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Tiantian Xuan,1 Zhanmei Wang,1 Sibo Meng,1 Jiaxin Li,1 Jisheng Li,2 Fangli Cao,1,* Linli Qu1,* 1Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangli Cao; Linli Qu, Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, People’s Republic of China, Tel +86-18561811936 ; +86-18561811457, Email caofangliqilu@163.com; qulinli2021@163.comPurpose: Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen.Patients and Methods: We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved disease control after induction therapy.Results: Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8– 12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0– 7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed.Conclusion: MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.Keywords: colorectal cancer, maintenance therapy, cetuximab, RAS and RAF wild-type, targeted therapy

Wenxia Tong, Shuqiao Meng College of Physical Education, Yangzhou University, Yangzhou, People’s Republic of ChinaCorrespondence: Wenxia Tong, College of Physical Education, Yangzhou University, Yangzhou, 225000, People’s Republic of China, Tel +86-15003998013, Email tongwenxia@yzu.edu.cnBackground: Smartphones have become an important tool for college students’ study and life, but mobile phone addiction caused by excessive dependence use of cell phones can have serious negative impacts on college students’ mental health, life behaviors, and so on. It is urgent to explore the causes and influence mechanisms of college students’ cell phone addiction.Purpose: The purpose of this study was to investigate the relationship between physical exercise and mobile phone addiction among Chinese college students and the mediating role of negative affect and e-health literacy between the two.Methods: The stratified sampling method was used to investigate the physical activity, mobile phone addiction, negative emotion and e-health literacy of 4621 university students in Jiangsu Province using the Physical Activity Rating scale, Mobile Phone Addiction scale, Depression-anxiety-stress scale and E-Health Literacy scale, Thus the data were statistically analysed using SPSS 26.0 and AMOS 23.0.Results: (1) Physical exercise was significantly negatively correlated with mobile phone addiction and negative emotion among college students (r=− .713, P< 0.01; r=− .571, P< 0.01), and physical exercise was significantly positively correlated with e-health literacy (r=0.616, P< 0.01); (2) Negative emotion and e-health literacy played independent mediating roles between physical exercise and mobile phone addiction, respectively; (3) Negative emotion and e-health literacy played chain mediating roles between physical exercise and mobile phone addiction.Conclusion: This study explored the potential mechanisms of cell phone addiction in college students and found that physical activity can influence Internet addiction through the independent mediating effect including the chain mediating effect of negative emotions and e-health literacy. This study further reveals the mechanism of action of physical exercise affecting college students’ cell phone addiction, and provides some reference value for the prevention and intervention of college students cell phone addiction.Keywords: physical exercise, mobile phone addiction, negative emotion, e-health literacy, chain mediation

Abstract Penicillin-binding proteins (PBPs) are essential for the formation of the bacterial cell wall. They are also the targets of β-lactam antibiotics. In Enterococcus faecium, high levels of resistance to β-lactams are associated with the expression of PBP5, with higher levels of resistance associated with distinct PBP5 variants. To define the molecular mechanism of PBP5-mediated resistance we leveraged biomolecular NMR spectroscopy of PBP5 – due to its size (>70 kDa) a challenging NMR target. Our data show that resistant PBP5 variants show significantly increased dynamics either alone or upon formation of the acyl-enzyme inhibitor complex. Furthermore, these variants also exhibit increased acyl-enzyme hydrolysis. Thus, reducing sidechain bulkiness and expanding surface loops results in increased dynamics that facilitates acyl-enzyme hydrolysis and, via increased β-lactam antibiotic turnover, facilitates β-lactam resistance. Together, these data provide the molecular basis of resistance of clinical E. faecium PBP5 variants, results that are likely applicable to the PBP family.

