1.Effect of calcitonin gene-related peptide on autophagy in hypoxic/reoxygenated cardiomyocytes through regulation of PI3K/Akt/mTOR signaling pathway.
Chinese Critical Care Medicine 2025;37(1):53-58
OBJECTIVE:
To investigate the effects of calcitonin gene-related peptide (CGRP) on autophagy in hypoxic/reoxygenated (H/R) cardiomyocytes and its relationship with the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway.
METHODS:
The rat cardiomyocyte cell line H9c2 was routinely cultured in vitro and passaged for experiments when the cells grew to 80% fusion. (1) CGRP dosage screening experiment: the cells were divided into blank control group, H/R group and different dosages of CGRP pretreatment groups. H9c2 cells were placed in a closed hypoxia chamber for 2 hours and then reoxygenated in a conventional incubator for 12 hours to prepare the H/R model. The CGRP pretreatment groups were pretreated with 0.01, 0.1, 0.5, 1, 5, and 10 μmol/L CGRP before the modeling process. The blank control group was not given any treatment. Cell counting kit-8 (CCK-8) was used to detect the cell survival rate, and the most suitable drug dosage was screened out. (2) Intervention experiment: H9c2 cells were divided into blank control group, H/R group, CGRP+H/R group, and CGRP+PI3K target inhibitor ly294002 (LY)+H/R group. H/R group was prepared as cellular H/R model. CGRP (1 μmol/L) alone or in combination with LY (10 μmol/L) was administered to CGRP+H/R group and CGRP+LY+H/R group, respectively, prior to the preparation of cellular H/R model. The blank control group was cultured routinely without treatment. The cell survival rate was detected by CCK-8. The level of lactate dehydrogenase (LDH) release was detected by colorimetric assay. The expressions of autophagy-related proteins [autophagy effector protein Beclin-1, microtubule-associated protein 1 light chain 3-II (LC3-II), autophagy protein p62] and PI3K/Akt/mTOR signaling pathway proteins [phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR)] were detected by Western blotting.
RESULTS:
(1) Results of CGRP dosage screening experiment: compared with the blank control group, the cell survival rate of the H/R group decreased significantly; and after giving 0.1, 0.5, 1, 5 μmol/L CGRP for pretreatment, the cell survival rate increased significantly, and intervention effect of 1 μmol/L CGRP was the best, and the difference was statistically significant when compared with that of the H/R group [(74.23±6.18)% vs. (23.43±4.09)%, P < 0.01], so it was used as the intervention dosage for the subsequent experiment. (2) Intervention experiment results: compared with the blank control group, the cell survival rate in the H/R group was significantly reduced, the level of LDH release was significantly increased, the protein expressions of Beclin-1 and LC3-II were significantly increased, and the protein expressions of p62, p-Akt and p-mTOR were significantly reduced, indicating that the death of cardiomyocytes occurred after the treatment of H/R and was accompanied by the elevation of autophagy level, and this process was associated with the activation of PI3K/Akt/mTOR signaling pathway. Compared with the H/R group, CGRP pretreatment increased cell survival rate [(76.02±2.43)% vs. (46.15±3.29)%, P < 0.01], decreased the level of LDH release (U/L: 169.83±11.65 vs. 590.17±34.50, P < 0.01), and down-regulated the protein expressions of Beclin-1 and LC3-II [Beclin-1 protein (Beclin-1/β-actin): 1.27±0.15 vs. 1.93±0.19, LC3-II protein (LC3-II/LC3-I): 1.27±0.13 vs. 1.98±0.18, both P < 0.01], up-regulated the protein expressions of p62, p-Akt, p-mTOR [p62 protein (p62/β-actin): 0.96±0.02 vs. 0.63±0.05, p-Akt protein (p-Akt/Akt): 0.76±0.04 vs. 0.48±0.02, p-mTOR protein (p-mTOR/mTOR): 1.13±0.09 vs. 0.68±0.15, all P < 0.05], suggesting that CGRP was able to reduce the H/R-induced cardiomyocyte injury, and this process was accompanied by a decrease in the level of cellular autophagy and activation of the PI3K/Akt/mTOR signaling pathway. Compared with the CGRP+H/R group, the cell survival rate was significantly lower than that in the CGRP+LY+H/R group [(56.95±6.63)% vs. (76.02±2.43)%, P < 0.01], LDH release level was significantly higher (U/L: 436.00±27.44 vs. 169.83±11.65, P < 0.01), and the protein expressions of Beclin-1 and LC3-II were significantly up-regulated [Beclin-1 protein (Beclin-1/β-actin): 1.63±0.12 vs. 1.27±0.15, LC3-II protein (LC3-II/LC3-I): 1.61±0.13 vs. 1.27±0.13, both P < 0.01], and significantly down-regulated p62, p-Akt, and p-mTOR protein expressions [p62 protein (p62/β-actin): 0.57±0.09 vs. 0.96±0.02, p-Akt protein (p-Akt/Akt): 0.45±0.01 vs. 0.76±0.04, p-mTOR protein (p-mTOR/mTOR): 0.66±0.06 vs. 1.13±0.09, all P < 0.05], suggesting that PI3K-targeted inhibitor was able to reverse the protective effect of CGRP on H/R cells.
