SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR

Farnesoid X receptor (FXR) is widely accepted as a promising target for various liver diseases; however, panels of ligands in drug development show limited clinical benefits, without a clear mechanism. Here, we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury, which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases. Upon inflammatory and apoptotic stimulation, enhanced FXR acetylation at K217, closed to the nuclear location signal, blocks its recognition by importin KPNA3, thereby preventing its nuclear import. Concomitantly, reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1, and thereby facilitating FXR export to the cytosol. Acetylation governs nucleocytoplasmic shuttling of FXR, resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP. SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation. More importantly, SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries. In conclusion, these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

Application of Three-dimensional Reconstruction in Single Utility-port Thoracoscopic Segmentectomy for Early Stage Non-small Cell Lung Cancer: A Propensity Score-matched Analysis / 肿瘤防治研究

Objective To evaluate the clinical value of 3D reconstruction in the single utility-port thoracoscopic segmentectomy of early stage NSCLC by propensity score matching (PSM). Methods We retrospectively analyzed clinical data of 150 early stage NSCLC patients undergoing single utility-port thoracoscopic segmentectomy. The patients were divided into reconstruction group (n=58) and non-reconstruction group (n=92) according to 3D reconstruction. PSM was performed on two groups to compare perioperative outcomes. Results Procedures were successfully completed on all patients, without perioperative death. In each group, 43 patients were successfully matched after PSM on the basis of 8 confounding factors, age, gender, smoking status, BMI, maximum tumor diameter on CT, tumor location, % FEV1 and type of planned segmentectomy. After PSM, in complex segmentectomy, the patients in the reconstruction group had shorter operation time (155.77±30.17 vs. 212.94±66.49min, P < 0.001) and less blood loss (46.00±25.94 vs. 88.79±68.36ml, P=0.002), compared with the non- reconstruction group. Conclusion Preoperative 3D reconstruction could help improve the efficiency of single utility-port thoracoscopic surgery for complex segmentectomy and reduce intraoperative bleeding.

Study on the correlation between carotid atherosclerosis and osteocalcin in patients with type 2 diabetes / 中国基层医药

Objective:To explore the relationship between carotid atherosclerosis (CAS) and bone metabolism marker osteocalcin (OC) in patients with type 2 diabetes (T2DM).Methods:A total of 100 patients with T2DM admitted to Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University) from January 2018 to August 2018 were selected as study subjects, and the carotid intima-media thickness (IMT) was detected.The patients were divided into CAS group and normal carotid IMT group (NC group), with 50 cases in each group.The levels of OC, fasting plasma glucose(FPG), fasting insulin(FINS), glycosylated hemoglobin(HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein(HDL-C), low density lipoprotein (LDL-C), insulin resistance index (HOMA-IR) were compared between the two groups.Results:The OC level of the CAS group[(11.86±4.46)ng/mL] was significantly lower than that of the NC group[(23.94±4.52)ng/mL] ( t=-9.640, P=0.001). The LDL-C level of the CAS group[(2.89±0.82)mmol/L] was significantly higher than that of the NC group[(2.55±1.16)mmol/L]( t=2.03, P=0.049). Pearson correlation analysis showed that IMT was positively correlated with age, LDL-C, HbA1c ( r=0.285, 0.190, 0.173; P=0.000, 0.020, 0.035), and negatively correlated with OC ( r=-0.603, P=0.000). Conclusion:CAS in patients with T2DM is closely related to OC, and the reduction of OC levels may be a risk factor for CAS in T2DM patients.

Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis

Obeticholic acid (OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl-injured mice, d-galactosamine/LPS (GalN/LPS)-treated mice and cycloheximide/TNF (CHX/TNF)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell (HSC) activation/proliferation and prevented fibrosis. Elevated bile acid (BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.

A high risk factors clinical study of low birth weight premature infants with wheezing / 中华实用儿科临床杂志

Objective To investigate the high risk factors for wheezing of low birth weight premature infants with wheezing.Methods A cohort study of 143 premature infants,whose gestation less than 37 weeks and birth weight less than 2 500 g,were collected from Neonatal Intensive Care Unit of Kunming Children's Hospital,from December 2012 to November 2013.Follow-up investigation was conducted,and those with wheezing were enrolled in the study.Many possible factors causing wheezing were analyzed,such as general conditions in the neonatal period,family conditions,and treatment.SPSS 17.0 statistical software was used to analyze the data.Single factor analysis was used by x2 test and rank sum test to evaluate the possible risk factors.Multiple factors analysis was made by Logistic regression analysis.P ＜ 0.05 was viewed as having statistical difference.Results (1) The risk factors for wheezing in the premature infants were:continuous positive airway pressure (CPAP) noninvasive ventilation (x2 =8.531,P =0.003),ventilation (x2 =4.800,P =0.028),caesarean section (x2 =6.787,P =0.009),the use of pulmonary surfactant (x2 =5.455,P =0.020),using antibiotics used at hospital (x2 =5.192,P =0.023),father smoking(x2 =5.406,P =0.020),maternal smoking (x2 =8.531,P =0.003),maternal allergic history (x2 =8.297,P =0.004),compatriot history of allergies (x2 =8.297,P =0.004) or asthma (x2 =9.774,P =0.002),family environment with dust and excitant gas (x2 =12.831,P =0.000) were the risk factors for the wheezing in the low birth weight premature infants.(2)Multi-factor classification Logistic regression analysis showed that CPAP (OR =58.414,95 ％ CI:3.317-1 028.646,P =0.005),mother smoking during pregnancy (OR =11.953,95 ％ CI:1.309-109.120,P =0.028),compatriot history of allergies (OR=135.769,95％ CI:4.914-3 751.419,P =0.004),family environment(OR =83.738,95％ CI:4.416-1 587.982,P =0.003),were independent risk factors for wheezing in low birth weight premature infants;natural labor was protective factor for wheezing in low birth weight premature infants (OR =0.045,95％ CI:0.004-0.574,P =0.017).(3)The sensitivity and specificity of risk factors were analyzed.The highest sensitivity was estimated for the father's history of allergy(83.3％).The highest specificity was estimated for the use of antibiotics at hospital (76.7％).Conclusions The study shows that CPAP noninvasive ventilation,mother smoking during pregnancy,allergy history of their brothers and sisters,family environment with dust and excitant gas are independent risk factors for wheezing in the low birth weight premature infants.There is no single risk factor with both high sensitivity and high specificity.