Carrier induced defect creation at the semiconductor-oxide interface has been known as the origin of electronic device degradation for a long time, but how exactly the interface lattice can be damaged by carriers (especially low-energy ones) remains unclear. Here we carry out real-time time-dependent density functional theory simulations on concrete interfaces to study the interaction between excited electrons and interface bonds. We show that the normal interface Si-H bonds are generally resistant to electrons due to the delocalized nature and high energy level of the Si-H antibonding states, and due to the high-energy barrier to break the Si-H bond. However, if an additional hydrogen atom exists by attaching to a nearby oxygen atom (forming a “Si-H···H-O” complex), the Si-H bond will be greatly weakened, including the reduction of energy barrier for bond breaking, and the lowering of the antibonding state energy level which favors electron injection. Together with the multiple vibrational excitation process, the corresponding Si-H bond can be broken much more easily. Thus we propose that the Si-H···H-O complex will be the center for defect creation and device degradation. We also explain why such a center might be relatively easy to form during the hydrogen annealing process.

Hong Li,1 Shuai Meng,2 Weiguang Chen,3 Xuan Lei,4 Xiangyun Kong,5 Huagang Zhu6 1Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Cardiology, 1st Hospital Affiliated of Hebei North University, Zhangjiakou, Hebei Province, People’s Republic of China; 4Department of Cardiology, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of General Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hong Li, Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13311573539, Email 13311573539@139.comBackground: The clinical value of the Syntax score in patients with non-ST segment elevation myocardial infarction (NSTEMI) has been well established. The neutrophil–lymphocyte ratio (NLR), the platelet–lymphocyte ratio (PLR), the high sensitivity C-reactive protein (hsCRP)-albumin ratio (hsCAR), and systemic immune-inflammatory (SII) index are promising systemic inflammation (SI) biomarkers in coronary artery diseases. However, studies which compare the predicting value of these SI indicators with the Syntax score in NSTEMI patients are limited.Material and Methods: NSTEMI patients who underwent coronary angiography (CAG) in our department were retrospectively enrolled. Both univariable and multivariable logistic regression analyses were performed to evaluate the clinical value between SI biomarkers and Syntax score in these patients. The area under the receiver operating characteristic curve (ROC) was used to compare the clinical values of these parameters in predicting 6-month major cardiovascular events (MACE) and over-all mortality.Results: A total of 429 NSTEMI patients were finally enrolled in this study. The level of NLR, PLR, as well as hsCAR, and SII in patients with high Syntax scores, are significantly higher than patients with the low Syntax score. Multivariable logistic regression analysis demonstrated that all of the SI indicators but not the Syntax score were the independent risk factors of 6-month MACE in NSTEMI patients. ROC showed that all of the SI indicators had better predictive value than the Syntax score in these patients (0.637, 0.592, 0.631, 0.590, 0.559, respectively) in predicting MACE and similar predictive value in over-all mortality (0.530, 0.524, 0.761, 0.553, 0.620, respectively).Conclusion: Novel SI biomarkers including NLR, PLR, hsCAR, and SII have better predictive value in MACE and similar predictive value in over-all mortality compared with Syntax score in NSTEMI patients.Keywords: neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, high-sensitivity C-reactive protein–albumin ratio, non-ST segment elevation myocardial infarction

Protein phosphatase 1 (PP1) is regulated by intrinsically disordered proteins like inhibitor-3, I3. The authors show that I3 does not inhibit PP1 by forming a rigid complex but instead by binding dynamically with its active site metals, showing how flexibility is used in biology.

