A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance / 药物分析学报

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Baicalin protects against 17α-ethinylestradiol-induced cholestasis via Sirt1/HNF-1α/FXR pathway / 中国药理学与毒理学杂志

OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis (EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol (EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum bio?markers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids (BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expres?sion of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat and Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflamma?tion through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.

Genetic Diversity Analysis of Erigeron breviscapus Based on SSR Markers / 中国实验方剂学杂志

Objective:To explore the genetic diversity and population structure of <italic>Erigeron breviscapus</italic>， so as to provide a scientific basis for its resource protection and rational utilization. Method:Twelve pairs of simple sequence repeat（SSR） primers were screened out from 243 individuals in 16 natural populations to calculate the genetic diversity parameters of <italic>E. breviscapus</italic>， which were then subjected to principal coordinate analysis and cluster analysis. Result:Twelve SSR markers generated 209 alleles， with an average of 17.417 alleles per locus. Based on 12 SSR markers and 16 populations of <italic>E. breviscapus</italic>， the observed heterozygosity （<italic>H</italic>₀） values were determined to be 0.603 and 0.613， the expected heterozygosity （<italic>H</italic>_e）to be 0.658 and 0.659， and the Shannon's information index （<italic>I</italic>） to be 1.443 and 1.446， respectively. The Wright's fixation index （<italic>F</italic>_st） was 0.123 and gene flow （<italic>N</italic>_m） was 2.077. Analysis of molecular variance （AMOVA） and genetic differentiation revealed that genetic variation within populations was the main source of total variation. The Nei's genetic distance and genetic identity coefficients were within the ranges of 0.107 （YA and XY）-0.713 （SZ and XZD） and 0.490 （SZ and XZD）-0.899 （YA and XY）， respectively. As demonstrated by the principal coordinate analysis and cluster analysis， the 16 populations of <italic>breviscapus </italic>were divided into two clusters. Conclusion:The genetic diversity of <italic>E. breviscapus</italic> was relatively high and there existed certain genetic differentiation and gene flow within and among populations. The genetic variation was mainly present within populations. All these have provided reference for subsequent study on good germplasm selection of <italic>E. breviscapus.</italic>

Selection of optimal qRT-PCR reference genes for Aconitum vilmorinianum / 中国中药杂志

Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.

Construction of core collection of Psammosilene tunicoides based on polymorphism of β-AS gene / 中国中药杂志

Psammosilene tunicoides is one of the main ingredients of the "Yunnan Baiyao". P. tunicoides is an endangered species included in the secondary protection list in China Plant Red Data Book as well as the endemic species in Southwest China. Its natural resources could not meet the needs of pharmaceutical production. Construction of core collection of P. tunicoides will lay the foundation for germplasm improvement and molecular breeding. The sequence variation of the key enzymes gene locus (β-AS) were carried out to survey the population structure and population history of the species. Among the 11 populations across its geographical range, 36 haplotypes were identified. The levels of haplotype diversity (Hd=0.905) were high, while the levels of population differentiation (GST=0.280) were low. Analysisof molecular variance (AMOVA) indicated that a significantly greater proportion of total genetic variationpartitioned among populations thanwithin populations (values of 77.43% and 22.57%, respectively). These results in combination with the star-like phylogenetic network analysis indicate that Hap1 as an ancestral haplotypewas shared in four populations, Hap2, Hap4, Hap15 and Hap16 are occurred in two populations, the remains as private haplotype only distributed in single population. The strategy of core collection was constructed in order to maximumpreserve genetic diversity of P. tunicoides.