Study on sleeping quality of medical students and its influential factors / 中华健康管理学杂志

Objective To understand the quality of sleeping in medical students, and provide a reference basis for designing sleep health management program for college students. Methods The survey was conducted at a medical college in Shanxi province with stratified random sampling and Pittsburgh Sleep Quality Index (PSQI) scale. Totally 210 individuals were enrolled, 199 completed the questionnaire, with a response rate of 93.5%. SPSS 21.0 statistical software was used for data analysis. Descriptive statistical analysis was carried out for socio-demographic data. Independent t-test, one-way analysis of variance and non-parametric test were used to compare the scores of PSQI between participants. Multiple stepwise linear regression was used to determine influencing factors of sleep quality. Results The average score of PSQI for the 199 medical students interviewed was (6.74±2.42), the incidence of sleep disorder was 50.25%, the overall sleep quality was not high. Learning pressure of medical student had statistically significant in PSQI (Completely unmatched, 5.14 ± 2.32, Mostly unmatched, 5.93 ± 2.73, Mostly matched, 6.70 ± 2.42, Absolutely matched, 7.39 ± 2.10, F=3.366, P=0.020), employment pressure of medical students in PSQI (Completely unmatched, 6.50 ± 0.71, Mostly unmatched, 6.80 ± 3.24, Mostly matched, 5.98 ± 2.14, Absolutely matched, 7.14 ± 2.35, F=3.134, P=0.027). Grade (β=-0.172, P<0.05) and learning pressure (β=0.210, P<0.01) were the main influence factors for students. Conclusion Sleep quality of medical students was not high, upper grade was worse than low grade, the incidence of sleep disorder had increasing trend as learning pressure and degree of employment pressure worsen.

Multifunctional Nursing Beds Based on Intelligent Detection and Recovery / 中国医疗器械杂志

With the advent of the aging society, there will be a wide range of applications if novel intelligent multifunctional nursing beds can be developed for hospitals, bead houses and families at the same time. By listing and analyzing existing products, this paper summarized four function categories for multifunctional nursing beds, including security assurance, treatment aid, comfortability optimization, and human-machine interaction and communication. Finally, by comparing existing functions and potential user requirements, this paper proposed four function development trends, including physiological parameter monitoring, sleep aid, intelligent temperature control, and video communication.

Clinical study on the relationship between the activation of the IKK-IκB-NFκB pathway and insulin resistance / 中华内分泌代谢杂志

Objective To explore the difference involved in the activation of inflammation pathway and the plasma level of inflammatory factors in the subjects with different sorts of insulin sensitivity. Methods The study was carried out in 38 women, consisting of obesity (n = 22 ) and control (n = 16 ) groups according to body mass index. The insulin sensitivity was assessed by homeostasis model assessment of insulin resistance (HOMAIR). Plasma concentrations of interleukin-6 (II-6) and IL-1β were determined by enzyme immunoassay. Western blot analysis was used to examine total protein expression and phosphorylation levels of IκB kinase (IKK) ,inhibitor of nuclear factor-κB ( IκB ) in peripheral blood leukcocytes. Electrophoretic mobility shift assay (EMSA)was used to detect the binding activity of NFκB. Results The levels of fasting plasma insulin[62.2 ( 20.0-127. 0) pmol/L vs 19. 15 ( 14. 2-47. 8 ) pmol/L, P<0. 01], HOMA-IR[2. 32 ( 0. 76-5.49 ) vs 0.70(0.53-1.7),P<0.0l], HbA1 C[(5.42±0. 45 ) % vs ( 5.08 ±0. 38) %, P<0. 05], triglyceride[( 1.75 ±0. 68 vs 1.22 ±0. 58 )mmol/L, P<0. 05], plasma IL-6[3. 15 (0. 03-22. 2) pg/ml vs 1.26 (0. 74-6.06 ) pg/ml, P<0. 01], and IL-1 β[6. 53 ( 0. 84-36 ) pg/ml vs 3. 16( 1.48-8. 86 ) pg/ml, P<0. 01]in obesity group were significantly higher than those in control group. Compared with control group, the levels of IKKo, IKKβ expression and IκBα serine phosphorylation in obesity group were markedly increased, while the expression of IκBα was significantly reduced. Accompanied with the degradation of IκBα protein, the binding activity of NFκB in obesity group was significantly increased. Conclusions The plasma levels of IL-6 and IL-1β were significantly raised in obesity group. The activation of IKK-IκB-NFκB pathway is closely associated with the genesis and development of insulin resistance in obese subjects.

Effect of combined chemotherapy including Navelbine in the treatment of 39 cases of advanced non-small cell lung cancer / 中国癌症杂志

Purpose:To study the effect of NVB in the treatment of advanced non small cell lung cancer (NSCLC).Methods:In 39 cases advanced stage, primary chemotherapy patients account for 30 cases and 9 were recurrent diseases.Results:CR 2 cases PR 20 cases NC 13 cases and PD 4 cases, total response rate 56.4%. The majory toxicity was bone marrow suppression.Conclusions:Combined chemotherapy including NVB has better curative effect for advanced NSCLC.