[Efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy as first-line treatment for epidermal growth factor receptor-mutant advanced non-small cell lung cancer].

Objective: To observe the clinical efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with chemotherapy as first-line treatment for EGFR mutant advanced non-small cell lung cancer (NSCLC). Methods: It was a retrospective, single-arm real-world study and a total of 39 patients with stage ⅢB to Ⅳ EGFR mutant NSCLC diagnosed in Cancer Hospital of Chinese Academy of Medical Sciences from July 2018 to December 2020 were collected. There were 16 males and 23 females, the age ranged from 25 to 73 years, with a median age of 53 years. All patients received EGFR-TKIs synchronously combined with pemetrexed and platinum-containing chemotherapy for 4-6 cycles as first-line treatment, followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse reactions were evaluated. Median follow-up time was 18.6 months (95%CI: 16.2-21.0 months). The Kaplan-Meier method was used for survival analysis. Results: The ORR was 61.5% (24/39), the DCR was 94.9% (37/39) and the median PFS was 16.4 months (95%CI: 12.1-20.7 months). The main adverse reactions were liver function injury (59.0%, 23/39), myelosuppression (43.6%, 17/39), skin reaction (25.6%, 10/39), gastrointestinal reaction (17.9%, 7/39), fatigue (12.8%, 5/39) and kidney injury (5.1%, 2/39). Most of the patients had grade 1-2 adverse reactions, and the rate of grade 3 adverse events were 12.8%(5/39), which were effectively alleviated after symptomatic support treatment, no grade 4 serious adverse events occurred. Conclusion: EGFR-TKIs synchronously combined with chemotherapy followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy has a certain therapeutic effect and fairly good safety, which can prolong PFS in patients with EGFR mutated advanced NSCLC.

[Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors].

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

LncRNA MAGI2-AS3 suppresses the proliferation and invasion of non-small cell lung carcinoma through miRNA-23a-3p/PTEN axis.

OBJECTIVE: To uncover the biological role of long non-coding RNA (lncRNA) MAGI2-AS3 in the progression of non-small cell lung carcinoma (NSCLC) and its molecular mechanism. PATIENTS AND METHODS: LncRNA MAGI2-AS3 level in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Chi-square test was conducted to analyze the correlation between MAGI2-AS3 level and pathological characteristics of NSCLC patients. Survival analysis was performed in NSCLC patients with high expression or low expression of MAGI2-AS3. In vitro influences of MAGI2-AS3 on viability and invasive ability of A549 and PC9 cells were evaluated. MicroRNA-23a-3p (miRNA-23a-3p), the target gene of MAGI2-AS3 was determined through the dual-luciferase reporter gene assay. In a similar way, the target gene of miRNA-23a-3p was identified. Finally, the regulatory effect of MAGI2-AS3/miRNA-23a-3p/PTEN (gene of phosphate and tension homology deleted on chromosome ten) axis on cellular behaviors of NSCLC cells was assessed. RESULTS: LncRNA MAGI2-AS3 was downregulated in NSCLC tissues and cell lines. Its level was closely related to tumor size, Tumor Node Metastasis (TNM) stage and distant metastasis of NSCLC patients. The worse prognosis was identified in NSCLC patients with low expression of MAGI2-AS3 relative to those with a high expression. Overexpression of MAGI2-AS3 markedly attenuated viability and invasive ability of A549 and PC9 cells. MiRNA-23a-3p was verified to be the target gene of MAGI2-AS3, and furthermore, PTEN was the target of miRNA-23a-3p. Overexpression of miRNA-23a-3p could reverse the inhibited viability and invasion in NSCLC cells overexpressing MAGI2-AS3. CONCLUSIONS: MAGI2-AS3 is downregulated in NSCLC. Overexpression of MAGI2-AS3 suppresses the proliferative and invasive abilities of NSCLC via miRNA-23a-3p/PTEN axis.

[Diagnostic efficacy of (18)F-FDG PET-CT for focal hypermetabolic thyroid nodules].

Objective: To explore the diagnostic efficacy of by (18)F-FDG PET-CT for hypermetabolic thyroid nodules. Methods: To retrospectively analyze the clinical data of 3 192 patients underwent (18)F-FDG PET-CT in our hospital from May 2012 to October 2014. Among them, 98 patients were diagnosed with focal hypermetabolic thyroid nodules. 61 of the 98 patients were diagnosed with malignant or benign thyroid nodules using histopathological or clinical follow-up (22 malignant nodules, 39 benign nodules). The average age of these 61 patients was 61.6±12.5 years. Results: The lgSUVmax of malignant group (0.69±0.31) was significantly higher than that in benign group (0.43±0.27) (P=0.001). There was no significant difference in age, gender, nodule size, minimum diameter of nodule, lgCT, calcification, the boundary definition, density uniformity, and history of malignancy between the two groups (P>0.05). Binary Logistic regression indicated the AUC of Logistic regressive model(AUC) was 0.866±0.049 (95% CI: 0.769-0.963), and the malignant AUCs of ROC curve was 0.747±0.068 (95%CI: 0.614-0.880) which was only determined by lgSUVmax. The difference was statistically significant (P<0.01). Conclusion: (18)F-FDG PET-CT imaging can not only detect hypermetabolic thyroid nodules, but also have a certain clinical value for the identification of benign and malignant nodules.

Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway.

OBJECTIVE: Mounting evidence suggests the role of microRNAs (miRNAs) in regulating inflammatory responses in various vascular diseases. Inflammation is the key mechanism leading to atherosclerosis (AS) and various miRNAs are aberrantly expressed in response to AS pathophysiology. However, there are very limited studies that serve to elucidate the role of specific miRNA in in vivo or in vitro AS models. MATERIALS AND METHODS: Microarray analysis of blood plasma of apolipoprotein deficient (apoE-/-) mice was performed followed by the confirmation using qPCR. Bone marrow mononuclear cells (BMMCs), plasma, and vessel tissue were obtained from apoE-/- mice that were induced with miR-126 mimic or inhibitor. Ox-LDL-induced THP-1 macrophages served as in vitro AS model. The release of inflammatory cytokines was detected using ELISA. The regulatory effect of miR-126 on MAP3K10 was confirmed by luciferase reporter activity and immunohistochemical analyses. RESULTS: The results showed that the miR-126 exhibited a greater fold change of expression in AS mice. Further, the functional role of miR-126 in atherosclerosis pathophysiology was demonstrated both in vivo and in vitro. miR-126 reduced the cytokine release and also decreased the AS progression. miR-126 was also found to be involved in mitogen-associated protein kinase (MAPK) signaling pathway. MAP3K10 was identified to be a direct target. CONCLUSIONS: miR-126 might serve as a biomarker of AS and its over-expression might prevent the AS progression and development.

Reversed aqueductal cerebrospinal fluid net flow in idiopathic normal pressure hydrocephalus.

OBJECTIVES: The changes of CSF flow dynamics in idiopathic normal pressure hydrocephalus (iNPH) are not fully elucidated. Most previous studies took the whole cardiac cycle as a unit. In this work, it is divided into systole and diastole phase and compared between iNPH patients and normal elderly and paid special attention to the change of netflow direction. MATERIALS AND METHODS: Twenty iNPH patients according to international guideline and twenty healthy volunteers were included in this study and examined by MRI. Three categories of CSF flow parameters were measured: peak velocity (Vpeak ), stroke volume (SV), and minute flow volume (MinV) covering the whole cycle; peak velocity (Vpeak-s , Vpeak-d ) and flow volume (Vols , Vold ) of the systole and diastole, respectively; net flow. Evans index (EI) was also measured and compared statistically between the two groups. RESULTS: EI, Vpeak , SV, MinV, Vols , Vold , and Vpeak-d significantly increased in iNPH group (P<0.05). Vpeak-s of the two groups were not significantly different (P>0.05). The net flow of 16 iNPH patients (16/20) was in the caudo-cranial direction, while 15 volunteers (15/20) were in the opposite direction, which showed statistically significant differences (P=.001). CONCLUSIONS: INPH patients present hyperdynamic flow with increased velocity and volume both in systole and diastole phase. Degree of rising in diastole phase exceeds that of systole phase. The resulting reversal of netflow direction may play a key role in the occurrence of ventriculomegaly in iNPH patients.

[Trend analysis and clinicopathological characteristics of 198 young patients with advanced lung adenocarcinoma].

Objective: The aim of this study was to analyze the trend of incidence, clinicopathological characteristics and therapy of young (less than 40 years old) patients with advanced lung adenocarcinoma, and to identify the prognostic factors. Methods: The clinical data of 198 young patients with advanced lung adenocarcinoma were collected from the Cancer hospital and Institute of Chinese academy of Medical Sciences from January 2001 to June 2012. To analyze the trend of incidence, clinicopathological characteristics and therapy and evaluate the independent prognostic factors affecting survival time with Cox proportional hazards model. Results: From 2001 to 2012, the incidence of lung adenocarcinoma in young patients was increased year by year. Among the 198 patients, 92 were males and 106 were females. Their age was from 20 to 40 with a median age of 34 years. Most patients had poorly differentiated adenocarcinoma (46.7%) whereas 36.7% of the cases had moderately differentiated tumor. Among the 198 patients, there were 25 patients with stage ⅢB (12.6%) and 173 (87.4%) cases of stage Ⅳ cancer.The 1-, 3- and 5-year survival rates were 70.7%, 21.6% and 10.3%, respectively. Among the198 cases, patients who received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, the median OS (25.6 months) was significantly longer than that of patients who never received EGFR-TKI therapy (13.3 months)(P<0.001). Since 2009, the number of cases detected for EGFR gene was gradually increased, and the median OS of patients diagnosed from 2010 to 2012 was 22 months, significantly higher than that of 16 months of patients diagnosed during 2001-2009 (P=0.019). The Cox regression analysis showed that the performance status, extra-pulmonary metastasis and whether received EGFR-TKI therapy were independent prognostic factors. Conclusions: The incidence rate of lung adenocarcinoma in young patients has an increasing trend. They have a high proportion of women and of poor differentiation. The patients can get benefits from EGFR-TKI therapy. Mutivariate Cox regression analysis shows that the performance status, extra-pulmonary metastasis and whether received EGFR-TKI therapy are independent prognostic factors for young patients with advanced lung adenocarcinoma.