Advance on persistent subretinal fluid after scleral buckle for rhegmatogenous retinal detachment / 国际眼科杂志(Guoji Yanke Zazhi)

·Delayed absorption of limited subretinal fluid occurs in some patients with rhegmatogenous retinal detachment (RRD) after scleral buckling. The macular-off patients may be effected more on visual function. The progress of recent researches on the epidemiology, diagnosis, pathogenesis and treatment of persistent subretinal fluid with rhegmatogenous retinal detachment has been summarized in this article. 视网膜下积液延迟吸收的情况,黄斑区受累者可能对视功能的影响更显著.本文就近年来RRD术后持续性视网膜下液(persistent subretinal fluid,PSF)的流行病学、检查方法、致病因素及发病机制、治疗及预防等方面的研究进展进行综述.

Study progress on the relationship between obstructive sleep apnea hypopnea syndrome and glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

·Glaucoma is a progressive optic neurodegenerative disease with specific characteristics of structural optic nerve head ( ONH) and with changes in the inner retinal layer (ganglion cell complex) along with the presence of corresponding functional visual field ( VF) changes that are irreversible. Obstructive sleep apnea hypopnea syndrome ( OSAHS ) is characterized by recurrent complete or partial interruption of normal breathing due to functional occlusion or collapse of upper airway during sleep that leads to apnea or hypopnea and hypoxia. This causes decrease in the arterial oxygen ( O2) saturation and a rise in the carbon dioxide saturation during sleep and results in transient hypoxia and increased vascular resistance in body tissues. OSAHS is an independent risk factor for cardiovascular and cerebrovascular, and many reports showed that OSAHS is one of the systemic risk factors for glaucoma which causes irreversible visual field damage, but lacks a systematic analysis of the relationship between the two. Comprehensive glaucoma evaluation should be recommended in patients with OSAHS.

Relationship Between Plasma Jagged1 Protein Level and Coronary Collateral Circulation in Patients With Coronary Artery Disease / 中国循环杂志

Objective: To explore the relationship between plasma Jagged1 protein level and coronary collateral circulation (CCC) formation in patients with coronary artery disease(CAD). Methods: According to coronary angiography (CAG) examination, our research was categorized in 2 groups: CAD group, n=89 patients with at least one of left anterior descending (LAD), left circumflex(LCX) or right coronary artery(RCA) stenosis ≥ 95％ and Control group, n=30 subjects without abnormal findings by CAG. Based on Rentrop grading system, CAD group was further divided into 2 subgroups: Good CCC subgroup, n=42 patients with Rentrop grade ≥ 2 and Poor CCC subgroup, n=47 patients with Rentrop grade≤1. Plasma levels of Jagged1 protein,vascular endothelial growth factor (VEGF) were measured by ELISA and the relevant correlation study was conducted by multivariate regression analysis. Results: Compared with Control group, CAD group had increased plasma levels of Jagged1 protein (38.74±10.60)ng/L vs (23.04±8.97)ng/L and elevated VEGF (113.98±30.80)pg/L vs (72.73±14.55)pg/L. Compared with Poor CCC subgroup, Good CCC subgroup presented increased Jagged1 protein (46.77±8.49)ng/L vs (31.56±6.26)ng/L and elevated VEGF (128.10±20.24) pg/L vs (92.43±21.09)pg/L. Correlation study showed that Jagged1 protein was positively related to VEGF in CAD patients (r=0.730, P<0.01); multivariate regression analysis indicated that Jagged1 protein (OR=1.318, P=0.000) and VEGF (OR=1.043, P=0.043) were the independent predictors for CCC processing.Conclusion: CAD patients with good CCC had the higher plasma Jagged1 protein level than the patients with poor CCC which implied that Jagged1 protein played important role in CCC processing, such finding may provide a new direction for treating CAD patients in clinical practice.