Shengwei Meng,1,&ast; Derong Xu,1,&ast; Shuo Han,1 Guanghui Li,1 Yan Wang,1 Yanqing Shen,2 Kai Zhu,1 Antao Lin,1 Ruiting Wang,3 Xuexiao Ma,1 Chuanli Zhou1 1Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Operating Room, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 3Medical Insurance Audit Department, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanli Zhou; Xuexiao Ma, Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of China, Tel +8618661809796 ; +8618661807895, Email justin_5257@hotmail.com; maxuexiaospinal@163.comPurpose: To evaluate the outcomes, feasibility, and safety of endoscopic unilateral laminectomy, bilateral decompression and discectomy (Endo-ULBDD) for central lumbar spinal stenosis (CLSS) combined with disc herniation (DH).Methods: This study includes 39 patients diagnosed with CLSS combined with DH who met the inclusion criteria and underwent surgery for Endo-ULBDD from April 2020 to March 2021. The mean age of the patients, operation time, hospitalization time, time in bed, and complications were recorded. Patients were followed up for at least 12 months. Visual analog scale (VAS) scores for low-back and lower-limb pain and Oswestry Disability Index (ODI) scores were evaluated preoperatively, before discharge, and at 3, 6, and 12 months postoperatively. To evaluate clinical effectiveness 12 months postoperatively, the modified MacNab criteria were used.Results: The mean age of the patients was 59.9 years, the mean operation time was 82.1 minutes, the mean hospitalization time was 3.7 days, and the mean time in bed was 20.9 hours. The mean VAS scores of low-back and lower-limb pain improved from 5.9 and 7.2 to 2.0 and 1.6, respectively (P < 0.05). The ODI score improved from 56.0 to 16.7 (P < 0.05). The overall excellent-good rate of the modified MacNab criteria was 89.7%. Two kinds of complications occurred in 4 patients (10.3%), including 1 patient whose inferior articular process was excessively removed and 3 patients who suffered from postoperative dysesthesia. No other severe complications were noted.Conclusion: Endo-ULBDD is a safe, feasible, efficient, and minimally invasive approach to treating CLSS combined with DH.Keywords: endoscopic spinal surgery, laminectomy, discectomy, lumbar spinal stenosis, intervertebral disc displacement

Shaoke Meng,1,&ast; Lei Guo,1,&ast; Zhishuai Ye,2 Junjie Wang,1 Huaiyu Ding,1 Shanshan Wu,3 Rongchong Huang2 1Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian City, People’s Republic of China; 2Cardiac Center/Division of Cardiovascular Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing City, People’s Republic of China; 3Department of Clinical Epidemiology and EBM, Beijing Friendship Hospital, Capital Medical University, Beijing City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchong Huang, Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Beijing City, 100053, People’s Republic of China, Email rchuang@ccmu.edu.cnBackground: Age is a strong predictor of adverse outcomes due both to a higher risk of bleeding and ischemia. The purpose of this study was to evaluate the safety and efficacy of ticagrelor in elderly patients.Methods: Patients ≥ 75 years of age admitted to our center from January, 2015 to December, 2019 who had undergone percutaneous coronary intervention (PCI) and received dual antiplatelet therapy (DAPT) were included in our study. Eligible patients were divided into clopidogrel and ticagrelor groups according to the P2Y12 receptor inhibitor and were followed up for 1 year. The primary safety endpoint was types 2, 3, and 5 bleeding, as defined by Bleeding Academic Research Consortium (BARC), and the primary efficacy endpoint was combined major adverse cardiovascular and cerebrovascular events (MACCEs). A Cox proportional hazard model and propensity score matching were used to correct confounding factors.Results: Of 1505 patients enrolled in this study, 442 were assigned to ticagrelor group and 1063 were assigned to clopidogrel group. The incidence of BARC 2, 3, and 5 bleeding (HR, 2.304; 95% CI, 1.540– 3.447), and any bleeding (HR, 2.476; 95% CI, 1.802– 3.403) in ticagrelor group was significantly higher than clopidogrel group. There were no significant difference between the two groups with respect to BARC 3 and 5 bleeding (HR, 1.566; 95% CI, 0.767– 3.198) and MACCEs (HR, 0.957; 95% CI, 0.702– 1.305).Conclusion: Compared with clopidogrel, DAPT with ticagrelor significantly increased the risk of BARC 2, 3, and 5 bleeding without reducing MACCEs in elderly patients who underwent PCI.Trial Registration: The study was retrospectively registered in clinicaltrials.gov (NCT 04999293).Keywords: ticagrelor, elderly, percutaneous coronary intervention, dual antiplatelet therapy

