1.ATP5J regulates mitochondrial function through TOMM20 and promotes metastasis of human hepatocellular carcinoma cells
Junzhi LENG ; Genwang WANG ; Di LIU ; Kejun LIU ; Qi WANG ; Yongfeng HUI
Chinese Journal of Pathophysiology 2024;40(3):431-437
AIM:To explore the mechanism of ATP synthase mitochondrial F0 complex H+ transporting,sub-unit F6(ATP5J)in affecting the metastasis of hepatoma carcinoma cells by regulating mitochondrial function-mediated cy-toskeletal remodeling.METHODS:Hepatocellular carcinoma cells Li-7 were used to construct the ATP5J overexpression and knockdown models.JC-1 staining was used to detect the mitochondrial membrane potential in each group,reactive oxygen species(ROS)levels were examined by DCHF-DA,and mitochondrial ATP fluorescence probe was used to assess mito-chondrial function.Cytoskeletal remodeling was detected with a microfilament green fluorescent probe(Actin-Tracker Green-488).Transwell assay was used to assess cell invasion ability.The expression levels of ATP5J and translocase of outer mitochondrial membrane 20(TOMM20)were determined by Western blot.RESULTS:Overexpression of ATP5J up-regulated mitochondrial membrane potential and mitochondrial ATP fluorescence intensity,induced cytoskeletal re-modeling,promoted cell invasion and TOMM20 expression,and inhibited ROS production(P<0.01).On the contrary,knockdown of ATP5J significantly decreased mitochondrial membrane potential and mitochondrial ATP fluorescence inten-sity,significantly decreased cell invasion ability and TOMM20 expression,promoted ROS production and blocked cyto-skeletal remodeling(P<0.01).CONCLUSION:ATP5J regulates mitochondrial energy transformation in hepatocellular carcinoma cells,and affects metastasis of hepatoma carcinoma cells by regulating mitochondrial membrane potential and mitochondrial ATP production-mediated cytoskeletal remodeling through TOMM20.
2.Design and implementation of mobile medical force information system for diversified medical rescue missions
Pei LIU ; Hao HUANG ; Kejun ZHANG ; Yaping YU ; Rong ZHANG
Military Medical Sciences 2024;48(8):614-619
Objective To design a safe,stable,flexible,and scalable information system for mobile medical forces to enhance the efficiency of command and casualty treatment during diversified medical rescue missions.Methods A mobile medical force information system was developed with a layered architecture based on both Browser/Server(B/S)and Client/Server(C/S)frameworks.In this system,the front-end presentation layer was developed with Vue.js architecture,the back-end application layer by SpringCloud and Mybatis frameworks,the data management layer was devised using MySQL and Redis databases to provide standard data interfaces for other systems.This system covered several functional modules including command,casualty triage and evacuation,minor injury treatment,severe injury rescue,emergency surgery,medical service,and logistical support,which could be flexibly configured according to different types of missions.Results Information about casualty treatment was recorded in detail,accessed and traced easily.The efficiency of information statistics was improved.Conclusion The developed system enhances the efficiency of decision-making and casualty management for mobile medical forces during varied medical rescue missions.
