Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Purpose: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. Materials and Methods: Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. Results: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. Conclusion Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Aim To observe the therapeutie effeet of (AA) rats and its effect on the aetivity of tryptophan allopurinol ( ALLO) on adjuvant induced arthritis 2,3 dioxygenase (TDO).Methods SD rats were randomly divided into normal group, AA model group, ALLO group (10,20 , 40 mg • kg 1 ) and methotrexate group (0.5 mg • kg 1 ).The AA rats were established by intracutaneous injection of complete Freund's adju¬vant into the right toes of rats.The body weight,joint swelling number, joint pathology, spleen index and fi¬broblast like synoviocytes ( FLS) proliferation of the rats were observed to explore the therapeutic effect of ALLO.Flow cytometry detected the number of CD68 ∗ macrophages and the ratio of Thl7/Treg of spleen.The concentration of tryptophan ( Trp) and kvnurenine ( Kyn) in the liver and the supernatant of FLS were de¬termined by high performance liquid chromatography.Results Compared with model group, ALLO adminis¬ tration significantly increased the body weight of AA rats, reduced the number of joint swelling, improved joint pathological injury,decreased spleen index,inhib¬ited the proliferation of FLS, reduced the number of macrophages in the spleen,decreased Thl7/Treg ratio, inhibited the metabolism of Tip and the production of Kyn in liver and FLS culture supernatant, and de¬creased the liver Kyn/Trp ratio (TOO activity).Con¬clusion ALLO has therapeutic effect on AA rats, which may be related to its regulation of TDO-mediated kyn metabolism pathway.

BACKGROUND: The cardiomyocyte apoptosis is considered as one of major contributions to cardiac remodeling after myocardial infarction (MI). Numerous studies find that circular RNAs (circRNAs) play pivotal roles in a variety of biological functions. However, the role of circ_0068655 in MI and human induced pluripotent stem-derived cardiomyocytes (HCMs) remains unknown. METHODS: The expression of circ_0068655, miR-498, and PRKC apoptosis WT1 regulator (PAWR) in human MI heart tissues and hypoxia subjected HCMs was evaluated with qRT-PCR and Western blot. The effects of circ_0068655 on hypoxia-induced apoptotic death and cell migration in HCMs were evaluated with qRT-PCR, cell viability, cell death ELISA (POD), and Caspase-3 activity assay, and Trans-well assay, respectively. Furthermore, luciferase assay, qRT-PCR, biotin-labeled miRNA pulldown assay, and Western blot were employed in the functional studies. RESULTS: We found that the expression of circ_0068655 and PAWR was enhanced in MI patients and hypoxia subjected HCMs; by contrast, the expression of miR-498 decreased. Inhibited expression of circ_0068655 in HMCs counteracted hypoxia-induced apoptotic death and impaired cell migration, in sharp contrast to circ_0068655 knockdown. We identified that circ_0068655 sponged an endogenous miR-498 to sequester and inhibit its activity, leading to the increased PAWR expression. CONCLUSIONS Our findings reveal that the expression of circ_0068655 can promote cardiomyocyte apoptosis through the modulation of miR-498-PAWR axis in vitro, which highlights the diagnostic and therapeutic value of circ_0068655 in patients with MI.

BACKGROUND: The cardiomyocyte apoptosis is considered as one of major contributions to cardiac remodeling after myocardial infarction (MI). Numerous studies find that circular RNAs (circRNAs) play pivotal roles in a variety of biological functions. However, the role of circ_0068655 in MI and human induced pluripotent stem-derived cardiomyocytes (HCMs) remains unknown. METHODS: The expression of circ_0068655, miR-498, and PRKC apoptosis WT1 regulator (PAWR) in human MI heart tissues and hypoxia subjected HCMs was evaluated with qRT-PCR and Western blot. The effects of circ_0068655 on hypoxia-induced apoptotic death and cell migration in HCMs were evaluated with qRT-PCR, cell viability, cell death ELISA (POD), and Caspase-3 activity assay, and Trans-well assay, respectively. Furthermore, luciferase assay, qRT-PCR, biotin-labeled miRNA pulldown assay, and Western blot were employed in the functional studies. RESULTS: We found that the expression of circ_0068655 and PAWR was enhanced in MI patients and hypoxia subjected HCMs; by contrast, the expression of miR-498 decreased. Inhibited expression of circ_0068655 in HMCs counteracted hypoxia-induced apoptotic death and impaired cell migration, in sharp contrast to circ_0068655 knockdown. We identified that circ_0068655 sponged an endogenous miR-498 to sequester and inhibit its activity, leading to the increased PAWR expression. CONCLUSIONS Our findings reveal that the expression of circ_0068655 can promote cardiomyocyte apoptosis through the modulation of miR-498-PAWR axis in vitro, which highlights the diagnostic and therapeutic value of circ_0068655 in patients with MI.

