Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease.

Excessive hepatic lipid droplets (LDs) accumulation-induced lipid metabolism disorder contributes to the development of non-alcoholic fatty liver disease (NAFLD). Exercise is a promising therapeutic strategy for NAFLD. However, the mechanism by which exercise ameliorates NAFLD through regulating the catabolism of hepatic LDs remains unclear. In the present study, we investigated the effect of perilipin2 (PLIN2)-lysosomal acid lipase (LIPA) axis mediating exercise-triggered lipophagy in a high-fat diet (HFD)-induced NAFLD mouse model. Our results showed that exercise could reduce HFD-induced hepatic LDs accumulation and change the expression of lipolysis-related enzymes. Moreover, exercise upregulated the expression of microtubule associated protein 1 light chain 3 (LC3) and autophagy-related proteins, and downregulated sequestosome 1 (P62) expression and promoted autophagosomes formation. Interestingly, exercise downregulated PLIN2 expression, upregulated LIPA expression, and increased the activity of hepatic LIPA and serum levels of LIPA in the NAFLD mouse model. Further mechanistic studies demonstrated that adenosine monophosphate-activated protein kinase (AMPK) activator-5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) treatment significantly increased mRNA levels and protein expression of LIPA and LC3II and decreased levels of PLIN2 and P62 in palmitic acid (PA)-treated HepG2 cells. PLIN2 silencing and LIPA overexpression notably increased the mRNA level and protein expression of LC3II and decreased the mRNA level and protein expression of p62, respectively. In summary, our findings reveal novel insights into the effect of exercise on improving lipid droplet metabolism disorder in NAFLD. Enhancing the PLIN2-LIPA axis-mediated lipophagy may be one of the key mechanisms involved in NAFLD alleviation by exercise.

Testing the effectiveness of motivation-based teaching in Nursing English course: A quasi-experimental study.

BACKGROUND: Motivation is a crucial factor in determining the student-learning process. Integrating the Attention, Relevance, Confidence, and Satisfaction (ARCS) motivation model into the Nursing English course has the potential to motivate nursing students and improve their learning outcomes. OBJECTIVES: To apply motivational tactics to the Nursing English course and explore the effects on the learning motivation, engagement, and performance of vocational college nursing students. DESIGN: A quasi-experimental study. SETTING: The study was conducted at a vocational college in XXXX. PARTICIPANTS: A total of 229 sophomore nursing students (experimental group = 114; comparison group = 115) participated. METHODS: Motivation-based teaching was applied to the experimental group, while traditional lecture-based teaching was used with the comparison group. The Course Interest Survey (CIS) was used to measure student learning motivation; the Utrecht Work Engagement Scale-Student (UWES-S) was used to assess student learning engagement (both pre- and posttest). Midterm and final examination scores were used to compare the learning performance between both groups. RESULTS: There were no significant differences between both groups at the pretest in the CIS, UWES-S, and midterm examination scores. Significant group ∗ time interactions were found for CIS, UWES-S, and examination scores. The simple effect analysis showed that the experimental group's CIS, UWES-S, and examination scores were significantly higher than the comparison group at the posttest. Furthermore, the motivation-based teaching led to significant improvements in the CIS scores (from 3.12 [0.43] to 3.66 [0.34], p < 0.001), UWES-S scores (from 3.72 [0.53] to 4.05 [0.69], p < 0.001) and the CIS and UWES-S sub-scale scores of the experimental group. No changes were observed in the comparison group. The experimental group showed more remarkable improvement than the comparison group in examination scores. CONCLUSIONS: Motivation-based teaching effectively improved learning motivation, learning engagement, and learning performance of students in the Nursing English course.

The predictive value of 18F-FDG PET/CT in an EGFR-mutated lung adenocarcinoma population.