CONCLUSIONS
CGRP pretreatment attenuated H/R-induced cardiomyocyte injury, increased cell survival rate, and reduced cellular LDH release. This effect may be achieved through inhibiting the activation of PI3K/Akt/mTOR signaling pathway.
Animals
;
Myocytes, Cardiac/drug effects*
;
Signal Transduction/drug effects*
;
Rats
;
TOR Serine-Threonine Kinases/metabolism*
;
Calcitonin Gene-Related Peptide/pharmacology*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Autophagy/drug effects*
;
Cell Line
;
Cell Hypoxia
;
Phosphatidylinositol 3-Kinases/metabolism*
2.Discussion on the Application Prospects and Challenges of Generative Artificial Intelligence Represented by ChatGPT in the Field of Hospital Management
Mingwang FANG ; Ling GUO ; Yingde HUANG ; Wei YUAN ; Yunyi GAO ; Yi ZHOU ; Yiyang ZHAO ; Bingxing SHUAI ; Xiangjun CHEN ; Weiyi ZHANG ; Dajiang LI
Journal of Medical Informatics 2024;45(10):18-21
Purpose/Significance To explore the changes,challenges,key application scenarios and future development directions of generative artificial intelligence(AI)represented by ChatGPT in the field of hospital management,and to provide references for the ap-plication of AI natural language processing(NLP)technology in the field of hospital management in China.Method/Process Through literature review and analysis,the changes and challenges brought about by the rapid development of generative AI in the field of hospital management are sorted out,its key application scenarios and future development directions in the field of hospital management are empha-sized and explored.Result/Conclusion AI has broad application prospects in the field of hospital management,and it should focus on exploring its practical application scenarios and strategic directions to provide reference and guidance for promoting the high-quality de-velopment of public hospitals.