OBJECTIVETo investigate the relationship between acute graft-versus-host disease and graft composition in patients with aplastic anemia(AA) after haploidentical hematopoietic stem cell transplantation.

METHODSFifty-seven cases of AA after haploidentical hematopoietic stem cell transplantation were retrospectively analyzed. All the patients were divided into 2 groups according to whether presence or absence grade Ⅱ-Ⅳ aGVHD, the relationship between aGVHD and graft composition was analyzed by comparing the differences of graft components between the 2 groups.

RESULTSFourteen out of 57 patients had grade Ⅱ-Ⅳ aGVHD and the other 43 did not have grade Ⅱ-Ⅳ aGVHD. The mononuclear cells, CD3, CD4, CD8, NK cells, NKT cells, B cells and Treg cells were not significantly different between the 2 groups (P>0.05), the CD34 cell count in the patients with grade Ⅱ-Ⅳ aGVHD was 3.85（1.73-10.61）×10/kg, which was significantly lower than that without grade Ⅱ-ⅣaGVHD: 6.31（2.98-19.35）×10/kg (P<0.05).

CONCLUSIONSThe incidence of grade Ⅱ-Ⅳ aGVHD may be related with CD34 cell count in AA after haploidentical hematopoietic stem cell transplantation..

Objective To study the effect of vibration environments on patients with posterior lumbar interbody fusion in daily life. Methods Finite element models of an intact lumbar spine and a postoperative model with fixed L4-5 segments were established. Subsequently, a 40-kg mass point was applied to the upper end plate of the L1 segment to perform a modal analysis. Results In comparison with an intact lumbar spine, the resonance frequency for each order of the whole lumbar spine was reduced after posterior lumbar interbody fusion, and the primary movement of the corresponding modes were also changed. The first two inherent frequencies of the modal in the fusion model were 2.94 Hz and 3.81 Hz, which were close to the vibration frequencies in daily life. In the first three order vibrations, the mode amplitudes of the posterior elements for the L2 and L3 segments increased in the fusion model, which could increase the risk of postoperative degeneration at such locations. In addition, the vibration amplitude of the intervertebral disc of the L3-4 segments clearly increased, particularly at the part of the disc near the L3 vertebral body, which could lead to increased stress and strain and further accelerate its degeneration. Conclusion sBased on the modal analysis of a lumbar spine after posterior lumbar interbody fusion, the investigation of the vibration characteristics of the postoperative lumbar spine will provide some theoretical guidance for the recovery and healthy life of the patients after the corresponding surgery.

Objective To evaluate the association between small,dense low-density lipoprotein cholesterol (sdLDL-C)and severity of coronary atherosclerosis disease (CAD).Methods A total of 436 outpatients with suspected coronary atherosclerotic heart disease (CAD) and underwent coronary computed tomography (CT) were consecutively enrolled from July 2015 to March 2016 in Fuwai Hospital.Correlations between serum sdLDL-C and the severity of CAD including characteristics of plaque,the number of stenosed coronary vessels,the degree of stenosis were analyzed.Results sdLDL-C was positively correlated with apolipoprotein B (apoB),triglyceride (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),blood glucose (Glu)with the coefficient correlation 0.644,0.631,0.558,0.434 and 0.145 successively(P ＜ 0.01),and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r =-0.241,P ＜ 0.01).sdLDL-C and apoB were the risk factors for severe CAD (triple-vessel disease and severe stenosis),independent of traditional risk factors (age,gender,hypertension,diabetes,smoking,alcohol consumption)and the use of lipidlowering agents.For the patients with triple-vessel disease,odds ratio of LDL-C,sdLDL-C and apoB were 1.936,2.673 and 31.707 respectively.For the patients with severe stenosis,LDL-C was not an independent factor,while sdLDL-C and apoB still had predictive value (odds ratio were 2.000 and 9.457 respectively).Conclusion sdLDL-C should be a predictor of severe CAD independent of traditional risk factors that may be useful for further risk stratification in the patients with CAD.

