2025-03-29 2015, Volume 35 Issue 4

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  • Qian Sun , Tao Zhu , Chang-yu Wang , Ding Ma

    SWI1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich interaction domain family (ARID), and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because ARID1A/BAF250a (SWI1) subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.

  • Qiu-ling Wu , Xiao-yun Liu , Di-min Nie , Xia-xia Zhu , Jun Fang , Yong You , Zhao-dong Zhong , Ling-hui Xia , Mei Hong

    Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK cells, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3+, CD3+CD4+ and CD3+CD8+ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4+ and CD8+ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.

  • Dan-yue Peng , Hui Song , Ling-bo Liu

    Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB1 and Sirtuin 1 (SIRT1), a regulator of pLKB1, were measured in CD34+CD38 KG1a cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34+CD38 KG1a cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34+CD38 KG1a cells. It was concluded that resveratrol-downregulated pLKB1 is involved in the senescence of AML stem cells.

  • Li Wang , Fei Xu , Xue-jun Zhang , Run-ming Jin , Xin Li

    Abnormal cholesterol metabolism is associated with an elevated risk of developing atherosclerosis, hypertension, and diabetes etc. Na+/K+-ATPase was found to regulate cholesterol synthesis, distribution and trafficking. This study aimed to examine the effect of high-fat diet on cholesterol metabolism in rats and the role of Na+/K+-ATPase/Src/ERK signaling pathway in the process. Forty male SD rats were evenly divided into high-fat diet group and control group at random. Animals in the former group were fed on high-fat diet for 12 weeks, and those fed on basic diet served as control. Blood lipids, including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesteral (LDL-C) levels, were detected at 3, 6 and 12 weeks. The ratio of cholesterol content in cytoplasm to that in cell membrane was detected in liver tissues. RT-PCR and Western blotting were used to measure the expression of lipid metabolism-associated genes (HMG-CoA reductase and SREBP-2) after 12-week high-fat diet. Na+/K+-ATPase/Src/ERK signaling pathway-related components (Na+/K+-ATPase α1, Src-PY418 and pERK1/2) were also measured by Western blotting. The results showed that the serum TC, TG, and LDL-C levels were significantly higher in high-fat diet group than those in control group, while the HDL-C level was significantly lower in high-fat diet group at 6 weeks (P<0.01). High-fat diet led to an increase in the cholesterol content in the cytoplasm and cell membrane. The ratio of cholesterol content in cytoplasm to that in cell membrane was elevated over time. The expression of HMG-CoA reductase and SREBP-2 was significantly suppressed at mRNA and protein levels after 12-week high-fat diet (P<0.05). Moreover, high-fat diet promoted the expression of Na+/K+-ATPase α1 but suppressed the phosphorylation of Src-PY418 and ERK1/2 at 12 weeks (P<0.05). It was concluded that high-fat diet regulates cholesterol metabolism, and Na+/K+-ATPase signaling pathway is involved in the process possibly by regulating the expression of lipid metabolism-associated proteins HMG-CoA reductase and SREBP-2.

  • Jin Shang , Xue-ling Guo , Yan Deng , Xiao Yuan , Hui-guo Liu

    Endothelial dysfunction induced by intermittent hypoxia (IH) participates in obstructive sleep apnea syndrome (OSAS)-associated cardiovascular disorders. Myeloid differentiation primary response 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) regulate numerous downstream adaptors like mitogen-activated protein kinases (MAPKs) and the subsequent oxidative stress and inflammatory responses. This study aimed to characterize the role of MyD88/TRAF6 in IH-treated cell function and its associated signaling. Human umbilical vein endothelial cells (HUVECs) were randomly exposed to IH or normoxia for 0, 2, 4 and 6 h. Western blotting was used to detect the expression pattern of target gene proteins [angiotensin 1 receptor (AT1R), p-ERK1/2, p-p38MAPK, MyD88 and TRAF6], and the relationships among these target genes down-regulated by the corresponding inhibitors were studied. Finally, the influence of these target genes on proliferation of HUVECs was also assessed by EdU analysis. Protein levels of AT1R, TRAF6 and p-ERK1/2 were increased after IH exposure, with a slight rise in MyD88 and a dynamic change in p-p38MAPK. The down-regulation of TRAF6 by siRNA reduced ERK1/2 phosphorylation during IH without any effects on AT1R. Blockade of AT1R with valsartan decreased TRAF6 and p-ERK1/2 protein expression after IH exposure. ERK1/2 inhibition with PD98059 suppressed only AT1R expression. IH promoted HUVECs proliferation, which was significantly suppressed by the inhibition of TRAF6, AT1R and ERK1/2. The findings demonstrate that TRAF6 regulates the proliferation of HUVECs exposed to short-term IH by modulating cell signaling involving ERK1/2 downstream of AT1R. Targeting the AT1R-TRAF6-p-ERK1/2 signaling pathway might be helpful in restoring endothelial function.