3.Risk factors for delirium in intensive care unit and its duration
Yanyan LI ; Dajiang YUAN ; Xiaoya LI ; Shao WANG
Chinese Critical Care Medicine 2020;32(1):62-66
Objective:To screen risk factors for delirium and its duration in intensive care unit (ICU)patients.Methods:1 200 patients admitted to ICU of the Second Hospital of Shanxi Medical University from May 2017 to May 2019 were enrolled. The gender, age, anesthesia mode, duration of mechanical ventilation and hypoxia, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sedative drug use, and length of ICU stay were recorded. The occurrence and duration of ICU delirium were recorded. Multivariate Logistic regression analysis and multiple linear regression analysis were used to analyze the factors with statistical significance differences between the groups for screening the risk factors for delirium and its duration in ICU patients.Results:397 of 1 200 patients developed delirium, the incidence of ICU delirium was 33.1%. The duration of delirium in 189 patients (47.6%) was 1.0 day, and the duration of delirium in 397 delirium patients was 2.0 (1.5, 2.5) days. ① Analysis of risk factors for delirium: univariate analysis showed that there was no significant difference in the incidence of ICU delirium among patients with different genders or ages. The incidence of ICU delirium in patients with duration of mechanical ventilation or hypoxia 4-9 days and ≥ 10 days was higher than that in patients with ≤ 3 days. The incidence of ICU delirium of general anesthesia and internal medicine patients was higher than that of patients with lumbar anesthesia. The incidence of ICU delirium in patients with APACHEⅡ score ≥ 20 was higher than that in patients with ≤ 10 and 11-19. The patients with length of ICU stay > 9 days had a higher ICU delirium incidence than those ≤ 8 days. Increased incidence of ICU delirium in sedative patients was found as compared with those who did not use sedatives. Multivariate Logistic regression analysis showed that APACHEⅡ score [odds ratio ( OR) = 5.491, 95% confidence interval (95% CI) was 4.361-6.913, P < 0.001], the length of ICU stay ( OR = 2.679, 95% CI was 1.822-3.941, P < 0.001) and the use of sedatives ( OR = 2.479, 95% CI was 1.821-3.374, P < 0.001) were risk factors for ICU delirium. ② Analysis of risk factors of ICU delirium duration: univariate analysis showed that there was no significant difference in ICU delirium duration in patients with different genders or ages. The duration of ICU delirium in patients with duration of mechanical ventilation or hypoxia ≥ 10 days was longer than that in patients with ≤ 3 days and 4-9 days. The duration of ICU delirium in general anesthesia and non-surgical patients was higher than that in patients with spinal anesthesia. The ICU delirium duration in patients with APACHEⅡ score ≥ 20 was longer than that in patients with ≤ 10 and 11-19. The duration of ICU delirium in patients with the length of ICU stay > 9 days was longer than that in patients with ≤ 8 days. The duration of ICU delirium in patients on sedatives was longer than those not taking sedatives. Multiple linear regression analysis showed that the duration of ICU delirium increased by an average of 0.061 days (β = 0.061, 95% CI was 0.032-0.090, P < 0.001) for each additional day of hypoxia (hypoxia duration was divided into three grades of ≤ 3, 4-9 and ≥ 10 days). For every one increase in APACHE Ⅱ score (APACHE Ⅱ score was divided into three grades of ≤ 10, 11-19 and ≥ 20), duration of ICU delirium extended an average of 0.058 days (β = 0.058, 95% CI was 0.048-0.068, P < 0.001). ICU delirium duration increased by an average of 0.065 days in patients with length of ICU stay > 9 days as compared with those ≤ 8 days (β = 0.065, 95% CI was 0.056-0.075, P < 0.001). On average, the duration of ICU delirium was prolonged by 0.362 days in patients on sedatives as compared with those who did not use sedatives (β = 0.362, 95% CI was 0.234-0.490, P < 0.001). Conclusions:APACHEⅡ score, the length of ICU stay and the use of sedatives were common risk factors for ICU delirium and its duration. The hypoxic duration was risk factors for ICU delirium duration.
4.Impact of accelerator operating errors on γ passing rate during dose verification of volumetric modulated arc therapy for pelvic tumors
Qingqing YUAN ; Yanlong LI ; Dajiang WANG ; Hong QUAN ; Guangjun LI ; Sen BAI
Chinese Journal of Radiation Oncology 2020;29(9):779-783
Objective:To investigate the impacts of gantry rotation angle errors, monitor unit (MU) errors, collimator and multi-leaf collimator (MLC) position errors upon the γ passing rate of dose verification in volumetric modulated arc therapy (VMAT).Methods:Ten patients with rectal cancer and 10 patients with uterine tumors were selected. The operating errors of accelerator parameters were introduced during the VMAT execution. By comparing the γ passing rates during dose verification between the simulating and original plans, the impact and sensitivity of the operating errors of each accelerator parameter on γ passing rate were analyzed.Results:When the γ criteria were set as 3%/3 mm, 3%/2 mm and 2%/2 mm, the γ passing rate decreasing gradient was less than 7.0% after the introduction of gantry rotation angle, MU and collimator position errors, respectively. However, after the reverse, opposite, and co-directional motion errors of the MLC blades on both sides were introduced, the γ passing rate decreasing was less than 19.13 %, 18.53%, 0.19 %; 19.87%, 20.01%, 0.42 % and 23.11%, 23.45%, 0.65 % for absolute dose verification, respectively.Conclusion:During VMAT, the reverse and opposite motion errors of MLC blades exert more significant effect on the γ passing rate compared with the gantry rotation angle errors, MU errors, collimator position errors and co-directional motion errors of the MLC blades. When the γ criteria of 3%/3 mm, 3%/2 mm and 2%/2 mm are adopted, the impact of accelerator operating errors upon the γ passing rate is strengthened in sequence. Therefore, when performing dose verification for a specific patient, appropriate γ criteria should be chosen and absolute dose verification should be taken as the reference index to evaluate the consistency between the calculated and measured dose distribution.