Background: A non-invasive, simple, and convenient method to evaluate the presence of epidermal growth factor receptor (EGFR) mutations is important for initial treatment decisions in lung adenocarcinoma. Methods: We retrospectively reviewed 297 untreated primary lung adenocarcinoma patients with exact EGFR status. Based on their EGFR status, the patients were divided into a mutant-type group (138 patients) and wild-type group (159 patients). General patient characteristics and possible factors reflecting the status of EGFR were also evaluated. Results: Of the 297 lung adenocarcinoma patients analyzed for EGFR status who underwent positron emission tomography (PET)/computed tomography (CT) between January 2013 and December 2017, mutations in the EGFR gene were detected in 138 patients (46.5%). EGFR mutations were more frequently associated with women, never smokers, and low 18F-fluoro-2-deoxy-glucose (18F-FDG) PET/CT maximal standard uptake value of the primary tumor (pSUVmax). Multivariate analysis indicated that women [odds ratio (OR) =2.853; 95% confidence interval (CI): 1.451-5.611; P=0.002], never smokers (OR =2.414; 95% CI: 1.217-4.789; P=0.012), tumor size <3.5 cm (OR, 2.170; 95% CI: 1.205-3.908; P=0.010), and pSUVmax <8.2 (OR =1.904; 95% CI: 1.098-3.302; P=0.022) were effective predictors of EGFR mutation. In addition, the area under the curve (AUC) of pSUVmax and tumor size was 0.623 and 0.600, respectively. Combined with clinical characteristics, including sex and smoking status, the AUC of the 4 predictors was 0.770. Conclusions: These indicators could be helpful for enhancing predictive accuracy of EGFR mutations in lung adenocarcinoma patients, especially in those for whom EGFR detection is unavailable.

Effects of atorvastatin doses on serum level of procalcitonin and predictors for major adverse cardiovascular events in patients with acute myocardial infarction: a pilot study and post hoc analysis.

BACKGROUND: Inflammation plays an important role in acute myocardial infarction (AMI). Procalcitonin levels rise in response to proinflammatory stimuli. This study aimed to investigate the effects of different doses of atorvastatin on the serum inflammatory profiles, especially procalcitonin and major adverse cardiovascular events (MACEs) in patients with AMI during hospitalization. METHODS: The patients who were admitted to the Coronary Care Unit of The Third Medical Center of PLA General Hospital (Beijing, China) between January 2015 and December 2015 with a diagnosis of AMI were enrolled, and randomized to atorvastatin 20 mg/day postoperatively (20-mg group), 40 mg/day postoperatively (40-mg group) and 80 mg preoperatively+40 mg/day postoperatively (80/40-mg group). Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and at 1 and 3 days after percutaneous coronary intervention (PCI). RESULTS: A total of 112 patients with AMI (23 women and 89 men) were prospectively eligible for the study. There were no significant differences in most clinical data among the three groups. The 80/40-mg group showed significantly reduced serum procalcitonin levels at 1 and 3 days after PCI (P < 0.001) and reduced hs-CRP levels at 3 days P = 0.001) compared with 20-mg and 40-mg groups. Serum procalcitonin (OR, 4.593; 95% CI, 1.476-8.387; P = 0.005), hs-CRP (OR, 1.149; 95% CI, 1.012-1.338; P = 0.018), highly sensitive cardiac troponin T (OR, 1.255; 95% CI, 1.004-1.569, P = 0.009) and Gensini score (OR, 1.022; 95% CI, 1.045-1.062; P = 0.013) were independently associated with MACEs during hospitalization. CONCLUSION: The use of atorvastatin 80 mg before and 40 mg/day after PCI in patients with AMI can effectively reduce serum inflammatory factors. procalcitonin and hs-CRP were independently associated with in-hospital MACEs.

[Effect of early goal directed sedation on cerebral oxygen metabolism in patients with acute brain injury].