  • Min Huang , Han-ming Wang , Yu Guo , Jie Ping , Man Chen , Dan Xu , Hui Wang

    In adult liver, CYP3A4 plays an important role in the metabolism of a wide range of endogenous and exogenous compounds. To investigate whether there is a single nucleotide polymorphism (SNP) of CYP3A4 intron 2 in the liver and its effects on the mRNA expression and enzymatic activity of CYP3A4, genomic DNA was extracted from 96 liver tissue samples obtained from patients who had undergone liver surgery. An SNP of CYP3A4 intron 2 was identified by polymerase chain reaction (PCR)-single-strand confirmation polymorphism and DNA sequencing. The mRNA expression of CYP3A4 was determined by the fluorescence quantitative PCR technique. The enzymatic activity of CYP3A4 was measured using erythromycin and testosterone as probe substrates. Twelve patients were found to have the SNP/T4127G CYP3A4 within intron 2. The mRNA levels of CYP3A4 in wild-type and SNP/T4127G samples were 2.62±1.09 and 2.79±1.63, respectively (P>0.05). Erythromycin N-demethylase activity in wild-type and SNP/T4127G samples were 121.2±32.8 and 124.7±61.6 nmol·mg−1·min−1, respectively (P>0.05). The activity of testosterone 6β-hydroxylase was significantly different between wild-type (648±173 pmol·mg−1·min−1) and SNP/T4127G samples (540±196 pmol·mg−1·min−1; P<0.05). In conclusion, the SNP/T4127G of CYP3A4 intron 2 exists in the liver. This SNP does not affect the mRNA expression of CYP3A4 but significantly decreases the hepatic microsomal testosterone 6β-hydroxylase activity of CYP3A4. Furthermore, this study indicates that the appropriate selection of probe substrates is very important in studying the relationship between the genotype and phenotype of CYP3A4.

  • Xiao-hui Wang , Xin Zhang , Chang-jun Mu , Yong He , Qing-ping Peng , Guo-sheng Yang , Ming-mei Li , Duan Liu , Jing Li , Guo-hua Ding

    The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group (n=28) and control group (n=26). The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC scores at third month after treatments were compared between the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen (BUN), serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, total cholesterol between case group and control group (P>0.05 for all). There was also no significant difference in the baseline itching scores between the case group and the control group (P>0.05). At 1st and 3rd month after treatment, the itching scores in the case group were 14.2±3.2 and 10.5±2.3, respectively, which were significantly lower than the baseline and those in the control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching scores in the control group were 23.6±5.9 and 24.8±6.3, respectively, which were significantly higher than the baseline (P<0.05). There was no significant difference in the baseline of serum calcium, phosphorus, calcium-phosphorus products, iPTH levels between the case group and control group (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group (P<0.05). The AAC scores showed statistically significant difference between the case group and the control group (P<0.05). The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phosphorus and iPTH levels, resulting in the attenuation of vascular calcification.

