSCLC patients.关键词：non-small cell lung cancer;checkpoint inhibitor-associated pneumonia;risk factors;emphysema- 13
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发布时间：2024-09-12 - “在婴儿癫痫性痉挛综合征治疗领域，成都市妇女儿童中心医院的专家团队通过回顾性分析，建立了ACTH疗效预测模型，为提高治疗效果提供新思路。”
摘要：ObjectiveTo explore the influence factors and predictors of treatment response after adrenocorticotropic hormone (ACTH) in infantile epileptic spasms syndrome(IESS).MethodsA retrospective analysis was conducted on 80 cases of IESS infants(50 males and 30 females) who were diagnosed and treated with ACTH in Chengdu Women's and Children's Central Hospital from January 2016 to December 2020. Patients were divided into effective group (n=39) and ineffective group (n=41) based on their response of ACTH treatment after 28 days, and their clinical data including the patients' basic information, etiology, treatment programmer, per- and post-treatment Kramer scores of electroencephalogram (EEG) hypsarrhythmia severity and so on, were collected to compare and analyze between the two groups. A modified Poisson regression model was constructed to discover predictors of outcome, and the receiver operating characteristic (ROC) curves were used to assess the prognosis evaluation of the positive predictive value.ResultsThe ages at seizure onset ranged from one month and seven days to one year and nine months. Seizure types included simple epileptic spasms in 66 cases and combined with other types(focal and secondarily generalized seizures) in 14 cases. Thirty-two cases had been given anti-seizure medications (ASMs) before ACTH treatment. The median Kramer scores per-treatment and at 14 days post-treatment were 10.0 (8.3, 12.0) and 6.0 (4.0, 7.0), respectively. After ACTH treatment, 39(48.8%) cases were effective. Compared with the effective group, the ineffective group had significantly higher proportion of abnormal perinatal conditions, unknown aetiology with normal development, ASMs given before ACTH treatment, the dosages of ACTH greater than 2 U/(kg·d), combinations of two or more ASMs, poor control, and still seizure attack after ACTH treatment of 14 days(P<0.05). Additionally, the Kramer scores after ACTH treatment of 14 days in the ineffective group were also significantly higher (P<0.05). The modified Poisson regression model showed that there were significant statistic differences between the two groups on ASMs given before ACTH treatment (RR=0.546, 95%CI 0.357-0.833, P=0.005) and Kramer scores of hypsarrhythmia severity (RR=0.701, 95%CI 0.620-0.792, P<0.001),while there were no significant differences between the two groups in term of ages, gender, perinatal conditions, etiologies, seizure types, Kramer scores before treatment, time lag between onset and treatment, duration of ACTH treatment, kinds of ASMs combination. ROC curve analysis showed that only Kramer scores at 14 days after ACTH treatment could predict the treatment response with sensitivity and specificity of 92.7% and 84.6%, respectively, with Youden index of 0.773. The area under the ROC curve was 0.930 (95%CI 0.873-0.987, P<0.001) and the cut-point of the score was 6, indicating that the higher the Kramer scores at 14 days after ACTH treatment, the worse the treatment response. The treatment response rate would reduce by about 30.0% if the Kramer score increased by one point.ConclusionASMs given before ACTH treatment may influence the treatment response. Kramer scores greater than 6 at day 14 after ACTH treatment may be used as a predictor of treatment response after ACTH in IESS patients.关键词：Infantile epileptic spasms syndrome;epileptic spasms;adrenocorticotropic hormone;electroencephalogram;treatment- 14
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发布时间：2024-09-12 - “在儿童磁共振成像(MRI)检查前，浙江大学医学院附属儿童医院的研究人员发现，联合使用咪达唑仑和右美托咪定进行镇静，可有效缩短患儿入睡和苏醒时间，且安全无副作用。”
摘要：ObjectiveTo determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image (MRI).MethodsThis is a prospective modified sequential study. Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023, aged 1 month to 6 years old, with a weight of 6.0-23.5 kg, were enrolled in this study. All children received 0.5 mg/kg oral midazolam, followed by intranasal dexmedetomidine. The initial dose of dexmedetomidine was 0.5 μg/kg, and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg. Probit analysis was used for calculating the half effective dose (ED50), 95% effective dose (ED95) and the corresponding 95% confidence interval (CI) of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI. The sedation onset time, wake-up time, vital signs and adverse reactions were recorded.ResultsAmong all the children,the sedation onset time of successful sedation children was (31.21±7.47) min, and the wake-up time was (81.21±26.04) min. The ED50 for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg, with a 95%CI of 0.302-0.461 μg/kg; the ED95 was 0.549 μg/kg, with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference (P<0.05) in heart rate and diastolic blood pressure after sedation compared to the baseline before medication. Two cases of restlessness during the awakening period were observed, but no other adverse reactions occurred.ConclusionsThe sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive, easy to implement, safe, and effective. It can be widely used in pediatric MRI.关键词：dexmedetomidine;midazolam;sedation;sequential method;magnetic resonance image- 14
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发布时间：2024-09-12 - “最新研究显示，中心静脉血氧饱和度(ScvO2)在预测老年患者机器人辅助肾部分切除术后急性肾损伤(AKI)方面具有重要价值。”
摘要：ObjectiveTo investigate the predictive value of central venous oxygen saturation (ScvO2) in elderly patients with acute kidney injury (AKI) after robot-assisted partial nephrectomy (RAPN).MethodsSeventy-eight elderly patients who underwent RAPN in the Department of Urology, the Third Medical Center of Chinese PLA General Hospital from February to September 2022 were selected. AKI was diagnosed according to the International Nephropathy Improving Global Prognosis Criteria, and the patients were divided into AKI group (n=22) and non-AKI group (n=56) according to whether AKI occurred after surgery. Blood gas analysis of venous blood was taken after central venous puncture (T0), 5 min after renal artery occlusion (T1), 5 min after renal artery opening (T2), and after surgery (T3). Hemoglobin (Hb), arterial blood lactic acid (Lac), arterial oxygen partial pressure (PaO2), ScvO2 were recorded respectively. Oxygen uptake rate (O2ER) were calculated. Multivariate logistic regression analysis was used to analyze the risk factors for postoperative AKI. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of ScvO2 for AKI in elderly patients after RAPN.ResultsCompared with non-AKI group, fasting plasma glucose (FPG) level in AKI group significantly increased at T1-T2 (P<0.05). Compared with T0, FPG level in two groups obviously increased at T1-T3 (P<0.01). Compared with T1, the FPG level in T3 significantly increased in non-AKI group (P<0.01). Compared with non-AKI group, ScvO2 in AKI group significantly increased at T1-T2 (P<0.01), Lac level at T2 significantly increased (P<0.05). There was no significant difference in O2ER between the two groups at each time point (P>0.05). Compared with T0, O2ER in T1-T3 significantly decreased (P<0.01), and ScvO2 in both groups significantly increased (P<0.01). Compared with T1, ScvO2 in non-AKI group significantly increased at T2-T3 (P<0.05 or P<0.01). Compared with T2, ScvO2 in non-AKI group significantly increased in T3 (P<0.05). Multiple-factor analysis showed that T1 ScvO2 (OR=1.127, 95%CI 1.006-1.263, P=0.039) was an independent risk factor for AKI after RAPN. ROC curve analysis showed that T1 ScvO2 had a sensitivity of 77.3%, specificity of 71.4%, truncation value of 81%, and area under the curve (AUC) of 0.761 in predicting AKI after RAPN.ConclusionScvO2 has certain predictive value for the occurrence of short-term AKI after RAPN.关键词：central venous oxygen saturation;robot;partial nephrectomy;acute kidney injury;predictive value- 24
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发布时间：2024-09-12 - “最新研究揭示了年轻肺腺癌晚期患者的预后影响因素，建立了预测模型，为治疗提供新方向。”
摘要：ObjectiveBased on data from the US SEER database, this study investigates the incidence, epidemiological characteristics, treatment modalities, prognosis assessment, and risk stratification of advanced-stage lung adenocarcinoma in young patients.MethodsSEER*Stat software was used to collect the incidence rates of lung adenocarcinoma among people under 50 in the US from 2000 to 2020, with annual percentage changes (APCs) calculated using Joinpoint software. Clinical data of 4490 advanced-stage lung adenocarcinoma patients under 50 years old from the SEER database (2010-2018) were retrospectively collected and analyzed. Kaplan-Meier method was used to calculate overall survival, log-rank test to estimate survival rates, and Cox proportional hazards regression model to conduct univariate and multivariate prognostic analyses, and a nomogram model was established to predict the survival of young advanced lung adenocarcinoma patients. The predictive performance of the nomogram was evaluated using ROC curves and calibration curves. X-Tile software was