OBJECTIVE: To observe the effect of early goal directed sedation (EGDS) on cerebral oxygen metabolism in patients with acute brain injury. METHODS: A prospective cohort study was conducted. A total of 108 patients with acute brain injury admitted to the intensive care unit (ICU) of the Third Medical Center of the PLA General Hospital from January 2015 to December 2019 were enrolled. According to the patient's condition, dexmedetomidine contraindication and tolerance, and combined with the wishes of patients' families, they were divided into EGDS group and on-demand sedation group. Routine treatments such as surgery, mechanical ventilation, dehydration and reduction of intracranial pressure with mannitol, hemostasis or antiplatelets therapy were given according to the patient's condition. All patients were continuously given sufentanil by intravenous infusion for analgesia. Patients in the EGDS group were sedated by continuously intravenous infusion of dexmedetomidine (0.2-0.7 µg×kg-1×min-1) for 72 consecutive hours. Patients in the on-demand sedation group received intravenous bolus of propofol (0.5-1.0 mg/kg) when treatments were interfered due to agitation. Hemodynamic indexes [heart rate (HR), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), intracranial pressure (ICP)], sedation indexes [bispectral index (BIS)], severity indexes [acute physiology and chronic health evaluation II (APACHE II) score, Glasgow coma score (GCS)] and cerebral oxygen metabolism indexes [jugular venous blood lactate (Lac), jugular venous oxygen saturation (SjvO2), cerebral arterial oxygen content (CaO2), cerebral extraction rate of oxygen (CERO2), cerebral arteriovenous blood oxygen content difference (a-vDO2)] were compared between the two groups before sedation and at 24, 48 and 72 hours of sedation. RESULTS: (1) Among the 108 patients, 3 patients with cerebral hemorrhage received secondary surgery or had worsening of cerebral hernia were excluded. 105 patients were enrolled in the study, including 54 patients in the EGDS group and 51 patients in the on-demand sedation group. There were no statistically significant differences in gender, age, type of craniocerebral injury, GCS score, proportion of mechanical ventilation and operation ratio between the two groups. (2) Compared with before sedation, Lac, CERO2 and a-vDO2 of both groups gradually reduced over time of sedation while SjvO2 and CaO2 were gradually higher. Those changes were more quickly in the EGDS group, Lac, SjO2, CERO2 and a-vDO2 significantly improved at 24 hours of sedation compared with those before sedation. Above indexes at 72 hours of sedation in the EGDS group were obviously better than those in the on-demand sedation group [Lac (mmol/L): 1.81±0.31 vs. 2.19±0.12, SjvO2: 0.714±0.125 vs. 0.683±0.132, CaO2 (mL/L): 201.21±15.25 vs. 179.65±14.07, CERO2: (27.87±3.66)% vs. (33.00±2.58)%, a-vDO2 (mL/L): 44.32±5.68 vs. 48.57±8.22, all P < 0.05]. (3) Compared with before sedation, HR, MAP and ICP decreased in the two groups over time while CPP, BIS and GCS score showed increasing trend, especially more quickly in the EGDS group, HR at 24 hours of sedation, MAP, CPP, BIS and GCS score at 48 hours significantly improved as compared with those before sedation. Hemodynamics and sedation related parameters and GCS score at 72 hours of sedation in the EGDS group were significantly better than those in the on-demand sedation group [HR (bpm): 70.69±7.80 vs. 79.85±9.77, MAP (mmHg, 1 mmHg = 0.133 kPa): 84.23±8.76 vs. 89.97±9.48, ICP (mmHg): 14.23±8.76 vs. 15.97±9.48, BIS: 60.56±24.58 vs. 56.86±33.44, GCS score: 8.06±3.63 vs. 7.86±2.98, all P < 0.05]. The APACHE II scores were significantly reduced at 72 hours of sedation in both groups as compared with those before sedation, while there was no statistical difference between the two groups. CONCLUSIONS: Compared with the on-demand sedation, EGDS could reduce cerebral oxygen metabolism, improve the coma degree, and reduce the severity of the disease in patients with acute brain injury.

[Clinical research of early goal directed sedation applying in acute brain injury].