Efficacy of glucocorticoids combined with immunoglobulin in initial treatment of Kawasaki disease: a Meta analysis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To systematically investigate the efficacy and safety of glucocorticoids (GCs) combined with intravenous injection of immunoglobulin (IVIG) in the initial treatment of Kawasaki disease (KD).</p><p><b>METHODS</b>EDLINE Database, PubMed Database, CNKI, Wanfang Data, and VIP Database were searched to collect prospective or retrospective controlled studies on the combination of GCs and IVIG as the initial treatment of KD, which were published up to March 2016. Two investigators independently screened the literature, extracted data, and assessed the quality of the articles included. Then, a Meta analysis was performed using RevMan 5.2 software.</p><p><b>RESULTS</b>A total of 11 articles in English were included, with 7 prospective studies and 4 retrospective studies. The results of the Meta analysis showed that compared with the group using IVIG alone, the combination group had a significantly lower incidence rate of coronary artery lesion (CAL) (OR=0.44, 95%CI 0.23-0.86, P=0.02) and a significantly shorter duration of fever (MD=-1.66, 95%CI -2.32 to -1.01, P<0.00001). The combination group had a significantly lower rate of no response to initial treatment than the IVIG alone group (OR=0.37, 95%CI 0.27-0.51, P<0.00001). The recurrence rate of KD and the incidence rate of adverse events showed no significant differences between the two groups.</p><p><b>CONCLUSIONS</b>GCs combined with IVIG as the initial treatment for KD can reduce the incidence rate of CAL and the rate of no response to initial treatment and shorten the duration of fever, and does not increase the recurrence rate of KD and the incidence rate of adverse events.</p>

Controlled release by novel lysostaphin-loaded hydroxyapatite/chitosan composites / 药学学报

Lysostaphin is highly effective on eliminating methicillin resistant Staphylococcus aureus (MRSA). In order to achieve controlled release of lysostaphin, a biocompatible drug carrier is needed. Hydroxyapatite/chitosan (HA/CS) composites were chosen to carry lysostaphin and sample composites with different weight ratios of HA to CS, including 80/20, 70/30, 60/40, and 40/60, were prepared. Multiple analyses were performed to determine the structural and physicochemical properties of the composites, including scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. We immersed HA/CS composites loaded with 1 wt% lysostaphin to test in vitro release activity and cultured MC3T3-E1 cells to carry out biocompatibility test. The result of the release behavior of the composites revealed that the controlled release of lysostaphin from 60/40 HA/CS composites was the highest release rate of (87.4 ± 2.8)%, which lasted for 120 hours. In biocompatibility testing, MC3T3-E1 cells were able to proliferate on the surface of these composites, and the extract liquid from the composites could increase the growth of the cells. These results demonstrate the controlled release of lysostaphin from HA/CS composites and their biocompatibility, suggesting the potential application of these composites to bone injury and infection applications.

Effect of angiotensin II type I receptor blocker losartan on bone deterioration in orchiectomized male hypertensive and normotensive rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health.</p><p><b>METHODS</b>Six-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test.</p><p><b>RESULTS</b>Urine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.</p><p><b>CONCLUSION</b>Angiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.</p>