Objective To investigate the effects of Modified Siwutang aqueous extract (mSWT) on bone marrow cell mobilization and plantation in mice after acute myocardial infarction (AMI).Methods The AMI model was established by ligating the left anterior descending artery in Kunming mice.Bone marrow cells were marked by injection of DAPI into the cavitas medullaris of shin bones.Mice were administered with mSWT 60 mg/kg by intragastric administration once a day after surgery.After haematoxylin-eosin and immunofluorescent staining,the plantation of bone marrow cells in AMI area and microvessel density were detected by histopathological assay.The EPCs proportion of peripheral blood was measured by flow cytometry.Results Compared with model mice,infarct size obviously was decreased after mSWT 60 mg/kg treatment,with EPCs ratio increased significantly.Inflammatory cell infiltration of myocardium was much less.Myocardium cellular degeneration and necrosis,fibrosis were reduced,which survival cardiac muscle tissue was increased.DAPI positive cells of plantation and survive were found in AMI region of mSWT group.The number of positive cells were increased in mSWT group than that of model group.There were lot of microvessels of vWF positive expresseion in mSWT than model group.Conclusion:mSWT significantly improved histopathology of AMI mice.The mechanism may be involved in moved bone marrow cells,homed to AMI area and promote angiogenesis.

OBJECTIVETo evaluate the early clinical effects of arthroscopic treatment for cruciate ligament cysts of the knee.

METHODSFrom September 2008 to January 2014, 23 patients with cruciate cysts were treated with arthroscopic surgery. There were 11 males and 17 females, with an average age of 28.3 years old (ranged, 16 to 56 years old). Twenty patients had injuries on the right knee and 8 patients had injuries on the left knee. Eight patients had a history of injury,5 patients had a history of chronic injury,and the other 15 patients had no obvious reasons for the symptom. Before the operation, 24 patients were clearly diagnosed as the cruciate ligament cysts of knee joint,and 4 patients were diagnosed as other problems of the knee, but the diagnosis were corrected after the operation. According to the MRI before the surgery,all the patients could be divided into 3 types: 14 were type I, 6 were type II, 8 were type III. After the operation, the patients were suggested to have a rest for 2 weeks, and take exercises everyday at the same time. The knee range of motion, Lysholm score, International Knee Documentation Committee (IKDC) 2000 subjective score, GLASGOW criteria, and McMurray test, pivot shift test, and anterior drawer test were observed to evaluate clinical results.

RESULTSAll the incisions healed at the first stage without complications. Twenty-five patients were followed up, and the duration ranged from 12 to 52 months, with a mean of 26.7 months. Three patients accepted the reconstruction of ACL or tightened elongated ACL using bipolar radio frequency. The Lysholm score increased from preoperative 59.80 +/- 6.58 to 75.32 +/- 6.49 at the latest follow-up; IKDC 2000 score increased from preoperative 65.36 +/- 6.26 to 81.00 +/- 5.76 at the latest follow-up. According to GLASGOW criteria,23 patients got an excellent result and 2 good.

CONCLUSIONIt has a satisfactory curative effect on ACL reconstruction using bipolar radio frequency. It has advantages of firm fixation, simple and secure operation as well as quick postoperative recovery. It's very important to check the MRI before operations, and carefully seek the cysts during the operations, avoiding the omission of any cysts,especially the cases of multiple cysts. Finally, patients should take exercises actively after operations.

Adolescent ; Adult ; Anterior Cruciate Ligament ; physiopathology ; surgery ; Anterior Cruciate Ligament Injuries ; Anterior Cruciate Ligament Reconstruction ; Arthroscopy ; Cysts ; surgery ; Female ; Humans ; Knee Injuries ; physiopathology ; surgery ; Knee Joint ; physiopathology ; surgery ; Male ; Middle Aged ; Range of Motion, Articular ; Young Adult