OBJECTIVE: To investigate the value and feasibility of early goal directed sedation (EGDS) in patients with acute brain injury. METHODS: A total of 110 patients with acute brain injury who were admitted to intensive care unit (ICU) of the Third Medical Center of the Chinese People's Liberation Army General Hospital from January 2015 to March 2019 were included and randomly divided into EGDS group and standard sedation group (STD) using the random number table. Patients in the EGDS group were sedated by continuous intravenous infusion of dexmedetomidine (initial dose of 0.2 µg×kg-1×min-1) for 72 consecutive hours. Patients in the STD group received intravenous bolus of propofol as appropriate clinically. Richmond agitation-sedation score (RASS) and electroencephalogram bispectral index (BIS) were used to continuously monitor the level of sedation. All patients were given sufentanil for analgesia. Routine treatments such as dehydration and reduction of intracranial pressure with mannitol, hemostasis or antiplatelet therapy were given according to the patients' condition. Vital signs, acute physiology and chronic health evaluation II (APACHE II) score, Glasgow coma scale (GCS) score, BIS value, artery blood gas analysis, duration of mechanical ventilation, analgesic dosage and adverse events were recorded in two groups before and 24, 48, and 72 hours after sedation. RESULTS: (1) Among the 110 patients, patients who received the second surgery due to cerebral hemorrhage, had worsening of cerebral hernia, withdrew during the course of the study, or whose family members abandoned treatment were excluded from the study. Finally, 105 patients were enrolled in the study, including 56 patients in the EGDS group and 49 in the STD group. There was no significant difference in gender, age, types of brain injury, baseline APACHE II or GCS score or rate of mechanical ventilation between the two groups. (2) Compared with before sedation, heart rate (HR) significantly decreased till 72 hours after sedation in both groups, and the decrease in the EGDS groups was more obvious as compared with the STD group (bpm: 70.49±7.53 vs. 79.83±9.48, P < 0.05). Besides HR, significant improvement was found in the APACHE II and GCS scores in the STD group at 72 hours of sedation as compared with before sedation, and no significant difference was found in other indicators. Compared with before sedation, arterial partial pressure of carbon dioxide (PaCO2) was significantly increased from the 24th hour of sedation, mean artery pressure (MAP) was decreased significantly and GCS score, BIS value were increased significantly from the 48th hour of sedation, till 72 hours, which were all improved significantly as compared with the STD group [72-hour PaCO2 (mmHg, 1 mmHg = 0.133 kPa): 40.30±5.98 vs. 31.57±8.20, 72-hour MAP (mmHg): 85.01±8.26 vs. 89.54±9.41, 72-hour GCS score: 8.62±3.34 vs. 7.89±2.74, 72-hour BIS: 60.87±24.79 vs. 56.68±33.43, all P < 0.05]. APACHE II score was significantly lower only at the 72nd hour of sedation as compared with before sedation in the EGDS group, and no significant difference was found as compared with the STD group (17.10±7.05 vs. 18.90±3.32, P > 0.05). Oxygenation index (PaO2/FiO2) was significantly increased only at the 24th hour of sedation in the EGDS group as compared with the STD group (mmHg: 261.05±118.45 vs. 226.45±96.54, P < 0.05). (3) The duration of mechanical ventilation was significantly shorter in the EGDS group than that in the STD group (hours: 20.56±9.03 vs. 27.75±11.23, P < 0.05), and the total administered dose of sufentanil was significantly lower in the EGDS group than that in the STD group (µg: 79.16±26.76 vs. 102.46±35.48, P < 0.05). (4) Compared with the STD group, the incidence of bradycardia in the EGDS group was increased significantly [10.71% (6/56) vs. 6.12% (3/49), P < 0.05], while the incidence of tachycardia was decreased significantly [14.29% (8/56) vs. 38.78% (19/49), P < 0.05], but no significant difference was found in the incidence of hypotension [5.36% (3/56) vs. 4.08% (2/49), P > 0.05]. The incidence of unexpected extubation in the STD group was 4.08% (2/49), which did not occurre in the EGDS group. CONCLUSIONS: EGDS can improve the GCS score and BIS value of patients with acute brain injury, suggesting that the EGDS is safe and feasible, which can help improve neurological function in patients with acute brain injury.