5.The dosimetric impacts of accelerator operation error on the volumetric modulated arc therapy for cervical cancer
Guangjun LI ; Yanlong LI ; Qingqing YUAN ; Dajiang WANG ; Qiang WANG ; Jianghong XIAO ; Sen BAI
Chinese Journal of Radiological Medicine and Protection 2018;38(11):824-829
Objective To investigate the dosimetric effect of accelerator gantry rotation angle errors, collimator and multileaf collimator ( MLC) leaf position errors on volumetric-modulated arc therapy ( VMAT) for cervical cancer. Methods A total of 10 patients with cervical cancer were selected. The plan. Trail file of each clinical plan was extracted from the Pinnacle3 V9. 2 planning system of USA Philips, then the operating parameters of tach control point were read and modified by Matlab programs, and thus the operating error of the accelerator was simulated. Results In this paper, it was discovered that systematic accelerator gantry rotation angle errors, systematic collimator position errors and systematic MLC shift errors which led to the maximum changes of the PTV dose limit were 0. 16%, 0. 46% and 0. 57%, respectively, and the maximum changes of the dose limit of organs at risk ( OAR) were 0. 38%, -1. 32% and -0. 44%, respectively. When the systematic MLC gap width errors were ± 0. 5, ± 1 and ± 2 mm, respectively, the maximum changes of PTV dose were 2. 11%, 3. 04% and 6. 03%, respectively, while the maximum changes of the OAR average dose were 2. 17%, 3. 92% and 7. 97%, respectively. Furthermore, the dose limits of PTV and OAR showed a strong linear correlation with MLC open or close errors(t=21. 201~90. 562,P<0. 05). If actual errors of each parameter of accelerator were introduced, the maximum changes of PTV and OAR dose limits were 0. 16% and 1. 30%, respectively, and conformity index (CI) and homogeneity index (HI) were barely changed. Conclusions No significant effect was found for systematic accelerator gantry rotation angle errors, systematic collimator position errors and systematic MLC shift errors for cervical cancer VMAT patients. However, there is a high sensitivity to dose distribution for MLC open or close errors. Therefore, it is necessary to pay more attention on the quality control of the accelerator running in particular MLC position errors to ensure the therapeutic accuracy.
