1.Dapagliflozin attenuates endothelial cell pyroptosis and dysfunction induced by oxidized low-density lipoprotein
Quanwei ZHAO ; Hui LI ; Danan LIU ; Caiwei GONG ; Long CHEN
Chinese Journal of Tissue Engineering Research 2024;28(1):80-85
BACKGROUND:Dapagliflozin,an inhibitor of sodium-glucose cotransporter 2,can delay the progression of atherosclerosis by regulating glucose metabolism,inhibiting inflammation and improving endothelial cell function. OBJECTIVE:To study the effect of dapagliflozin on cell pyroptosis and endothelial dysfunction induced by oxidized low-density lipoprotein. METHODS:Human umbilical vein endothelial cells were divided into a control group(no intervention),a model group(treated with oxidized low-density lipoprotein for 24 hours),and a dapagliflozin group(treated with oxidized low-density lipoprotein + dapagliflozin for 24 hours).Endothelial cell proliferation activity was measured by cell counting kit-8 assay.The levels of intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 in cell supernatant were detected using ELISA.Nitric oxide level in the cells was detected by nitrate reductase assay.The pyroptosis rate and characteristics of endothelial cells were detected by Hoechst 33342/PI fluorescence co-staining and lactate dehydrogenase release assay.The protein expression levels of NLRP3,caspase-1,GSDMD,interleukin-1β,and interleukin-18 were detected by western blot assay. RESULTS AND CONCLUSION:(1)Oxidized low-density lipoprotein could cause pyroptosis and dysfunction of endothelial cells.(2)Compared with the control group,the level of nitric oxide and cell activity were decreased(P<0.05),while lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly increased in the model group(P<0.05).Compared with the model group,cell activity and nitric oxide levels significantly increased(P<0.05),but lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly diminished in the dapagliflozin group(P<0.05).(3)Compared with the model group,cell pyroptosis rate and the protein expression of pyroptosis factor NLRP3,caspase-1,GSDMD,interleukin-18 and interleukin-1β significantly reduced in the dapagliflozin group(P<0.05).(4)The results indicate that dapagliflozin inhibits oxidized low-density lipoprotein-induced endothelial pyroptosis and ameliorates endothelial cell dysfunction.
2.The role of dapagliflozin in ox⁃LDL⁃triggered pyroptosis of THP⁃1 ⁃derived foam cells
Caiwei Gong ; Guangjian Zhao ; Danan Liu ; Hangjun Ou ; Quanwei Zhao ; Hui Li
Acta Universitatis Medicinalis Anhui 2023;58(8):1366-1373
Objective :
To investigate the role of dapagliflozin ( DAPA) in ox⁃LDL⁃induced pyroptosis of human myeloid leukemia monocytes (THP⁃1) derived foam cells .
Methods :
THP⁃1 ⁃derived foam cell pyroptosis model was constructed by ox⁃LDL⁃induced THP⁃1derived macrophages . The experimental groups were set as follows : the blank control group(NC) , the ox⁃LDL group(ox⁃LDL) , and the drug intervention group(ox⁃LDL + DAPA) . Oil Red Ostaining was used to detect the foam cell levels of macrophages . The cell proliferation and toxicity assay kit was used to detect the effect of DAPA on foam cell viability . Hoechst 33342/propidium iodide(PI) double staining was used to detect THP⁃1 derived foam cell pyroptosis . Cell immunofluorescence double staining was used to detect the effect of DAPA on the expression of pyroptosis key factor Caspase⁃1 in foam cells . The activity of lactate dehydrogenase (LDH) in the cell culture medium was detected using a microplate enzyme⁃linked immunosorbent assay. qRT⁃PCR and Western blot were used to detect the mRNA and protein expression levels of Nod⁃like receptor pyrindomain containing 3 (NLRP3) , cystein⁃containing aspartate⁃specific protease⁃1( Caspase⁃1 ) , apoptosis⁃associated⁃speck⁃like protein containing CARD(ASC) ,gasdermin⁃D (GSDMD) , interleukin(IL) Ⅳ18 and IL⁃1β , respectively .
