1.A cisplatin prodrug-based self-assembling ozone delivery nanosystem sensitizes radiotherapy in triple-negative breast cancer.
Tianyue XU ; Dan ZHENG ; Meixu CHEN ; Linlin SONG ; Zhihui LIU ; Yan CHENG ; Yujie ZHAO ; Liwen HUANG ; Yixuan LI ; Zhankun YANG ; Cong LI ; Biao DONG ; Jing JING ; Hubing SHI
Acta Pharmaceutica Sinica B 2025;15(5):2703-2722
Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.
2.Clinical characteristics of elderly patients with sepsis and development and evaluation of death risk assessment scale.
Fubo DONG ; Liwen LUO ; Dejiang HONG ; Yi YAO ; Kai PENG ; Wenjin LI ; Guangju ZHAO
Chinese Critical Care Medicine 2025;37(1):17-22
OBJECTIVE:
To analyze the clinical characteristics of elderly patients with sepsis, identify the key factors affecting their clinical outcomes, construct a death risk assessment scale for elderly patients with sepsis, and evaluate its predictive value.
METHODS:
A retrospective case-control study was conducted. The clinical data of sepsis patients admitted to intensive care unit (ICU) of the First Affiliated Hospital of Wenzhou Medical University from September 2021 to September 2023 were collected, including basic information, clinical characteristics, and clinical outcomes. The patients were divided into non-elderly group (age ≥ 65 years old) and elderly group (age < 65 years old) based on age. Additionally, the elderly patients were divided into survival group and death group based on their 30-day survival status. The clinical characteristics of elderly patients with sepsis were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for 30-day death in elderly patients with sepsis, and the regression equation was constructed. The regression equation was simplified, and the death risk assessment scale was established. The predictive value of different scores for the prognosis of elderly patients with sepsis was compared.
RESULTS:
(1) A total of 833 patients with sepsis were finally enrolled, including 485 in the elderly group and 348 in the non-elderly group. Compared with the non-elderly group, the elderly group showed significantly lower counts of lymphocyte, T cell, CD8+ T cell, and the ratio of T cells and CD8+ T cells [lymphocyte count (×109/L): 0.71 (0.43, 1.06) vs. 0.83 (0.53, 1.26), T cell count (cells/μL): 394.0 (216.0, 648.0) vs. 490.5 (270.5, 793.0), CD8+ T cell count (cells/μL): 126.0 (62.0, 223.5) vs. 180.0 (101.0, 312.0), T cell ratio: 0.60 (0.48, 0.70) vs. 0.64 (0.51, 0.75), CD8+ T cell ratio: 0.19 (0.13, 0.28) vs. 0.24 (0.16, 0.34), all P < 0.01], higher natural killer cell (NK cell) count, acute physiology and chronic health evaluation II (APACHE II) score, ratio of invasive mechanical ventilation (IMV) during hospitalization, and 30-day mortality [NK cell count (cells/μL): 112.0 (61.0, 187.5) vs. 95.0 (53.0, 151.0), APACHE II score: 16.00 (12.00, 21.00) vs. 13.00 (8.00, 17.00), IMV ratio: 40.6% (197/485) vs. 31.9% (111/348), 30-day mortality: 28.9% (140/485) vs. 19.5% (68/348), all P < 0.05], and longer length of ICU stay [days: 5.5 (3.0, 10.0) vs. 5.0 (3.0, 8.0), P < 0.05]. There were no statistically significant differences in the levels of inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukins (IL-2, IL-4, IL-6, IL-10) between the two groups. (2) In 485 elderly patients with sepsis, 345 survived in 30 days, and 140 died with the 30-day mortality of 28.9%. Compared with the survival group, the patients in the death group were older, and had