Objective:To understand the current status and its associated factors of dual use of e-cigarettes and cigarettes among adolescents in Shandong Province and explore the reasons for dual use behavior.Methods:A self-administered survey was conducted among 7 999 middle school students who were selected by stratified multi-stage cluster sample method. Data were weighted and analyzed by the SPSS 25.0 complex program.Results:In Shandong Province, the prevalence rates of attempting and current dual use of e-cigarettes and cigarettes among adolescents appeared as 7.7% and 1.3%, respectively. Male, friends smoking, and secondhand smoke exposure in the past 7 days were risk factors for dual use. Compared with cigarette smokers, dual users have no differences in cognition and behavior in quitting smoking ( P>0.05). The main reason for dual users to smoke e-cigarettes was curiosity. Conclusions:Dual use of e-cigarettes and cigarettes is common among adolescents in Shandong Province, and its influencing factors are similar to traditional cigarettes. Dual use is not a transitional stage for smoking cessation. Dual users are more likely to continue smoking in the future, which should be paid attention and concern.

Objective To explore the relationship between pyroptosis and treatment in non-small cell lung cancer patients treated with tyrosine kinase inhibitors targeted therapy. Methods Stable transfection strains with common EGFR mutations found in clinical practice were constructed through lentiviral transfection. LDH and Western blot experiments were conducted to determine the degree and mechanism of pyroptosis after osimertinib treatment. Animal experiments verified the effect of pyroptosis on treatment efficacy. ELISA was used to explore the potential connection between pyroptosis and tumor immunotherapy. Results After osimertinib treatment on stable lines, the EGFR-L858R mutation had obvious pyroptosis at the morphology and protein levels. Western blot experiment confirmed that pyroptosis was mediated by GSDME (P < 0.0001). Experiments through the overexpression of GSDME and corresponding animal studies discovered that the degree of pyroptosis affected the treatment outcome. Blood analysis revealed that the level of IL-1β secreted by EGFR-L858R and EGFR-L858R-GSDME-OE mice after treatment was higher than that of the control group (P < 0.0001), and it may regulate tumor immunity to a certain extent. Conclusion Osimertinib can induce pyroptosis in EGFR-L858R mutant strains mediated by GSDME, and the level of pyroptosis in cell lines is positively correlated with therapeutic effect to a certain extent.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

Objective To evaluate the effect of epidural labor analgesia with different concentra-tions of ropivacaine combined with sufentanil on fever. Methods A total of 104 healthy parturients, of A-merican Society of Anesthesiologists physical status Ⅰ or Ⅱ, with New York Heart Association gradeⅠ orⅡ, with body height 150-175 cm, weighing 50-90 kg, at 37-45 weeks of gestation, scheduled for elec-tive labor analgesia, were divided into 0. 075％ ropivacaine group ( group R1, n=51) and 0. 125％ ropiva-caine group ( group R2, n=53) by a random number table method. Epidural labor analgesia was performed with 0. 075％ ropivacaine plus 0. 25μg∕ml sufentanil and with 0. 125％ ropivacaine plus 0. 25μg∕ml sufen-tanil in group R1 and group R2, respectively, to maintain visual analog scale score<3. Body temperature was measured before analgesia ( T0 ) , at 30 min, 1, 3 and 5 h of analgesia ( T1-4 ) , immediately after de-livery and at 2 h after delivery ( T5,6 ) . Venous blood samples were collected at T0,3,5 to detect the concen-tration of interleukin-6 ( IL-6) in serum. The incidence of fever, plane of anesthesia, fluid infusion rate, consumption of sufentanil and ropivacaine, the number of increment of drugs and length of labor were recor-ded. Results Compared with group R1, the degree of increase in body temperature was significantly in-creased at T1-6 , the consumption of ropivacaine and concentration of IL-6 at T3 were increased in group R2 (P<0. 05). There was no significant difference in the rate of fever, plane of anesthesia, fluid infusion rate, consumption of sufentanil and ropivacaine, the number of increment of drugs or length of labor be-tween two groups ( P>0. 05) . Conclusion Epidural labor analgesia with different concentrations of ropiva-caine combined with sufentanil exerts no effect on fever, 0. 075％ ropivacaine induces less changes in body temperature of parturients than 0. 125％ ropivacaine, which is related to the lower concentration of IL-6.

SIRT6 is a NAD(+)-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD) has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS) production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.
Adenine ; analogs & derivatives ; toxicity ; Autophagy ; drug effects ; Autophagy-Related Protein 5 ; antagonists & inhibitors ; genetics ; metabolism ; Blotting, Western ; Cell Line, Tumor ; Humans ; Hydrogen Peroxide ; toxicity ; Microtubule-Associated Proteins ; metabolism ; Oxidative Stress ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; metabolism ; Reactive Oxygen Species ; metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Sirtuins ; antagonists & inhibitors ; genetics ; metabolism ; Transfection

Objective To explore the cause,treatment and prognosis of delayed massive haemorrhage (DMH) after pancreatic resection.Method Clinical data of 1554 patients undergoing pancreatectomy in our hospital from Aug 2003 to Aug 2013 were retrospectively analyzed.Results 16 patients suffered from DMH,including 13 patients who had undergone pancreaticoduodenectomy,and 3 patients who had had resection of pancreatic body and tail.Gastrointestinal haemorrhage occurred in 6 patients,intra-abdominal haemorrhage occurred in 10 patients,respectively.Reoperations were performed in 11 patients,transcatheter arterial embolization (TAE) undertaken in 2 patients,and endoscopic treatment in 3 patients.10 patients recovered after treatment,6 patients (6/16) died.Conclusions The mortality of DMH after pancreatic surgery is high.Postoperative pancreatic leak and gastrointestinal stress ulcer are the most possible risk factors,intra-abdominal arterial haemorrhage is the main cause of death.