1.Clinical trial of tislelizumab combined with chemotherapy in the treatment of patients with stage Ⅲb-Ⅳ non-small cell lung cancer
Xiao-Xue LI ; Yi ZHANG ; Shu-Yang YAO ; Jing-Ying NONG
The Chinese Journal of Clinical Pharmacology 2024;40(3):335-339
Objective To analyze the effect of tislelizumab combined with chemotherapy in the treatment of stage Ⅲb-Ⅳ non-small cell lung cancer(NSCLC)and its influence on T lymphocyte immunity and survival prognosis.Methods Patients with NSCLC were divided into control group and treatment group according to different treatment methods.The control group was treated with platinum-containing dual-drug combined chemotherapy regimen(PC regimen:intravenous drip of pemetrexed 500 mg·m-2 on the 1st day and intravenous drip of carboplatin with area under plasma concentration-time curve(AUC)=5 mg·mL-1·min-1 on the 1st day;TP regimen:intravenous drip of taxol 135 mg·m-2 on the 1st day,and intravenous drip of carboplatin with AUC=5 mg·mL-1·min-1 on the 1st day to 3rd day).The treatment group was given tislelizumab 200 mg intravenously once every 3 weeks on the basis of the control group.Both groups were treated for 2 cycles by taking 3 weeks as 1 treatment cycle.The clinical efficacy,serum tumor markers levels,T lymphocyte immune function,progression-free survival(PFS)and overall survival(OS)and occurrence of adverse drug reactions during treatment were compared between the two groups.Results There were 40 cases in control group and 40 cases in treatment group.After treatment,the total effective rates in control group and treatment group were 40.00%(16 cases/40 cases)and 62.50%(25 cases/40 cases),the disease control rates were 70.00%(28 cases/40 cases)and 90.00%(36 cases/40 cases),carcinoembryonic antigen(CEA)levels were(9.21±2.03)and(5.42±1.36)ng·mL-1,carbohydrate antigen 125(CA125)levels were(72.53±8.16)and(31.95±5.08)U·mL-1,carbohydrate antigen 19-9(CA19-9)levels were(25.79±3.31)and(10.38±2.04)U·mL-1,cytokeratin19 fragment antigen 21-1(CYFRA21-1)levels were(6.47±1.34)and(4.26±0.91)ng·mL-1,CD3+levels were(54.36±5.81)%and(61.85±4.96)%,CD4+levels were(31.28±2.93)%and(43.08±3.15)%,CD4+/CD8+were 1.43±0.40 and 1.91±0.46,survival rates were 47.37%(18 cases/38 cases)and 67.57%(25 cases/37 cases),PFS were 7.73 months(95%CI:6.42-9.03)and 9.75 months(95%CI:8.68-10.82),and OS were 8.96 months(95%CI:7.94-9.97)and 10.52 months(95%CI:9.78-11.27)respectively(all P<0.05).There were no statistically significant differences in the incidence of gastrointestinal reactions,liver dysfunction,bone marrow suppression,hypothyroidism and non-infectious pneumonia between both groups(all P>0.05).Conclusion Tislelizumab combined with chemotherapy has a good effect in the treatment of stage Ⅲb-Ⅳ NSCLC,and it can effectively reduce the levels of serum tumor markers,improve the T lymphocyte immune function,and prolong the survival time of patients,with good safety.
2.Expression of LINC01152 in glioma and its effect on malignant biological behavior of glioma cells
Xin Li ; Chang Liu ; Chunhong Xue ; Ping Wang ; Feng Li ; Yingying Ge ; Weixia Nong ; Qingmei Zhang ; Xiaoxun Xie ; Bin Luo
Acta Universitatis Medicinalis Anhui 2023;58(4):622-629
Objective:
To study the expression of long non-coding RNA LINC01152 in glioma and its influence on the malignant biological behavior of glioma cells.
Methods:
LINC01152 expression in glioma was analyzed by LncSpA V2.0 and GEPIA database.qRT-PCR was applied to detect the expression of LINC01152 mRNA in 10 samples of human normal brain tissues,40 samples of glioma tissues and 5 glioma cell lines.GO and KEGG enrichment analysis of LINC01152 co-expressed genes were performed using the DAVID database to predict the related functions. The AnoLnc2,TargetScan,LinkedOmics and miRDB databases were used to predict the LINC01152 related miRNAs and target genes to construct a ceRNA regulatory network.LINC01152 expression was knocked down in glioma cell lines by small interfering RNA (siRNA) transfection.The CCK-8 test,scratch healing experiments,Transwell,flow cytometry and Western blot experiments were used to measure the influence of LINC01152 on the proliferation,migra- tion,invasion and apoptosis of glioma cells.