6.Role of mitochondrial ATP-sensitive potassium channel in reduction of myocardial ischemia-reperfusion injury by calcitonin gene-related peptide in rats : an in vitro experiment
Dajiang YUAN ; Jiarong HAO ; Zheng GUO
Chinese Journal of Anesthesiology 2017;37(6):744-747
Objective To evaluate the role of the mitochondrial ATP-sensitive potassium (mitoKATP) channel in reduction of myocardial ischemia-reperfusion (I/R) injury by calcitonin gene-related peptide (CGRP) in rats in an in vitro experiment.Methods Healthy adult male Sprague-Dawley rats,weighing 250-300 g,were used in this study.After the animals were anesthetized,their hearts were immediately removed and retrogradely perfused with oxygenated K-H solution at 37 ℃ in a Langendorff apparatus.Twenty-four isolated rat hearts were assigned into 4 groups (n =6 each) using a random number table:control group (C group),I/R group,CGRP group and 5-hydroxydecanoate (5-HD) group.The hearts were first perfused with K-H solution for 30 min in the three groups.The hearts were continuously perfused with K-H solution for 150 min in group C.The hearts were subjected to ischemia for 30 min followed by 120 min of reperfusion to establish the model of myocardial I/R injury.In group CGRP,after the hearts were perfused with K-H solution for 10 min,10-8 mol/L CGRP was infused for 20 min at a rate of 0.5 ml/min via the aorta,and then the model of myocardial I/R injury was established.In 5-HD group,specific mito-KATP channel blocker 5-HD 100 μmol/L was infused for 10 min at a rate of 0.5 ml/nin via the aorta,and the other treatments were similar to those previously described in CGRP group.At the end of equilibration and 30,60,90 and 120 min of reperfusion,heart rate (HR),left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP) and the maximum rate of increase or decrease in left ventricular pressure (±dp/dtmax) were recorded.The myocardial infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining at 120 min of reperfusion.Results Compared with C group,HR,LVSP and ±dp/dtmax were significantly decreased and LVEDP was increased during reperfusion,and the percentage of myocardial infarct size was increased at 120 min of reperfusion in the other three groups (P<0.05).Compared with I/R group,HR,LVSP and ±dp/dtmax were significantly increased and LVEDP was decreased during reperfusion,and the percentage of nyocardial infarct size was decreased at 120 min of reperfusion in CGRP group (P<0.05).Compared with CGRP group,HR,LVSP and ±dp/dtmax were significantly decreased and LVEDP was increased during reperfusion,and the percentage of myocardial infarct size was increased at 120 min of reperfusion in 5-HD group (P<0.05).Conclusion Opening of mito-KATP channels is involved in CGRP-iuduced reduction of myocardial I/R injury in rats in an in vitro experiment.
7.The comparison of clinical features of 2 cases of intracranial otogenic complications.
Yuan YUAN ; Xin ZHAO ; Dajiang XIAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(24):2175-2176
Two cases of special intracranial otogenic complications were analyzed in the aspects of clinical characteristics, diagnosis and therapy. We concluded that for patients with huge cholesteatoma which damaged the bone of skull base, or chronic otitis media patients with sharp deterioration in symptoms, accompanied by headache and fever, we should promptly do the enhanced magnetic resonance to avoid the missed diagnosis of intracranial complications.
Cholesteatoma
;
diagnosis
;
physiopathology
;
Chronic Disease
;
Headache
;
Humans
;
Otitis Media
;
diagnosis
;
physiopathology
;
Skull Base
;
pathology
8.The clinical value of sentinel lymph node detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck by methylene blue method and radiolabeled tracer method.
Xin ZHAO ; Dajiang XIAO ; Jianming NI ; Guochen ZHU ; Yuan YUAN ; Ting XU ; Yongsheng ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(21):1652-1654
OBJECTIVE:
To investigate the clinical value of sentinel lymph node (SLN) detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck (cN0) by methylene blue method, radiolabeled tracer method and combination of these two methods.
METHOD:
Thirty-three patients with cN0 laryngeal carcinoma and six patients with cN0 hypopharyngeal carcinoma underwent SLN detection using both of methylene blue and radiolabeled tracer method. All these patients were accepted received the injection of radioactive isotope 99 Tc(m)-sulfur colloid (SC) and methylene blue into the carcinoma before surgery, then all these patients underwent intraopertive lymphatic mapping with a handheld gamma-detecting probe and blue-dyed SLN. After the mapping of SLN, selected neck dissections and tumor resections were peformed. The results of SLN detection by radiolabeled tracer, dye and combination of both methods were compared.
RESULT:
The detection rate of SLN by radiolabeled tracer, methylene blue and combined method were 89.7%, 79.5%, 92.3% respectively. The number of detected SLN was significantly different between radiolabeled tracer method and combined method, and also between methylene blue method and combined method. The detection rate of methylene blue and radiolabeled tracer method were significantly different from combined method (P < 0.05). Nine patients were found to have lymph node metastasis by final pathological examination. The accuracy and negative rate of SLN detection of the combined method were 97.2% and 11.1%.