Yejing Shen,1,2 Xiaowen Xu,2 Siming Meng,2 Meng Qin,2 Hailing Li,2 Dejie Chu,1 Cuixia Zheng2 1Department of Respiratory Medicine, Shanghai Eighth People’s Hospital, Shanghai, 200235, People’s Republic of China; 2Department of Respiratory Medicine, Yangpu Hospital Affiliated to Tongji University, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Dejie ChuDepartment of Respiratory Medicine, Shanghai Eighth People’s Hospital, 8 Caobao Road, Shanghai, 200235, People’s Republic of ChinaEmail chudejie@yandex.comCuixia ZhengDepartment of Respiratory Medicine, Yangpu Hospital Affiliated to Tongji University, 450 Tengyue Road, Shanghai, 200090, People’s Republic of ChinaEmail zhengcuixiash@163.comObjective: To assess the impact of blood glucose levels on the prognosis of patients with community-acquired pneumonia (CAP) who were elderly or middle-aged.Methods: From January 1, 2018, to December 31, 2020, patients with CAP (≥ 45 years) were retrospectively enrolled in this observational study. They were stratified by age (45– 64 or ≥ 65 years) and blood glucose level (≥ 11.1 or < 11.1 mmol/l). The effect of admission blood glucose on 28-day mortality was assessed with the Cox proportional hazards model, adjusted for demographic factors and comorbidity.Results: Among 1656 patients with CAP, increased blood glucose (HR=2.08, 95% CI: 1.38– 3.49; P< 0.01) and advanced age (HR=2.76, 95% CI: 1.65– 3.77; P< 0.01) were significantly associated with a higher risk of 28-day mortality, after controlling for potential confounding factors. The strength of the association of blood glucose level with 28-day mortality decreased with age (P=0.01 for the interaction) as the adjusted HRs for death were 4.48 (95% CI: 1.40– 13.65; P< 0.01) for middle-age patients 45– 64 years and 1.52 (95% CI: 1.09– 2.17; P=0.05) for elderly patients ≥ 65 years.Conclusion: The association of blood glucose level upon admission for CAP with all-cause mortality was stronger at younger ages.Keywords: age, community-acquired pneumonia, hyperglycemia, mortality, prognosis

Wei Liu,&ast; Wei Wang,&ast; Jiangmei Liu, Yunning Liu, Shidi Meng, Feixue Wang, Zheng Long, Jinlei Qi, Jinling You, Lin Lin, Lijun Wang, Maigeng Zhou, Peng Yin National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng YinNational Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No. 27 Nanwei Road, Beijing, 100050, People’s Republic of ChinaTel +86 010-63015058Email yinpeng@ncncd.chinacdc.cnBackground: To examine trends in chronic obstructive pulmonary disease (COPD) mortality and years of life lost (YLL) due to COPD for all provinces in China during 2005– 2020.Methods: Data for COPD mortality were derived from China National Mortality Surveillance System (NMSS). We analyzed the numbers and age-standardized rates of death and YLL due to COPD in China, during 2005– 2020. We carried out decomposition analysis to analyze the drivers of change in COPD deaths during the study period.Results: The age-standardized mortality rate of COPD in China decreased significantly from 99.5/100,000 in 2005 to 50.5/100,000 in 2020. Similar trend was seen in the age-standardized YLL rate. The mortality rate increased with age. During 2005– 2020, the age-standardized mortality rate decreased in all provinces (except for Tibet) with the largest decline in Jilin (− 77.8%), Henan (− 68.4%) and Fujian (− 67.1%). The decreased number of deaths was decomposed as population growth (8.5%) and population ageing (69.7%) with offset by decline of age-specific mortality (− 87.5%).Conclusion: COPD remains an important public health problem in China, though significant reductions of COPD mortality and YLL rate were observed. Vigorous prevention and control strategies should be enhanced to improve the quality of life of COPD patients and reduce the premature death caused by COPD in Chinese population.Keywords: COPD, mortality, YLL