  • Li Ma , Zu-neng Lu , Pei Hu , Chang-jiang Yao

    The neuroprotective effects of escitalopram oxalate in rats with chronic hypoperfusion and the possible mechanism were explored. Chronic hypoperfusion (2-VO) model was prepared and given escitalopram oxalate (experimental group) or PBS (control group) after 6 weeks. Eight weeks after the operation, Morris water maze test was carried out to evaluate the learning and memory ability of the rats. The cell proliferation, three-dimensional vascular distribution, cell morphological changes in ischemic area and the plasma vascular endothelial growth factor (VEGF) were detected to explore the possible mechanisms. (1) Morris water maze test showed that the escape latency in the experimental group was significantly shorter than in the control group, while the first quadrant swimming time in the experimental group was significantly longer than the control group (both P<0.01). (2) Cerebrovascular confocal detection results showed that the inside diameter of capillaries was significantly less in the experimental group than in the control group; the vascular density was significantly increased in the experimental group and the total area of capillaries was also significantly increased in the experimental group as compared with the control group. (3) There was statistically significant difference in BrdU-positive cells in the ischemic brain tissue between the experimental group and the control group (P=0.003<0.01). (4) VEGF concentrations in the plasma and the ischemic area were higher in the experimental group than in the control group (P<0.05). It was concluded that escitalopram oxalate could significantly improve the learning and memory ability of the rats with chronic cerebral ischemia probably by the VEGF-mediated angiogenesis.

  • Lin Wu , Pi-qi Zhou , Ji-wen Xie , Rui Zhu , Sun-chang Zhou , Geng Wang , Zhong-xu Wu , Sha Hao

    In order to investigate whether Yinchenhao decoction (YCHD) attenuates hepatic fibrogenesis in the bile duct ligation (BDL) model via recovering and restoring the self-regulation and balance of the renin-angiotensin system (RAS), 33 specific-pathogen-free (SPF) male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows: G1, the sham group (n=4); G2, BDL 7-day group (n=5); G3, BDL+YCHD 430 mg/mL (n=8); G4, BDL+losartan 0.65 mg/mL (ARB group, n=8); G5, model group (BDL without any treatment, n=8). YCHD and losartan (10 mL·kg−1·day−1) were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respectively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IDBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological changes were observed by transmission electron microscopy (TEM) and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system (RAS) components including angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), ACE2, angiotensin II (AngII) as well as transforming growth factor β1 (TGFβ1). The experimental data were analyzed by principle component analytical method of pattern recognition. The results showed that biochemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group (P<0.05). Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups (P<0.05). Serum AST level in G3 was significantly lowered than in G5 group (P<0.05), but there was no significant difference in ALT among G3, G4 and G5 groups (P>0.05). Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression levels of ACE2, ACE, AngII, AT1R and TGFβ1 in G2, G3 and G4 groups were significantly higher than in sham group (P<0.05), and lower than in G5 group (P<0.05). However, the differences among G2, G3 and G4 groups were not significant (P>0.05). ACE2 protein expression in G3 group was significantly higher than in G2 group (P<0.05) and there was no significant difference in comparison with G4 group (P>0.05). Moreover, the protein expression of TGFβ1 in G3 group was significantly lower than in G5 and G4 groups (P<0.05). Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFβ1 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.

  • Yan-ping Yang , Bo Shuai , Lin Shen , Xiao-juan Xu , Chen Ma , Lin Lv

    Serum sclerostin is positively associated with serum 25 hydroxyvitamin D concentration. Our preliminary studies confirmed that Qing’e formula (QEF) could effectively increase serum 25 hydroxyvitamin D concentration in patients with postmenopausal osteoporosis (PMOP), but the effect of supplementation with QEF on serum sclerostin is unknown. This study investigated the effects of supplementation of QEF on serum sclerostin levels in patients with PMOP. Totally 120 outpatients and inpatients with PMOP treated in our hospital between January and October 2012 were randomly divided into QEF+calcium group, alfacalcidol+calcium group, and placebo+calcium group (n=40 each), with a follow-up period of 2 years. The serum levels of sclerostin, 25 hydroxyvitamin D, and bone turnover markers (β-CTX, N-MID and T-PINP) at baseline and at the 6th month, 1st year, 1.5th year, and 2nd year after treatment were measured. The results showed that the levels of circulating sclerostin were increased significantly at the 6th month after treatment in QEF+calcium group and alfacalcidol+calcium group as compared with placebo+calcium group (P<0.05), but there was no significant difference between the former two groups (P>0.05). The levels of β-CTX, N-MID and T-PINP in serum were decreased in both QEF+calcium group and alfacalcidol+calcium group at the 6th month after treatment, without significant difference between the two groups (P>0.05). But the levels were significantly lower than that in placebo+calcium group (P<0.05). These results suggest that the mechanism by which QEF modulates bone metabolism in patients with PMOP might be related with the effect of QEF in increasing sclerostin expression. Our findings provide a scientific rationale for using QEF as an effective drug to prevent bone loss in PMOP.