used for risk stratification of the prognosis of young advanced lung adenocarcinoma patients.ResultsFrom 2000 to 2020, the incidence rates of young lung adenocarcinoma in men and women in the US decreased from 2.1/100 000 and 2.2/100 000 to 1.1/100 000 and 1.5/100 000 respectively, with APCs of -2.16 and -1.39 (P<0.05). Compared to patients aged 40 to <50 years, patients under 40 were more likely to develop bone metastasis, liver metastasis, and lung metastasis, had a higher probability of receiving chemotherapy, tumors were more likely to occur in the lower or middle lobes of the lung, but had a lower probability of receiving radiotherapy, with statistically significant differences (P<0.05). Cox regression analysis showed that gender, age, race, N stage, M stage, subsite, liver metastasis, and bone metastasis were prognostic factors for young advanced lung adenocarcinoma patients (P<0.05); male patients had worse prognosis than female patients (HR=1.17, 95%CI 1.09-1.25); African American patients had worse prognosis than Caucasian patients (HR=1.12, 95%CI 1.02-1.23), other races had better prognosis than Caucasian patients (HR=0.83, 95%CI 0.77-0.97); patients aged 40 to <50 had worse prognosis than those under 40 (HR=1.34, 95%CI 1.21-1.48); patients with bone metastasis (HR=1.29, 95%CI 1.19-1.40) and liver metastasis (HR=1.40, 95%CI 1.28-1.54) had worse prognosis, with statistically significant differences (P<0.05). Based on the above prognostic factors, a nomogram model was established to predict 1-year, 3-year, and 5-year survival with areas under the curve (AUC) of 0.717, 0.692, and 0.699 respectively, and the calibration curve was close to the 45° diagonal. According to the risk scores, patients were divided into low-risk group [1017 cases (22.7%)], medium-risk group [2871 cases (63.9%)], and high-risk group [602 cases (13.4%)]. The difference is statistically significant comparing the survival rates among three groups (P<0.0001).ConclusionGender, age, race, N stage, M stage, subsite, liver metastasis, and bone metastasis are prognostic factors for young advanced lung adenocarcinoma patients, and the nomogram model established based on these factors has high predictive performance.关键词：young;adenocarcinoma of lung;prognosis;prediction model;risk stratification- 13
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发布时间：2024-09-12
Clinical Research
- “在医学研究领域，一项新研究揭示了不同侧张力性气胸对猪血流动力学的影响，为气胸现场救治提供数据支持。研究通过监测血流动力学指标，发现右侧张力性气胸在较小压力下更易导致严重后果。”
摘要：ObjectiveTo explore the effects of different side tension pneumothorax on hemodynamics in pigs, providing data support for the optimization of on-site first-aid procedures for pneumothorax.MethodsTwelve Bama pigs were randomly divided into left-sided tension pneumothorax group and right-sided tension pneumothorax group (6 in each group). During the occurrence of pneumothorax and as the pleural pressure gradually increases by 1 mmHg increments, the key indicators were collected using pulse indicator continuous cardiac output (PICCO) technology: hemodynamic indicators [global ejection fraction (GEF), cardiac output (CO), global end-diastolic volume (GEDV), intrathoracic blood volume (ITBV), stroke volume (SV), mean arterial pressure (MAP)], basic vital signs [heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP)], and arterial blood gas parameters [partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2)]. Mediastinal localization was subsequently performed using radiographs. Differences were investigated through comparison between the two groups and within each group before and after the procedure.ResultsBy comparing the hemodynamic changes and X-ray examination results, twelve Bama pigs tension pneumothorax models were successfully constructed. Hemodynamic analysis showed that in left-sided tension pneumothorax model when the pleural pressure reached 8 mmHg, SBP, DBP, MAP, CO, GEF, SV, GEDV and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax (P<0.05). In right-sided tension pneumothorax model, when the pleural pressure reached about 3 mmHg, SBP, DBP, MAP, SV, GEDV, and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax (P<0.05). Blood gas analysis showed that at 8 mmHg for left-sided and 3 mmHg for right-sided tension pneumothorax, compared with the occurrence of their respective ipsilateral pneumothorax, PO2 was significantly lower (P<0.05) and PCO2 was significantly higher (P<0.05).ConclusionsThere are different effects on hemodynamics in different side tension pneumothorax. Compared with left tension pneumothorax, right tension pneumothorax can lead to serious consequences under a smaller pleural pressure. Different side tension pneumothorax models can be constructed according to the actual situation when performing pneumothorax related experiments.关键词：tension pneumothorax;animal model;autonomous respiration;hemodynamics- 15
