1.Comparison of Short-term Efficacy of Neoadjuvant Immunotherapy Combined with Chemotherapy and Surgery Alone for Locally Advanced Resectable Non-small Cell Lung Cancer
LI HAITIAN ; LIU QING ; LI BIN ; CHEN YUZHEN ; LIN JUNPING ; MENG YUQI ; FENG HAIMING ; ZHENG ZHIZHONG ; HUI YIMING
Chinese Journal of Lung Cancer 2024;27(6):421-430
Background and objective Lung cancer is the cancer with the highest incidence and mortality rates in China,and non-small cell lung cancer(NSCLC)accounts for 80%-85%of all malignant lung tumors.Currently,surgical treat-ment remains the primary treatment modality for lung cancer.In recent years,the effectiveness of immune checkpoint inhibi-tors for NSCLC has become a consensus,and neoadjuvant immunochemotherapy(nICT)has shown promising efficacy and safety in early to intermediate stage NSCLC.However,there are fewer studies related to nICT for locally advanced NSCLC.This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC.Methods 85 con-firmed resectable stage ⅢA and ⅢB patients treated in the Department of Thoracic Surgery,Second Hospital of Lanzhou University,from January 2021 to April 2024,were divided into the nICT group(n=32)and the surgery alone group(n=53).Clinical baseline data,perioperative indicators,postoperative complications,imaging response rate,pathological response rate,incidence of adverse events,and quality of life were compared between the two groups.Results There were no statisti-cally significant differences in clinical baseline data between the two groups(P>0.05).Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group(P=0.002).There were no significant differences in surgical time,intraoperative blood loss,number of dissected lymph nodes,duration of chest tube placement,postoperative hospital stay,and R0 resection rate between the two groups(P>0.05).The overall incidence of postoperative complications was 31.25%in the nICT group and 22.64%in the surgery alone group,with no statistically significant difference(P=0.380).In the nICT group,the objective response rate(ORR)was 84.38%,with 5 cases of complete response(CR)(15.63%),22 cases of partial response(PR)(68.75%),15 cases of pathological response rate(pCR)(46.88%),and 11 cases of major pathological reaponse(MPR)(34.38%).During nICT treatment,12 cases(37.50%)experienced grade 3 treatment-related adverse events,no death induced by adverse events or immune related adverse events.Moreover,the symptoms of the patients were improved after nICT treat-ment.Conclusion Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC,with manageable treatment-related adverse events.It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.
2.Impact of pumpkin polysaccharides on hypoxia/reoxygenation-induced myocardial cell injury by regulating Nrf2/γ-GCS pathway
Wan ZHENG ; Shanshan YANG ; Yun LIN ; Junping WEI ; Yani YAN
Chinese Journal of Immunology 2024;40(9):1871-1875
Objective:To investigate the impact of pumpkin polysaccharide(PP)on hypoxia/reoxygenation(H/R)-induced myocardial cell(H9C2)injury by regulating Nrf2/γ-GCS pathway.Methods:HR cell models were established,and the concentration of pumpkin polysaccharide(PP)was determined.H9C2 cells were grouped into Control group,H/R group,pumpkin polysaccharide group(PP group,2 mg/L PP),Nrf2 inhibitor group(ML385 group,2.0 μmol/L ML385),and PP+ML385 group(2.0 mg/L PP+2.0 μmol/L ML385),the apoptosis,mitochondrial membrane potential changes,oxidative stress(LDH,MDA,SOD,ROS),the lev-els of inflammatory factors(TNF-α,IL-6,IL-1β)and the protein expressions of Nrf2 and γ-GCS in H9C2 cells were detected,respec-tively.Results:Compared with Control group,H/R group had changes in cell morphology,the cell injury and mitochondrial membrane potential decreased,the H9C2 cell viability,SOD and protein expression levels of Nrf2 and γ-GCS were significantly decreased,while the apoptosis rate,LDH,MDA,ROS,and levels of TNF-α,IL-6 and IL-1β were significantly increased(P<0.05);compared with H/R group,the cell injury in PP group was reduced,the mitochondrial membrane potential was restored,the H9C2 cell viability,SOD and protein expression levels of Nrf2 and γ-GCS were significantly increased,and the apoptosis rate,LDH,MDA,ROS,and levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05),the effect of ML385 was opposite to that of PP,and ML385 could reverse the antioxidant and anti-inflammatory effects of PP.Conclusion:PP up-regulates the Nrf2/γ-GCS pathway to exert antiox-idant and anti-inflammatory effects,and reduces H/R-induced H9C2 cell injury.