  • Yuan-gui Hu , Yun-feng Shen , Yi Li

    This study aimed to evaluate the effects of Pin1 inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7Adr. MCF7Adr cells were cultured and separately treated with Pin1 inhibitor Juglone (treatment group) and DMEM without drug (control group). The cell cycle was examined by flow cytometry. Cell migration was measured by wound-healing assay. Cyclin E protein content was detected by Western blotting. The angiogenesis factor vascular endothelial growth factor (VEGF) in cell media was determined by enzyme linked immunosorbent assay. The results showed that the percentage of cells in G2/M phase in treatment group was significantly higher than that in control group (25.5% vs. 10.1%, P<0.05), and that in G0/G1 phase and S stage in treatment group was significantly lower than that in control group (40.5% vs. 48.2%, and 33.7% vs. 41.7%, P<0.05). Cyclin E protein content in treatment group was significantly lower than that in control group (39.2±7.4 vs. 100±23.1, P<0.05). (A0–A24)/A0 value in treatment group was significantly lower than that in control group (23.9±3.8 vs. 100±14.4, P<0.05). VEGF-A, -B, and -C contents in cell media of treatment group were significantly lower than those in control group (P<0.05). It was suggested that Pin1 inhibitor Juglone can effectively inhibit the proliferation, migration and the angiogenic ability of MCF7Adr cells, and can be used as an alternative drug therapy for breast cancer.

  • Bin-yong Liang , Min Xiong , Gui-bao Ji , Er-lei Zhang , Zun-yi Zhang , Ke-shuai Dong , Xiao-ping Chen , Zhi-yong Huang

    Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and histone deacetylase (HDAC) inhibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor PJ34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines (HepG2, Hep3B and HCC-LM3) treated with PJ34 (8 μmol/L) and SAHA (1 μmol/L), alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bearing subcutaneous HepG2 tumors were administered different groups of drugs (10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34+25 mg/kg SAHA), and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of PJ34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34+SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone (P<0.05). In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34+SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of PJ34 or SAHA alone (P<0.05). It was led to conclude that PJ34 and SAHA can synergistically suppress the proliferation of liver cancer cells.

  • Miao Wang , Tao Huang , Gang Luo , Chao Huang , Xing-yuan Xiao , Liang Wang , Guo-song Jiang , Fu-qing Zeng

    This study aimed to examine the effect of long non-coding RNA (LncRNA) MEG3 on the biological behaviors of renal cell carcinoma (RCC) cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in tumor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 (MEG3 overexpression plasmid) and GV144 (control plasmid) were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues (P<0.05) and RCC cell lines (P<0.05). The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h (P<0.05). Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h (P<0.05). Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm (P<0.05). Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression (P<0.05). It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.

  • Hui Chen , Wei Chai , Bin Li , Ming Ni , Guo-qiang Zhang , Hua-wei Liu , Zhuo Zhang , Ji-ying Chen , Yong-gang Zhou , Yan Wang

    This study aimed to identify the differentially expressed genes after silencing of β-catenin in multiple myeloma transduced with β-catenin shRNA. The DNA microarray dataset GSE17385 was downloaded from Gene Expression Omnibus, including 3 samples of MM1.S (human multiple myeloma cell lines) cells transduced with control shRNA and 3 samples of MM1.S cells transduced with β-catenin shRNA. Then the differentially expressed genes (DEGs) were screened by using Limma. Their underlying functions were analyzed by employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Moreover, DEGs annotation was conducted based on the databases of tumor associated genes, tumor suppressed genes and the transcriptional regulation from patterns to profiles. Furthermore, the protein-protein interaction (PPI) relationship was obtained from STRING and the protein-protein interaction network and the functional modules were visualized by Cytoscape. Then, the pathway enrichment for the DEGs in the functional module was performed. A total of 301 DEGs, including 124 up-regulated and 117 down-regulated DEGs, were screened. Functional enrichment showed that CCNB1 and CDK1 were significantly related to the function of cell proliferation. FOS and JUN were related to innate immune response-activating signal transduction. Pathway enrichment analysis indicated that CCNB1 and CDK1 were most significantly enriched in the pathway of cell cycle. Besides, FOS and JUN were significantly enriched in the Toll-like receptor signaling pathway. FOXM1 was identified as a transcription factor. Moreover, there existed interactions among CCNB1, FOXM1 and CDK1 in PPI network. The expression of FOS, JUN, CCNB1, FOXM1 and CDK1 may be affected by β-catenin in multiple myeloma.