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发布时间：2024-09-12 - “在脊髓损伤研究领域，科学家们筛选并验证了关键基因IL1B和PLA2G4A，为脊髓损伤的诊断和治疗提供了新靶标。”
摘要：ObjectiveTo investigate the role of necroptosis key genes in spinal cord injury using bioinformatics methods to provide new targets for the diagnosis and treatment of spinal cord injury.MethodsThe peripheral blood transcriptome data of spinal cord injury samples (n=38) and healthy control samples (n=10) were obtained from GSE151371 data set in Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes and perform functional enrichment analysis. Machine learning algorithms (random forest and LASSO) and protein-protein interaction (PPI) networks are used to screen for necroptosis key genes and construct a diagnostic nomogram for spinal cord injury. Establish a rat spinal cord injury model to further verify the expression of necroptosis key genes by Western blotting and immunofluorescence staining.ResultsA total of 2050 differentially expressed genes were identified in the two groups. KEGG pathway enrichment analysis showed that the differentially expressed genes were involved in the nucleotide-binding oligomerization domain (NOD)‑like receptor signaling pathway, hematopoietic cell lineage, and necroptosis; GO enrichment analysis showed that the differentially expressed genes were involved in the activation of leukocytes, tertiary granulation, and regulation of the defense response, and so on. Intersection analysis screened 15 necroptosis differentially expressed genes. KEGG pathway enrichment analysis showed that necroptosis differentially expressed genes were involved in necroptosis, influenza, and NOD-like receptor signaling pathways; GO enrichment analysis showed that necroptosis differentially expressed genes were significantly enriched in the cellular response to cytokine stimulation, cytokine-mediated signaling pathways, and response to cytokines. Integration of two machine learning algorithms and PPI analysis further screened two necroptosis key genes (IL1B and PLA2G4A). The nomogram established using IL1B and PLA2G4A can be used for early prediction of the occurrence of spinal cord injury. The validation results of the rat spinal cord injury model showed that the protein expression of IL-1β and PLA2G4A in the spinal cord injury group were significantly higher than those in the sham group (P<0.05).ConclusionsIL1B and PLA2G4A as key genes of necroptosis involved in the development of spinal cord injury, can be used to predict the development of spinal cord injury with the promise of being new targets for the prevention and treatment of spinal cord injury关键词：spinal cord injury;necroptosis;machine learning;diagnosis;biomarkers- 13
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发布时间：2024-09-12 - “在神经科学领域，研究者们发现黄芪甲苷(AS-Ⅳ)能显著促进实验性自身免疫性脑脊髓炎(EAE)小鼠的轴突修复和再生。通过抑制Nogo-A及其下游通路分子ROCK2，AS-Ⅳ减轻了神经元损伤，为神经再生研究提供了新思路。”
摘要：ObjectiveTo investigate the effects of astragaloside Ⅳ (AS-Ⅳ) on axon growth inhibitory factor A (Nogo-A) and its downstream pathway protein RHO-associated coiled spiral kinase 2 (ROCK2) in experimental autoimmune encephalomyelitis (EAE) mice, and to explore the mechanism by which it promotes axon repair and regeneration.MethodsEAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55 (MOG35-55). Mice were randomly divided into EAE group and AS-Ⅳ group (n=8 per group). EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization, while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d) once daily, 0.2 ml per injection, for 25 consecutive days. On the 28th day post-immunization, the expression levels of growth-associated protein 43 (GAP-43), neuronal core antigen (NeuN), microtubule associated protein 2 (MAP-2), glial fibroacidic protein (GFAP), and Iba1 in the spinal cord were detected using immunofluorescence assay. Real-time fluorescence quantitative PCR (qRT-PCR) was conducted to detect mRNA expression levels of GAP-43, Nogo-A, and Nogo receptor (NgR) genes. Western blotting was utilized to determine the expression levels of GAP-43, Nogo-A, ROCK2, phosphorylated myosin phosphatase (p-MYPT1), B-lymphoblastoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax).ResultsCompared with EAE group, AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord (P<0.01 and P<0.001,respectively), while it also increased the positive expression rates of NeuN and