3.Effect of bone marrow mesenchymal stem cell-derived exosomes on myocardial fibrosis in rats induced by isoproterenol and its mechanism
Junping WEI ; Dajia FU ; Qingwen MENG ; Daofei LIN ; Yanzai LIN
Journal of Jilin University(Medicine Edition) 2024;50(5):1348-1357
Objective:To discuss the effect of bone marrow mesenchymal stem cells(BMSCs)-derived exosomes(Exo)on isoproterenol(ISO)-induced myocardial fibrosis in the rats,and to clarify its mechanism.Methods:The Exo was isolated from the BMSCs and characterized by transmission electron microscope,nanoparticle tracking analysis,and Western blotting methods.Forty SD rats were divided into control group,model group,BMSCs-Exo group,and BMSCs-Exo+ferroptosis activator(Erastin)group,and there were 10 rats in each group.The myocardial fibrosis models were established by subcutaneous injection of ISO in all the rats except control group.The rats in BMSCs-Exo and BMSCs-Exo+Erastin groups were given BMSCs-Exo,and the rats in BMSCs-Exo+Erastin group were additionally injected with Erastin intraperitoneally.After 4 weeks,echocardiography was used to detect the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end diastolic diameter(LVEDD),and left ventricular end systolic diameter(LVESD)of the rats in various groups;HE staining was used to observe the pathomorphology of myocardium tissue of the rats in various groups;Masson staining was used to observe the fibrosis degrees of myocardium tissue of the rats in various groups;immunohistochemistry was used to detect the positive expression rates of α-smooth muscle actin(α-SMA),type Ⅰ collagen(COL-Ⅰ),and type Ⅲ collagen(COL-Ⅲ)in myocardium tissue of the rats in various groups;colorimetry was used to detect the Fe2+level in myocardium tissue of the rats in various groups;Western blotting method was used to detect the expression levels of acyl-CoA synthetase long chain family member 4(ACSL4),ferritin heavy chain 1(FTH1),glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11)proteins in myocardium tissue of the rats in various groups.Results:The particles isolated from BMSCs had a typical lipid bilayer structure,and most particle sizes distributed around 100 nm.High expression levels of CD63,CD9,tumor susceptibility gene 101(TSG101),and heat shock protein 70(HSP70)proteins confirmed the particles as Exo.Compared with control group,the LVEF and LVFS of the rats in model group were significantly decreased(P<0.05),LVEDD and LVESD were increased(P<0.05),the myocardial cell arrangement was disordered,some nuclear shrinkage and necrosis were seen,the collagen volume fraction(CVF)was significantly increased(P<0.05),the positive expression rates of α-SMA,COL-Ⅰ,and COL-Ⅲ were significantly increased(P<0.05),the Fe2+level in myocardium tissue was significantly increased(P<0.05),the expression level of ACSL4 protein was significantly increased(P<0.05),and the expression levels of FTH1,GPX4,and SLC7A11 proteins were significantly decreased(P<0.05).Compared with model group,the LVEF and LVFS of the rats in BMSCs-Exo group were significantly increased(P<0.05),the LVEDD and LVESD were significantly decreased(P<0.05),the myocardial tissue damage was significantly alleviated,the CVF was significantly decreased(P<0.05),the positive expression rates of α-SMA,COL-Ⅰ,and COL-Ⅲ were significantly decreased(P<0.05),the Fe2+level in myocardium tissue was significantly decreased(P<0.05),the expression level of ACSL4 protein was significantly decreased(P<0.05),and the expression levels of FTH1,GPX4,and SLC7A11 proteins were significantly increased(P<0.05).Compared with BMSCs-Exo group,the LVEF and LVFS of the rats in BMSCs-Exo+Erastin group were significantly decreased(P<0.05),the LVEDD and LVESD were significantly increased(P<0.05),the myocardial cell edema and necrosis were seen,the CVF was significantly increased(P<0.05),the positive expression rates of α-SMA,COL-Ⅰ,and COL-Ⅲ were significantly increased(P<0.05),the Fe2+level in myocardium tissue was significantly increased(P<0.05),the expression level of ACSL4 protein was significantly increased(P<0.05),and the expression levels of FTH1,GPX4,and SLC7A11 proteins were significantly decreased(P<0.05).Conclusion:BMSC-derived Exo can improve the myocardial fibrosis in the rats induced by ISO,and its mechanism may be related to the inhibition of ferroptosis.