Reemergence of human plague in Yunnan, China in 2016.

The third plague pandemic originated from Yunnan Province, China in the middle of the 19th century. The last human plague epidemic in Yunnan occurred from 1986-2005. On June 6, 2016, a case of human plague was reported in the Xishuangbanna Prefecture, Yunnan. The patient suffered from primary septicemic plague after exposure to a dead house rat (Rattus flavipectus), which has been identified as the main plague reservoir in the local epizootic area. Moreover, a retrospective investigation identified another bubonic plague case in this area. Based on these data, human plague reemerged after a silent period of ten years. In this study, three molecular typing methods, including a clustered regularly interspaced short palindromic repeats (CRISPR) analysis, different region analysis (DFR), and multiple-locus variable number of tandem repeats analysis (MLVA), were used to illustrate the molecular characteristics of Yersinia pestis (Y. pestis) strains isolated in Yunnan. The DFR profiles of the strains isolated in Yunnan in 2016 were the same as the strains that had previously been isolated in this Rattus flavipectus plague focus. The c3 spacer present in the previously isolated strains was absent in the spacer arrays of the Ypc CRISPR loci of the strains isolated in 2016. The MLVA analysis using MLVA (14+12) showed that the strains isolated from the human plague case and host animal plague infection in 2016 in Yunnan displayed different molecular patterns than the strains that had previously been isolated from Yunnan and adjacent provinces.

Mechanism study on a plague outbreak driven by the construction of a large reservoir in southwest china (surveillance from 2000-2015).

BACKGROUND: Plague, a Yersinia pestis infection, is a fatal disease with tremendous transmission capacity. However, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma. METHODOLOGY/PRINCIPAL FINDINGS: We studied a plague outbreak caused by the construction of a large reservoir in southwest China followed 16-years' surveillance. CONCLUSIONS/SIGNIFICANCE: The results show the prevalence of plague within the natural plague focus is closely related to the stability of local ecology. Before and during the decade of construction the reservoir on the Nanpan River, no confirmed plague has ever emerged. With the impoundment of reservoir and destruction of drowned farmland and vegetation, the infected rodent population previously dispersed was concentrated together in a flood-free area and turned a rest focus alive. Human plague broke out after the enzootic plague via the flea bite. With the construction completed and ecology gradually of human residential environment, animal population and type of vegetation settling down to a new balance, the natural plague foci returned to a rest period. With the rodent density decreased as some of them died, the flea density increased as the rodents lived near or in local farm houses where had more domestic animals, and human has a more concentrated population. In contrast, in the Himalayan marmot foci of the Qinghai-Tibet Plateau in the Qilian Mountains. There are few human inhabitants and the local ecology is relatively stable; plague is prevalence, showing no rest period. Thus the plague can be significantly affected by ecological shifts.

Paternal smoking and breastfeeding in Xinjiang, PR China.

A cohort of 1088 couples in Xinjiang, PR China, were recruited to study infant feeding practices and paternal smoking. Mothers were interviewed in hospital and at 0.5, 1.5, 2.5, 3.5, 4.5, and 6 months. Survival analysis was used to calculate breastfeeding rates in smokers and nonsmokers. The paternal smoking rate was 64.8% and maternal smoking rate 1.7% (P < .01). The rates for any breastfeeding in the smoking group were significantly lower than in the nonsmoking group from 3.5 months to 6 months (P < .05). The rates for exclusive breastfeeding in the paternal smoking group were lower than in the nonsmoking group from discharge to 6 months (P < .05). The median duration of exclusive breastfeeding in the paternal smoking group was shorter than in the nonsmoking group. Paternal smoking was a risk factor for stopping any breastfeeding (hazard risk, 1.84; 95% confidence interval, 1.11-3.04) and exclusive breastfeeding (hazard risk, 1.33; 95% CI, 1.09-1.64) compared with nonsmokers.