CONCLUSION
The combined method using radiolabeled tracer and methylene blue can improve the detection rate and accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately represent the cervical lymph node status in cN0 laryngeal and hypopharyngeal carcinoma.
Carcinoma
;
pathology
;
secondary
;
Carcinoma, Squamous Cell
;
pathology
;
secondary
;
Female
;
Head and Neck Neoplasms
;
pathology
;
secondary
;
Humans
;
Hypopharyngeal Neoplasms
;
pathology
;
Laryngeal Neoplasms
;
Larynx
;
Lymph Nodes
;
pathology
;
Lymphatic Metastasis
;
Male
;
Methylene Blue
;
Neck Dissection
;
Squamous Cell Carcinoma of Head and Neck
;
Staining and Labeling
9.Clinical efficacy of mouse nerve growth factor in the treatment of sudden deafness.
Ting XU ; Dajiang XIAO ; Sihai WU ; Yuan YUAN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(10):735-737
OBJECTIVE:
To study the clinical efficacy of mouse nerve growth factor (NGF) in the treatment of sudden deafness.
METHOD:
A retrospective analysis was performed on 115 cases of hospitalized patients who were suffered from sudden deafness. Patients were divided into two groups according to treatment medicine. Control group: patients were treated with intravenous vasodilators, energy mixture, steroid pulse therapy, and methylcobalamin neurotrophic therapy. NGF group: intramuscular NGF treatment was added on the basis of conventional therapy mentioned above. Both treatments lasted 14 days, the total efficiency were compared. Patients were further divided into sub-groups according to age, duration and the level of pre-treatment PTA, and the treatment efficiency was further compared. By SPSS 11.0 statistical analysis, a P < 0.05 was considered as statistical significant difference.
RESULT:
(1) The total efficiency of NGF group was significantly higher than control group. (2) Regard of age, the efficiency of NGF treatment group was significantly higher than control group. (3) For the patients whose duration were less than 7 d, or the PTA < or = 60 dBHL, the efficiency of NGF group were significantly higher. For the patients whose duration were more than 7 d, or the PTA>60 dBHL, the efficiency of NGF therapy was not superior to the traditional treatment.
CONCLUSION
NGF can significantly improve the symptom of patients with short duration or low PTA. For this kind of patients, NGF adjuvant therapy should be recommended. For the patients with longer duration and higher level of PTA, NGF therapy is not advocated. NGF treatment should not be in consideration of the age.
Adolescent
;
Adult
;
Aged
;
Female
;
Hearing Loss, Sudden
;
drug therapy
;
Humans
;
Male
;
Middle Aged
;
Nerve Growth Factor
;
therapeutic use
;
Retrospective Studies
;
Treatment Outcome
;
Young Adult
10.Study on treatment of 26 cases with nasal basal cell carcinoma.
Yongsheng ZHANG ; Dajiang XIAO ; Yuan YUAN ; Guochen ZHU ; Sihai WU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(8):357-359
OBJECTIVE:
To discuss the relationship between surgical margin and recurrence of nasal basal cell carcinoma.
METHOD:
Twenty-six cases of nasal basal cell carcinoma were analyzed. Mohs microsurgical operation was used in 15 cases and conventional operation was used in 11 cases.
RESULT:
Twenty-six cases of the tumors were resected and the wound defect was repaired concurrently. Two cases with tumor recurrence were subjected secondary resection and then no recurrence occurred.
CONCLUSION
Intraoperation frozen section can help guide the surgical margin. Skin tissue was saved and the repair was facilitated, it also help save the skin tissue , facilitate the repair, reduce the recurrence rate but increased the operation cost and time.
Aged
;
Aged, 80 and over
;
Carcinoma, Basal Cell
;
surgery
;
Female
;
Humans
;
Male
;
Middle Aged
;
Nose Neoplasms
;
surgery
;
Treatment Outcome

Result Analysis
Print
Save
E-mail