Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
Apoptosis ; Cell Proliferation ; Dependovirus ; Genetic Vectors ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Serpins ; metabolism ; Signal Transduction ; Transfection

Acute-On-Chronic Liver Failure ; blood ; pathology ; Case-Control Studies ; Cytochrome Reductases ; metabolism ; Humans ; Prospective Studies ; alpha-Fetoproteins ; metabolism

Objective To investigate the etiologic effect of the lumbar facet joint morphology on the occurrence of degener?ative lumbar spondylolisthesis (DLS). Methods From January 2007 to July 2013, 115 patients with DLS treated in our hospi?tal were randomly selected. There were 28 males and 87 females with an average age of 57.3 years (range, 41-76 years). 115 age? and sex? matched people including 31 males and 84 females with an average age of 56.4 years (range, 45-77 years) free from DLS and back or leg pain were selected randomly as control group from a group coming for routine physical examination in our hospital. Both groups received lumbar anteroposterior and lateral X?ray films、CT scanning and multiplanar reformation, the degree of spondylolisthesis (Taillard index) was measured in DLS group on lateral radiographs; at L3,4 and L4,5 level of both groups the facet joint angles on CT scan images were measured and facet tropism was evaluated, the pedicle?facet angle (the P?F angle) was measured in the sagittal plane on multiplanar reformation CT images, and then all angles of corresponding level were compared and analyzed; L4,5 facet joint degeneration in both groups was evaluated and compared in bone window, the de?gree of spondylolisthesis (Taillard index) in DLS group at different degenerative grade of facet joints were analyzed. The corre?lation between L4,5 facet joint angle、P?F angle and degrees of spondylolisthesis were analyzed. Results All L4,5 spondylolisthe?sis in DLS group were grade I, the facet joint angles were more sagittal in DLS group than those in the control group at L 3,4 and L4,5 levels, and the P?F angles were more horizontal in DLS group compared with control group;the facet tropism in DLS group at L 4,5 level were significantly different as compared to the control group, but there was no significant difference at L 3,4 level between the two groups. Significant difference was found in L4,5 facet joint degeneration grade between two groups,but there was no significant difference in degree of spondylolisthesis during different degeneration grades in DLS group. There was no significant correlation between the facet joint angle and the P?F angle and degree of spondylolisthesis at L4,5 level in DLS group. Conclusion The facet joint morphology abnormality (smaller facet joint angle, horizontal P?F angle, the facet tropism) has an important etiologic meaning in the occurrence of degenerative lumbar spondylolisthesis, however its role cannot be excessively exaggerated. The facet joint de?generation is a secondary change with aging,while the development of DLS aggravates the degeneration.

OBJECTIVETo observe the protective effects of histone deacetylase inhibitor on stress-induced myocardial injury.

METHODSHealthy male Wistar rats were randomly divided into 3 groups( n = 6), and the stress-induced myocardial injury model was established with chronic restraint stress method. The protective effects of histone deacetylase inhibitor on stress-induced myocardial injury were observed with Trichostatin A (TSA) intervention. Histone acetylation levels in myocardium of rats were detected by Western blot method, spectrophotometry method was used to dynamically determine the activity of rat serum lactate dehydrogenase (LDH), serum creatine kinase isoenzyme-MB (CK-MB) and Caspase 3, and nagar Olsen staining were used to observe the early myocardial damage.

RESULTSRestraint stress could significantly reduce the level of histone acetylation of myocardium in rats, and TSA intervention could inhibit the stress-induced reduction of myocardial levels of histone acetylation. Restraint stress could cause the significant increase of serum LDH activity ( P < 0.05), serum CK-MB activity ( P < 0.05), and the Caspase 3 activity of myocardial tissue (P < 0.05), and early myocardial damage also occurred during restraint stress. ISA intervention could significantly reduce the serum LDH activity (P < 0.05), the serum CK-MB activity (P < 0.05), the activity of myocardial tissue caspase 3 induced by restraint stress (P < 0.05), and the stress-induced myocardial injury was also attenuated by TSA intervention.

CONCLUSIONThe histone deacetylase inhibitor TSA can protect stress-induced myocardial injury.

Acetylation ; Animals ; Cardiotonic Agents ; pharmacology ; Caspase 3 ; blood ; Creatine Kinase, MB Form ; blood ; Histone Deacetylase Inhibitors ; pharmacology ; Hydroxamic Acids ; pharmacology ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardium ; pathology ; Rats ; Rats, Wistar ; Restraint, Physical ; Stress, Physiological

OBJECTIVEHigh altitue pulmonary edema (HAPE) impacts seriously people's health at high altitude. Screening of susceptibility genes for HAPE will be used for the evaluation and protection of susceptible people.

METHODSWe performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 23 HAPE patients and 17 healthy controls. GO and Pathway analysis softwares were used to analyze and draw gene network.

RESULTSThirty-nine SNPs were found to be significantly different between case and control groups (P < 10(-4)). GO and Pathway analysis of 27 genes around the 39 SNPs indicated that these genes mainly participate in the regulating of cell proliferation, regulation of nitrogen compound metabolic process and G-protein coupled receptor protein signaling pathway and so on.

CONCLUSIONIt suggests that these SNPs and genes found in this study may be associated with the susceptibility of HAPE.