3.CT Imaging Characteristics of Severe(Grade 3-4)Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer
Bofeng ZHAO ; Yamin ZHANG ; Ping CHEN ; Wei FENG ; Jinpeng LIU ; Kejun NAN ; Baoying CHEN
Chinese Journal of Medical Imaging 2024;32(9):903-907
Purpose To observe the clinical and CT features of severe immune checkpoint inhibitor-related pneumonitis(CIP)in lung cancer patients.Materials and Methods A total of 174 patients with lung cancer who received immune checkpoint inhibitor(PD-1/PD-L1 inhibitors)in Xi'an International Medical Center Hospital from September 1,2019 to March 31,2022 were retrospectively collected.Clinical and imaging features of patients with severe CIP were analyzed.Results There were 23 patients who met the diagnostic criteria of severe CIP.Among them,22 were male patients,15 were younger(<65 years old),17 had a history of underlying lung disease,16 had a history of chemoradiotherapy and other treatments,and 21 had a history of combined radiotherapy and chemoradiotherapy.The median time from the initiation of immune checkpoint inhibitor to CIP was 128(74,348)days.19 patients were non-small cell carcinoma.CIP occurred in 16 patients with right lung cancer,15 had tumor central airway invasion,14 had radiographic features of diffuse alveolar injury/acute interstitial pneumonia pattern,and 20 died during follow-up.Conclusion Severe CIP is likely to occur in male lung cancer patients with a history of basic medical history and radiotherapy and chemotherapy.The clinical manifestations are varied,and the main imaging features are diffuse alveolar injury/acute interstitial pneumonia pattern,and the prognosis is poor.
4.Study on the Diagnosis Model of Phlegm-Dampness Obstruction Syndrome in Patients with Stable Angina Pectoris Due to Coronary Heart Disease Based on Machine Learning
Haoran CHEN ; Tong JIANG ; Yi ZHENG ; Weiwei WANG ; Ying LIU ; Kejun WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(12):142-150
Objective To construct a diagnostic model for the phlegm-dampness obstruction syndrome in patients with coronary heart disease stable angina pectoris(CSAP);To provide a reference for clinical syndrome differentiation.Methods Totally 305 patients'clinical data were collected from the Department of Cardiology,Dongying Hospital Affiliated to Shandong University of Traditional Chinese Medicine,from May 2022 to January 2024.The least absolute shrinkage and selection operator(LASSO)was used to select features,and multiple models were constructed and compared using machine learning(ML)algorithms.The optimal ML model was selected for training,validation,and testing.Finally,the operational logic of the optimal model was explained using Shapley Additive Explanations(SHAP),and two typical examples were provided to help users understand the model's operational logic.Results LASSO regression identified chest pain,body mass index(BMI),limb heaviness,drinking history,age,triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)as features included in the model.After comparing multiple models,the Gaussian Naive Bayes(GNB)model demonstrated the best performance.The final constructed GNB model achieved an average AUC of 0.938(95%CI:0.903-0.972)in the training set,an average AUC of 0.927(95%CI:0.851-0.992)in the validation set,and an AUC of 0.856(95%CI:0.751-0.961)in the test set.The learning curve showed that the error between the training and validation sets in the model converged as the number of training samples increased.The calibration curve showed that the model had good consistency in predicting the probability of observed phlegm-dampness obstruction syndrome patients.The clinical decision curve(DCA)showed that the model could provide clinical benefits for patients at a decision threshold below 0.7.The features ranked by SHAP importance in order were chest pain,BMI,LDL-C,TG,limb heaviness,TC,drinking history and age.Conclusion The diagnostic model for CSAP phlegm-dampness obstruction syndrome constructed in this study can assist physicians in the syndrome differentiation of patients,thereby enabling the formulation of integrated clinical treatment plans combining traditional Chinese and Western medicine,and aiding patients in achieving better clinical therapeutic outcomes.
