GG Genotype at rs1275988 and rs2586886 Loci of TWIK-related Acid-sensitive K Channel-1 Gene is A Potential Risk Factor for Severe Obstructive Sleep Apnea / 中国医学科学院学报

To explore the mechanism of obstructive sleep apnea(OSA) by assessing the association between human TWIK-related acid-sensitive K channel-1(TASK-1) gene and OSA. A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region,China,from April to December 2016.Two single nucleotide polymorphisms(rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a Kompetitive Allele Specific PCR genotyping system. In patients with blood potassium 3.95 mmol/L in patients with TASK-1 GG genotype may be conducive to reducing the incidence of severe OSA.

Characteristics of benign and malignant lesions of ampullary polyps and the accuracy of forceps biopsy / 北京大学学报(医学版)

OBJECTIVE@#To distinguish the endoscopic and clinical features of ampullary polyps, to investigate the endoscopic cancer risk factors of ampullary polyps based on the compared differences of benign lesions and adenocarcinoma, and to assess the accuracy of forceps biopsy.@*METHODS@#Authors retrospectively analyzed the data extracted from patients treated with endoscopic papillectomy (EP) from January 2009 to May 2019 in the Department of Gastroenterology, Peking University Third Hospital. Endoscopic pictures and pathology reports were reevaluated and analyzed. Differences between benign and cancer groups were conducted.@*RESULTS@#In the study, 42 cases were involved, 35 to 83 years old, containing 83.3% older than 50 years old patients. The histological types were as follows, 2 for inflammatory polyps (4.8%), 1 for neuroendocrine tumor (2.4%), 1 for hyperplastic polyp (2.4%), 5 for grade Ⅰ adenoma (11.9%), 10 for grade Ⅱ adenoma (23.8%), 4 for grade Ⅲ adenoma (9.5%) and 19 for adenocarcinoma (45.2%), and 90.5% were adenoma or adenocarcinoma. The average age of benign group (inflammatory polyps and adenomas) was (56.7±9.2), which was significantly younger than that of adenocarcinoma group [(66.0±9.8), P=0.004]. Tumor diameter in adenocarcinoma group[(2.3±0.8) cm] was significantly larger than that in benign group[(1.6±0.6) cm, P=0.002]. Benign lesions only showed Yamada type Ⅰ(57.1%)and type Ⅱ(42.9%). The percentage of Yamada type Ⅰ (36.8%)and type Ⅱ(31.6%) in adenocarcinoma group was lower than that in benign group. Moreover, Yamada type Ⅲ (31.5%) was only found in the adenocarcinoma group. Significant differences were observed between the two groups in Yamada types (P=0.046). Most of the benign lesions had clear boundary(18/21, 85.7%). The percentage of clear boundary in adenocarcinoma group (2/19, 10.5%) was significantly lower than that in the benign group (P < 0.001). No significant differences were investigated in color (P=0.353) and surface (P=0.324) between benign and adenocarcinoma lesions. Pooling age, lesion diameter, Yamada type and clear boundary into Logistic regression analysis, only age (OR=1.186, 95%CI 1.025-1.373, P=0.022) and clear boundary (OR=66.218, 95%CI 3.421-1 281.840, P=0.006) were the independent cancer risk factors. Only 2 (10.5%) in the 19 cancer patients had positive biopsy results before EP. As compared with post-EP, 55.3% (21/38) biopsies were under-estimated, including 17 (17/19, 89.5%) adenocarcinomas and 4 (4/10, 40%) grade Ⅱ adenomas.@*CONCLUSION@#adenoma and adenocarcinoma were the major histological type of ampullary po-lyps. Age and unclear boundary were the independent risk factors of ampullary adenocarcinoma. Forceps biopsy was not enough for ampullary polyp differentiation.

Genetic variants of rs1275988 and rs2586886 in TWIK-related acidsensitive K+ channel-1 gene may be potential risk factors for obese patients with obstructive sleep apnea / 中华医学杂志(英文版)