Results :
The CCK⁃8 assay indicated that the optimal intervention concentration of DAPA was 10 μmol/L. Oil Red O staining confirmed the successful construction of the THP⁃1 ⁃derived foam cell pyroptosis model . Compared with the blank control group , the expression levels of NLRP3 , Caspase⁃1 , ASC , GSDMD , IL⁃18 , IL⁃1β mRNA and protein significantly increased in ox⁃LDL group(P < 0. 05) , as well as the number of PI⁃positive cells and LDH activity(P < 0. 05) , the fluorescence intensity of Caspase⁃1 and the number of redlipid droplets in the cytoplasm of the cells . However , these effects were significantly reversed after DAPA intervention in the ox⁃LDL + DAPA group(P < 0. 05) .
Conclusion
DAPA inhibits ox⁃LDL⁃induced pyroptosis in THP⁃1 ⁃derived foam cells .
3.Prenatal ultrasonographic characteristics of fetal cortical dysplasia during second trimester
Li HOU ; Dongmei ZHANG ; Liuying ZHOU ; Qi ZHOU ; Yi YANG ; Caiwei YE ; Chuanqin LUO ; Hua LAI
Chinese Journal of Ultrasonography 2023;32(6):523-529
Objective:To analyze the fetal ultrasonographic features of malformation of cortical development (MCD) during the second trimester, and explore and summarize the relevant diagnostic clues, so as to improve the ability of diagnosis and differential diagnosis of fetal MCD.Methods:A total of 313 fetuses with brain abnormalities suspected on ultrasound in Chengdu Women′s and Children′s Central Hospital from April 2018 to August 2022 were retrospectively analyzed. The fetuses were examined using MRI. The ultrasonographic characteristics of fetal MCD were summarized, and the fetal ultrasound and MRI imaging data were compared for fetal MCD.Results:Nineteen fetuses were diagnosed with MCD from 313 fetuses(6.07%, 19/313). Seventeen cases of MCD were identified by ultrasonography and subsequently validated by fetal MRI, including 6 cases of schizencephaly, 2 cases of hemimegalencephaly(HMEG), 3 cases of periventricular nodular heterotopia(PVNH), 3 cases of lissencephaly, 2 cases of microcephaly and 1 case of polymicrogyria(PMG). There were 3 cases with two concurrent MCD, 1 case of HMEG, and MRI increased the diagnosis of left parietal PMG; 1 case of lissencephaly, and MRI increased the diagnosis of PVNH. The other case was PMG, and MRI increased the diagnosis of lissencephaly. Two cases of fetal MCD were not indicated by ultrasonography, one of which was diagnosed as tuberous sclerosis and another one as schizencephaly by MRI, both due to ventriculomegaly.Conclusions:Various types of MCD in the second trimester have ultrasonographic characteristics. Abnormal lateral ventricles, intracranial structural changes such as sulci and gyrus can provide reliable ultrasound diagnostic clues for fetal MCD.