In this paper, an effective equivalent modeling technique has been proposed to describe small-signal characteristics of InP-based high electron mobility transistors (HEMTs) after proton radiation, which is composed of an artificial neural network and equivalent-circuit models. Small-signal intrinsic parameters of InP-based HEMTs are extracted from S-parameters before and after 2 MeV proton radiation as modeling objects. The deep learning model of a generative adversarial network has been explored to expand the measured finite data samples. Four feedforward neural networks are incorporated to equivalent-circuit topology to form the equivalent model, which are trained to accurately predict the radiation-induced variations of Cgs, Cgd, Rds, and gm, respectively. The prediction accuracy of the developed equivalent model has been well verified in terms of the broad-band S-parameters under radiation fluence of 1 × 1014 and 5 × 1013 H+/cm2. This equivalent modeling method with characterization of radiation damage effects could provide significant guidance for the aerospace monolithic millimeter-wave integrated circuit design. [ABSTRACT FROM AUTHOR]

Laser-induced breakdown and subsequent plasma are produced in ambient air in the proximity of an aqueous surface using a Nd:YAG Q-switched laser at 1064 nm with a pulse width of 9 ns and a delivered focused input energy of 170 mJ. The distance between the focal point of a 10 cm convex lens and the aqueous surface is 4 mm with laser propagation perpendicular to the surface. Using an intensified CCD camera attached to a 1-m spectrometer, spatial and wavelength-resolved plasma emission data are obtained for delay times after breakdown ranging from 50 ns to 10 μs with a gate window typically 5 ns. Plasma electron density is determined by applying Lorentzian fitting and FWHM extraction to three Stark-broadened spectral lines: N II 3P-3Do multiplet (593.85 nm), Hα (656.27 nm), and the Na D doublet (589.00 and 589.59 nm). One-dimensional spatially resolved measurements of the total emission intensity and electron density are obtained by binning the camera image along the laser axis in intervals of 250 μm and are reported as a function of time from 50 ns to 10 μs. Two plasmas are ignited from a single laser pulse; one from laser breakdown at the water surface and the other a few nanoseconds later from laser-induced air breakdown at the focal point of 4 mm above the water surface. Comparisons between the evolution of the air plasma near and far from the water surface are presented along with data for the water surface plasma itself. [ABSTRACT FROM AUTHOR]

Chong Zhao,&ast; Hao Zhang,&ast; Yan Wang, Derong Xu, Shuo Han, Shengwei Meng, Jialuo Han, Houchen Liu, Chuanli Zhou, Xuexiao Ma Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuexiao Ma; Chuanli ZhouDepartment of Spine Surgery, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of ChinaTel +86 18661807895; +86 18661809796Email ma_xuexiao@126.com; justin_5257@hotmail.comPurpose: To investigate the preoperative radiological risk factors for recurrent lumbar disc herniation (rLDH) within 1 year after percutaneous endoscopic transforaminal discectomy (PETD).Patients and Methods: A retrospective case–control study was conducted. Between January 2013 and November 2019, a total of 1210 patients with single-level L4/5 LDH who underwent PETD were enrolled in the present study. In total, 62 rLDH patients were diagnosed and collected based on the clinical and radiological manifestations, and 224 non-rLDH controls were selected from the remaining 1148 patients. Preoperative radiological parameters were collected and measured. An age threshold to distinguish patients into subgroups was established using the Youden index. The relationships between the risk factors and rLDH were evaluated by univariate and multivariate analyses in two subgroups. Predictive models were established based on logistic analysis. The area under the curve (AUC) of receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) were used to assess the predictive models.Results: In the present study, logistic analysis identified six significant predictors associated with rLDH in the young group: superior endplate concave angle (ECA), sacral slope, Modic changes, sagittal range of motion (sROM), extension intervertebral angle (IVA), and lumbar lordosis. Four significant predictors were identified in the elderly group: disc height index (DHI), retrolisthesis (posterior spondylolisthesis), sROM, and extension IVA. Validation of both models demonstrated excellent model discrimination (AUC= 0.940 and 0.946, respectively). DCA also showed excellent clinical utility and benefits.Conclusion: The nomograms that we constructed could accurately predict individual patient recurrence risk. Individualized measures should be taken for patients of different ages with the above risk factors, and tailored postoperative surveillance of patients who underwent PETD can be planned.Keywords: lumbar disc herniation, percutaneous endoscopic transforaminal discectomy, recurrent LDH, risk factor

