Objective To study the effect of lumbrokinase treatment on hemorheology, glucose and lipids of type 2 diabetes mellitus (T2DM). Methods 76 cases with T2DM whose blood glucose was controlled at FPG<8mmol/L and 2hPG<11mmol/L were involved in the study. All patients were divided into two groups:lumbrokinase (600ku tid for eight weeks) group (n=40) and control group (n=36). The levels of the blood rheology, glucose and lipids were measured. Results The levels of the whole blood viscosity, plasma viscosity, fibrinogen, platelet aggregation rate and triglyceride were decreased in lumbrokinas group as compared with control groups (all P<0.01).There were no differences in FPG and 2hPG between two groups(P>0.05). Conclusions Lumbrokinase can decrease the levels of the blood rheology and triglyceride in T2DM. It may prevent and cure the complication of diabetes mellitus

OBJECTIVE: To observe the effect of electroacupuncture (EA) on bone mineral density (BMD) and expression of calcium transport-related receptors in ovariectomized rats, so as to explore its mechanisms underlying improvement of osteoporosis. METHODS: Thirty-two three-month female SD rats were randomly divided into control, sham operation, model and EA groups (n=8 in each group). The ovariectomy model was established by resection of bilateral ovaries. EA (2 Hz/15 Hz, 2 mA) was applied to "Guanyuan"(CV4)+"Sanyinjiao"(SP6) or "Shenshu"(BL23)+"Housanli"(ST36) alternatively for 20 min, once daily (except the weekends) for 12 weeks. BMD of the tibia and femur were detected by using a bone densitometer. The expression levels of transient receptor potential vanillic receptor 5 (TRPV5), transient receptor potential vanillic receptor 6 (TRPV6), sodium calcium exchanger 1 (NCX1), membrane calcium adenosine triphosphate hydrolase (PMCA1b), zonula occludens 1 (ZO-1), occludin and claudin in intestinal mucosa were detected by quantitative real-time PCR and Western blot, respectively. RESULTS: Following modeling, BMD of both tibia and femur, and expression levels of TRPV5, PMCA1b, ZO-1, occludin and claudin mRNAs were significantly decreased in the model group compared with the control and sham operation groups (P<0.05, P<0.01)，while the mRNAs levels of TRPV6 and NCX1 in the model group were increased (P<0.01). After the treatment, BMD of both tibia and femur, and expression levels of TRPV5, PMCA1b, ZO-1 and occludin mRNAs were significantly increased(P<0.01，P<0.05)，and TRPV6 and NCX1 were significantly decreased(P<0.01，P<0.05) in the EA group than those in the model group. Compared with the control and sham operation groups, protein expression levels of TRPV5, PMCA1b, ZO-1, occludin and claudin in the model group were significantly decreased (P<0.05), while the protein levels of TRPV6 and NCX1 in the model group were increased (P<0.05). After EA intervention, modeling-induced decrease of TRPV5, PMCA1b, ZO-1, occludin and claudin protein levels and increase of TRPV6 and NCX1 protein levels were all completely reversed in the EA group relevant to the model group (P<0.05). CONCLUSION: EA intervention can improve bone mineral density and up-regulate the mRNA and protein expression of TRPV5, PMCA1b, ZO-1 and occludin, which may be one of the mechanisms of acupuncture in the treatment of osteoporosis.

OBJECTIVE: To investigate the proteome of hepatocyte transformation by hepatitis C virus (HCV) nonstructural protein 3 (NS3). METHODS: Human hepatocyte line QSG7701 stably expressing HCV NS3 C-terminal deleted protein was constructed, which was named pRcHCNS3/QSG. Two-dimensional electrophoresis (2-DE) was used to separate the total protein of pRcHCNS3/QSG and pRcCMV transfected cells (pRcCMV/QSG) respectively. Differentially expressed protein spots were identified by mass spectrometry. Western blot confirmed the differentially expressed proteins. RESULTS: 2-DE profiles with high resolution and reproducibility were obtained. The average spots of pRcHCNS3/QSG and pRcCMV/QSG were (1183+/-77) and (1095+/-82) respectively, and (920+/-60) spots were matched. Twenty-one differentially expressed protein spots were chosen randomly and 15 were identified by mass spectrometry. Some proteins such as Ras, P38 and HD53 which were involved in signal transduction were increased in pRcHCNS3/QSG cells. Western blot also showed strong expression of phosphorylated P44/42 and P38 in pRcHCNS3/QSG cells. Other differentially expressed proteins were related to cell cycle regulation, immunoreaction, tumor invasion and metastasis, and liver metabolizability. CONCLUSION HCV NS3 might be involved in cell malignant transformation through affecting protein expression and signal transduction such as MAPK cascade. Further study on the signal transductions and their relationship would not only be helpful to explore the mechanism of HCV related HCC, but also provide a new idea for the molecular treatment of HCC.
Cell Line ; Cell Transformation, Neoplastic ; Electrophoresis, Gel, Two-Dimensional ; methods ; Hepatocytes ; metabolism ; pathology ; Humans ; Mass Spectrometry ; methods ; Proteome ; analysis ; Proteomics ; methods ; Transfection ; Viral Nonstructural Proteins ; biosynthesis ; genetics