5.Effects of glycosylated nanoparticles on radiation-induced the polarization of macrophages in early injured lung tissue
Kejun LI ; Liqing DU ; Qiang LIU ; Huijuan SONG
Chinese Journal of Radiological Medicine and Protection 2023;43(11):858-865
Objective:To explore the effects of glycosylated nanoparticles on early radiation responses including the generation of reactive oxygen species (ROS), the polarization of pulmonary macrophages, and secretion of inflammatory cytokines in mice lung tissues.Methods:Twenty mice were randomly divided into control group, drug administration group, irradiation group and irradiation + drug administration group. The irradiation group and irradiation + drug administration group were subjected to whole lung irradiation with X-rays. The antioxidant ability of glycosylated nanoparticles was characterized using ROS indicator (CM-H 2DCFDA). The M2 polarization of pulmonary macrophages was detected by flow cytometry and PCR. The mRNA and protein expression levels of inflammatory cytokines were investigated by PCR and ELISA assay, respectively. Results:Compared with the irradiation group, the intensity of ROS fluorescence signals was significantly lower ( t=15.76, P < 0.05), the proportion of M2-type macrophages was significantly higher ( t=2.89, P < 0.05), the expression level of arginase 1 (ARG-1) gene was elevated, and the expression levels of tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) inflammatory factors were significantly reduced ( t=3.32, 2.90, 2.85, 4.55, 2.88, P < 0.05) in the lung tissues of irradiation + treatment group. Conclusions:Glycosylated nanoparticles can effectively scavenge ROS, trigger polarization of M2 macrophage, dampen inflammatory responses, and thus potentially alleviate radiation-induced lung injury.
6.Research about clinical comprehensive evaluation methods of pediatric drugs :taking pediatric anti-allergic drugs as an example
Lu LIU ; Yue XIAO ; Chang LIU ; Suxin QU ; Rong LI ; Baodong YU ; Xiaomei MO ; Kejun LIU ; Meixing YAN
China Pharmacy 2022;33(2):142-145
OBJEC TIVE To provide reference for clinical comprehensive evaluation of pediatric drugs in China. METHODS Taking pediatric anti-allergic drugs as an example ,the clinical comprehensive evaluation methods of pediatric drugs in medical institutions were explored from the aspects of theme selection ,evaluation content and dimension ,evaluation index ,evaluation method and evaluation result report. RESULTS & CONCLUSIONS During the clinical comprehensive evaluation of pediatric drugs,under the guidance of relevant national guidelines for clinical comprehensive evaluation ,the evaluation topics could be selected according to the three principles of importance ,relevance and evaluability ,and then an appropriate evaluation index system could be developed around the six dimensions of safety , effectiveness, economy, suitability,accessibility and innovativeness;qualitative and quantitative data integration analysis of the drugs to be evaluated were performed. In the evaluation , it is necessary to focus on children ’s clinical basic drug use practice and decision-making needs ,normatively,scientifically and reasonably define the core index set and standard data set required by different dimensions of evidence ,standardize the collection and use of real-world data ,and effectively combine other types of evidence to truly play its advantageous role in the clinical comprehensive evaluation of pediatric drugs in China.
7.Gingival mesenchymal stem cells inhibited senescence of type Ⅱ alveolar epithelial cells and prevented radiation-induced pulmonary fibrosis
Wenyue ZHAO ; Na LI ; Kejun LI ; Yan WANG ; Ningning HE ; Liqing DU ; Qiang LIU
Chinese Journal of Radiological Medicine and Protection 2022;42(11):830-838
Objective:To investigate whether transplantation of gingival mesenchymal stem cells (GMSCs) can inhibit radiation-induced senescence of alveolar epithelial cells type Ⅱ (AECⅡ) and its role in the prevention of radiation-induced pulmonary fibrosis (RIPF).Methods:Mouse type Ⅱ alveolar epithelial cells (MLE12) were irradiated with 6 Gy X-rays and then co-cultured with GMSCs. The extent of cellular senescence of MLE12 cells was assessed by cell morphology, β-Gal staining, and senescence secretion-associated phenotype (SASP) assay. RIPF model was constructed by unilaterally irradiating the right chest of C57BL/6 mice with 17 Gy X-rays. GMSCs were transplanted 1 d after irradiation. At 180 d after irradiation, the pulmonary organ ratio, HE staining, and Masson staining were used to assess intra-pulmonary structure and interstitial collagen deposition in the lung. β-Gal immunohistochemistry and immunofluorescence co-localization with AECⅡ were measured to assess the degree of cellular senescence in the lung. The SASP expression changes in lung tissue were detected by qRT-PCR. The protein expressions in P53-P21 and P16 pathways were detected by Western blot assay. P21 expression in AECⅡ was detected by immunofluorescence co-localization assay.Results:GMSCs effectively inhibited radiation-induced senescence of MLE12 cells, reduced the ratio of radiation-elevated β-Gal positive cells by 11.8% ( t=6.72, P<0.05), and decreased the expressions of SASP (IL-6, IL-8, IL-1β) ( t=28.43, 28.43, 4.82, P<0.05). GMSCs transplantation improved the survival rate of irradiated mice, prevented radiation-induced alveolar structural collapse thickening and collagen deposition, reduced the number of senescent cells in the irradiated lung tissues by 23.9% ( t=21.83, P<0.05), and inhibited the expressions of SASP ( t=8.86, 20.63, P<0.05). GMSCs also inhibited the expression of P53-P21, P16-related proteins in MLE12 cells and lung tissues of mice after irradiation. Conclusions:GMSCs inhibit senescence-related P53-P21 and P16 pathways, prevent radiation-induced AECⅡ senescence, as well as the development of RIPF.