Lei Zhang,1,* Shijie Meng,2,* Bo Yan,2,* Jie Chen,2 Li Zhou,2 Letian Shan,2 Ying Wang3 1School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, People’s Republic of China; 2The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Letian ShanThe First Affiliated Hospital, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, People’s Republic of ChinaEmail letian.shan@zcmu.edu.cnYing WangSchool of Basic Medicine, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, People’s Republic of ChinaEmail ellawang@zcmu.edu.comPurpose: Theaflavin (TF) is a primary pigment of tea, exhibiting anti-proliferative, pro-apoptotic and anti-metastatic activities on cancer cell lines. However, it is unknown whether TF is effective in treating melanoma cells.Methods: To determine the effects of TF on melanoma cells, we conducted in vitro assays of cell viability, DAPI staining, wound healing, transwell, and flow cytometry as well as in vivo experiments on B16F10-bearing mouse model. Real-time PCR (qPCR) and Western blot (WB) were conducted to explore the molecular actions of TF.Results: The cell viability assay showed that TF exerted inhibitory effect on B16F10 cells in a dose-dependent manner from 40 to 400 μg/mL, with IC50 values ranging from 223.8± 7.1 to 103.7± 7.0 μg/mL. Moreover, TF induced early and late apoptosis and inhibited migration/invasion of B16F10 cells in a dose-dependent manner, indicating its pro-apoptotic and anti-migrative effects. In vivo, TF significantly inhibited B16F10 tumor size in mice model from 40 to 120 mg/kg, which exerted higher effect than that of cisplatin. The molecular data showed that TF significantly up-regulated the mRNA expressions of pro-apoptotic genes (Bax, Casp3, Casp8, c-fos, c-Jun, and c-Myc), up-regulated the protein expressions of apoptosis-related p53 and JNK signaling molecules (ASK1, phosphorylated Chk1/2, cleaved caspase 3, phosphorylated JNK, c-JUN, cleaved PARP, and phosphorylated p53), and down-regulated the protein expressions of proliferation-related MEK/ERK and PI3K/AKT signaling molecules (phosphorylated MEK1/2, phosphorylated ERK1/2, phosphorylated PI3K, and phosphorylated AKT) as well as the expressions of MMP2 and MMP9.Conclusion: It can be concluded that TB exhibited anti-proliferative, pro-apoptotic, anti-migrative, and tumor-inhibitory effects on melanoma cells through pleiotropic actions on the above pathways. This study provides new evidence of anti-melanoma efficacy and mechanism of TF, contributing to the development of TF-derived natural products for melanoma therapy.Keywords: theaflavin, apoptosis, B16F10, melanoma, JNK, p53

