LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.

Application status and the model of quality management of point-of-care testing in Shanghai / 中华检验医学杂志

Point-of-care testing (POCT) has developed rapidly in various fields including medical health, customs quarantine, agriculture, graziery, forestry, fire-fighting, environment and food testing. It poses a huge challenge to the traditional inspection mode. Yet POCT still has many problems in terms of technical ability, quality control, regulation and industry-university-research cooperation and so on. Thus it is necessary for the health administrative departments, manufacturers and hospitals to establish consensus, and implement the total quality management system. The establishment of an independent evaluation system and the application of advanced quality control technologies of POCT is also essential given its particularity. This article focuses on the POCT application status and quality management in Shanghai based on the series of quality management measures for the POCT project carried out by the Shanghai Center for Clinical Laboratory, and raises some thoughts and suggestions for the existing problems.

Ensuring efficiency and reliability of equipment with optimization of integrated tests.

The paper suggests a method for optimization of the process of integrated tests for complex technical equipment of automotive, aviation, and rocket systems based on an analysis of efficiency dynamics models. The method makes it possible to determine scopes of ground tests for complex technical equipment, which are minimally required to start field tests under the necessity to combine ground and field development. Exponential models of complex systems' development are used as efficiency dynamics models for the whole testing process as well as efficiency dynamics models at various levels of the hierarchy of tests. The paper addresses an optimization task when the structure of tests at each level of the hierarchy is specified, i.e. efficiency dynamics models are determined for each level. The authors determine optimal points of transition from one level of tests to another, considering the random nature of efficiency dynamics parameters. A method for optimization using determination of the optimal scope of field tests is given.

The role of TSH in bone metabolism / 中国医师杂志

Thyrotropin (TSH) has been thought to play a bone regulatory role by increasing the expression and release of thyroid hormones through the hypothalamus-pituitary-thyroid axis.Recent studies have shown that TSH can directly regulate bone metabolism independently of thyroid hormones.Based on this,the concept of pituitary-bone axis has been proposed.However,the mechanism of TSH in bone metabolism is still unclear.In this paper,the clinical relationship between TSH and osteoporosis,the effects of TSH on chondrocytes,osteoblasts and osteoclasts,the polymorphism of thyroid-stimulating hormone receptor (TSHR) gene and bone mass,and the effects of TSH injection on bone metabolism are discussed,which provide theoretical basis for finding new targets for prevention and treatment of osteoporosis.

Periostin promotes migration and invasion of renal cell carcinoma through the integrin/focal adhesion kinase/c-Jun N-terminal kinase pathway.

Periostin (POSTN) is an extracellular matrix protein which is overexpressed in a variety of cancers and has been related to tumorigenesis of renal cell carcinoma. However, the involvement of POSTN in renal cell carcinoma migration, invasion, and their underlying mechanisms has not been established. In this study, renal cell carcinoma cell lines stably overexpressing POSTN were established using a lentiviral vector, and the effects of POSTN on renal cell carcinoma cell migration and invasion were investigated. POSTN overexpression increased the migration and invasion capabilities of renal cell carcinoma cell lines as well as activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. Integrin αvß3 and αvß5 antibodies inhibited POSTN overexpression or recombinant POSTN-induced focal adhesion kinase activation, cell migration, and invasion. Furthermore, lentivirus-mediated focal adhesion kinase knockdown and c-Jun N-terminal kinase inhibitor reduced POSTN-enhanced phosphorylation of c-Jun N-terminal kinase, matrix metalloproteinase-9 and matrix metalloproteinase-2 expressions, cell migration, and invasion. Our research thus indicates that POSTN promotes renal cell carcinoma cell migration and invasion through interaction with integrins αvß3 and αvß5 and subsequent activation of the focal adhesion kinase/c-Jun N-terminal kinase pathway. These results suggest that POSTN plays a critical role in renal cell carcinoma metastasis and may represent a potential target for novel therapeutic approaches against renal cell carcinoma.

Simultaneous Determination of 7 Kinds of Components in Qing'e Pills by HPLC / 中国药房

OBJECTIVE:To develop a method for simultaneous determination of psoralen,isopsoralen,bergapten,imperato-rin,trimethylpsorale,neobavaisoflavone and bavachin in Qing'e pills. METHODS:HPLC method was adopted. The separation was performed on Kinetex-C18 column with mobile phase consisted of methanol-0.1% glacial acetic (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was set at 248 nm. The column temperature was 30 ℃. The sample size was 20 μL. RESULTS:The linear ranges were 1.012-101.2 μg/mL for psoralen(r=0.9999),1.007-100.7 μg/mL for isopsoralen(r=0.9997), 1.010-101.0μg/mL for bergapten(r=0.9999),1.021-102.1μg/mL for imperatorin(r=0.9999),1.002-100.2μg/mL for trimethyl-psorale(r=0.9996),1.008-100.8 μg/mL for neobavaisoflavone(r=0.9999),1.025-102.5 μg/mL for bavachin(r=0.9998),re-spectively. The limits of quantitation were 0.15,0.15,0.30,0.30,0.15,0.30,0.30 μg/mL,and the limits of detection were 0.05, 0.05,0.10,0.10,0.05,0.10,0.10 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were lower than 2.0%. The recoveries were 95.3%-99.6%(RSD=1.9%,n=6),96.1%-99.3%(RSD=1.2%,n=6),95.2%-98.4%(RSD=1.4%,n=6),95.4%-99.2%(RSD=1.5%,n=6),96.1%-99.3%(RSD=1.5%,n=6),95.6%-98.9%(RSD=1.4%,n=6), 95.2%-99.6%(RSD=1.6%,n=6),respectively. CONCLUSIONS:The method is simple and accurate,can be used for simultane-ous determination of 7 kinds of components in Qing'e pills.