4.Combination of cervical elastographic parameters and cervical length for the prediction of spontaneous preterm birth in second trimester of pregnancy
Dongmei ZHANG ; Li HOU ; Yang LIU ; Qi ZHOU ; Caiwei YE ; Yi YANG ; Guo LIN
Chinese Journal of Ultrasonography 2021;30(1):70-75
Objective:To evaluate the characteristics of cervical hardness and softness in the second trimester, and to explore the predictive value of the combination of cervical elastographic parameters and cervical length(CL) in spontaneous preterm birth (sPTB).Methods:The clinical data of 147 women with full-term birth(full-term birth group) and 24 women with sPTB(sPTB group) who received prenatal examination in Chengdu Women′s and Children′s Central Hospital from January 2018 to December 2019 were reviewed. Multiple parameters were measured between 16-28 gestational weeks by the transvaginal ultrasound E-cervix technique. CL, elasticity contrast index(ECI), hardness ratio(HR), mean strain at internal os(IOS), mean strain at external os(EOS), the ratio of IOS to EOS(IOS/EOS) were obtained.Elastographic parameters and CL were compared between the two groups. Furthmore, binary regression was established, while the area under ROC curve(AUC) was used to evaluate the predictive efficiency of elastographic parameters and CL in sPTB, both alone and in combination with other parameters.Results:The elastographic parameters IOS and IOS/EOS in the sPTB group were higher than those in the full-term birth group, while HR and CL were lower than those in the full-term birth group (all P<0.05). There were no statistical differences of ECI and EOS between the two groups(both P>0.05). The AUCs of predicting sPTB with single IOS, IOS/EOS were 0.684 and 0.625, higher than the AUCs of HR, CL. The combination of IOS/EOS and CL, IOS and CL showed higher AUCs than elastographic parameters alone, with the AUC 0.788 of IOS/EOS combined with CL. The sensitivity was 70.8%, and the specificity was 87.3% corresponding to the optimum cutoff value(IOS/EOS was 1.22, CL was 3.46 cm). Conclusions:In the second trimester, sPTB has a lower hardness cervix than that of full-term women, especially the internal os of cervix. The combination of IOS/EOS and CL tends to improve the ability of predicting sPTB in pregnant women.
5.A Retrospective Study of Mean Computed Tomography Value to Predict the Tumor Invasiveness in AAH and Clinical Stage Ia Lung Cancer.
Hanran WU ; Changqing LIU ; Meiqing XU ; Ran XIONG ; Guangwen XU ; Caiwei LI ; Mingran XIE
Chinese Journal of Lung Cancer 2018;21(3):190-196
BACKGROUND:
Recently, the detectable rate of ground-glass opacity (GGO ) was significantly increased, a appropriate diagnosis before clinic treatment tends to be important for patients with GGO lesions. The aim of this study is to validate the ability of the mean computed tomography (m-CT) value to predict tumor invasiveness, and compared with other measurements such as Max CT value, GGO size, solid size of GGO and C/T ratio (consolid/tumor ratio, C/T) to find out the best measurement to predict tumor invasiveness.
METHODS:
A retrospective study was conducted of 129 patients who recieved lobectomy and were pathological confirmed as atypical adenomatous pyperplasia (AAH) or clinical stage Ia lung cance in our center between January 2012 and December 2013. Of those 129 patients, the number of patients of AAH, AIS, AIS and invasive adenocarcinoma were 43, 26, 17 and 43, respectively. We defined AAH and AIS as noninvasive cancer (NC), MIA and invasive adenocarcinoma were categorized as invasive cancer(IC). We used receiver operating characteristic (ROC) curve analysis to compare the ability to predict tumor invasiveness between m-CT value, consolidation/tumor ratio, tumor size and solid size of tumor. Multiple logistic regression analyses were performed to determine the independent variables for prediction of pathologic more invasive lung cancer.
RESULTS:
129 patients were enrolled in our study (59 male and 70 female), the patients were a median age of (62.0±8.6) years (range, 44 to 82 years). The two groups were similar in terms of age, sex, differentiation (P>0.05). ROC curve analysis was performed to determine the appropriate cutoff value and area under the cure (AUC). The cutoff value of solid tumor size, tumor size, C/T ratio, m-CT value and Max CT value were 9.4 mm, 15.3 mm, 47.5%, -469.0 HU and -35.0 HU, respectively. The AUC of those variate were 0.89, 0.79, 0.82, 0.90, 0.85, respectively. When compared the clinical and radiologic data between two groups, we found the IC group was strongly associated with a high m-CT value, high Max CT value, high C/T ratio and large tumor size. Gender, solid tumor size, tumor size, C/T ratio, m-CT value and MaxCT value were selected factor for multivariate analysis, when using the preoperatively determined variables to predict the tumor invasiveness, revealed that tumor size, C/T ratio, m-CT value and Max CT value were independent predictive factors of IC.