  • Jia-qi Dong , Xiong Chen , Ying Xiao , Rui Zhang , Xun Niu , Wei-jia Kong

    Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a serious health issue, which can impact the hormone secretion. The aim of this study is to analyze the relationship between serum sex hormone concentrations and different severity degree of OSAHS, and to evaluate the influence of OSAHS on sex hormone levels. We enrolled 116 subjects who were subjected to polysomnography (PSG). They were divided into three groups: control group (n=10) [apnea hypopnea index (AHI) <5/h], mild-moderate OSAHS group (n=15) (5≤AHI<30/h), and severe OSAHS group (n=91) (AHI≥30/h). The patients in OSAHS group were subdivided into obesity and non-obesity subgroups. The parameters such as AHI, body mass index (BMI), lowest oxygen saturation (LSaO2), and mean oxygen saturation (MSaO2) were recorded. Serum levels of testosterone, polactin, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined in the morning immediately after waking up. Mean levels of hormones were compared among groups. The correlation between hormone levels and sleep-breathing parameters was analyzed. No significant differences in serum sex hormone levels were found among control, mild-moderate OSAHS, and severe OSAHS groups (P>0.05). There was no correlation between AHI and sex hormone levels (P>0.05). Testosterone was significantly negatively correlated with BMI (P<0.05). These results suggested that BMI might have a direct effect on testosterone level, and it might be an important factor affecting testosterone level in male OSAHS patients, and there may be no correlation between severity of OSAHS and sex hormones levels.

  • Hai-yu Hong , Yan-ni Li , Yun-ping Fan , Shao-yan Feng , Jie-bing Gao

    The aim of this study was to develop a less invasive trans-septal approach for the endoscopic management of sphenoid sinus lesions. We performed a septal-assisted surgical procedure for endoscopic sphenoidectomy in 38 patients with isolated or combined sphenoidal sinus lesions, including fungal balls, mucoceles, purulent cystic sphenoidal sinusitis, etc. The posterior portion of the nasal septum became flexible after removal of the vomer and the sphenoidal rostrum. The superior portion of the common meatus was expanded to accommodate the endoscope after the septum was repositioned contra-laterally. The lesions were individually managed through the enlarged ostiums while damage to the mucosa of the front sphenoidal wall was avoided. All the procedures were completed successfully without intraoperative complications, and the bony ostiums were identified easily and enlarged accurately. During the follow-up period of 16 weeks to 2 years, no re-atresia or restenosis was observed. The recurrence rate was 0. No postoperative complications were recorded. All the responses from the patients were satisfactory. It was concluded that endoscopic sphenoidectomy assisted by trans-septal approach is a feasible, safe, effective and minimally invasive approach for selected cases with unilateral or bilateral lesions in the sphenoid sinuses.

  • Ning Hu , Xing-huo Wu , Rong Liu , Shu-hua Yang , Wei Huang , Dian-ming Jiang , Qiang Wu , Tian Xia , Zeng-wu Shao , Zhe-wei Ye

