Cigarette Smoke Induces Gefitinib Resistance in NSCLC Cells via ROS/Sirt3/SOD2 Pathway / 中国肺癌杂志

BACKGROUND@#Epidermal growth factor receptor (EGFR) gene mutations are the most common driver mutations in non-small cell lung cancer (NSCLC). To prolong the survival of the patients, EGFR tyrosine kinase inhibitors (TKIs) resistance in NSCLC is a major challenge that needs to be addressed urgently, and this study focuses on investigating the mechanism of cigarette smoke (CS) induced Gefitinib resistance in NSCLC.@*METHODS@#PC-9 and A549 cells were cultured in vitro and treated with 1 µmol/L Gefitinib for 4 h and 10% cigarette smoke extract (CSE) for 48 h. Western blot was used to detect Sirtuin 3 (Sirt3) and superoxide dismutase 2 (SOD2) protein expressions; DCFH-DA probe was used to detect intracellular reactive oxygen species (ROS); CCK-8 kit was used to detect cell activity, and EdU was used to detect cell proliferation ability. Sirt3 overexpression plasmid (OV-Sirt3) was transfected in PC-9 and A549 cells and treated with 1 µmol/L Gefitinib for 4 h and 10% CSE for 48 h after N-acetylcysteine (NAC) action. The expressions of Sirt3 and SOD2 were detected by Western blot; the ROS level in the cells was detected by DCFH-DA probe, and the cell activity was detected by CCK-8.@*RESULTS@#CSE induced an increase in the 50% inhibitory concentration (IC50) of both PC-9 and A549 cells to Gefitinib (P<0.01) and enhanced the proliferation of PC-9 and A549 cells, suggesting that CS induced Gefitinib resistance in NSCLC. ROS was involved in CSE-induced Gefitinib resistance (P<0.05). CSE induced low expressions of Sirt3 and SOD2 (P<0.01), and Sirt3/SOD2 was associated with poor prognosis in lung cancer patients (P<0.05). OV-Sirt3 in PC-9 and A549 cells reversed CSE-induced Gefitinib resistance (P<0.05) and significantly reduced ROS production. NAC reversed CSE-induced Gefitinib resistance in PC-9 and A549 cells (P<0.05).@*CONCLUSIONS@#The ROS/Sirt3/SOD2 pathway is involved in CS-induced Gefitinib resistance in NSCLC.

The clinical analysis of scleral buckling for rhegmatogenous retinal detachment of 376 patients / 中华眼底病杂志

Objective:To analyze the clinical efficacy of scleral buckling surgery for rhegmatogenous retinal detachment (RRD) of 376 patients.Methods:A retrospective analysis was performed about 376 patients (391 eyes) who underwent scleral buckling surgery in Chengdu Aidi Eye Hospital from January 2018 to December 2019. There were 214 males (224 eyes) and 162 females (167 eyes). There were 15 binocular cases and 361 monocular cases. The average age was 37.16±16.36 years. The average course of disease was 3 months. There were 1 to more than 10 retina holes for all patients. Retinal breaks occur in all quadrants and at ora serrata. The preoperative average BCVA was 0.27 and the postoperative average BCVA was 0.41. Retinal detachment ranges was observed in 268 eyes in 1 quadrant, 97 eyes in 2-3 quadrants, 26 eyes in total, and 231 eyes with macular involvement. There were 376 eyes treated with scleral buckling, 9 eyes treated with scleral buckling combined with scleral encircling, 6 eyes treated with scleral encircling. The average follow-up time was 5 months. Postoperative follow-up was conducted to observe retinal reduction, BCVA, complications and patient compliance.Results:After the first operation, retinal reattachmnents were successfully achieved in 375 eyes (95.91%); 16 eyes (4.09%) failed in retinal reattachmnents. Eight eyes were treated with scleral buckling again, 5 eyes were treated with vitrectomy silicone oil filling, and 3 eyes were treated with air injection. After the second operation, retinal reattachmnents were ultimately achieved in 16 eyes (100.00%). The average BCVA after operation was 0.15. Postoperative intraocular pressure increased by 45 eyes (11.51%). The intraocular pressure increased from the next day to 3 days after operation. The intraocular pressure was completely controlled 1-3 days after the treatment of topical medication and 20% mannitol. Vitreous and subretinal hemorrhage in 1 eye caused by drainage of the subscleral liquid. There was no cases with postoperative infection.Conclusion:The retinal reattachment rate is 95.91% in 376 patients with RRD treated by scleral buckling surgery, and the visual acuity has significantly improved.