Correlation between sleep quality and parasympathetic intensity at nighttime / 中华神经科杂志

Objective To clarify the effect of cardio pulmonary coupling (CPC) technology on sleep quality and the effect of Shichen-based physiological function index analysis on sleep health assessment.Methods CPC and Shichen-based physiological function index were used to evaluate the sleep quality of 242 volunteers from 9:00 pm to 9:00 am for 12 hours.Based on CPC technology score,volunteers wree seperated to three sleep quality groups (scoring 85-100 in 63 volunteers,scoring 60-84 in 80 volunteers,scoring ＜ 60 in 99 volunteers).The results of sleep quality and parasympathetic intensity over the whole nighttime and the different time period of each sleep quality group were compared and the correlation analysis was done.Results The whole nighttime sleep quality test showed that there was significant difference (t =-12.754-19.030,all P ＜ 0.01) in the time to the stable sleep ratio (52.78％ ± 10.32％,43.99％ ± 14.48,20.95％ ± 10.41％),the disturbed sleep ratio (25.65％ ± 7.81％,34.18％ ± 12.71％,53.65％ ± 14.81％),and the apnea-hypopnea index (2.79 ±2.95,7.93 ± 6.61,23.94 ± 16.09)in the different sleep quality groups.The Shichen-based sleep quality test showed that there was significant difference among the stable sleep ratio,the disturbed sleep ratio during the 23:00 pm to 5:00 am period in the different sleep quality groups.There existed significant difference with parasympathetic intensity in the different sleep quality groups.There was positive correlation between the parasympathetic intensity and the stable sleep ratio in the same sleep quality group (r =0.508,P ＜ 0.05).Conclusions CPC evaluation can commendably distinguish and evaluate different sleep quality groups on the whole night sleep.The Shichen-based physiological function index can not only distinguish the sleep quality,but also evaluate the multiple physiological function,the parasympathetic intensity between different sleep quality groups during different sleep periods.Thus they can be widely used to assess the sleep quality.

The effect of real time continuous blood glucose monitoring system versus intermittent blood glucose monitoring in critically ill patients under the intensive insulin therapy: a Meta-analysis / 中华急诊医学杂志

Objective To evaluate the value of real time continuous blood glucose monitoring system (RT-CGMS) versus intermittent blood glucose monitoring (IGM) in the critically ill patients under intensive insulin therapy (IIT).Methods A systematic searching randomized and controlled trials (RCT) in databases was performed for meta-analysis by Review Manager 5.2 software.Outcomes were hypoglycemia episode,alteration of mean blood glucose level,the percentage of time at a blood glucose level within optimal target range,and the early mortalities.Results Six studies,totally 531 patients,were included in this meta-analysis.The pooled SMD of mean blood glucose level was =-0.21 (95％ SMD:-0.43-0.01,P=0.07).The pooled SMD of percentage of time at a blood glucose level within optimal target range was 0.20 (95％ SMD:-0.09-0.49,P =0.18).The pooled OR of hypoglycemia episode frequency was 0.20 (95％ CI:0.09-0.43,P ＜ 0.01).The pooled OR of early mortalities was 0.35 (95％ CI:0.14-0.89,P =O.03).Conclusions In critically ill patients under the intensive insulin therapy,RT-CGMS had obvious beneficial effect on reducing hypoglycemic events.RT-CGMS had no obvious beneficial effect on keeping blood glucose level within optimal target range.

The efficacy of disodium Pamidronate in the treatment of primary hyperparathyroidism complicated by hypercalcemic crisis / 中华急诊医学杂志

Objective To study the efficacy of disodium pamidronate in the treatment of patients with primary hyperparathyroidism (PHPT) complicated by hypercalcemic crisis.Methods A total of 9 patients (12 cases) admitted into our hospital were diagnosed as PHPT complicated by hypercalcemic crisis.Of them,4 patients had parathyroid carcinoma,3 patients had parathyroid adenoma,2 patients had parathyroid hyperplasia.The intravenous disodium pamidronate was given for 12 times in all 9 patients.Serum calcium were monitored before and after treatment.Results Before the treatment,the serum calcium levels was 3.75 (3.66,3.99) mmol/L.On the second and third day after the treatment with disodium pamidronate,the serum calcium levels were 3.44 (2.95,3.78) mmol/L and 2.79 (2.50,3.14) mmol/L.The lowest level of serum calcium after treatment was 2.25 (2.00,2.55) mmoL/L.There were significant differences in the level of serum calcium of different days (P ＜ 0.05).On the second and third day,the change of serum calcium were 0.46 (0.10,0.88) mmol/L,0.60 (0.25,0.75) mmol/L,there were no differences.After intravenous disodium pamidronate,the serum calcium level decreased below 3.5 mmol/L in (2.27 ± 0.65) days,and were kept below 3.5mmol/L for 18.45 ± 12.30 days.Conclusions Disodium pamidronate can decrease serum calcium levels in hypercalcemic crisis caused by primary hyperparathyroidism effectively with mild adverse events.

A randomized controlled clinical trial on the two-days course of oseltamivir in treatment of influenzalike diseases / 中华全科医师杂志

Eighty six patients with influenza-like diseases were randomly assigned to trial group (n=42,oseltamivir 75 mg,twice daily for 2 days)and control group(n=44,osehamivir 75 mg,twice daily for 5 days).The results showed that there Was no statistical difierence in the duration of fever between trial groups[(56±14)h]and control group[(54±13)h,P=0.623],the cost of the trial group[(193±38)yuan]Was 189 yuan less than that in the control group[(382±61)yuan,P=0.016].It is suggested that the efficacy of two-day course of oseltamivir is the same as that of five-day course in tlle treatment for influenza-like diseases,but with lower cost.