Effect of CO₂ pneumoperitoneum on the expression of the chemokine receptors CXCR4 and CCR7 in colorectal carcinoma cells in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The ability of pneumoperitoneum in laparoscopic surgery to promote proliferation and metastasis of colorectal cancer has become a focus of research in the field of minimally invasive surgery. The aim of this research was to investigate the effect of CO2 pneumoperitoneum under different pressures and exposed times on the expression of chemokine receptors in colorectal carcinoma cells.</p><p><b>METHODS</b>We constructed an in vitro pneumoperitoneum model. SW480 colon carcinoma cells were exposed to CO2 pneumoperitoneum under different pressures (6, 9, 12, and 15 mmHg) for 1, 2, and 4 hours. These cells were then cultivated under the same conditions as normal SW480 colon carcinoma cells without CO2 pneumoperitoneum (control group), treated at 37°C, and 5% CO2. The expression of the chemokine receptors CXC receptor 4 (CXCR4) and chemokine C receptor 7 (CCR7) was detected by immunocytochemistry and reverse transcriptase polymerase chain reaction after being cultivated for 0, 24, 48, and 72 hours.</p><p><b>RESULTS</b>Immunocytochemistry showed that CXCR4 expression in SW480 cells was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups for the same exposure times compared with controls (P < 0.05). CCR7 expression in SW480 cells was significantly decreased in the 12 and 15 mmHg CO2 pneumoperitoneum-treated groups compared with controls (P < 0.05). CXCR4 and CCR7 expression increased up to the level of the control group after 24 and 48 hours (P > 0.05). If the CO2 pneumoperitoneum pressure increased, CXCR4 and CCR7 expression decreased at all exposure times. If the CO2 pneumoperitoneum exposure time prolonged, there were no significant differences in CXCR4 and CCR7 expression under the same pressure. Under all exposure times, CXCR4 and CCR7 mRNA expression was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups (P < 0.05) compared with controls, and it increased up to the level of controls after being cultivated for 48 hours (P > 0.05). If the CO2 pneumoperitoneum pressure increased (with all exposure times) and exposure time prolonged (under the same pressure), there were no significant differences in CXCR4 and CCR7 expression.</p><p><b>CONCLUSIONS</b>CXCR4 and CCR7 expression is temporarily affected after continuous CO2 pneumoperitoneum treatment. The high pressure of CO2 pneumoperitoneum plays an important role in suppressing the expression of these chemokine receptors. Different lengths of time of exposure to a CO2 pneumoperitoneum-like environment do not change CXCR4 and CCR7 expression.</p>

A multi-center, randomized, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in the treatment of anal fissure / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of glyceryl trinitrate (GTN) ointment in the treatment of anal fissure.</p><p><b>METHODS</b>In this multi-center, randomized, double-blind and placebo-controlled trial, 240 chronic anal fissure patients from 7 clinical centers were randomized to receive eight-week treatment with GTN ointment (treatment group) or vaseline ointment (control group) respectively. Healing rate, visual analogue score (VAS), maximum anal resting pressure (MARP) and adverse reactions were recorded and compared.</p><p><b>RESULTS</b>A total of 221 patients (92.1%) finished the trial, including 114 patients in treatment group (95.0%, 114/120) and 107 in control group (89.2%, 107/120). At the endpoint of treatment (56 d), 90 patients in treatment group (78.9%, 90/114) healed completely compared to 31 patients in control group (29.0%, 31/107), and decrease rates of VAS in the two groups were (94.8±15.7)% and (61.2±35.7)% respectively, both differences were statistically significant (P<0.01). MARP after first administration was (20.2±18.5) mm Hg in treatment group (n=12) and (7.1±14.7) mm Hg in control group (n=6), which was not significantly different (P=0.152). Adverse reaction incidence was higher in treatment group (42.1% vs. 9.3%, P<0.05), while these adverse reactions were mainly headache and fullness in head, which were self-limiting.</p><p><b>CONCLUSION</b>GTN ointment can effectively promote healing and relieve pain in anal fissure with safety and tolerance.</p>

Screening of serum marker proteins in osteosarcoma and preliminary bioinformatic analysis on POLR3F / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To screen potential serum marker proteins of osteosarcoma, and to make a preliminary bioinformatics analysis of RNA polymerase III polypeptide F (POLR3F).</p><p><b>METHODS</b>Gene chip and SELDI-TOF MS was used to screen genes differentially expressed in osteosarcoma. The associations of potential biomarkers from SELDI data and microarray analysis were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. MATLAB was used to search transcription factors binding site in the promoter region and miRNAs binding site in 3'-UTR of POLR3F, respectively.</p><p><b>RESULTS</b>653 differentially expressed genes were found in osteosarcoma cells, while six differentially expressed protein peaks with significant statistical significances were detected by SELDI-TOF MS in patient's serum. 13 potential biomarkers for early diagnosis of osteosarcoma were screened by link-test. A conserved STAT3 binding site and a miRNA target site were found in proximal promoter regions and 3'-UTR region of POLR3F, respectively.</p><p><b>CONCLUSIONS</b>Link-test is a effective method to identify osteosarcoma biomarkers from both microarray and SELDI-TOF MS database. The results confirmed that POLR3F may be a promising biomarker for early diagnosis and a therapy target of osteosarcoma.</p>