lower body mass index (BMI), white blood cell count (WBC), PCT, platelet count (PLT) and higher IL-6, IL-10, N-terminal pro-brain natriuretic peptide (NT-proBNP), total bilirubin (TBil), blood lactic acid (Lac), and ratio of in-hospital IMV and continuous renal replacement therapy (CRRT). Multivariate Logistic regression analysis indicated that BMI [odds ratio (OR) = 0.783, 95% confidence interval (95%CI) was 0.678-0.905, P = 0.001], IL-6 (OR = 1.073, 95%CI was 1.004-1.146, P = 0.036), TBil (OR = 1.009, 95%CI was 1.000-1.018, P = 0.045), Lac (OR = 1.211, 95%CI was 1.072-1.367, P = 0.002), and IMV during hospitalization (OR = 6.181, 95%CI was 2.214-17.256, P = 0.001) were independent risk factors for 30-day death in elderly patients with sepsis, and the regression equation was constructed (Logit P = 1.012-0.244×BMI+0.070×IL-6+0.009×TBil+0.190×Lac+1.822×IMV). The regression equation was simplified to construct a death risk assessment scale, namely BITLI score. Receiver operator characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) of BITLI score for predicting death risk was 0.852 (95%CI was 0.769-0.935), and it was higher than APACHE II score (AUC = 0.714, 95%CI was 0.623-0.805) and sequential organ failure assessment (SOFA) score (AUC = 0.685, 95%CI was 0.578-0.793). The determined cut-off value of BITLI score was 1.50, while achieving a sensitivity of 83.3% and specificity of 74.0%.
CONCLUSIONS
Elderly patients with sepsis often have reduced lymphocyte counts, severe conditions, and poor prognosis. BMI, IL-6, TBil, Lac, and IMV during hospitalization were independent risk factors for 30-day death in elderly patients with sepsis. The BITLI score constructed based above risk factors is more precise and reliable than traditional APACHE II and SOFA scores in predicting the outcomes of elderly patients with sepsis.
Humans
;
Sepsis/mortality*
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Aged
;
Retrospective Studies
;
Risk Assessment
;
Case-Control Studies
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Prognosis
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Male
;
Female
;
Intensive Care Units
;
Risk Factors
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Aged, 80 and over
;
Logistic Models
;
Middle Aged
3.Investigation and determination of relative correction factor of pre-vitamin D
Jieming SHI ; Cheng WANG ; Liwen ZHANG ; Shunling DONG ; Jian LE ; Song YUAN ; Yihong LU ; Dandan WANG ; Wankui XU ; Shufeng ZHENG
Drug Standards of China 2024;25(2):147-153
Objective:To determine the relative correction factor of pre-vitamin D and simplify the calculation method of vitamin D assay.Methods:By studying the calculation method of vitamin D content in drug standards of various countries,HPLC was used to determine the relative correction factor of pre-vitamin D,and the influencing factors of determination were investigated.Results:The relative correction factors of pre-vitamin D at 254 nm and 265nm wavelength were determined by statistical analysis of 7 laboratories in China.Conclusion:Using the pre-vi-tamin D relative correction factor method to calculate the total amount of vitamin D simplified the experimental steps can be simplified by the pre-vitamin D relative correction factor method to calculate the total amount of vitamin D and the random operating errors can be avoided.The method is rapid and accurate,and lay a solid foundation for further improving the standard of vitamin D preparations.