Background@#The pathogenesis of obstructive sleep apnea (OSA) remains not fully understood. This study aimed to explore the mechanism of OSA by assessing the association between the human tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid-sensitive K+ channel-1 (TASK-1) gene and OSA.@*Methods@#A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Center for Hypertension of People’s Hospital of Xinjiang Uygur Autonomous Region (China) from April to December in 2016. Two single nucleotide polymorphisms (rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a kompetitive allele specific polymerase chain reaction genotyping system. Clinical-pathological characteristics and genotype data were compared between the severe and non-OSA groups to explore the association between TASK-1 gene polymorphism and severe OSA.@*Results@#There were no significant differences in genotype distribution, allele frequency, and the recessive and dominant model of the two selected single nucleotide polymorphisms (rs1275988 and rs2586886) between the severe and non-OSA groups in the total population (P < 0.05). However, for patients with a body mass index (BMI) ≥28 kg/m2, the distribution of genotypes and alleles, and the recessive model (GG + GA vs. AA) exhibited significant differences between the severe and non-OSA group (for genotypes: P = 0.014 and P = 0.026; for alleles: P = 0.006 and P = 0.011; for the recessive model: P = 0.005 and P = 0.009, respectively). The simple logistic regression analysis revealed that the GG genotype was a risk factor for OSA. The odds ratio (OR) and 95% confidence intervals (CI) were 4.902 (1.582–15.186, P = 0.006) for rs1275988 and 4.420 (1.422–13.734, P = 0.010) for rs2586886, respectively. In multivariate logistic regression analysis, the combination of GG genotypes of rs1275988 with BMI ≥28 kg/m2 increased the risk of severe OSA (OR = 8.916, 95% CI 4.506–17.645, P < 0.001).@*Conclusion@#Both the GG genotype of rs1275988 and GG genotype of rs2586886 in the TASK-1 gene may play as potential risk factors in obese patients with OSA.

Genetic variants of rs1275988 and rs2586886 in TWIK-related acid-sensitive K+ channel-1 gene may be potential risk factors for obese patients with obstructive sleep apnea / 中华医学杂志(英文版)

BACKGROUND@#The pathogenesis of obstructive sleep apnea (OSA) remains not fully understood. This study aimed to explore the mechanism of OSA by assessing the association between the human tandem of P domains in a weak inwardly rectifying K channel (TWIK)-related acid-sensitive K channel-1 (TASK-1) gene and OSA.@*METHODS@#A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Center for Hypertension of People's Hospital of Xinjiang Uygur Autonomous Region (China) from April to December in 2016. Two single nucleotide polymorphisms (rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a kompetitive allele specific polymerase chain reaction genotyping system. Clinical-pathological characteristics and genotype data were compared between the severe and non-OSA groups to explore the association between TASK-1 gene polymorphism and severe OSA.@*RESULTS@#There were no significant differences in genotype distribution, allele frequency, and the recessive and dominant model of the two selected single nucleotide polymorphisms (rs1275988 and rs2586886) between the severe and non-OSA groups in the total population (P > 0.05). However, for patients with a body mass index (BMI) ≥28 kg/m, the distribution of genotypes and alleles, and the recessive model (GG + GA vs. AA) exhibited significant differences between the severe and non-OSA group (for genotypes: P = 0.014 and P = 0.026; for alleles: P = 0.006 and P = 0.011; for the recessive model: P = 0.005 and P = 0.009, respectively). The simple logistic regression analysis revealed that the GG genotype was a risk factor for OSA. The odds ratio (OR) and 95% confidence intervals (CI) were 4.902 (1.582-15.186, P = 0.006) for rs1275988 and 4.420 (1.422-13.734, P = 0.010) for rs2586886, respectively. In multivariate logistic regression analysis, the combination of GG genotypes of rs1275988 with BMI ≥28 kg/m increased the risk of severe OSA (OR = 8.916, 95% CI 4.506-17.645, P < 0.001).@*CONCLUSION@#Both the GG genotype of rs1275988 and GG genotype of rs2586886 in the TASK-1 gene may play as potential risk factors in obese patients with OSA.