Role of phospholipid transfer protein in cigarette smoke-induced apoptosis of RLE-6TN cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of phospholipid transfer protein (PLTP) in cigarette smoke extract (CSE)-induced apoptosis of rat alveolar type II cells (RLE-6TN) in vitro.</p><p><b>METHODS</b>Rat alveolar epithelial cell line RLE-6TN were transfected with a small interfering RNA (siRNA) targeting PLTP prior to exposure to different concentrations of CSE for 24 or 48 h. The morphological changes of the apoptotic cells were observed by fluorescence microscopy with Hochest staining, and the cell apoptosis rate was measured with flow cytometry. The expression level of PLTP and caspase-3 activity in the cells were examined with Western blotting.</p><p><b>RESULTS</b>Exposure to CSE significantly increased the cell apoptosis rate from (1.68∓0.098)% to (18.663∓0.964)% (P<0.001). Hoechst staining revealed distinct apoptotic changes in CSE-treated cells, which showed increased PLTP expression and caspase-3 activity. PLTP knockdown with the specific siRNA partly suppressed the SCE-induced enhancement of caspase-3 activity in the cells.</p><p><b>CONCLUSION</b>PLTP may play a role in CSE-induced apoptosis of rat alveolar cells in vitro.</p>

Modulatory effect of Evodiamine on JAK2/STAT3 signal pathway in HCT-116 cells / 中国药理学通报

Aim To investigate the inhibitory effect of Evodiamine on JAK2/STAT3 signal pathway in human colorectal cancer cell line HCT-116 . Methods Cells were cultured with 6. 0 μmol·L-1 Evodiamine for 2, 4 and 6 h, respectively. Cell nuclear morphology was detected by Hoechst staining and protein expression levels of JAK2 , p-JAK2 , STAT3 and p-STAT3 were examined by Western blot. Cells were treated with dif-ferent concentrations of AG490 for 48 h to select proper working concentration and cells treated with 6 μmol · L-1 EVO and 50 μmol · L-1 AG490 to compare the modulatory effect of EVO with AG490 on JAK2/STAT3 signal pathway. Results Hoechst staining revealed that Evodiamine could induce cells apoptosis, chroma-tin condensation gathered and typical apoptotic mor-phological changes in a time-dependent manner;West-ern Blot suggested that EVO could inhibit p-STAT3 significantly. After treatment with AG490, JAK2/STAT3 signal pathway was inactivated, the inhibitory effect of EVO on p-STAT3 was stronger than that of AG490 , while EVO combined with AG490 could fur-ther inhibit the expression of p-STAT3 significantly. Conclusions The anticancer effect of Evodiamine is mainly mediated by the modulation of JAK2/STAT3 signal pathway in HCT-116 cells.

Correlation of CYP3A5 * 3 gene polymorphisms with sirolimus blood concentration in Chinese stable renal transplant recipients / 中华器官移植杂志