Jing Nan, Shuai Meng, Hongyu Hu, Ruofei Jia, Zening Jin Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zening JinDepartment of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaEmail Jin_zening@163.comIntroduction: The efficacy of fibrinolysis therapy with deferred percutaneous coronary angioplasty (FPCI) versus primary angioplasty (PPCI) during the coronavirus disease 2019 (COVID-19) pandemic is unclear when medical quarantine is needed.Patients and Methods: Acute ST segment elevation myocardial infarction (STEMI) patients underwent PPCI after finishing the screening protocol from January 23, 2020 to June 10, 2020 while FPCI was applied when COVID-19-confirmed cases reoccurred in Beijing near our hospital from June 11, 2020 to July 20, 2020. The door-to-balloon time (DTB) or door-to-needle time (DTN) as well as in-hospital adverse clinical outcomes were compared between the two groups. A propensity score-matched (PSM) analysis was performed to diminish the potential influence of confounding factors on the clinical outcomes.Results: A total of 126 STEMI patients underwent PPCI after finishing the screening protocol and 17 patients received FPCI before PSM. Patients who received FPCI were younger than patients who underwent PPCI (50.8± 14.0 versus 64.1± 14.2 years, p=0.001), and chronic kidney disease (CKD) was less common in FPCI patients than in patients who underwent PPCI (0% versus 24.6%, p=0.024). The DTN was significantly shorter than DTB (25.8± 4.2 versus 61.1± 10.7, p=0.000) before PSM. The DTN was significantly shorter than DTB (26.9± 4.2 versus 64.9± 23.6, p=0.000); however, the incidence rate of in-hospital ischemia and bleeding adverse clinical outcomes were comparable between the two groups after PSM.Conclusion: Fibrinolysis therapy combined with deferred PCI can reduce the ischemia time and has a similar in-hospital adverse clinical outcome rate compared with patients who underwent primary PCI during the COVID-19 pandemic.Keywords: ST elevation myocardial infarction, fibrinolysis therapy, percutaneous coronary intervention, coronavirus disease 2019, propensity score-matched analysis

Jing Nan,1,* Shuai Meng,1,* Hongyu Hu,1,* Ruofei Jia,1 Ce Chen,2 Jianjun Peng,2 Zening Jin1 1Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun PengDepartment of Cardiology, Beijing Shijitan Hospital, Capital Medical University, No. 4 Tieyi Road, Haidian Distict, Beijing 100038, People’s Republic of ChinaTel +86 18811332608Email pjj1972@sina.comZening JinDepartment of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel +86 15652966904Email jin_zening@ccmu.edu.cnBackground: The clinical value of monocyte count to high-density lipoprotein cholesterol ratio (MHR) in in-stent restenosis (ISR) of patients who have undergone bare metal stent implantation has been studied. However, the predictive value of MHR in ISR for patients who have undergone drug-eluting stent (DES) implantation has not been explored.Methods: Non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients who had undergone DES implantation and coronary angiography follow-up at the Beijing Shijitan Hospital, Capital Medical University, between January 1, 2008, and December 31, 2018, were retrospectively enrolled. Patients were divided into ISR and non-ISR groups depending on the follow-up coronary angiography results. Relative clinical information was recorded and analyzed. The receiver operating characteristic curve analysis was used to determine the optimum cut-off pre-procedural MHR to predict ISR.Results: A total of 214 patients were enrolled in our study. The mean period between two coronary angiography procedures was 25.4± 9.8 months. Percutaneous coronary intervention due to NSTE myocardial infarction, a bifurcation lesion, increased platelet count, and a high MHR were the independent risk factors in multivariate logistic regression analyses.Conclusion: Our results indicated that elevated MHR is an independent and useful predictor of ISR in NSTE-ACS patients who have undergone DES implantation.Keywords: monocyte count to high-density lipoprotein cholesterol ratio, in-stent restenosis, drug-eluting stent