Analysis of influencing factors on circadian blood pressure of hypertensive patients with obstructive sleep apnea-hypopnea syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of obesity, arousal, hypoxia and sympathetic activation on the circadian blood pressure of hypertensive patients with obstructive sleep apnea-hypopnea syndrome.</p><p><b>METHODS</b>Polysomnography (PSG) was performed in 436 hypertensive patients complaining of snoring, daytime sleepiness, lips cyanosis, hyperhemoglobinemia of unknown etiology, or with refractory hypertension. Hypertensive subjects were divided into four groups according to apnea-hypopnea index (AHI): hypertensive with mild obstructive sleep apnea-hypopnea syndrome (OSAHS) (n = 131), hypertensive with moderate OSAHS (n = 95), hypertensive with severe OSAHS (n = 95) and hypertensive without OSAHS as control group (n = 115). The ambulatory blood pressure monitoring (ABPM), PSG, urine electrolyte, and urine vanillylmandelic acid (VMA) were compared among groups. Factor analysis was employed to identify common factors related to the alterations of circadian blood pressure. Multiple linear regression analysis was used to analyze the influencing factors of the observed variables.</p><p><b>RESULTS</b>There were significant differences among groups in age, neck circumference and waist circumference(P < 0.001). In severe group, 24 hour average systolic blood pressure (24 hSBP)[ (137.0 ± 16.8) mm Hg vs.(131.3 ± 11.9)mm Hg, (131.3 ± 13.2)mm Hg (1 mm Hg = 0.133 kPa)], daytime systolic blood pressure (day-SBP) [(140.8 ± 16.8) mm Hg vs. (135.7 ± 11.9) mm Hg, (135.3 ± 13.5) mm Hg]and night systolic blood pressure (night-SBP)[ (130.9 ± 17.0) mm Hg vs.(124.5 ± 14.0 )mm Hg, (124.3 ± 13.2) mm Hg] were significantly higher than those of control or mild OSAS groups (P < 0.01). Factor analysis showed that body mass (BM), life style, urine electrolyte, age and course of disease (ACD) were the common factors influencing circadian blood pressure. OSAHS was correlated with declining percentage of SBP (β = -0.128, P < 0.01) and declining percentage of DBP (β = -0.126, P < 0.01). The contribution according to priority was ACD > OSAHS > BM for declining percentage of SBP (β = -0.148, P = 0.002;β = -0.128, P = 0.007;β = 0.099, P = 0.035), OSAHS > ACD > BM for declining percentage of DBP(β = -0.126, P = 0.008;β = -0.105, P = 0.026;β = 0.097, P = 0.042).</p><p><b>CONCLUSION</b>OSAHS, ACD and BM are the independent risk factors contributing to the alterations of circadian blood pressure in hypertensive patients with obstructive sleep apnea-hypopnea syndrome.</p>

Anatomic assessment of femoral tunnel by transtibial drilling technique in double-bundle anterior cruciate ligament reconstruction: an in vivo study / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the anatomy of femoral tunnels created by simulated transtibial technique in double-bundle anterior cruciate ligament (ACL) reconstruction.</p><p><b>METHODS</b>Two tibial tunnels, anteromedial (AM) and posterolateral (PL), were drilled 45?and 55?to tibial plateau respectively. On the femoral side, the AM and PL tunnels were drilled through anteriomedial portal. After the four tunnels were established, the shaft of a reamer was introduced into the joint through tibial tunnel and reached against the lateral wall of intercondylar notch. The position that the reamer shaft can reach was marked and recorded.</p><p><b>RESULTS</b>Neither femoral AM nor PL tunnel opening can be fully or partially reached by the reamer shaft through the tibial AM tunnel in all cases. The evaluation through the tibial PL tunnel showed that only in 8 of 50 cases (16%) the femoral AM tunnel opening and in 4 cases (8%) the PL opening can be fully reached. On the other hand, in 12 cases (24%) the femoral AM tunnel opening and in 10 cases (20%) the PL opening can be partially reached by the shafts through the tibial PL tunnel.</p><p><b>CONCLUSION</b>The result strongly suggests that transtibial technique is not well competent for femoral tunnel drilling in anatomic double-bundle ACL reconstruction as we have hypothesized.</p>

Increased susceptibility of recombinant type 2A von Willebrand factor mutant A1500E to proteolysis by ADAMTS13 / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the susceptibility of von Willebrand factor (VWF) type 2A mutant A1500E to proteolysis by metalloprotease ADAMTS13 and to provide the direct supports for the pathogenesis of VWF mutation A1500E responsible for von Willebrand disease (VWD) type 2A.</p><p><b>METHODS</b>Recombinant wild-type VWF (WT-VWF) and A1500E mutant VWF transiently expressed on transfected HeLa cell lines. Expression media were collected and concentrated, then cleaved directly by recombinant ADAMTS13 (rADAMTS13). Compared with WT-VWF, the susceptibility of A1500E mutant VWF to proteolysis by ADAMTS13 was analyzed using SDS-agarose gel VWF multimers analysis.</p><p><b>RESULTS</b>In vitro the expression of VWF:Ag in the supernatants of WT-VWF and A1500E mutant VWF were 1.10 U/ml and 0.78 U/ml, respectively, while VWF:Ag in cells lysates of A1500E mutant VWF was 90.6% of that of WT-VWF. The SDS-agarose gel VWF multimers analysis showed that there were no differences between WT-VWF and A1500E mutant VWF. The A1500E mutant VWF could be efficiently cleaved by ADAMTS13 under static condition without denaturants such as urea and guanidine HCl. VWF multimeric analysis showed that high and intermediate molecular weight multimers dramatically decreased while low molecular weight multimers obviously increased. Conversely, WT-VWF could not be cleaved by ADAMTS13 under the same condition.</p><p><b>CONCLUSION</b>The A1500E mutation resulted in VWF more susceptible to ADAMTS13-dependent proteolysis, which belonged to VWD type 2A group 2 mutation.</p>