4.Mechanism of X-ray radiation-induced rat myocardial cell apoptosis based on miRNA-134-5p/BDNF/Akt signaling pathway
Jing GU ; Liwen FU ; Xiaofei HAN ; Dan FANG ; Ge JIN ; Xiaoli DONG ; Yahui XIE ; Min HOU
Academic Journal of Naval Medical University 2024;45(11):1352-1361
Objective To investigate the effect of radiation on cardiomyocyte apoptosis and its related mechanism.Methods Rat H9C2 cardiomyocytes were divided into blank control group,X-ray irradiation group(X-ray group),X-ray irradiation+microRNA(miRNA)-134-5p inhibitor group(X-inhibitor group)and X-ray irradiation+miRNA-134-5p inhibitor negative control group(X-NC group).H9C2 cardiomyocytes were irradiated with 6 Gy X-ray,and the changes of various indexes were detected 48 h after irradiation.Cell viability was detected by cell counting kit 8 assay.The apoptosis rate was detected by flow cytometry and Hoechst 33342 staining.The level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescence probe.The mitochondrial membrane potential was detected by JC-1 method.The activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in cells were measured by kits.The expression of miRNA-134-5p was detected by quantitative polymerase chain reaction.The protein expression of brain-derived neurotrophic factor(BDNF),protein kinase B(Akt),phosphorylated Akt(p-Akt),Bcl2 and Bax was detected by Western blotting.Results Compared with the blank control group,in the X-ray group the levels of ROS and MDA were significantly increased,the activity of SOD was significantly decreased,the decreased percentage in mitochondrial membrane potential was significantly increased,the number of micronuclei of DNA damage was significantly increased,and the apoptosis rate was significantly increased(all P<0.01).Compared with the X-ray group,all the indexes of the X-inhibitor group were reversed(P<0.05 or P<0.01),while there was no significant difference in the above parameters in the X-NC group(all P>0.05).Compared with the blank control group,the X-ray group had a significant increase in the miRNA-134-5p level and significant reductions in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P<0.01).Compared with the X-ray group,the X-inhibitor group had a significant reduction in the level of miRNA-134-5p and significant increases in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P<0.01),and there was no significant difference in all parameters in the X-NC group(all P>0.05).Conclusion X-ray irradiation can induce oxidative stress,mitochondrial damage,and DNA damage,eventually leading to apoptosis in rat cardiomyocytes,and the mechanism may involve miRNA-134-5p/BDNF/Akt signaling pathway.
5.Differential expression and clinical significance of miR-124-3p in β-thalassemia
Luoyuan CAO ; Wenxu DONG ; Jing YANG ; Liwen GUO ; Jiaojiao LU ; Xian ZHENG ; Xianguo FU
Basic & Clinical Medicine 2024;44(12):1633-1637
Objective To investigate the differential expression of miR-124-3p in peripheral blood and clinical sig-nificance of patients with β-thalassemia.Methods Peripheral blood samples were collected from 33 patients with β-thalassemia and 30 healthy controls in Ningde Municipal Hospital Affiliated to Ningde Normal University from June 2021 to August 2022.The expression level of miR-124-3p was detected.Luciferase reporter gene was used to verify the interaction between miR-124-3p and ERF 3'UTR.The correlation between differential expression of miR-124-3p and β-thalassemia was analyzed and the clinical diagnostic value of miR-124-3p for β-thalassemia was eval-uated.Results Compared with healthy control individuals,the expression of miR-124-3p was significantly up-reg-ulated in patients with β-thalassemia(P<0.001).The genotype of miR-124-3p high expression group was 84.2%β0(16/19),the genotype of low expression group was 55.6%β+(10/18).ROC curve analysis showed that miR-124-3p had predictive efficacy for β-thalassemia(AUC:0.842).Luciferase reporter gene analysis showed that ERF gene was the regulatory target of miR-124-3p.Conclusions The differential expression of miR-124-3p in patients with β-thalassemia is closely related to the genotype and clinical severity of thalassemia,and ERF is negatively reg-ulated by miR-124-3p.miR-124-3p may be an effective diagnostic biomarker for β-thalassemia.