Adult ; Altitude Sickness ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Hypertension, Pulmonary ; genetics ; Polymorphism, Single Nucleotide ; Young Adult

Resveratrol, as a natural polyphenolic compound, has a wide range of beneficial effects, which includes anti-tumor, cardiovascular protection, anti-oxidant and estrogen-like effects, and so on. Its various physiological properties are closely related to the therapeutic principle for prevention and treatment of high altitude hypoxia injury. Resveratrol may play an important role in relieving or curing high altitude diseases, especially high altitude polycythemia(HAPC). However, the literature about study and application of resveratrol in plateau medicine field is rarely reported up to now. In this review, we summarized the physiological effects of resveratrol, discussed the possible main principle of resveratrol for HAPC therapy, and looked forward to resveratrol's perspective or potential application in high altitude medicine.
Altitude ; Humans ; Hypoxia ; drug therapy ; Polycythemia ; drug therapy ; Stilbenes ; pharmacology

The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.

A total of 108 subjects were enrolled in this study, including 21 healthy subjects(control group), 34 non-obese patients with polycystic ovary syndrome [PCOS1 group, body mass index(BMI)<25 kg/m²], 32 obese patients with PCOS(PCOS2 group, BMI≥25 kg/m²), and 21 simple obese patients whose age and BMI matched with PCOS2(OB group). BMI, waist-hip ratio(WHR), fasting plasma glucose(FPG), postprandial 2h plasma glucose(2hPG), HbA_1C, fasting insulin(FINS), postprandial 2h insulin(2hINS), sex hormones, and lipid parameters were determined. The status of insulin resistance was assessed by homeostasis model assessment for insulin resistant index(HOMA-IR)and insulin sensitivity index(ISI). Levels of plasma galectin-3 and interleukin-6(IL-6)were detected by ELISA. The results showed that the plasma level of galectin-3 was significantly higher in PCOS group than those in control and OB groups(all P<0.05). Moreover, the level of galectin-3 was also higher in OB group compared with control group, while galectin-3 level in PCOS2 group was higher than that in PCOS1 group(all P<0.05). After adjusted by age, BMI, and WHR, correlation analysis showed that the level of galectin-3 was positively correlated with FPG, 2hPG, FINS, HOMA-IR, highly-sensitive C-reactive protein, and IL-6, while negatively correlated with ISI. A multiple linear regression analysis revealed that the plasma galectin-3 concentration was independently associated with IL-6, HOMA-IR, and BMI(all P<0.05). These data suggest that plasma galectin-3 is closely associated with glucose metabolism, chronic inflammation, and insulin resistance, which may be involved in the pathogenesis of PCOS. (Chin J Endocrinol Metab, 2018, 34: 578-582)

Objective: To analyze the change in community first diagnosis and two-way referral rate under the condition of the regional longitudinal medical consortium implementation in the country at large. According to the simulation results,some suggestions for hierarchical medical system were put forward. Methods : The community first diagnosis and two-way referral rates were determined using the literature meta-analysis, and were simulated under different conditions by means of the system dynamics. Results :The analysis results confirmed that simply increasing the financial subsidies can increase the community first diagnosis rate within a range from 0.08％ to 0. 17％. For in case increases are made by the government in technical financial input to enhance the technical level of the community health service centers and in compensatory financial input to reduce the higher hospitals dependence on the light disease, results showed that the lower conversion rate increased within the range of 0.33％～0.45％ in terms of the two-way referral rating. On the contrary, when technical financial input is increased to improve the technical level of community health service centers, the rate of change was in the range of 7.52％ '- 12.61％ - Conclusions : Firstly, the diversified strategy should be used to promote the achievement of graded diagnosis and treatment. Secondly, the Health Commission plays a key role in the promotion of themedical consortiumconstruction. Thirdly, medical insurance reimbursement differential strategy should be implemented and the supply-side reform should be strengthened. At last,attention should be paid to the rational development of existing referrals, especially the upper and lower ones.

OBJECTIVEHigh-altitude cerebral edema (HACE) is one of the most serious acute mountain sickness and its underlying mechanism is still unknown clearly. The aim of this study was to determine the changes of plasma proteins in high altitude cerebral edema patients for discovering essential biomarkers used for the routine prophylaxis, diagnosis and treatment.

METHODSPlasma protein profiling two dimensional gel electrophoresis followed by mass spectrometry was used to explore protein alterations in one patient with high-altitude cerebral edema (HACE). Striking differences in two-dimensional gel proteomes of plasma were observed between high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) and between high-altitude cerebral edema (HACE) and mild acute mountain sickness (mAMS). Furthermore, apolipoprotein E altered in high-altitude cerebral edema was validated by ELISA.

RESULTSDifferent six spots were found in this study from the comparison between HACE and HAPE, and there were different six spots which were detected from the plasma of HACE patient in comparison to mAMS. Apolipoprotein E was identified in the two groups of comparative maps and results of ELISA consisted with the results of 2-DE.

CONCLUSIONIn this study, we used proteomic approach to explore HACE firstly and found different proteins that were probably associated with HACE. This would offer a clue to a better understanding of HACE for precaution, diagnosis and treatment.

Adult ; Altitude ; Altitude Sickness ; complications ; Apolipoproteins E ; blood ; Blood Proteins ; metabolism ; Brain Edema ; blood ; etiology ; Female ; Humans ; Proteomics ; methods