4.Relationship between DDX46 gene and invasion and metastasis behaviors of TE-1 esophageal squamous cell carcinoma cells
Junping LIN ; Yuqi MENG ; Bin LI ; Haiming FENG ; Zheng LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):1030-1037
Objective To investigate the relationship between DDX46 genes and invasion and migration of esophageal squamous cell carcinoma cells. Methods Human esophageal squamous cell carcinoma cells TE-1 were transfected by fluorescent marker shRNA lentivirus (shDDX46 group), and an empty vector was transfected as a control (shCtrl group). The expression rate of green fluorescent protein under the microscope was used to evaluate the cell transfection efficiency. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blotting (WB) detected the knockdown efficiency of the target gene at the mRNA and protein expression levels. Wound healing, invasion assay and migration assay detected the changes of invasion and metastasis ability. Classical pathway analysis was used to explore signaling pathway changes and the possible mechanism of DDX46 in the invasion and metastasis was explored by detecting fibronectin expression. Results DDX46 gene at mRNA and protein levels was significantly inhibited after lentiviral transfection. Wound healing showed that after 8 h the cell mobility of TE-1 cells decreased significantly (P=0.001). Invasion assay showed that after 24 h the average cell metastasis rate of TE-1 cells was lower in the shDDX46 group than that in the shCtrl group (P<0.001). The cell metastasis rate in the shDDX46 group corresponding to observation points in the transwell assay was lower than that in the shCtrl group (P<0.001) after 24 h culture. The results of the classical pathway analysis showed that the integrin signaling pathway activity was inhibited, further exploration of the mechanism of action found that the expression of fibronectin associated with cell adhesion was decreased. Conclusion DDX46 gene is related to the invasion and migration ability of esophageal squamous cell carcinoma cells. Knockdown of DDX46 genes may reduce cell adhesion by downregulating the integrin pathway signaling.
5.Application progress of mobile health in nursing of patients with infertility
Xiaoyan WANG ; Lin LIU ; Zhuoqun YANG ; Huihui LIU ; Mengyue PEI ; Junping HU
Chinese Journal of Practical Nursing 2023;39(23):1836-1841
This article firstly reviews the current application status of mobile health based on social networking media, mobile health applications, wearable devices in infertility patients′nursing. Then, this paper analyzes the application effects of mobile health in the five aspects of treatment process management, health education, medication management, lifestyle management and psychological care for infertility patients based on the literature. The existing problems are analyzed and prospected on this basis, in order to provide a reference for the application of mobile health to infertility patients′nursing in China.
6.Status of HVPG clinical application in China in 2021
Wen ZHANG ; Fuquan LIU ; Linpeng ZHANG ; Huiguo DING ; Yuzheng ZHUGE ; Jitao WANG ; Lei LI ; Guangchuan WANG ; Hao WU ; Hui LI ; Guohong CAO ; Xuefeng LU ; Derun KONG ; Lin SUN ; Wei WU ; Junhui SUN ; Jiangtao LIU ; He ZHU ; Dongliang LI ; Wuhua GUO ; Hui XUE ; Yu WANG ; Jiancuo GENGZANG ; Tian ZHAO ; Min YUAN ; Shirong LIU ; Hui HUAN ; Meng NIU ; Xin LI ; Jun MA ; Qingliang ZHU ; Wenbo GUO ; Kunpeng ZHANG ; Xiaoliang ZHU ; Birun HUANG ; Jianan LI ; Weidong WANG ; Hongfeng YI ; Qi ZHANG ; Long GAO ; Guo ZHANG ; Zhongwei ZHAO ; Kai XIONG ; Zexin WANG ; Hong SHAN ; Mingsheng LI ; Xueqiang ZHANG ; Haibin SHI ; Xiaogang HU ; Kangshun ZHU ; Zhanguo ZHANG ; Hong JIANG ; Jianbo ZHAO ; Mingsheng HUANG ; Wenyong SHEN ; Lin ZHANG ; Feng XIE ; Zhiwei LI ; Changlong HOU ; Shengjuan HU ; Jianwei LU ; Xudong CUI ; Ting LU ; Shaoqi YANG ; Wei LIU ; Junping SHI ; Yanming LEI ; Jinlun BAO ; Tao WANG ; Weixin REN ; Xiaoli ZHU ; Yong WANG ; Lei YU ; Qiang YU ; Huiling XIANG ; Wenqiang LUO ; Xiaolong QI
Chinese Journal of Hepatology 2022;30(6):637-643
Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.