Results :
Database analysis showed that compared with other tumor types,LINC01152 was highly expressed in glioblastoma (GBM) and low grade glioma (LGG) ,and was higher than normal brain tissue.qRT-PCR showed that the expression of LINC01152 mRNA in glioma tissues was significantly higher than that in normal brain tissues (P<0. 01).The expression of LINC01152 was correlated with Ki-67 (P < 0. 05) ,but not with clinical parameters such as gender,age,tumor size,P53 protein,glial fibrillary acidic protein (GFAP) ,O-6-methylguanine-DNAmethyltransferase ( MGMT) and WHO grade of glioma patients. Functional enrichment analysis of co-expressed genes indicated that the LINC01152 was mainly involved in biological processes such as cell adhesion and synaptic signaling.LINC01152-miRNA-mRNA regulatory network was constructed according to predicted target genes.After down-regulation of LINC01152 expression,the proliferation,migration and invasion abilities of A172 and U87 cells decreased(P<0. 01) ,while the apoptosis of glioma cells significantly increased (P<0. 001) .
Conclusion
LINC01152 is highly expressed in glioma,which can promote the malignant biological behavior of glioma cells by enhancing proliferation,migration as well as invasion and inhibition of apoptosis.
3.Study on knowledge, attitudes and practices of pulse oximetry among pediatric healthcare providers in China and their influencing factors
Fengxia XUE ; Yuejie ZHENG ; Adong SHEN ; Hanmin LIU ; Xing CHEN ; Lili ZHONG ; Guangmin NONG ; Xin SUN ; Gen LU ; Shenggang DING ; Yuanxun FANG ; Jiahua PAN ; Zhiying HAN ; Yun SUN ; Qiang CHEN ; Yi JIANG ; Xiaoping ZHU ; Suping TANG ; Xiufang WANG ; Changshan LIU ; Shaomin REN ; Zhimin CHEN ; Deyu ZHAO ; Yong YIN ; Rongfang ZHANG ; Ming LI ; Yunxiao SHANG ; Yaping MU ; Shuhua AN ; Yangzom YESHE ; Peiru XU ; Yan XING ; Baoping XU ; Jing ZHAO ; Shi CHEN ; Wei XIANG ; Lihong LI ; Enmei LIU ; Yuxin SONG ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(23):1807-1812
Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.
4.Type 1 diabetes induced by immune checkpoint inhibitors.
Rui ZHANG ; Xiao-Ling CAI ; Liu LIU ; Xue-Yao HAN ; Li-Nong JI
Chinese Medical Journal 2020;133(21):2595-2598
With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.
CTLA-4 Antigen
;
Diabetes Mellitus, Type 1/chemically induced*
;
Humans
;
Immune Checkpoint Inhibitors
;
Immunologic Factors/therapeutic use*
;
Immunotherapy/adverse effects*
;
Neoplasms/drug therapy*
5.Effects of Ganoderma Triterpenoids on Learning and Memory Impairment in Rats with Epilepsy
Xue-juan NONG ; Jia-xi JIN ; Bing-yu ZHOU ; Li-feng ZHANG ; Jian-wei HONG ; Shuang ZHAO
Chinese Journal of Rehabilitation Theory and Practice 2020;26(4):440-446
Objective:To study the effect of Ganoderma triterpenoids combined with exogenous monosialoteterahexosyl ganglioside (GM1) on cognitive dysfunction in rats with epilepsy. Methods:A total of 75 Sprague-Dawley rats were divided randomly into blank control group, epileptic model group, Ganoderma triterpenoids group, GM1 group and GM1 combined with Ganoderma triterpenoids group (combination group), with 15 rats in each group. All the groups, except the blank control group, were intraperitoneally injected with pentylenetetrazol (PTZ) 35 mg/kg once a day for 28 days. Medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ. They were tested with Morris Water Maze; and were observed with transmission electron microscopy and HE staining for hippocampal neurons. Real-time quantitative polymerase chain reaction was used to detect the expression of actin-binding protein (Cofilin), synaptophysin (SYN) and growth-associated protein 43 (GAP-43) mRNA in hippocampus of rats. Results:Compared with the blank control group, the escape lantency prolonged in the epileptic model group in all the time points (
6.Effect of Mixed Inoculation of Arbuscular Mycorrhizal on Growth and Chemical Composition of Aucklandia lappa Seedlings
Wen-chao GU ; Wen-wu YANG ; Jie ZHANG ; Min YANG ; Bo DING ; Dong-qin GUO ; Xing-jiao PAN ; Yan-bin XUE ; Nong ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(14):173-181
Objective:To explore the synergistic effect of arbuscular mycorrhizal(AM) fungi mixed inoculation on the growth,physiological and biochemical characteristics,root biomass and terpenoid component accumulation of
7.Advances on nonviral vectors of CRISPR/Cas9 system for genome editing
Yu WANG ; Gui HUANG ; Han YANG ; Xue-nong ZHANG
Acta Pharmaceutica Sinica 2020;55(11):2606-2617
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein system exerts genome editing effect through cleaving DNA double strands using RNA-guided endonuclease. Double-strand breaks were repaired
8.Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma.