BACKGROUNDInterleukin (IL)-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion (MPE) remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon (IFN)-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE.

METHODSThe distribution of IL-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions of cytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription (STAT) signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored.

RESULTSThe expression of IL-27 was increased in MPE when compared with blood (147.3 ± 25.1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04). IL-27 was noted to suppress both proliferation (18.33 ± 0.21 vs. 27.77 ± 0.88, P = 0.0005) and migration (1.82 ± 0.44 vs. 3.13 ± 0.07, P = 0.04) of A549 cells, but obviously promoted apoptosis of A549 cells (9.47 ± 1.14 vs. 4.96 ± 0.17, P = 0.02) by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities of A549 cells to pleural mesothelial cell monolayer by activating different STAT signalings.

CONCLUSIONSIL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.

Adult ; Aged ; Aged, 80 and over ; Cell Line ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; genetics ; physiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukins ; metabolism ; Lung Neoplasms ; metabolism ; Male ; Middle Aged ; Pleural Effusion, Malignant ; metabolism ; Signal Transduction

OBJECTIVETo investigate the influence of insulin growth factor-I (IGF-I) on apoptosis of cardiomyocytes subjected to ischemia and hypoxia and its possible mechanism.

METHODSCardiomyocytes were cultured in vitro, and randomized into hypoxia group, treatment group (T, the cells were treated with IGF-1 before subjected to hypoxia and ischemia) and control group (C, normal cardiomyocytes as controls). Changes in the OD value of cell apoptosis, mitochondrial membrane potential and relative amount of phospho-Akt protein were observed at different time-points by ELISA, laser scanning with TMRE staining and Western blot, respectively.

RESULTSThe OD value of cell apoptosis in control group was 0.18 +/- 0.03, while that in hypoxia group was gradually increased to 0.33 +/- 0.05, 0.61 +/- 0.06, 1.17 +/- 0.08, 2.25 +/- 0.11, respectively at 1, 3, 6, 12 post-hypoxia hours (PHH), showing an increasing tendency (P < 0.01). The OD values of cell apoptosis in T group were 0.26 +/- 0.04, 0.49 +/- 0.05, 0.84 +/- 0.06, 1.63 +/- 0.09, respectively, which were obviously lower than those in hypoxia group (P < 0.05 or P < 0.01). The mitochondrial membrane potential (Dymt) values in hypoxia group at 6 and 12 PHH were 18.7 +/- 5.1 and 6.3 +/- 1.9, respectively, which were obviously lower than that in control group (40.2 +/- 10.1, P < 0.01). The DYmt in T group at 6 and 12 PHH were 28.8 +/- 6.2, 12.5 +/- 3.1, respectively, which were obviously higher compared with those in hypoxia group (P < 0.05). The amount of phospho-Akt protein was increased by IGF-I administration.

CONCLUSIONIGF-I exhibits an anti-apoptotic effect on cardiomyocytes subjected to ischemia and hypoxia, and this may be related to the activation of PI3K/Akt signal pathway and stabilization of mitochondrial membrane potential.

Animals ; Apoptosis ; Cell Hypoxia ; Cells, Cultured ; Hypoxia ; metabolism ; Insulin-Like Growth Factor I ; pharmacology ; Ischemia ; metabolism ; Membrane Potential, Mitochondrial ; Myocytes, Cardiac ; cytology ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Both T helper IL-17-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in malignant pleural effusion (MPE). However, the possible imbalance between Th17 cells and Tregs, as well as the association of Th17/Treg and Th1/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as Th1/Th2 balance in MPE. The number of Th17, Tregs, Th1, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Th17, Tregs, Th1, and Th2 cells was explored. It was found that the number of Th17, Tregs, Th1, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Th17 cells was correlated negatively with Tregs in MPE, but not in blood. Th17 cells and Th17/Treg ratio were positively, and Tregs were negatively, correlated with Th1 cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Th17 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Th17/Treg imbalance exists in MPE.
Adult ; Female ; Humans ; Male ; Middle Aged ; Pleural Effusion, Malignant ; immunology ; pathology ; T-Lymphocytes, Regulatory ; immunology ; pathology ; Th17 Cells ; immunology ; pathology

Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

BACKGROUNDThe clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment.