7.Expression of PD-1/PD-L1 in esophageal squamous cell carcinoma and its relationship with survival prognosis: A systematic review and meta-analysis
Qiyao YU ; Bin LI ; Haiming FENG ; Junping LIN ; Ci YIN ; Zheng LI ; Xuan LI ; Yiming SUN ; Wenjie MAO ; Jie LI ; Cui XIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(11):1352-1359
Objective To systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis. Methods The literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis. Results A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.000 1). Conclusion PD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.
8.Screening for differential genes of the esophageal squamous cell carcinoma after DDX46 knockdown and bioinformatics analysis of their interaction
LI Bin ; LI Zheng ; YIN Ci ; LIN Junping ; YANG Jianbao ; ZHU Duojie ; FENG Haiming ; JING Tao
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(01):61-67
Objective To explore the mechanism of DDX46 regulation of esophageal squamous cell carcinoma. Methods Picture signals of fluorescence in gene array were scanned and differential expression of gene in two groups (a DDX46-shRNA-LV group and a control-LV group) were compared by GCOSvL.4 software. These differential expressed genes were analyzed by bioinformatics methods finally, and validated by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Results According to the screening criteria of fold change ≥2 and P<0.05, 1 006 genes were differentially expressed after DDX46 knockdown, including 362 up-regulated and 644 down-regulated genes. Bioinformatics analysis and gene co-expression network building identified that these differentially expressed genes were mainly involved in cell cycle, proliferation, apoptosis, adhesion, energy metabolism, immune response, etc. Phosphatidylinositol 3-kinase (PI3K) was the key molecule in the network. The results of RT-qPCR were completely consistent with the results of gene microarra. Conclusion Bioinformatics can effectively exploit the microarray data of esophageal squamous cell carcinoma after DDX46 knockdown, which provides a valuable clue for further exploration of DDX46 tumorigenesis mechanism and helps to find potential drug therapy.
9.Stratified outcomes of "Kidney Disease: Improving Global Outcomes" serum creatinine criteria in critical ill patients: a secondary analysis of a multicenter prospective study
Guiying DONG ; Junping QIN ; Youzhong AN ; Yan KANG ; Xiangyou YU ; Mingyan ZHAO ; Xiaochun MA ; Yuhang AI ; Yuan XU ; Yushan WANG ; Chuanyun QIAN ; Dawei WU ; Renhua SUN ; Shusheng LI ; Zhenjie HU ; Xiangyuan CAO ; Fachun ZHOU ; Li JIANG ; Jiandong LIN ; Erzhen CHEN ; Tiehe QIN ; Zhenyang HE ; Lihua ZHOU ; Bin DU
Chinese Critical Care Medicine 2020;32(3):313-318
Objective:To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China.Methods:A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKI SCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL·min -1·1.73 m -2, and AoCKD was defined as meeting the KDIGO-AKI SCr standard and baseline eGFR was 15-59 mL·min -1·1.73 m -2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. Results:Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients ( n = 322), AoCKD patients ( n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL·min -1·1.73 m -2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (μmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio ( HR) = 4.458, 95% confidence interval (95% CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU ( HR = 5.181, 95% CI was 2.033-13.199, P = 0.001), and AoCKD ( HR = 5.377, 95% CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. Conclusion:Further detailed classification (PAKI, AoCKD) based on KDIGO-AKI SCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.
10.Pituitary abscess: Report of three cases
Xiaojuan DU ; Wei LIN ; Liangchun CAI ; Nengying WANG ; Junping WEN ; Gang CHEN
Chinese Journal of Endocrinology and Metabolism 2020;36(4):337-341
Pituitary abscess is a rare but potentially life-threatening disease. Headache, visual disturbance, and hypopituitarism are the most common presenting symptoms of pituitary abscess. On magnetic resonance imaging(MRI), pituitary abscess may present as a round sellar cystic lesion, hypo- or isointense on T1 imaging and hyper- or isointense on T2 imaging with peripheral gadolinium enhancement. Diagnosis usually is made during surgical exploration when pus is found in a cystic lesion. The mainstay of treatment is transsphenoidal surgical resection in combination with antibiotic therapy, although a craniotomy approach is warranted in select conditions. Here we report 3 cases of pituitary abscess in our hospital and review the literatures.

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