Surgical strategy for presacral tumors: analysis of 33 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Presacral tumors are highly infrequent tumors located in the space known as presacral or retrorectal space. Although there have been substantial improvements in the prognosis of patients with malignant presacral tumors, the development of newer surgical strategy is likely to further improve the oncologic outcomes of malignant presacral tumors. The aim of this article was to report our experience in 33 cases, and to review the surgical strategy, pathological features and the prevention of complications from our experience.</p><p><b>METHODS</b>A retrospective analysis was conducted on 33 cases (20 male and 13 female) with presacral tumors surgically treated in our hospital between January 1998 and April 2009. The surgical approaches included trans-abdominal in 10 cases (30%), trans-sacral in 18 cases (55%) and combined abdominal-sacral in 5 cases (15%). All patients got followed up (14 - 123 months, mean of 45.1 months). At last, the general information, clinical symptoms, histodiagnosis, surgical types and postoperative complications of all cases in our series were assessed.</p><p><b>RESULTS</b>Ages of 33 patients ranged from 18 to 71 years, with an average of 48.5 years.</p><p><b>PATHOLOGICAL FINDINGS</b>6 epidermoid cysts, 5 teratomas, 3 leiomyomas, 9 neurofibromas, 5 neurilemmomas, 1 enterogenous cyst, 1 liposarcoma, 1 leiomyosarcoma, 1 angiosarcoma, and 1 neurofibrosarcoma. All tumors were excised with no perioperative death. A colostomy was taken in one case with angiosarcoma involving the rectum because of the intraoperative injury of the rectum. Blood loss during surgery was 400 - 11 000 ml (mean of 2400 ml). Four (12%) cases had local recurrence during follow-up: 2 because of inadequate drainage after dermoidectomy, both of them were cured by surgical resection and drainage; recurrence occurred in a case of teratoma in 18 months after surgery, cured by a trans-sacral excision; local recurrence and lung metastasis occurred simultaneously in a case of angiosarcoma in 6 months postoperatively and the patient died one month later of respiratory failure.</p><p><b>CONCLUSIONS</b>The main treatment of most presacral tumors is surgical resection. Selection of surgical approach is very important for complete resection of the presacral tumors. The location, size and peculiarities of tumors, conditions of the skin and soft tissues and the patients' somatotype are all determinative factors. Multidisciplinary cooperation is also very necessary.</p>

Notch signaling: a novel regulating differentiation mechanism of human umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) could be induced to differentiate into insulin producing cells (IPCs) in vitro, which have good application potential in the cell replacement treatment of type-1 diabetes. However, the mechanisms regulating this differentiation have remained largely unknown. Notch signaling is critical in cell differentiation. This study investigated whether Notch signaling could regulate the IPCs differentiation of human UCB-MSCs.</p><p><b>METHODS</b>Using an interfering Notch signaling protocol in vitro, we studied the role of Notch signaling in differentiation of human UCB-MSCs into IPCs. In a control group the induction took place without interfering Notch signaling.</p><p><b>RESULTS</b>Human UCB-MSCs expressed the genes of Notch receptors (Notch 1 and Notch 2) and ligands (Jagged 1 and Deltalike 1). Human UCB-MSCs with over-expressing Notch signaling in differentiation resulted in the down-regulation of insulin gene level, proinsulin protein expression, and insulin-positive cells percentage compared with the control group. These results showed that over-expressing Notch signaling inhibited IPCs differentiation. Conversely, when Notch signaling was attenuated by receptor inhibitor, the induced cells increased on average by 3.06-fold (n = 4, P < 0.001) in insulin gene level, 2.60-fold (n = 3, P < 0.02) in proinsulin protein expression, and 1.62-fold (n = 6, P < 0.001) in the rate of IPCs compared with the control group. Notch signaling inhibition significantly promoted IPCs differentiation with about 40% of human UCB-MSCs that converted to IPCs, but these IPCs were not responsive to glucose challenge very well both in vitro and in vivo. Hence, further research has to be carried out in the future.</p><p><b>CONCLUSIONS</b>Notch signaling may be an important mechanism regulating IPCs differentiation of human UCB-MSCs in vitro and Notch signaling inhibition may be an efficient way to increase the number of IPCs, which may resolve the shortage of islet of cell replacement treatment of type-1 diabetes.</p>