Objective To investigate the effect of CYP3A5 * 3 and MDR1C3435T polymorphisms on the blood trough concentration of sirolimus in the Chinese renal transplantation recipients with stable renal function and the influencing factors for individual differences.Method 112 cases of Chinese renal transplantation recipients with stable renal function were recruited in this study.Related data of the recipients,including gender,age,height and body mass,were recoded.CYP3A5 and MDR1 genotypes were determined by the direct sequencing.Blood trough concentration of sirolimus was measured by using chemiluminescence microparticle immuno assay (CMIA).The influencing factors of individual differences in sirolimus blood trough concentration was analyzed,and the correlation of CYP3A5 * 3 and MDR1C3435T gene polymorphisms with sirolimus blood trough concentration was evaluated.Result Of the 112 cases,there were 10 cases (8.93％) of CYP3A5 * 1/* 1,49 cases (43.75％) of CYP3A5 * 1/* 3,and 53 cases (47.32％) of CYP3A5 * 3/* 3.Allele frequencies of CYP3A5 * 1 and * 3 were 30.81％ and 69.19％,respectively.There were 31 recipients (27.68％) with MDR1 3435CC,60 (53.57％) with MDR1 3435CT,and 21 (18.75％) with MDR1 3435TT.Allele frequencies for C and T at position 3435 of MDR1 were 54.46％ and 45.54％,respectively.In this study,recipients' CYP3A5 * 3 genotype was the main factor (P =0.000) of sirolimus blood trough concentration,but dose,gender,age,height,postoperative time,the level of serum creatinine,hemoglobin levels,combined use of CsA and MDR1C3435T genotype had no effects on sirolimus blood trough concentration (P ＞ 0.05).sirolimus blood trough concentration/(dose weight) in * 1/* 1,* 1/* 3 and * 3/* 3 recipients was (0.0721 ± 0.0202),(0.1055 ± 0.0395),and (0.1395 ± 0.0537) μg·L-1 ·mg-1 ·kg-1,respectively,The sirolimus blood trough concentration/ (dose weight) in * 1/* 3 recipients was 1.46 times higher than that in * 1/* 1 recipients,and that in * 3/* 3 recipients were 1.93 times higher than that in * 1/* 1 recipients.There was significant difference in sirolimus blood trough concentration/(dose weight) between recipients with different CYP3A5 * 3 genotypes (P =0.000).Conclusion The CYP3A5 * 3 gene polymorphism is closely related to the blood trough concentration/dose of sirolimus,and is the main factor of the blood trough concentration of sirolimus between individuals.

New Views of the Translational Vestibulo-ocular Reflex in Healthy Human Subjects and in Patients with Neurological Disease who Fall / 대한평형의학회지

BACKGROUND AND OBJECTIVES: The vestibulo-ocular reflexes (VOR) act a short latency to optimize vision during locomotion. The angular VOR (aVOR) has been widely studied in human subjects and preserves clear, stable vision during rotational head perturbations by generating eye movements that hold the line of sight on the target of interest. Less is known about the properties of the linear or translational VOR (tVOR), mainly due to technical difficulties posed by testing head or body translations. Geometric considerations indicate that different properties should be expected of tVOR, which can only provide stable vision of objects lying in one depth plane. MATERIALS AND METHODS: We studied the human tVOR using a moving platform to translate normal human subjects vertically at frequencies similar to those occurring during locomotion. We found that, whereas aVOR is concerned with holding retinal images fairly stable to optimize clear vision, tVOR seems best suited to minimize relative motion of retinal images belonging to objects lying in different depth planes-and thereby to optimize motion parallax information. We also investigated whether the tVOR functioned abnormally in patients with neurological disorders causing falls-progressive supranuclear palsy (PSP) and cerebellar ataxia. RESULTS: Both groups of patients showed impaired ability to modulate their tVOR during viewing of near targets; in PSP this might be attributed to failure of convergence, but cerebellar patients failed to modulate tVOR at near despite intact convergence. CONCLUSION: In both disorders, an impaired ability to adjust tVOR for viewing distance points to central disturbance of otolithic vestibular reflexes, which may also contribute to postural instability.

Analysis of motor performance status in students of Han nationality in fifteen provinces in China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To analyze the motor performance status in students of Han nationality in fifteen provinces in china.</p><p><b>METHODS</b>Totally, 161 804 students of Han nationality aged from 7 to 18 years old were involved in the Chinese Surveillance on Students' Physical Fitness and Health in 2004. Motor abilities were accessed with the aid of gripping power, 50 m dash, standing long jump, and 1-min sit-ups. Based on general statistical description, principal component analysis and linear regression, the development characters of students' motor performance were explored.</p><p><b>RESULTS</b>This research showed some characters similar to those of last ones: motor capability was improved in correlation with age; boys did better than girls, the difference between 18 year-old rural boys and rural girls was 15.3 kg, -2.0 s, 58.6 cm, 8.7/min; the urban students performed better than the rural ones, the difference between 15 year-old urban boys and rural boys was 0.9 kg, -0.2 s, 3.5 cm, 3.5/min. The first principal component might represent the 4 tests greatly. Regression analysis on principal component quantitatively interpreted the influence of factors such as age, sex and area.</p><p><b>CONCLUSIONS</b>The general principles of exercise quality development of students are still in work. Principal component analysis should be adequate and convenient in motor performance analysis.</p>