CONCLUSIONS
The musurements of Max CT value, GGO size, solid size of GGO and C/T ratio were significantly correlated with tumor invasiveness, and the evaluation of m-CT value is most useful musurement in predicting more invasive lung cancer.
Adenocarcinoma
;
diagnosis
;
diagnostic imaging
;
mortality
;
pathology
;
Adult
;
Aged
;
Female
;
Humans
;
Lung Neoplasms
;
diagnosis
;
diagnostic imaging
;
mortality
;
pathology
;
Male
;
Middle Aged
;
Neoplasm Invasiveness
;
Neoplasm Staging
;
ROC Curve
;
Retrospective Studies
;
Tomography, X-Ray Computed
;
methods
6.A Comparative Study of Acute and Chronic Pain between Single Port and Triple Port Video-assisted Thoracic Surgery for Lung Cancer.
Caiwei LI ; Meiqing XU ; Guangwen XU ; Ran XIONG ; Hanran WU ; Mingran XIE
Chinese Journal of Lung Cancer 2018;21(4):279-284
BACKGROUND:
Through the comparative analysis of the acute and chronic pain postoperative between the single port and triple port video-assisted thoracic surgery to seek the better method which can reduce the incidence of acute and chronic pain in patients with lung cancer.
METHODS:
Data of 232 patients who underwent single port -VATS (n=131) or triple port VATS (n=101) for non-small cell lung cancer (NSCLC) on January 1, 2016 to June 30, 2017 in our hospital were analyzed. The clinical and operative data were assessed, numeric rating scale (NRS) was used to evaluate the mean pain score on the 1th, 2th, 3th, 7th, 14th days, 3th months and 6th months postoperative.
RESULTS:
Both groups were similar in clinical characteristics, there were no perioperative death in two groups. In the 1th, 2th, 7th, 14th days and 3th, 6th months postoperative, the NRS score of the single port group was superior, and the difference was significant compared with the triple port (P<0.05). There was no statistically significant difference between the two groups in operative time, blood loss, postoperative hospitalization time, duration of chest tube, the NRS scores in the 3 d (P>0.05). Univariate and multivariate analysis of the occurrence on the chronic pain showed that the operation time, surgical procedure and the 14th NRS score were risk factors for chronic pain (P<0.05).
CONCLUSIONS
The single port thoracoscopic surgery has an advantage in the incidence of acute and chronic pain in patients with non-small cell lung cancer. Shorter operative time can reduce the occurrence of chronic pain. The 14th day NRS score is a risk factor for chronic pain postoperative.
Acute Pain
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epidemiology
;
etiology
;
Aged
;
China
;
Chronic Pain
;
epidemiology
;
etiology
;
Female
;
Humans
;
Lung Neoplasms
;
complications
;
surgery
;
Male
;
Middle Aged
;
Pain, Postoperative
;
epidemiology
;
etiology
;
Retrospective Studies
;
Thoracic Surgery, Video-Assisted
;
methods
7.Analysis of short-and long-term outcomes after esophagectomy in elderly cancer pa-tients
Caiwei LI ; Hanran WU ; Guangwen XU ; Ran XIONG ; Meiqing XU ; Mingran XIE
Chinese Journal of Clinical Oncology 2018;45(10):508-512
Objective:To analyze the short-and long-term outcomes of elderly patients after esophagectomy by comparing preopera-tive comorbidities, postoperative complications, and survival rates among different age groups. Methods:We retrospectively reviewed the data of 253 patients who underwent esophagectomy from January to December 2010 in The First Affiliated Hospital of University of Science and Technology of China. Eighty-eight (34.8%) patients were aged<60 years (group A), 145 (57.3%) were aged 60-75 years (group B), and 20 (7.9%) were aged≥75 years (group C). The short-and long-term outcomes of the patients were