Effective evaluation of multiple level surgery in obstructive sleep apnea-hypopnea syndrome / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of multiple level surgery in treating obstructive sleep apnea-hypopnea syndrome (OSAHS).</p><p><b>METHODS</b>One hundred ninety two patients with OSAHS diagnosed by polysomnography were treated through uvulopalatopharyngoplasty (UPPP). Thirty patients were combined with sub-mucous resection of the nasal septum. Forty four patients received sub-mucous resection of the nasal septum and partial inferior turbinectomy. Two patients received sub-mucous resection of the nasal septum and partial resection of the tongue base. Two patients received genioglossus advancement and partial resection of the tongue base. Three patients received partial resection of the tongue base. In addition, the patients with the nasal disease and/or the lingual fat, AHI > 40 times/h, LSaO(2) < 0.64 and/or BMI > 30 kg/m(2) received tracheotomy before general anaesthesia.</p><p><b>RESULTS</b>One hundred ninety two patients were treated through UPPP. One hundred ninety one patients were successful, one patient died of pneumothorax and cardiac arrest during the incision of the trachea. All patients were followed-up for 6-37 months, among them, 132 patients showed therapeutic effect, with the effective rate as 68.7%. Fifty five patients were cured (AHI < 5 times/h); 39 patients had significant effect (AHI < 20 times/h and decreased > or = 50%); 38 patients were effective (AHI decreased > or = 50%). However, 60 patients did not have any therapeutic effect, with the ineffective rate as 31.3%. Fifty four patients had palatopharyngeal and nasal cavity emphasis, 24 patients had palatopharyngeal and oropharyngeal emphasis, 96 patients had palatopharyngeal and nasal cavity and oropharyngeal emphasis. Some patients were treated with UPPP, which made effective rate as 15 (68.2%), 12 (63.2%), 29 (55.8%). The others were treated with multiple level operations, which made effective rate as 25 (78.1%), 5 (5/5), 33 (75.0%). The effective rate was 60.2% (56/93) by simple UPPP and it was 77.8% (63/81) by multiple level treatment in patients with multiple level obstruction. There was statistical significance between them (chi(2) = 6.2, P = 0.01).</p><p><b>CONCLUSIONS</b>The effective rate was improved through multiple level operations in OSAHS patients. The serious complications could be prevented through tracheotomy before general anaesthesia in patients with severe OSAHS who needed multiple level surgery.</p>

Relaxation laryngoplasty in the management of mutational falsetto / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To observe the result of relaxation laryngoplasty in the management of mutational falsetto.</p><p><b>METHODS</b>The thyroplasty type 3 was applied and improved (the saturation was improved in the traditional operation, which the thyroid cartilage stick was cut off and overlapped without saturation in improved group 1, while the thyroid cartilage stick was not cut off and overlapped inward without saturation in improved group 2) in 30 adult patients who failed in voice modification. Preoperative and postoperative fundamental frequency (F0), normalised noise energy (NNE) and reading essay were compared.</p><p><b>RESULTS</b>F0 dropped significantly from the preoperative mean of (276.5 +/- 46.7) Hz [see equation in text] to the postoperative mean of (127.5 +/- 32.1) Hz in one month (t = 13.68, P < 0.001), while the NNE dropped significantly from the preoperative mean of (-10.9 +/- 4.9) dB to the postoperative mean of (-7.7 +/- 4.1) dB, the difference was statistically significant (t = 4.07, P < 0.001). In the three kinds of operation, the postoperative F0 in the improved group 1 dropped most significantly (compared with traditional operation group t = 2.64, P< 0.05). The postoperative NNE in the improved group 2 increased minimally. The difference was not significant statistically compared with other two kinds of operations (P > 0.05). The pitch dropped in all cases during reading aloud and conversation, while the voice breaks was disappeared.</p><p><b>CONCLUSIONS</b>Relaxation laryngoplasty was proved to be an efficient procedure in the surgical management of mutational falsetto.It was a preferable option for the patients who failed in voice modification. The improved operation profited to recover natural intonation and lighten the hoarseness due to glottic incompetence.</p>