Xu He LIAO ; Rong Fu WANG ; Meng LIU ; Xue Qi CHEN ; Yan XIONG ; Lin NONG ; Lei YIN ; Bing Ye ZHANG ; Yu Jing DU
Journal of Peking University(Health Sciences) 2020;53(2):246-254
OBJECTIVE:
To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics.
METHODS:
Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve.
RESULTS:
The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis.
CONCLUSION
High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.
Adenocarcinoma of Lung/genetics*
;
Anaplastic Lymphoma Kinase/genetics*
;
ErbB Receptors/genetics*
;
Fluorodeoxyglucose F18
;
Genes, erbB-1
;
Humans
;
Lung Neoplasms/genetics*
;
Mutation
;
Positron Emission Tomography Computed Tomography
;
Prognosis
;
Radiopharmaceuticals
;
Retrospective Studies
;
Tumor Burden
9.Study on the ARIMA model application to predict echinococcosis cases in China
En-Li TAN ; Zheng-Feng WANG ; Wen-Ce ZHOU ; Shi-Zhu LI ; Yan LU ; Lin AI ; Yu-Chun CAI ; Xue-Jiao TENG ; Shun-Xian ZHANG ; Zhi-Sheng DANG ; Chun-Li YANG ; Jia-Xu CHEN ; Wei HU ; Xiao-Nong ZHOU ; Li-Guang TIAN
Chinese Journal of Schistosomiasis Control 2018;30(1):47-53
Objective To predict the monthly reported echinococcosis cases in China with the autoregressive integrated mov-ing average(ARIMA)model,so as to provide a reference for prevention and control of echinococcosis. Methods SPSS 24.0 software was used to construct the ARIMA models based on the monthly reported echinococcosis cases of time series from 2007 to 2015 and 2007 to 2014,respectively,and the accuracies of the two ARIMA models were compared. Results The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2015 was ARIMA(1,0,0)(1,1, 0)12,the relative error among reported cases and predicted cases was-13.97%,AR(1)=0.367(t=3.816,P<0.001),SAR (1)=-0.328(t=-3.361,P=0.001),and Ljung-Box Q=14.119(df=16,P=0.590).The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2014 was ARIMA(1,0,0)(1,0,1)12,the relative error among reported cases and predicted cases was 0.56%,AR(1)=0.413(t=4.244,P<0.001),SAR(1)=0.809(t=9.584, P<0.001),SMA(1)=0.356(t=2.278,P=0.025),and Ljung-Box Q=18.924(df=15,P=0.217).Conclusions The different time series may have different ARIMA models as for the same infectious diseases.It is needed to be further verified that the more data are accumulated,the shorter time of predication is,and the smaller the average of the relative error is.The estab-lishment and prediction of an ARIMA model is a dynamic process that needs to be adjusted and optimized continuously accord-ing to the accumulated data,meantime,we should give full consideration to the intensity of the work related to infectious diseas-es reported(such as disease census and special investigation).
10.Effect of osthole on p38 MAPK signaling related pathway of rat model with inflammatory radicular pain induce by nucleus pulposus in the spinal horn
Jia-Ming ZHANG ; Zeng-Xing YI ; Shi-Qing LIN ; Yi-Min WANG ; Zhe CAI ; Ming WEI ; Lai-Bao SUN ; Xue-Nong ZOU
Chinese Pharmacological Bulletin 2018;34(2):237-243
Aim To observe the effect of epidurally application of osthole on the model of nucleus pulposusinduced inflammatory radicular pain and the expression of p38 MAPK signaling related pathway in the spinal dorsal horn of rats.Methods The model of radicular pain was generated by putting nucleus pulposus to the L5 dorsal root ganglion (DRG).50% MWT was measured using Von Frey filaments to calculate mechanical pain threshold before and after operation.50 μL of 20 g · L-1 osthole was administered epidurally in group Ost and 50 μL of 100 mL · L-1 DMSO in group DMSO at postoperative day (POD).The expression of phosphorylated p38 (p-p38),IL-18 and IL-18R in the lumbar spinal dorsal horn was detected by Western blot.IL-18 mRNA was assessed by real-time PCR.Results The mechanical pain threshold significantly decreased after operation (P < 0.05),while the expression of protein p-p38 MAPK,IL-18,IL-18R and IL-18 mRNA was significantly different.Compared with DMSO group,50% MWT was significantly increased and accompanied with the decrease of protein p-p38,IL-18,IL-lgR and IL-18 mRNA in Ost group after drug administration (P < 0.05).The correlation analysis between protein concentration of p38 MAPK and IL-18 mRNA showed that the Spearman correlation coefficient was 0.9 (P < 0.05).Conclusion p-p38 and IL-18 of spinal dorsal horn participate in the rat model with inflammatory radicular pain induced by nucleus pulposus,and IL-18R plays a role in maintenance of the pain.Osthole administered epidurally in the early stage of pain could alleviate the pain for a long time,which may be related with inhibiting p38 MAPK signaling related pathways.


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