8.Role of umbilical cord mesenchymal stem cell transplantation in alleviating alveolar cell senescence
Wenyue ZHAO ; Na LI ; Kejun LI ; Liqing DU ; Qiang LIU
Chinese Journal of Radiological Health 2022;31(3):259-265
Objective:
To investigate whether the transplantation of umbilical cord mesenchymal stem cells (UC-MSCs)
can alleviate radiation-induced pulmonary fibrosis (RIPF) and attenuate intrapulmonary cellular senescence in mice with
RIPF.
Methods:
The C57BL/6 mice were unilaterally irradiated with 17 Gy in the right lung to construct RIPF models. UC-
MSCs were injected into the caudal vein at 3 months after radiation, and samples were taken at 6 months. The survival rate of
mice was recorded, and the lung organ ratio was calculated. Lung structure and collagen deposition were observed by hem-
atoxylin-eosin staining and Masson staining. The expression of senescence secretion-associated phenotype (SASP) was
measured by quantitative real-time polymerase chain reaction. Intrapulmonary cellular senescence was assessed by β-Gal im-
munohistochemistry. The expression of key proteins in the P53-P21 and P16 pathways was measured by Western blot. P21
expression in the lung was measured by tissue immunofluorescence.
Results:
Compared with the untreated group, RIPF
mice treated with UC-MSCs showed an improved survivalrate, reduced collagen deposition, and an improvement incollapse
and thickening of alveolar structure. Increased β-Gal-positive senescent cells and high expression of SASP (IL-6, IL-8, IL-
1β) in the lung of RIPF mice were all reduced after UC-MSC treatment. The abnormally increased levels of P53, p-P53, P21
and P16 proteins in RIPF mice were reduced by UC-MSC treatment.
Conclusion
UC-MSCs may reduce cellular senes-
cence in fibrotic lungs and alleviate RIPF by inhibiting P53-P21 and P16 pathways, which is expected to be used for the
treatment of radiation-induced lung injury.
9.Clinical efficacy of an integrated traditional Chinese and Western medication regimen on depression in the elderly
Fang HUANG ; Zhiyuan HUANG ; Kejun LIU ; Yuan ZHANG ; Guiwen LI
Chinese Journal of Geriatrics 2021;40(12):1565-1567
Objective:To evaluate the clinical efficacy of an integrated traditional Chinese and Western medication regimen on depression in the elderly.Methods:Sixty elderly patients with depression were randomly divided into two groups.The integrated traditional Chinese and Western medicine group was treated with an in-house preparation composed of traditional Chinese medicine ingredients plus Escitalopram oxalate for 4 weeks, and the control group was treated with Escitalopram oxalate for 4 weeks.The clinical efficacy was assessed by the Hamilton depression(HAMD)scale.Adverse drug reactions were assessed by the treatment emergent symptoms scale(TESS).Results:After 4 weeks of treatment, HAMD scores in both groups were decreased compared with those before treatment, with a greater reduction in HAMD scores in the integrated traditional Chinese and Western medicine group than in the control group(0.71±4.36 vs. 0.52±3.45, t=2.54, P=0.03). TESS scores were lower in the integrated traditional Chinese and Western medicine group than in the control group after 4 weeks of treatment(8.42±5.30 vs.16.01±7.02, t=3.25, P=0.02). Conclusions:Compared with Western medicine therapy alone, the integrated traditional Chinese and Western medication regimen has better efficacy and fewer adverse drug reactions for the treatment of depression in the elderly.