Chemoprevention of Barrett's esophagus by celecoxib in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To examine the chemopreventive effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib for Barrett's esophagus in rats.</p><p><b>METHODS</b>Fifty 8-week-old male Sprague Dawley rats underwent esophagojejunostomy to induce Barrett's esophagus model. Four weeks after operation the animals were given celecoxib 10 mg/(kg*d(-1))(celecoxib group), or saline 1 ml (control group). Another 10 rats were sham operation group. All animals were sacrificed at 20 week after surgery. The degree of inflammation, Barrett's esophagus, adenocarcinoma, COX-2 expression and PGE(2) of animals were assessed.</p><p><b>RESULT</b>Among 60 rats, 6 rats died in celecoxib group, 8 rats died in control group, 1 rat died in sham operation group, and 45 (75%) rats completed the study. The incidence of mild, moderate and severe degree esophageal inflammation in celecoxib group and control group was 14/19(73.68%), 4/19(21.05%), 1/19(5.26%); 4/17(23.53%), 5/17(29.41%), 8/17(47.06%)(P<0.05), respectively. The incidence of Barrett's esophagus was 7/19(36.84%), 13/17(76.47%) in two group respectively(P<0.05); The incidence of Barrett's esophagus with dysplasia was 2/19(10.53%), 8/17(47.06%)(P<0.05), respectively. The expression of COX-2 was 1/7(14.29%), 10/13(76.92%)(P<0.05) in two groups. PGE2 content was significantly lower in the celecoxib group than that in control group(P<0.001). No esophageal pathological changes were found in sham operation group.</p><p><b>CONCLUSION</b>Selective COX-2 inhibitors celecoxib can inhibit inflammations, development of Barrett's esophagus and esophagus adenocarcinoma.</p>

Gene profiling of MAPK pathway in human osteosarcoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the functional effects of MAPK pathway in the pathogenesis of human osteosarcoma.</p><p><b>METHODS</b>Gene microarray (Human Genome U133A, Affymetrix) was used to screen the differential expression of genes involved in MAPK pathway between osteosarcoma cell lines and 3 osteoblastic cell lines. KEGG metabolic pathway analysis was performed among significantly increased or decreased genes using the MATLAB software. Immunohistochemical technique was used to detect the expressions of ERK1/2, JNK and p38 proteins among 48 osteosarcoma and benign 24 osteoblastic tumor samples.</p><p><b>RESULTS</b>Using an entrance limit of > or = 2.0, 18 differentially expressed MAPK pathway-related genes were selected (10 up-regulated, 8 down-regulated) to mapped to the MAPK pathway of KEGG which are all important node genes. The positive rates of ERK1/2, JNK and p38 proteins were 83.3% (40/48), 72.9% (35/48) and 85.4% (41/48) in osteosarcomas,and 12.5% (3/24), 8.3% (2/24) and 16.7% (4/24) in the control group, respectively. The positive rates and expression intensities were statistically different between the 2 groups (P<0.01).</p><p><b>CONCLUSION</b>MAPK pathway plays an important role in the pathogenesis of osteosarcoma. ERK, JNK and p38 form an intercoordinating network and regulate the cell proliferation, differentiation, apoptosis, invasion and migration in osteosarcoma.</p>