6.Role of three-dimensional speckle tracking imaging in predicting the prognosis of light-chain cardiac amyloidosis with normal left ventricular ejection fraction
Changhui LEI ; Liwen LIU ; Shengjun TA ; Jipeng YAN ; Wenxia LI ; Dong QU ; Xumei OU ; Lu YAO
Chinese Journal of Ultrasonography 2022;31(4):277-282
Objective:To evaluate the left ventricular myocardial strain in patients with light chain cardiac amyloidosis (AL-CA) with normal left ventricular ejection fraction (LVEF) by three-dimensional speckle tracking imaging(3D-STI), and to explore the clinical value of 3D-STI in predicting the prognosis of AL-CA patients with normal LVEF.Methods:A total of 80 patients with AL-CA and LVEF≥50% were retrospectively analyzed in the Xijing Hospital of Air Force Military Medical University from October 2014 to May 2020.According to whether the patients had endpoint events, they were divided into endpoint event group and non-endpoint event group. The clinical data, conventional echocardiographic parameters, 3D-STI related parameters and follow-up results were collected. Cox regression proportional hazards model was used to analyze the survival status of AL-CA patients with univariate and multivariate regression analyses, in order to find the relevant indicators of conventional echocardiography and 3D-STI to predict adverse events.Results:All patients were followed up for 20(7.3, 40.8) months. At the end of follow-up, 25 patients had all-cause deaths. Compared with the non-endpoint group, the endpoint event group had significantly increased left ventricular end diastolic maximum wall thickness (MLVWT), peak early diastolic flow velocity/peak early diastolic velocity at mitral annulus(E/e′) (all P<0.05), and decreased LVEF, left ventricular global longitudinal strain (GLS) and basal segment longitudinal strain (LS) (all P<0.05). Multivariate cox regression analysis after adjusting for age and gender showed that basal segment LS ( HR=0.812, 95% CI=0.675-0.976, P=0.026) was an independent predictor of end-point events in patients with AL-CA. Kaplan-Meier survival curve showed that AL-CA patients with basal segment LS≤13.07% were more likely to have endpoint events. Conclusions:Basal segment LS can be used as a predictor of endpoint events in patients with AL-CA.
7.Application of cosmetic suture technique in professional skill training of plastic surgery
Yuangang LU ; Liwen DONG ; Yuanyuan WANG ; Junbo ZHANG ; Xingcun ZHANG
Chinese Journal of Medical Aesthetics and Cosmetology 2021;27(3):187-190
Objective:To explore the training methods to improve the cosmetic suture technique of junior surgeons.Methods:The training course of cosmetic suture techniques was carried out for junior residents such as plastic surgery professional graduate students and standardized training residents, through the study of the basic knowledge of cosmetic suture and the practical training of minimally invasive principles, to help them master cosmetic suture techniques systematically for the need of future clinical practice. Compared with the level of operation skills before and after cosmetic suture training in different groups (graduate students of plastic surgery and other majors, standardized training residents of plastic surgery and other majors), the residents' performance had been significantly improved. The incisions healing after half a year follow-up in cases they sutured were observed.Results:After cosmetic suture training, the suture skills of the students were significantly improved, and there was a significant correlation with the time of clinical practice. The incidence of incisions inflammation and postoperative scar formation in the cases sutured by the students with practice for 6 months was significantly lower than those for 1 month (6.42% vs 21.67%, 1.13% vs 5.56% respectively).Conclusions:The training of cosmetic suture techniques is very important to improve the professional ability of junior residents in plastic and cosmetic surgery, and it needs a long time practice to master the suture skills.