MAP-2 (P<0.001 and P<0.05, respectively). The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2 (P<0.001) and downregulated the expression level of pro-apoptotic factor Bax (P<0.05), leading to an increase in Bcl-2/Bax ratio (P<0.05). Furthermore, AS-Ⅳ enhanced the expression of GAP-43 protein (P<0.05) and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor (NgR) and ROCK2 gene (P<0.001, P<0.05, respectively); as well as decreased the expression levels of Nogo-A, ROCK2 and p-MYPT1 proteins (P<0.05, P<0.001).ConclusionAS-IV may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK2, thereby promoting the expression of GAP-43, NeuN and MAP-2, alleviating neuronal damage, and facilitating axon repair and regeneration.关键词：autoimmune encephalomyelitis;astragaloside;axon growth inhibition factor;apoptosis;axon regeneration- 12
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发布时间：2024-09-12 -
Effect and mechanism of dexmedetomidine on alleviating heat stroke related rhabdomyolysis in rats AI导读
“最新研究发现，右美托咪定通过激活肾上腺素能α2受体缓解劳力性热射病大鼠横纹肌溶解，为热射病治疗提供新策略。”
摘要：ObjectiveTo explore whether dexmedetomidine (DEX) can alleviate exertional heatstroke (EHS)-induced rhabdomyolysis (RM) in rats by activating adrenergic α2 receptors, and to explore its potential mechanism based on the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) pathway.MethodsThirty-six male Sprague-Dawley (SD) rats, after a 7-day acclimatization training, were randomly divided into six groups: control group (CN group), EHS group, low-dose DEX group (EHS+low DEX group), high-dose DEX group (EHS+high DEX group), DEX combined with yohimbine (YOH) group (EHS+high DEX+YOH group), and YOH group (EHS+YOH), with six rats in each group. Before modeling, EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg, while the other four groups were injected intraperitoneally with an equal dose of physiological saline (0.9% NS). During modeling, except for CN group, the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model. After successful modeling, EHS+low DEX group was intraperitoneally injected with DEX at 10 μg/kg, EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30 μg/kg, and CN group, EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline. After 6 h of observation, all rats were anesthetized, and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and myoglobin (MB) in rats; biochemical assay kit was used to measure the level of creatine kinase (CK) in rat serum; HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues; transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle; 2′,7′-dichlorofluorescent yellow diacetate (DCFH-DA) fluorescent probe was used to detect the level of reactive oxygen species (ROS); and Western blotting was performed to detect the expression levels of NOD-like receptors 3 (NLRP3), aspartic protease-1 (caspase-1) and adrenergic α2A receptor (ADRA2A).ResultsCompared with CN group, the levels of serum IL-6, IL-1β, TNF-α, CK and MB in EHS group rats were significantly elevated (P<0.01). HE staining results revealed that the gastrocnemius muscle tissues of rats in EHS group had these pathological manifestations such as disarray of muscle fibrous structure, hemorrhage, edema, and infiltration of inflammatory cells. Transmission electron microscopy results showed that the ultrastructure of the gastrocnemius muscle in EHS group exhibited myofibroblasts with swelling and enlarging in size, cytoplasmic vacuolization, and mitochondria with obvious swelling, degranulation, and disappearance of double cristae. Compared with CN group, the expression levels of ROS, NLRP3, and caspase-1 in gastrocnemius of rats in EHS group significantly increased (P<0.01); Compared with EHS group, the levels of TNF-α, IL-6, IL-1β, CK, MB and the expression levels of ROS, NLRP3, caspase-1 in gastrocnemius tissue of rats in EHS+low DEX group and EHS+high DEX group decreased in a dose-dependent manner (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was alleviated by DEX. After YOH pretreatment, compared with the EHS+high DEX group, the serum levels of TNF-α, IL-6, IL-1β, CK, MB and ROS, NLRP3 and caspase-1 in the gastrocnemius muscle tissue of rats in EHS+high DEX+YOH group relatively increased (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was exacerbated. The expression of ADRA2A in gastrocnemius muscle of EHS group significantly decreased compared with CN group (P<0.01), and the expression of ADRA2A in muscle of rats in DES+low DEX group and EHS+high DEX group was higher than that in EHS group (P<0.05).ConclusionsDEX can alleviate EHS-induced RM by activating ADRA2A, potentially through inhibiting the ROS-dependent NLRP3/IL-1β inflammatory pathway.关键词：exertional heat stroke;dexmedetomidine;NOD-, LRR- and pyrin domain-containing protein 3;α2 adrenergic receptor;rhabdomyolysis- 12