    Traumatic gas gangrene is a fatal infection mainly caused by Clostridium perfringens. It is a challenge to manage gas gangrene in open wounds and control infection after debridement or amputation. The aim of the present study was to use vacuum sealing drainage (VSD) with continuous irrigation of potassium permanganate to manage infective wounds of gas gangrene and observe its clinical efficacy. A total of 48 patients with open traumatic gas gangrene infection were included in this study. Amputations were done for 27 patients, and limb salvage procedures were performed for the others. After amputation or aggressive debridement, the VSD system, including polyvinyl alcohol (PVA) foam dressing and polyurethane (PU) film, with continuous irrigation of 1:5000 potassium permanganate solutions, was applied to the wounds. During the follow-up, all the patients healed without recurrence within 8–18 months. There were four complications. Cardiac arrest during amputation surgery occurred in one patient who suffered from severe septic shock. Emergent resuscitation was performed and the patient returned to stable condition. One patient suffered from mixed infection of Staphylococcal aureus, and a second-stage debridement was performed. One patient suffered from severe pain of the limb after the debridement. Exploratory operation was done and the possible reason was trauma of a local peripheral nerve. Three cases of crush syndrome had dialysis treatment for concomitant renal failure. In conclusion, VSD can convert open wound to closed wound, and evacuate necrotic tissues. Furthermore, potassium permanganate solutions help eliminate anaerobic microenvironment and achieve good therapeutic effect on gas gangrene and mixed infection. VSD with continuous irrigation of potassium permanganate is a novel, simple and feasible alternative for severe traumatic open wounds with gas gangrene infection.

  • Wen-bin Hua , Qiang Wu , Bo Zhang , Shu-hua Yang , Zeng-wu Shao , Wei-hua Xu , Ye Wang , Xu-dong Zhang

    This study aimed to examine the diagnostic accuracy and clinical efficacy of initial CT-guided percutaneous biopsy of the vertebral lesions. A total of 305 percutaneous biopsies of the vertebral lesions were performed under either CT guidance (n=127) or C-arm guidance (n=178). The diagnostic accuracy rate was evaluated by comparing the histopathological diagnosis with the ultimate diagnosis. The histopathological diagnosis was consistent with the ultimate diagnosis in 108 (85.0%, 108/127) cases of CT-guided biopsy and in 135 (75.8%, 135/178) cases of C-arm guided biopsy and there was a significant difference. The accuracy of diagnosis based on biopsies varied with different diseases, including primary benign or malignant tumors, metastatic tumors, inflammatory lesions and fractures. A second biopsy or further examinations were required for patients with negative result obtained in the initial biopsy. The complication rate was 3.1% (4/127) in CT-guided biopsy and 7.3% (13/178) in C-arm guided biopsy. In conclusion, CT-guided percutaneous biopsy is an accurate and safe technique for biopsy of the vertebral lesions.

  • Bin-yu Zhou , Jing Wang , Ming-xing Xie , Man-wei Liu , Qing Lv

    Intraventricular hydrodynamics is considered an important component of cardiac function assessment. Vector flow mapping (VFM) is a novel flow visualization method to describe cardiac pathophysiological condition. This study examined use of new VFM and flow field for assessment of left ventricular (LV) systolic hemodynamics in patients with simple hyperthyroidism (HT). Thirty-seven simple HT patients were enrolled as HT group, and 38 gender- and age-matched healthy volunteers as control group. VFM model was used to analyze LV flow field at LV apical long-axis view. The following flow parameters were measured, including peak systolic velocity (Vs), peak systolic flow (Fs), total systolic negative flow (SQ) in LV basal, middle and apical level, velocity gradient from the apex to the aortic valve (ΔV), and velocity according to half distance (V1/2). The velocity vector in the LV cavity, stream line and vortex distribution in the two groups were observed. The results showed that there were no significant differences in the conventional parameters such as left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and left atrium diameter (LAD) between HT group and control group (P>0.05). Compared with the control group, a brighter flow and more vortexes were detected in HT group. Non-uniform distribution occurred in the LV flow field, and the stream lines were discontinuous in HT group. The values of Vs and Fs in three levels, SQ in middle and basal levels, ΔV and V1/2 were higher in HT group than in control group (P<0.01). ΔV was positively correlated with serum free thyroxin (FT4) (r=0.48, P<0.01). Stepwise multiple regression analysis showed that LVEDD, FT4, and body surface area (BSA) were the influence factors of ΔV. The unstable left ventricular systolic hydrodynamics increased in a compensatory manner in simple HT patients. The present study indicated that VFM may be used for early detection of abnormal ventricle contraction in clinical settings.