[Retrospective analysis of albumin-bound paclitaxel in the treatment of elderly patients with advanced non-small cell lung cancer].

OBJECTIVE: To observe the safety and short-term efficacy of sigle drug albumin-bound paclitaxel (ABP) in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 23 elderly patients with advanced NSCLC who received weekly ABP regimen (130 mg/m(2)/week) in our hospital from October 2011 to March 2014 were retrospectively evaluated. The short-term efficacy, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median treatment period was 4 cycles (2-10 cycles). Partial response, stable disease, progressive disease, overall response rate, and disease control rate were 26.1%, 43.5%, 30.4%, 26.1% and 69.6%, respectively. The median PFS was 5.33 months (95% CI: 2.95-7.70 months), while the median OS was 40.33 months (95% CI: 29.82-50.83 months). Major adverse events included leucopenia (82.6%), neutropenia (78.3%), nausea or vomiting (56.5%), fatigue (52.2%), peripheral neuropathy (26.1%), myalgia/arthralgia (30.4%), thrombocytopenia (13.0%) and arrhythmia (4.3%). The patients accompanied with chronic diseases had significantly higher incidence rate of peripheral neuropathy and myalgia/arthralgia compared with the patients without accompanied chronic diseases (50.0% vs. 9.1% and 66.7% vs. 9.1%, P<0.05 for both). CONCLUSION: The weekly single drug ABP regimen is effective and well-tolerated in elderly patients with advanced NSCLC.

Preparation and characterization of tea polyphenols and vitamin E loaded nanoscale complex liposome.

The purpose of the present work was to prepare nanoscale complex liposome loaded both aqueous soluble drug tea polyphenols (TP) and insoluble drug vitamin E (VE) by reverse-phase evaporation method. The preparation formulation of TP-VE complex liposome was optimized by the orthogonal experiment. The entrapment efficiency of TP was (50.81 +/- 1.91)% while that of VE was (94.05 +/- 3.45)% for the optimal formulation. The results of penetration experiments of TP-VE liposome demonstrated a slight influence of the concentration of TP and the content of cholesterol on the penetration quantity of TP. These results indicate that the complex liposome offers a new approach to entrap aqueous soluble drug and poorly soluble drug, an inner liposome protection, a relatively high drug encapsulation efficiency and a sustained transdermal penetration.

[Inductive differentiation effect of ginsenosides on human acute non-lymphocytic leukemic cells in 58 patients].

Ginsenosides are the main active component of Panax ginseng. It has been shown that ginsenosides have antineoplastic, antiaging, immunologic function enhancing and other pharmacological actions. In this article, result of experimental studies showed ginsenosides extracted from stem and leaf of Panax ginseng (GSL) has inductive differentiation effect on all types of acute nonlymphocytic leukemia cells in primary culture. The effect on M5, M4 was most potent, followed by M1, M2 and the least, on M3. Through analysis, it was considered that the inductive differentiation effect of ginsenosides might be due to the comprehensive effect of increasing intracellular cAMP and inducing interferon. Since GSL have some other important actions, therefore, if it could be used as a differentiation inducer in clinical practice or combined with other antineoplastic drugs, it would show co-antineoplastic actions in many aspect.

Electroconvulsive treatment attenuates behavioral response to SKF 38393 in reserpine-treated mice.

Electroconvulsive treatment (ECT) of mice, once daily for 7 days, significantly reduced the stimulation of motor activity induced by the selective dopamine (DA) D1-receptor agonist SKF 38393 (15 mg/kg IP), but significantly increased the motor stimulation by the unselective DA-receptor agonist apomorphine (1.5 mg/kg IP) in reserpine-treated (10 mg/kg IP) mice, when compared to control mice, receiving sham ECT. The results provide a functional correlate to previously observed ECT-induced down-regulation of D1 receptor sites in DA-rich regions of the rodent brain. Such an effect may be significant for clinical actions of ECT in affective disorders and, possibly, in Parkinson's disease.