10.Effect of hybrid intensity modulated radiotherapy on the immune function of patients with locally advanced breast cancer surgery and efficacy observation
Kejun DAI ; Xujing LU ; Xifa ZHOU ; Mingming FANG ; Ling CHEN ; Jun LIU ; Yuqiong DING ; Cheng GU
Cancer Research and Clinic 2020;32(11):766-771
Objective:To investigate the effect of hybrid intensity modulated radiotherapy (Hy-IMRT) on immune function in patients with locally advanced breast cancer surgery and the treatment efficacy.Methods:A total of 94 patients with locally advanced breast cancer who underwent modified radical mastectomy for breast cancer and required postoperative radiotherapy in Changzhou Cancer Hospital in Jiangsu Province from January 2015 to January 2017 were selected. The patients were divided into Hy-IMRT group (observation group, 47 cases) and three-dimensional conformal radiotherapy (3DCRT) group (control group, 47 cases) according to the random number table method. The dose and related radiophysical parameters of the respective target areas of the two groups, adverse reactions during and after radiotherapy, cytokines and T lymphocyte subsets before and after radiotherapy, 3-year local recurrence rate, distant metastasis rate and mortality were observed and compared between the two groups.Results:The dose obtained by 95% (D 95%) [(4 945.6±36.1) Gy vs. (4 754.0±35.6) Gy] and target area conformity (CI) of the target volume (0.7±0.1 vs. 0.5±0.1) in the observation group were greater than those in the control group, and the differences were statistically significant (both P<0.05); the target volume of 110% of the prescription dose (V 110%) [(1.6±0.5) cm 3 vs. (8.4±1.2) cm 3], the target volume of more than 105% of the prescription dose (V 105%) [(19.3±3.5) cm 3 vs. (26.6±5.6) cm 3] and the heterogeneity index (HI) (1.1±0.1 vs. 1.3±0.1) in the observation group were all smaller than those of the control group, and the differences were statistically significant (all P < 0.05). The incidence of acute skin adverse reactions [53.2% (25/47) vs. 74.5% (35/47)] and the incidence of bone marrow suppression [40.4% (19/47) vs. 70.2% (33/47)] in the observation group were lower than those in the control group, and the differences were statistically significant (both P < 0.05). There were no significant differences in levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), CD4 +, CD8 +, and CD4 +/CD8 + between the two groups before radiotherapy (all P > 0.05). At the end of radiotherapy, the levels of IL-6, TNF-α and CD8 + were higher in both groups than before radiotherapy (all P < 0.05), and CD4 + and CD4 +/CD8 + were lower than before radiotherapy (both P < 0.05). The levels of IL-6, TNF-α and CD8 + in the observation group were lower than those in the control group, while the CD4 + and CD4 +/CD8 + were higher than those in the control group (all P < 0.05). The 3-year local recurrence rate [34.04% (16/47) vs. 42.55% (20/47)], distant metastasis rate [25.53% (12/47) vs. 38.30% (18/47)] and mortality rate [14.89% (7/47) vs. 19.15% (9/47)] in the observation group were lower than those in the control group, but the differences were not statistically significant (all P > 0.05). Conclusion:Compared with 3DCRT, the Hy-IMRT has less effect on the immune function of locally advanced breast cancer patients after modified radical resection, and the incidences of acute skin reaction and bone marrow adverse reaction are low.


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