  • Yan-rong Zhang , Ling-yun Fang , Cheng Yu , Zhen-xing Sun , Yan Huang , Juan Chen , Tao Guo , Fei-xiang Xiang , Jing Wang , Cheng-fa Lu , Tian-wei Yan , Qing Lv , Ming-xing Xie

    This study aimed to examine the optimal conditions of laser-induced interstitial thermotherapy (LITT) via a single-needle delivery system, and the ablation-related pathological and ultrasonic changes. Ultrasound (US)-guided LITT (EchoLaser system) was performed at the output power of 2–4 Wattage (W) for 1–10 min in ex vivo bovine liver. Based on the results of the ex vivo study, the output power of 3 and 4 W with different durations was applied to in vivo rabbit livers (n=24), and VX2 tumors implanted in the hind limbs of rabbits (n=24). The ablation area was histologically determined by hematoxylin-eosin (HE) staining. Traditional US and contrast enhanced ultrasound (CEUS) were used to evaluate the treatment outcomes. The results showed: (1) In the bovine liver, ablation disruption was grossly seen, including a strip-like ablation crater, a carbonization zone anteriorly along the fiber tip, and a surrounding gray-white coagulation zone. The coagulation area, 1.2 cm in length and 1.0 cm in width, was formed in the bovine liver subjected to the ablation at 3 W for 5 min and 4 W for 4 min, and it extended slightly with the ablation time. (2) In the rabbit liver, after LITT at 3 W for 3 min and more, the coagulation area with length greater than or equal to 1.2 cm, and width greater than or equal to 1.0 cm, was found. Similar coagulation area was seen in the implanted VX2 carcinoma at 3 W for 5 min. (3) Gross examination of the liver and carcinoma showed three distinct regions: ablation crater/carbonization, coagulation and congestion distributed from the center outwards. (4) Microscopy revealed four zones after LITT, including ablation crater/carbonization, coagulation, edema and congestion from the center outwards. A large area with coagulative necrosis was observed around a vessel in the peripheral area with edema and hyperemia. (5) The size of coagulation was consistent well to the CEUS findings. It was concluded that EchoLaser system at low power can produce a coagulation area larger than 1.0 cm×1.0 cm during a short time period. The real-time US imaging can be used to effectively guide and assess the treatment.

  • Qing-hua Wang , Yun Peng , Xin-yong Cai , Meng Wan , Yu Liu , Hong Wei

    Somatic cell nucleus transfer (SCNT) has been considered the most effective method for conserving endangered animals and expanding the quantity of adult animal models. Bama miniature pigs are genetically stable and share similar biological features to humans. These pigs have been used to establish animal models for human diseases, and for many other applications. However, there is a paucity of studies on the effect of ear fibroblasts derived from different age of adult Bama miniature pigs on nucleus transfer (NT). The present study examined the NT efficiency of ear fibroblasts from fetal, newborn, 1-, 2-, 4-, 6-, 12-month-old miniature pigs by using trypan blue staining, flow cytometry and NT technique, etc., and the cell biological function and SCNT efficiency were compared between groups. The results showed that ear fibroblasts grew well after passage in each group. Spindle-shaped cells initially predominated, and gradually declined with increase of culture time and replaced by polygonal cells. Irregular cell growth occurred in the 2-month-old group and the elder groups. The growth curves of the ear fibroblasts were “S-shaped” in different age groups. The cell proliferation of postnatal ear fibroblasts, especially those from 2-, 4-, 6-, 12-month-old miniature pigs was significantly different from that of fetus ear fibroblasts (P<0.05 or P<0.01). Two-month- and 4-month-old ear fibroblasts had a significantly higher proportion of G1 stage cells (85% to 91%) than those at 6 and 12 months (66% to 74%, P<0.01). The blastocyst rate of reconstructed embryos originating from newborn, 1-, 2-, 4-month-old donor pigs was 6.06% to 7.69% with no significant difference from that in fetus fibroblast group (8.06%). It was concluded that <4-month-old adult Bama miniature pigs represent a better donor cell resource than elder pigs.