8.Evaluation of the accuracy of the right superior pulmonary vein sheath compression in the closure of atrial septal defect based on multi-layer perceptron by ultrasound
Jieli ZHOU ; Dong HAN ; Liwen LIU ; Rui SI ; Huan LI ; Shiqian ZHANG ; Yun HU
Chinese Journal of Ultrasonography 2020;29(5):384-388
Objective:To evaluate the accuracy of measuring the siae of atrial septal defect(ASD) by transthoracic echocardiography(TTE) on " compression of right superior pulmonary vein sheath during operation" (compression-size) using multi-layer perceptron.Methods:From January 2016 to January 2019, 460 cases of ASD with soft margin, thin growth or central type with atrial septal tumor in the First Hospital Affiliated of Air Force Medical University were analyzed retrospectively. The age was (34.32±18.84)years, 129 males and 331 females. Preoperative TTE and intraoperative TTE were performed to measure the size of ASD and compression-size. With the final occluder size selected as the dependent variable, the preoperative and intraoperative ultrasound measurements were used as covariates, and all patients were randomly divided into training set, test set and verification set according to the proportion of 5∶2∶3, which were imported into multi-layer perceptron. Gradient descent method was used to optimize and adjust the weight, and 10 operations were carried out respectively, and the average value was calculated to evaluate the two ultrasound methods for blocking.Results:The mean values of ASD were (15.26±5.33)mm for preoperative, (23.83±6.39)mm for compression-size intraoperative TTE, and (25.14±6.55)mm for the occluder, respectively. The difference was statistically significant (χ 2=850.450, P<0.001). There were significant differences between the pairwise ( P<0.001). Ten times of multi-layer perceptron were used to obtain a training model for predicting the size of the occluder based on preoperative transthoracic ultrasound and TTE measurement after right upper pulmonary vein sheath compression. The average relative error of the model obtained by preoperative ultrasound measurement in the validation set was (16.55±0.02)%, and that of the model obtained by intraoperative ultrasound measurement in the validation set was (4.81±0.01)%. The difference between the two methods was statistically significant ( t=16.185, P<0.001). Conclusions:It is more accurate to measure the ASD size for selection of occluder by the use of the right superior pulmonary vein sheath compression and TTE, especially for ASD patients with soft margin, thin growth or atrial septal tumor.
9. Epidemiological characteristics of acute paraquat poisoning in children in southwest Shandong and related factors of pulmonary interstitial fibrosis
Mengxiao SHEN ; Jinlong LIU ; Lei HAN ; Xuemei SUN ; Shengying DONG ; Chengjun LIU ; Baohai SHI ; Hongfeng ZHU ; Liping CHEN ; Tong CHEN ; Liwen LI ; Bo LI ; Zhaohua ZHANG ; Youpeng JIN
Chinese Pediatric Emergency Medicine 2020;27(1):30-34
Objective:
To analyze the epidemiological characteristics of acute paraquat(PQ)poisoning in children in southwest Shandong, and the risk factors for pulmonary interstitial fibrosis.
Methods:
This retrospective study was performed on the clinical data of children with acute PQ poisoning admitted from January 2013 to December 2017 in 12 hospitals in southwest Shandong.All participants were divided into pulmonary interstitial fibrosis group and no pulmonary interstitial fibrosis group on the basis of the chest CT 14 days after poisoning.The epidemiological characteristics and risk factors of pulmonary interstitial fibrosis were analyzed.
Results:
During the study period, a total of 307 children with acute PQ poisoning were admitted to 12 hospitals, of which 61 (19.87%) were suffering from acute PQ poisoning.Forty-nine cases with complete clinical data were analyzed, including 26 male and 23 female patients poisoned by oral.The age distribution ranged from 8 months to 14 years.Poisoning mainly occured from July to September of each year.The mortality of acute PQ poisoning was 8.2%(4/49), and the incidence of pulmonary interstitial fibrosis in survival patients was 44.4%(20/45). Statistical differences (
10.Construction of clinical case database of scar prevention and treatment and its application in the teaching of plastic surgery
Yuangang LU ; Xiang LI ; Liwen DONG ; Junbo ZHANG ; Yuanyuan WANG ; Xingcun ZHANG
Chinese Journal of Medical Education Research 2020;19(10):1218-1221
This study introduces that we have established a clinical case database of scar prevention and treatment with medical histories, diagnosis and treatment ideas, and case expansion according to the scar diseases that professional postgraduates of plastic surgery need to master, and applied it to the practical teaching for plastic surgery postgraduates. Through the comprehensive evaluation from three aspects of mastering basic knowledge, applying knowledge and developing discipline, it's suggested that the professional postgraduates can better grasp the knowledge of scar prevention and treatments after learning from the clinical scar database, and the application of the teaching case database has further improved students' teaching and learning participations and innovative thinking abilities.

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