Shushi Meng, Ganwei Liu, Shaodong Wang, Fan Yang, Jun Wang Department of Thoracic Surgery, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Shaodong Wang; Jun WangDepartment of Thoracic Surgery, Peking University People’s Hospital, No. 11, Xizhimen South Street, Beijing 100044, People’s Republic of ChinaTel +86 10-88326652; +86 10-88326650Email 13651217347@163.com; wangjunpkuph@sina.comPurpose: The purpose of this study was to investigate lymph node involvement pattern in clinical stage IA non-small cell lung cancer (NSCLC).Patients and Methods: Clinical stage ⅠA NSCLC patients who underwent lobectomy and lymph node resection were included in this retrospective study. Mediastinal lymph node involvement was distinguished by different lobes and tumor size.Results: From 2000 to 2015, a total of 759 patients were identified: 282 (37.2%) with tumors in the right upper lobe (RUL), 183 (24.1%) in the left upper lobe (LUL), 124 (16.3%) in the right lower lobe (RLL), 103 (13.6%) in the left lower lobe (LLL), and 67 (8.8%) in the right middle lobe (RML). Patients with tumor size ≤ 1 cm accounted for 19.6%, > 1 and ≤ 2 cm for 47.8%, > 2 and ≤ 3 cm for 32.5%. Patients with pN1 accounted for 8.2%, and pN2 for 12.5%. Among patients with pN2, the inferior mediastinum was involved in 9.7% of RULs and 17.4% of LULs; the superior mediastinum was involved in 52.2% of RLLs and 36.4% of LLLs. Mediastinal lymph node metastasis was found in 13.2% of patients with size > 1 and ≤ 2 cm, and 19.0% of > 2 and ≤ 3 cm. Patients with tumors ≤ 1 cm had no N2 lymph node involved.Conclusion: Selective lymph node dissection based on tumor location is not recommended in clinical stage ⅠA NSCLC, and systemic lymph node dissection should be performed for NSCLC with size > 1 cm.Keywords: non-small cell lung cancer, clinical stage ⅠA, lymph node dissection, nodal involvement pattern

Lijuan Gao,1,2,* Xiaoqiong Li,1,2,* Shi Meng,1,2,* Tengyun Ma,1,2 Lihong Wan,3,* Shijun Xu1,2,* 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, People’s Republic of China; 2Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, People’s Republic of China; 3Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shijun XuCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, People’s Republic of ChinaTel +86-28-61800231Fax +86-28-61800234Email xushijun@cdutcm.edu.cnLihong WanDepartment of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of ChinaTel/ Fax +86-28-85501278Email wanlihong1976@sina.comPurpose: Chlorogenic acid (CGA), a phenolic acid isolated from fruits and vegetables, has been established to have neuroprotective properties in relation to Alzheimer’s disease (AD). However, the precise mechanism by which CGA prevents cognitive deficits in AD has not been well studied. This study aimed to explore the potential molecular mechanism of CGA action using an Aβ25-35-induced SH-SY5Y neuron injury and cogxnitive deficits model in APP/PS1 mice.Methods: Three-month-old male APP/PS1 double transgenic mice and a human neuroblastoma cell line (SH-SY5Y) were used to assess the effects of CGA on AD in vivo and in vitro, respectively. Cognitive function in mice was measured using a Morris water maze (MWM) test. Hematoxylin and eosin, monodansylcadaverine fluorescence, LysoTracker Red (LTR), and immunofluorescence staining were used to evaluate the morphological changes in vivo and in vitro. The protein expressions of autophagy markers (LC3B-II/LC3B-I, p62/SQSTM, beclin1 and Atg5) and lysosomal-function-related markers (cathepsin D, mTOR, p-mTOR P70S6K, p-p70s6k and TFEB) were analyzed with Western blot analyses.Results: CGA treatment significantly improved spatial memory, relieved neuron damage, and inhibited autophagy in APP/PS1 mice (P< 0.05). Moreover, CGA notably suppressed autophagosome production and enhanced autophagy flux in SH-SY5Y cells induced by Aβ25-35 (P< 0.05). Further analysis showed that CGA markedly promoted lysosomal activity, and this was accompanied by upregulated cathepsin D protein expression, which was induced by the mTOR/TFEB signaling pathway in APP/PS1 mice and Aβ25-35-exposed SH-SY5Y cells (P< 0.05).Conclusion: CGA treatment restored autophagic flux in the brain and alleviated cognitive impairments in APP/PS1 mice via enhanced activation of the mTOR/TFEB signaling pathway.Keywords: autophagy, chlorogenic acid, cognitive impairment, TFEB