METHODSThe data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared.

RESULTSThe frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 ± 1.9 cm vs. 1.7 ± 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05).

CONCLUSIONSPDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs.

Adult ; Aged ; Carcinoma ; diagnosis ; pathology ; Carcinoma, Papillary ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Thyroid Neoplasms ; diagnosis ; pathology ; Ultrasonography

Objective To investigate the role of ultrasound in the decision-making of surgery for thyroid nodules.Methods The cases receiving surgical excision of thyroid nodules in Peking Union Medical College Hospital during the period of January 2004 to December 2014 were collected.We randomly sampled 10%-15%cases from the collections in 2004, 2006, 2008, 2010, 2012 and 2014, and reviewed the outpatient and inpa-tient records of these sampled cases, extracting information about whether preoperative ultrasonography examina-tion was ordered, whether the ultrasound report provided specific diagnostic suggestion, and whether that diagno-sis was correct judging from pathological results.The rates of preoperative ultrasound, ultrasound diagnostic sug-gestion, specific diagnostic suggestion, and correct ultrasound diagnosis were calculated.Results The number of thyroid nodule surgery increased year by year from 2004 to 2014, with the proportion of malignant nodules ris-ing from 15.65% in 2004 to 69.91% in 2014.The rate of preoperative ultrasound ranged from 80.65% to 96.65%.The rate of ultrasound diagnostic suggestion demonstrated a constantly ascending trend, ranging from 46.94%to 92.36%.The rate of specific diagnostic suggestion was in the range of 78.26%-93.61%, while the rate of correct ultrasound diagnosis grew year by year, from 36.73% to 81.40%.Conclusions The num-bers of patients with thyroid nodules and thyroid cancer have been soaring in the past 11 years.With the improve-ment in its diagnostic capacity, ultrasonography is playing an increasingly important role in the decision-making of surgery for thyroid nodules.

BACKGROUNDBiliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI.

METHODSLungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model. After an initial 15 min stabilization period, the isolated lungs were subjected to ischemia for 60 min, followed by 90 min of reperfusion with or without BV treatment.

RESULTSLungs in the I/R group exhibited significant decrease in tidal volume (1.44 ± 0.23 ml/min in I/R group vs. 2.41 ± 0.31 ml/min in sham group; P< 0.001), lung compliance (0.27 ± 0.06 ml/cmH2O in I/R group vs. 0.44 ± 0.09 ml/cmH2O in sham group; P< 0.001; 1 cmH2O=0.098 kPa), and oxygen partial pressure (PaO2) levels (64.12 ± 12 mmHg in I/R group vs. 114 ± 8.0 mmHg in sham group; P< 0.001; 1 mmHg = 0.133 kPa). In contrast, these parameters in the BV group (2.27 ± 0.37 ml/min of tidal volume, 0.41 ± 0.10 ml/cmH2O of compliance, and 98.7 ± 9.7 mmHg of PaO2) were significantly higher compared with the I/R group (P = 0.004, P< 0.001, and P< 0.001, respectively). Compared to the I/R group, the contents of superoxide dismutase were significantly higher (47.07 ± 7.91 U/mg protein vs. 33.84 ± 10.15 U/mg protein; P = 0.005) while the wet/dry weight ratio (P < 0.01), methane dicarboxylic aldehyde (1.92 ± 0.25 nmol/mg protein vs. 2.67 ± 0.46 nmol/mg protein; P< 0.001), and adenosine triphosphate contents (297.05 ± 47.45 nmol/mg protein vs. 208.09 ± 29.11 nmol/mg protein; P = 0.005) were markedly lower in BV-treated lungs. Histological analysis revealed that BV alleviated LIRI. Furthermore, the expression of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-β) was downregulated and the expression of cyclooxygenase-2, inducible nitric oxide synthase, and Jun N-terminal kinase was significantly reduced in BV group (all P< 0.01 compared to I/R group). Finally, the apoptosis index in the BV group was significantly decreased (P < 0.01 compared to I/R group).

CONCLUSIONBV protects lung IRI through its antioxidative, anti-inflammatory, and anti-apoptotic effects.