analyzed. Results:There were significant differences in three group of patients with hypertension before operation (P<0.05). There were statistically sig-nificant differences among all complications, major complications, pulmonary infection, arrhythmia, and respiratory insufficiency (P<0.05), except for anastomotic leakage and other complications (P>0.05). The mean follow-up was 50.7 months. The median overall sur-vival and 1-, 3-, and 5-year overall survival rates were 68 months and 98.9%, 86.8%, and 69%, respectively, for group A;61 months and 93.1%, 76.1%, and 51%, respectively, for group B;and 32 months and 63.3%, 46%, and 28.8%, respectively, for group C (P<0.001). The median progression-free survival (PFS) and 1-, 3-, and 5-year PFS rates were 60 months and 98.86%, 85.2%, and 45.5%, respectively, for group A;43 months and 87.6%, 53.1%, and 26.9%, respectively, for group B;and 11 months and 30%, 20%, and 10%, respectively, for group C (P<0.001). The differences in survival rates between groups A and B, A and C, and B and C were statistically significant (P<0.001). The multivariate analysis showed that age and TNM stage IV were independent risk factors for overall survival and PFS (P<0.05). Conclusions:The long-term survival rate decreases significantly in elderly patients with esophageal cancer. In addition, age and advanced pathological stage of tumor are independent risk factors for long-term outcomes.
8.Short-term Outcome of Uniportal and Three Portal Video-assisted Thoracic Surgery for Patients with Non-small Cell Lung Cancer.
Gaoxiang WANG ; Ran XIONG ; Hanran WU ; Guangwen XU ; Caiwei LI ; Xiaohui SUN ; Shibin XU ; Meiqing XU ; Mingran XIE
Chinese Journal of Lung Cancer 2018;21(12):896-901
BACKGROUND:
Currently, there are many reports on the advantages of three portal video-assisted thoracic surgery (VATS) in the treatment of lung cancer, but there are few reports on the comparison between uniportal and three portal video-assisted thoracic surgery. In this study, we aimed to evaluate the recent curative effect of the postoperative short-term quality of life between uniportal and three portal video-assisted thoracic surgery for non-small cell lung cancer.
METHODS:
We retrospectively evaluated 266 patients with NSCLC who underwent intended VATS lobectomy by a single surgical team in our ward between January 2016 and August 2017. The general clinical date, perioperative data and short-term life quality were individually compared and analyzed between the two groups.
RESULTS:
The two groups were similar in terms of clinicopathological features, total number of dissected lymph nodes and nodal stations, postoperative complications and pulmonary complications (P>0.05). Compared with three portal VATS, the intraoperative blood loss, chest tube duration, postoperative thoracic drainage, length of stay and NRS score were significantly decreased in uniportal VATS, with significant differences (P<0.05).
CONCLUSIONS
As a more minimally invasive surgery, uniportal VATS can be safely and effectively performed for resectable lung cancer, which would achieve even better operation curative effect than three portal VATS.
Aged
;
Carcinoma, Non-Small-Cell Lung
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pathology
;
surgery
;
Female
;
Humans
;
Lung
;
pathology
;
surgery
;
Lung Neoplasms
;
pathology
;
surgery
;
Middle Aged
;
Operative Time
;
Postoperative Complications
;
etiology
;
Quality of Life
;
Retrospective Studies
;
Thoracic Surgery, Video-Assisted
;
adverse effects
;
methods
;
Treatment Outcome
9.Prognostic Value of Neutrophil-to-lymphocyte Ratio in Patients with Lung Adenocarcinoma Treated with Radical Dissection.