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发布时间：2024-09-12 - “最新研究发现，黄卡瓦胡椒素B能显著抑制三阴性乳腺癌细胞的增殖和迁移，为治疗提供新策略。”
摘要：ObjectiveTo investigate how flavokawain B (FKB) affects the proliferation and migration of triple-negative breast cancer (TNBC) cells by downregulating the androgen receptor (AR).MethodsThe expression of AR in breast cancer and normal tissues was analyzed using the GEPIA2 database. Expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and AR was detected in six breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, Hs-578T, and MDB-MA-231) by Western blotting. The effect of FKB (0, 10, 20, 30, 40, 50, 60 μmoL/L) treatment of 24, 48, and 72 h on the proliferative activity of SUM159PT breast cancer cells was assessed using the CCK-8 assay under normal or androgen deprivation conditions. The mRNA and protein of AR expression was measured by qRT-PCR and Western blotting after 30 μmoL/L FKB treatment of SUM159PT cells for 0, 4 and 8 h. SUM159PT cells were set as control group (treatment with 0.1% DMSO), dihydrotestosterone (DHT) group (treatment with 10 nmol/L DHT), FKB group (treatment with 15 μmol/L FKB), DHT+FKB group (treatment with 10 nmol/L DHT and 15 μmol/L FKB), AR antagonist enzalutamide (ENZA) group (treatment with 40 μmol/L ENZA), and DHT+ENZA group (treatment with 10 nmol/L DHT and 40 μmol/L ENZA) under androgen deprivation conditions. Cell proliferation, migration, and colony formation abilities in the above groups were determined using the CCK-8 method, Transwell assay, and clone formation test. Western blotting was also used to detect the expression levels of EMT-related proteins (N-cadherin, Occludin, Vimentin) and AR protein.ResultsAR mRNA expression level was significantly higher in breast cancer tissue than in normal breast tissue (P<0.05). AR was expressed at comparable levels in five different breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, and Hs-578T) in addition to MDB-MA-231. FKB can downregulate AR mRNA and protein levels (P<0.05). Western blotting results showed that DHT could upregulate AR protein levels in SUM159PT cells, but FKB could prevent the DHT-induced upregulation of AR protein levels (P<0.05). FKB and ENZA decreased SUM159PT cell proliferation and migration and DHT-mediated cell proliferation and migration (P<0.05). FKB and ENZA can reduce N-cadherin and Vimentin protein levels and counteract DHT-induced increases in N-cadherin and Vimentin protein levels (P<0.05). In addition, FKB may increase Occludin expression and counteract the DHT-induced decrease in Occludin protein expression (P<0.05).ConclusionFlavokawain B could inhibit the proliferation, migration, and clonogenic ability of TNBC cells by regulating AR expression.关键词：androgen receptor;Flavokawain B;triple-negative breast cancer- 10
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发布时间：2024-09-12
Basic Research
- “在糖尿病研究领域，专家深入探讨了尿酸代谢异常与2型糖尿病关联，为早期防治提供新思路。”
摘要：Uric acid, the end product of purine metabolism in human body, can lead to uric acid metabolism abnormality when its production and excretion are out of balance. This abnormality has emerged as one of the important risk factors for metabolic diseases, including diabetes, obesity, hypertension and metabolic syndrome. Recent studies have found that abnormal uric acid metabolism increases the risk of occurrence and development of type 2 diabetes mellitus (T2DM) and its complications, suggesting that uric acid metabolism could be a novel approach for intervening in T2DM. This review summarizes the research progress on how uric acid metabolism abnormality influences the occurrence, development and pathogenesis of T2DM, the beneficial effects of uric acid-lowering therapy, and the selection of hypoglycemic drugs on T2DM, which provide evidence for the early prevention and treatment of T2DM and its complications.关键词：uric acid;diabetes mellitus, type 2;metabolism;purine- 17
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发布时间：2024-09-12 - “在慢性肾脏病膳食评估领域，中国专家建立了适合亚洲人群的FFQ体系，为改善患者营养状况提供参考。”摘要：Chronic kidney disease (CKD) commonly used dietary assessments including 24-hour dietary recall (24 h DR)/3-day dietary recall (3DDR), food frequency questionnaire (FFQ), dietary records, and estimation of dietary protein intake based on nitrogen balance. Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method, it is crucial to develop an FFQ suitable for Chinese CKD patients. This review summarizes the advantages and disadvantages of dietary assessment methods for CKD, the current research status, and the content and steps involved in establishing an FFQ, with the aim of providing reference for the modification of FFQ for Chinese CKD patients.关键词：chronic kidney disease;dietary assessment;24 h dietary recall;food frequency questionnaire
