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OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.
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Background Phenolic compounds, which are widely used as plasticizers, antibacterial agents, and preservatives in industrial production, have endocrine disrupting effects on humans. Previous epidemiological studies on the associations between phenolic compound exposure and blood lipids are mainly based on single measurement of spot urine samples, neglecting potential lag effects of phenolic compounds, and the conclusions are inconsistent. Objective To investigate the effects of short-term exposure to phenolic compounds at different lag days on blood lipid levels in adults. Methods We recruited 143 adults (43 males and 100 females) in Wuhan for three consecutive seasonal rounds of repeated visits: summer and autumn rounds of 2017 and winter of 2018. Morning urine samples were collected for four consecutive days during each round. A set of questionnaires were also distributed on the first day. Physical examinations and fasting venous blood sample collection were conducted on the fourth day. A total of 126 adults were included for analysis (340 person-time, 1251 urine samples). The concentrations of six urinary phenolic compounds [bisphenol A (BPA), bisphenol S (BPS), triclosan (TCS), methyl paraben (MeP), ethyl paraben (EtP), and propyl paraben (PrP)] were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. Linear mixed-effect models (LMEs), multiple informant models, and generalized linear models were utilized to estimate the associations of urinary phenolic compounds at different lag days with total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and the ratio of TG to HDL-C (TG/HDL-C). Stratified analyses were conducted by selected characteristics. Results After covariate and multiple adjustments, the LMEs indicated that a change in urinary BPA at lag 0 day from the low concentration group (<LOD) to the high concentration group (≥LOD) was associated with a 16.48% (95%CI: 4.41%, 29.94%) increase in TG/HDL-C (P FDR<0.05), and this association was more pronounced in men (P interaction=0.028) and smokers (P interaction=0.040). In addition, a change in urinary TCS at lag 2 day from the low concentration group (<LOD) to the high concentration group (≥LOD) was associated with a 13.22% (95%CI: 3.73%, 23.56%) increase in TG (P FDR<0.05). The positive association of TCS with TG was more evident in subjects aged < 50 years (P interaction=0.037). No significant associations were found between urinary phenolic compounds at other lag days and blood lipids. Conclusion Short-term exposures to BPA and TCS are positively correlated with unfavorable changes in blood lipids in adults, and the association seem to be more pronounced in men, smokers, or individuals aged < 50 years.
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Objective:To explore the changes of intracranial pressure in intensive care unit (ICU) patients during the occurrence and evolution of delirium by using bedside ultrasound to measure the optic nerve sheath diameter (ONSD) to evaluate intracranial pressure.Methods:A retrospective observational study was conducted. Adult patients who developed delirium during hospitalization in the general ICU of Beihai People's Hospital from October 2020 to November 2021 were enrolled, and patients who did not have ultrasonographic ONSD records within 24 hours after the diagnosis of delirium were excluded. The ONSD measured before delirium was recorded as ONSD 0, the ONSD measured within 24 hours of the onset of delirium recorded as ONSD 1, and the ONSD reexamined after ONSD 1 recorded as ONSD 2. Patients were divided into intracranial hypertension group (ONSD 1 > 5 mm) and normal intracranial pressure group (ONSD 1 ≤ 5 mm) according to the size of ONSD 1. According to the outcome of delirium, the patients were divided into cured, improved, and non-improved groups. The reduction ratio of ONSD 2 to ONSD 1 in the three groups were calculated and compared. Pearson correlation test was used to analyze the correlation between fluid balance and ONSD changes after delirium. Results:There were 43 patients, including 40 cases in the intracranial hypertension group (the incidence rate was 93.0%), 3 cases in the normal intracranial pressure group, 23 cases were cured, 13 cases were improved, and 7 cases were not improved. In the intracranial hypertension group, 11 cases had ONSD 0 and ONSD 1 records, and ONSD 1 was significantly higher than ONSD 0 [mm: 5.88±0.61 vs. 5.34±0.57, 95% confidence interval (95% CI) -0.85 to -0.23, P = 0.003]. The reduction ratio of ONSD 2 to ONSD 1 in the cured group was significantly higher than that in the improved group and the non-improved group [(12.04±6.20)% vs. (5.68±4.10)%, (0.17±3.96)%; 95% CI were 2.37 to 10.33, 6.41 to 17.31, P values were 0.003 and 0.000, respectively]. The correlation analysis showed that the reduction ratio of ONSD 2 to ONSD 1 was negatively correlated with fluid balance ( r = -0.42, 95% CI was -0.66 to -0.10, P = 0.012). Conclusions:The incidence of intracranial hypertension in ICU delirium patients is high. A more pronounced decrease in intracranial pressure predicts a better delirium outcome. Dynamic ONSD measurement can provide valuable information for the prevention and treatment of delirium.
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Objective To improve the clinical practice ability and the comprehensive ability to assist in the rescue of the medical staff by the medical cooperation mode.Methods 30 nurses and 12 doctors in department of emergency were divided into 6 combinations and 4 combinations,each group consisted of 1-2 doctors and several nurses,who following the 2010 USA Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care and America Heart Association advanced cardiovascular life support curriculum (AHA ACLS) training method.Theory teaching and Sub skill practice and Comprehensive simulation training and Summarize and analyze the feedback pattern,training,exercises and assessment to rescue patients with sudden cardiac respiratory arrest of simulations were carried out with the team combat form in scenario.Results Implementation of health cooperation cardiopulmonary resuscitation team training exercise improved the rescue team support ability.97.6％ (41/42) trainees were considered to improve the order of the rescue while 100.0％ (42/42) trainees were considered that this training model was worthy to popularize.Conclusions The medical cooperation cardiopulmonary resuscitation team training exercise improves the timeliness and comprehensive help rescue ability.
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To solve the calibration transmission problem in near-infrared ( NIR) spectroscopy, a novel model transfer method, Simple Linear Regression Direct Standard-ization ( SLRDS ) , has been presented. To investigate the validity of the proposed method, a real corn sample NIR dataset was tested and the direct standardization ( DS ) method and piecewise direct standardization ( PDS ) method were involved as a comparison. Our results indicated that SLRDS can correct compressed NIR data differences among instruments and enable the user to share corn sample PLS calibration model among three instruments, at the same time it has higher prediction accuracy, fewer parameters and simpler model than DS and PDS.
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AIM:To study the feasibility of online monitoring and controlling of the key process of column chromatographic separation in the production of Salvianolate by combining near-infrared(NIR) spectrum and HPLC fingerprinting. METHODS: Partial Least Square(PLS) regression was used to model the correlation of NIR spectra with the concentrations of salvianolic acid B,and the influences of light path,wavelength selection,and preprocessing method on the PLS model were investigated systematically. RESULTS: A 2 mm light path was better than 1 mm one,and with 2 mm light path,the optimal wave-number was in the range of 6 102.1-5 446.3 cm~(-1) and the optimal preprocessing method was the vector normalization.The root mean-square error of PLS model on test samples was 0.234 mg/mL,and R~2 was 0.995 2. CONCLUSION: This method is proved to be fast,convenient,and precise.It can be used to online monitoring and quality control of the manufacturing of Salvianolate.