Gaoxiang WANG ; Ran XIONG ; Hanran WU ; Guangwen XU ; Caiwei LI ; Xiaohui SUN ; Mingran XIE
Chinese Journal of Lung Cancer 2018;21(8):588-593
BACKGROUND:
Previous studies have shown that the neutrophil-to-lymphocyte ratio (NLR) has a significant impact on the prognosis of many malignant tumors such as gastric cancer, colorectal cancer and pancreatic cancer, but the study on the prognosis of patients with resectable lung adenocarcinoma is less. The aim of this study is to investigate the correlation between the NLR and the clinicopathologic features of adenocarcinoma of lung patients who underwent radical pneumonectomy. Furthermore, this study aimed to clarify the predictive and prognostic significance of NLR in patients who underwent pneumonectomy for lung adenocarcinoma.
METHODS:
This study reviewed the medical records of 163 patients with lung adenocarcinoma who underwent pneumonectomy. The receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off value of the NLR. Survival curves were described by Kaplan-Meier method and compared by Log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors.
RESULTS:
When the NLR value was 2.96, the Youden index was maximal, with a sensitivity of 77.5% and a specificity of 75.9%. The 5-year survival rate in the low NLR group was higher than that in the high NLR group (P<0.05). The univariate and multivariate analyses showed that TNM staging and NLR were independent factors in predicting survival rate.
CONCLUSIONS
The NLR value was a simple and useful tool to predict the prognosis of lung adenocarcinoma after radical pneumonectomy.
Adenocarcinoma
;
diagnosis
;
immunology
;
pathology
;
surgery
;
Adenocarcinoma of Lung
;
Aged
;
Cell Count
;
Female
;
Follow-Up Studies
;
Humans
;
Kaplan-Meier Estimate
;
Lung Neoplasms
;
diagnosis
;
immunology
;
pathology
;
surgery
;
Lymphocytes
;
cytology
;
Male
;
Middle Aged
;
Neoplasm Staging
;
Neutrophils
;
cytology
;
Pneumonectomy
;
Prognosis
;
ROC Curve
;
Retrospective Studies
10.A retrospective study of lymphadenectomy and conversive rate in uniportal video-assisted thoracoscopic pneumonectomy
Hanran WU ; Caiwei LI ; Ran XIONG ; Guangwen XU ; Jun WANG ; Meiqing XU ; Mingran XIE
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(9):513-517
Objective To discribe the technique for uniportal video-assisted thoracoscopic pneumonectomy and lymphadenectomy,and to evaluate the feasibility,safety and the short-term clinical outcomes of this approach.Methods The clinical data of 283 patients with resectable non-small cell lung cancer who received uniportal or three-port video-assisted thoracoscopic pneumonectomy between January 2015 and December 2016 was analyzed retrospectively.Of those 283 patients,151 underwent uniportal video-assisted thoracoscopic pneumonectomy and 132 underwent three-port video-assisted thoracoscopic pneumonectomy.The clinicopathologic factors,operatinal factors,postoperative complications,the number of total lymph nodes dissected or the stations of the total lymph nodes dissected,and conversive rate of the two groups were compared by t test and x2 test.Results The two groups were similar in terms of clinicopathologic data,postoperative complications,length of opertion and conversive rate(P > 0.05).The approach of uniportal video-assisted thoracoscopic pneumonectomy was associated with a significant decrease in surgical blood loss [(126.12 ± 212.13) ml vs.(178.61 ± 173.17) ml,P =0.02],volume of 3 days of post operative chest drainage [(505.25 ± 109.60) ml vs.(566.67 ± 233.35) ml,P =0.004],chest tube duration [(4.31 ±3.12)dvs.(6.93 ±3.10)d,P<0.001] and postoperative stay [(5.49 ± 4.77) d vs.(7.23±4.24)d,P=0.001].There was no significant difference between the two groups in the number of total lymph nodes dissected or the stations of the total lymph nodes dissected (P > 0.05).The stations of 4L and 5-13 in left lymphadenectomy and the stations of 2 R,3,4R and 7-13 in the right lymphadenectomy did not differ between the two groups(P > 0.05).Conclusion Our uniportal video-assisted thoracoscopic pneumonectomy can be safety and effectively performed for resectabte non-small cell lung cance with favorable early outcomes.


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