  • Yu-jia Ma , Xiu-ling Deng , Hui-qing Li

    Recent studies have demonstrated that the BRAFV600E mutation is associated with aggressive clinicopathological features of papillary thyroid carcinoma (PTC). However, the BRAF mutation as a prognostic biomarker in papillary thyroid microcarcinoma (PTMC) is unclear. A systematic search of the electronic databases, including Medline, Scopus, CNKI and the Cochrane Library was performed up to July 1, 2014. Outcomes of interest included age, gender, concomitant hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall cell variant of PTMC (TCVPTMC), multifocality, extrathyroidal extension (ETE) and lymph node metastasis (LNM). A total of 19 studies published from 2008 to 2014 comprising 2253 patients fulfilled the inclusion criteria and were included in the meta-analysis, and 1143 (50.7%) of these patients were BRAF mutation positive. BRAF mutation was associated with larger tumor size (OR: 1.64; 95% CI: 1.16–2.32), multifocality (OR: 1.58; 95% CI: 1.25–2.00), ETE (OR: 2.59; 95% CI: 2.03–3.29), LNM (OR: 1.73; 95% CI: 1.14–2.62), advanced stage (OR: 2.03; 95% CI: 1.14–3.64) and TCVPTMC (OR: 5.07; 95% CI: 1.49–17.27; P=0.009). Additionally, the BRAF mutation was found to be not associated with age, gender, concomitant hashimoto thyroiditis or nodular goiter (P>0.05 for all). This meta-analysis revealed that in patients with PTMC, BRAF mutation is associated with tumor size, multifocality, ETE, LNM, advanced stage and TCVPTMC, and it may be used as a predictive factor for prognosis of PTMC.

  • Peng-sheng Yi , Ming Zhang , Ming-qing Xu

    Living donor liver transplantation (LDLT) is a curative treatment for end stage liver disease. It is advantageous due to the shortage of deceased donors. However, in LDLT, whether the middle hepatic vein (MHV) should be preserved in donors remains controversial. We conducted searches in Pubmed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar using the key words “living donor liver transplantation” and “middle hepatic vein”. Due to ethical issues, there were no randomized control trails focusing on MHV in LDLT. The majority of reports were retrospective studies. We examined the reference lists to identify related investigations. Google Scholar was then used to obtain full texts. Nine observational studies were analyzed. There were no significant differences in liver function (WMD, −5.51; P=0.12) and complications (RR, 0.98; P=0.89) in donors with or without MHV. However, the liver function in recipients was greatly improved after LDLT with MHV (WMD, −78.32; P=0.01). No definite conclusion was obtained in terms of the liver regeneration indices between LDLT with or without MHV. It was conclude that grafts with MHV in LDLT favor recipient outcomes and do not harm the living donor if a careful preoperative evaluation is performed.

  • Xi-fan Zhang , Xiang-yang Tian , Yu-lan Cheng , Zhan-chun Feng , Liang Wang , Jodi Southerland

    Health disparities between the western, central and eastern regions of rural China, and the impact of national health improvement policies and programming were assessed. A total of 400 counties were randomly sampled. ANOVA and Logistic regression modeling were employed to estimate differences in health outcomes and determinants. Significant differences were found between the western, central and eastern rural regions in community infrastructure and health outcomes. From 2000 to 2010, health indicators in rural China were improved significantly, and the infant mortality rate (IMR), maternal mortality rate (MMR) and under 5 mortality rate (U5MR) had fallen by 62.79%, 71.74% and 61.92%, respectively. Central rural China had the greatest decrease in IMR (65.05%); whereas, western rural China had the greatest reduction in MMR (72.99%) but smallest reduction in U5MR (57.36%). Despite these improvements, Logistic regression analysis showed regional differences in key health outcome indicators (odds ratios): IMR (central: 2.13; western: 5.31), U5MR (central: 2.25; western: 5.69), MMR (central: 1.94; western: 3.31), and prevalence of infectious diseases (central: 1.62; western: 3.58). The community infrastructure and health outcomes of the western and central rural regions of China have been improved markedly during the first decade of the 21st century. However, health disparities still exist across the three regions. National efforts to increase per capita income, community empowerment and mobilization, community infrastructure, capacity of rural health facilities, and health literacy would be effective policy options to attain health equity.