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发布时间：2024-09-12 - “在恶性血液病领域，专家系统性综述了成人噬血细胞综合征的诊断与治疗新进展，为临床诊疗和预后评估提供参考。”
摘要：Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is a rare and highly malignant hematologic disease with a poor prognosis. It can be divided into two categories: primary HLH and secondary HLH. HLH is characterized by a large number of abnormal immune cells that continuously activate and regulate out of control, leading to systemic inflammatory factor storm and multiple organ failure. Clinical manifestations mainly include persistent malignant hyperthermia, pancytopenia, hepatosplenomegaly, and hemophagocytosis in tissues and organs. The pathogenesis of adult HLH is complex, with rapid onset and rapid disease progression, and the fatality rate remains high. The main causes of death in HLH patients are multiple organ failure, abnormal coagulation and septic shock. Due to the specificity of HLH and the lack of effective understanding of the severity and prognosis in clinical practice, some HLH patients are misdiagnosed or overlooked, missing the best opportunity for diagnosis and treatment. Therefore, this review systematically explores and discusses the latest diagnostic and treatment progress of adult HLH, aiming to provide reference for clinical diagnosis, treatment and prognosis assessment of HLH.关键词：hemophagocytic syndrome;malignant hematological diseases;diagnosis and differentiation;treatment;prognosis- 243
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发布时间：2024-09-12 - “在创伤急救领域，REBOA技术展现出巨大潜力，为大出血救治提供新方案。”
摘要：Incompressible massive hemorrhage at the junction of trunk and limbs is the major cause of the potential preventable death in modern military conflicts, natural disasters and sudden trauma accidents. Because of the failure of direct compression hemostasis, aortic occlusion can reduce the amount of bleeding and provide a short time for injury recovery and accurate control of bleeding. As an effective assistant hemostasis method, resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown initial potential in military and civilian hospitals and even pre-hospital trauma emergency treatment. With the continuous development of catheter guide technology, it is expected to achieve the emergency hemostasis treatment of war wound and massive hemorrhage. Basic and pre-clinical studies have been carried out in Europe and America, and the technology has been applied to the treatment of some patients with massive bleeding, but rarely reported in China. This paper reviews the history, scope, limitations and improvement of application and military application of REBOA in the treatment of traumatic hemorrhage, so as to promote the recognition of REBOA.关键词：resuscitative endovascular balloon occlusion of the aorta;massive hemorrhage;emergency hemostasis- 16
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发布时间：2024-09-12 - “报道指出，利奈唑胺作为抗菌药，其临床使用率上升，但伴随血液及代谢系统不良反应。专家探讨了不良反应机制与预防策略，为临床防治提供参考。”
摘要：Linezolid, a fully synthetic oxazolidinone antibiotic, is mainly used to treat severe infections caused by Gram-positive drug-resistant bacteria. In recent years, with the rise in drug-resistant bacteria, the clinical utilization rate of linezolid and the incidence of linezolid-related adverse reactions in the hematological system and metabolic system have increased. The main adverse reactions include thrombocytopenia, anemia and lactic acidosis. Studies have shown that the causes of adverse reactions in linezolid-induced hematological system and metabolic system are diverse, and the mechanisms are not fully elucidated. In this review, the pharmacokinetic characteristics, mechanism of adverse reactions, risk factors, as well as preventive measures and individualized drug administration strategies of linezolid in vivo were discussed based on literature reports at home and abroad, aiming to provide references for clinical prevention and treatment of linezolid-related adverse reactions of hematological system and metabolic system.关键词：linezolid;blood;metabolism;adverse reaction;individualized drug administration- 13
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发布时间：2024-09-12
Review
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