Matrix metalloproteinase-9/tissue inhibitors of metalloproteinase-1 expression and atrial structural remodeling in a dog model of atrial fibrillation: inhibition with angiotensin-converting enzyme.

INTRODUCTION: Matrix metalloproteinases and tissue inhibitors of metalloproteinases regulate extracellular matrix turnover in cardiac tissues. However, alteration of matrix metalloproteinases and tissue inhibitors of metalloproteinases during atrial fibrillation is unclear. This study aims to determine (a) the relationship between altered expressions of matrix metalloproteinases and tissue inhibitors of metalloproteinases and atrial structural remodeling; (b) the role of changes in the atrial angiotensin system and in calcium concentration; and (c) the effect of captopril on the expressions of matrix metalloproteinase-9/tissue inhibitors of metalloproteinase-1 and atrial structural remodeling. METHODS: In left atrial tissue samples, the mRNA expression of angiotensin-converting enzyme, matrix metalloproteinase-9, and tissue inhibitors of metalloproteinase-1; the protein expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1; and Ca(2+) concentration and angiotensin II were measured. RESULTS: Compared with controls, dogs under atrial fibrillation showed significantly increased contents of Ca(2+), angiotensin II , and interstitial fibrous tissue (P<.05-.001). The mRNA levels of angiotensin-converting enzyme, matrix metalloproteinase-9, and tissue inhibitors of metalloproteinase-1 were significantly increased as compared with controls (P<.05-.01). The protein level of matrix metalloproteinase-9 was higher, and that of tissue inhibitors of metalloproteinase-1 was lower, in dogs with atrial fibrillation than in controls (P<.01-.001). All findings highlighted above were reversed by treatment with captopril. CONCLUSIONS: Altered expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 contributes to atrial extracellular matrix remodeling and atrial dilatation. Angiotensin-II-mediated intracellular Ca(2+) overload may be the mechanism of altered expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1. Angiotensin-converting enzyme inhibitor treatment may attenuate atrial structural remodeling by normalizing the balance between matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1.

[Effects of matrix metalloproteinase-9 and tissue inhibitor-1 of metalloproteinase expression on atrial structural remodeling during chronic atrial fibrillation].

OBJECTIVE: To investigate the matrix metalloproteinase-9 (MMP-9) and tissue inhibitor-1 of metalloproteinase (TIMP-1) mRNA and protein expression in chronic fibrillating human atria and to evaluate the influence of MMP-9 and TIMP-1 expression on the progress of atrial structural remodeling. METHODS: Twenty-four patients with chronic atrial fibrillation (AF) and 12 patients with sinus rhythm as control group underwent transthoracic echocardiography and left atrial appendage (LAA) tissue samples were obtained from these patients during mitral/aortic valve replacement operation. MMP-9 and TIMP-1 protein expressions were detected by immunohistochemistry and their mRNA expressions were determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The left atrial and right atrial diameters increased significantly in the fibrillation group in comparison with the control group (57 +/- 6 vs 45 +/- 7, 62 +/- 10 vs 51 +/- 17, P < 0.05 approximately 0.001) The expressions of MMP-9 mRNA and protein in the LAA tissue of the AF group is upregulated (0.70 +/- 0.12 vs 0.53 +/- 0.22, and 2.25 +/- 0.73 vs 1.12 +/- 0.58, P < 0.05 approximately 0.001) and the expressions of TIMP-1 mRNA and protein were downregulated significantly (0.20 +/- 0.07 vs 0.31 +/- 0.15, and 1.12 +/- 0.48 vs 1.75 +/- 0.46, P < 0.05 approximately 0.01). The MMP-9 mRNA level was positively correlated with AF duration and the left atrial diameter (P < 0.05 approximately 0.001). CONCLUSION: There is a selective downregulation of TIMP-1 expression along with the upregulation of MMP-9 in AF, which indicates that the disturbance expression of MMP/TIMP system may promote the process of atrial structural remodeling. Enhanced MMP-9 activity may be a molecular mechanism contributing to the dilation of fibrillating human atria.