Serum neuropeptide Y level in hypertensive patients with obstructive sleep apnea syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the potential role of neuropeptide Y (NPY) in the pathophysiological process of hypertension caused by obstructive sleep apnea syndrome (OSAS).</p><p><b>METHODS</b>The concentration of serum NPY were measured with radioimmunoassay (RIA) in 417 subjects (97 normotensive controls without OSAS, 113 cases of normotensive with OSAS, 73 cases of hypertensive without OSAS and 134 cases of hypertensive with OSAS. Further, the mean NPY level were compared in four groups and the possible effective factors on NPY were discussed.</p><p><b>RESULTS</b>(1) The concentration of NPY in four groups were (50.5 +/- 37.2) pmol/L in normal controls, (76.0 +/- 39.9) pmol/L in normotensive with OSAS group, (66.9 +/- 36.2) pmol/L in hypertensive without OSAS group and (86.8 +/- 36.8) pmol/L in hypertensive with OSAS group. Whether the patients with OSAS combined with hypertension or not, the concentration of NPY in the serum raised remarkably compared with those without OSAS and hypertension, the highest level of serum NPY was detected in OSAS combined with hypertension group. (2) Pearson correlation analysis indicated that both SBP and DBP related to the serum NPY significantly in non-OSAS group (AHI <10), while the BMI, abdominal circumference, AHI as well as the lowest level of SaO2 correlated to NPY besides SBP in OSAS group with (AHI > or =10). (3) Multiple linear regression model showed that the abdominal circumference and AHI were contributing factors to SBP, while neck circumference and BMI were contributing factors to DBP. The level of NPY in the serum were significantly affected by AHI and BMI, in which the former one had greater influence.</p><p><b>CONCLUSION</b>The increased level of serum NPY may play weakly potential roles in the pathophysiological process of hypertension caused by OSAS.</p>

A case-control study on road-related traffic injury in Shanghai / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the risk factors that influencing the occurrence of road-related traffic injuries, so as to provide related bases for controlling injuries.</p><p><b>METHODS</b>A case-control study was conducted on 256 drivers with histories of accidents and their controls. EPQ questionnaire and a self-designed questionnaire were used to collect data. Risk factors would include behaviors as driving time per day, types of vehicles, time and status of sleep, degree of education, diet habits, feeling of tiredness, alcohol intake, time of watching television before driving and marriage status. Physiological index as blood type, blood pressure, cordial, using tranquillizers, disease history, reaction time, eyesight, overweight, etc. were also tested. Conditional logistic regression model was used to analyze risk factors.</p><p><b>RESULTS</b>From all these tests, risk factors which including dietetic rhythm (OR = 1.815), tiredness (OR = 3.263), history of digestive disease (OR = 3.504), weak eye sight (OR = 3.825), being divorced (OR = 3.226), wake up early (OR = 4.931), mixed insomnia (OR = 5.719), simple reaction time (OR = 3.498), complex reaction time (OR = 2.292), P score (OR = 1.352), E score (OR = 1.439) were noticed to be significantly important.</p><p><b>CONCLUSION</b>The occurrence of road-related injuries were related to a series of physiological, psychological and behavioral risk factors among drivers.</p>

Morphotype diversity of Cistanche deserticola / 中国中药杂志

<p><b>OBJECTIVE</b>To provide theoretical basis for selecting high quality seeds by studying the modality diversity of Cistanche deserticola.</p><p><b>METHOD</b>Four populations were collected in the field and its biodiversity was studied by comparative morphoaanatory to identify its mutation of nutrition organ and reproduction organ in laboratory and herbarium.</p><p><b>RESULT AND CONCLUSION</b>There are several types of C. deserticola that come from different types, which results in the difference in pharmacody and effect of medicine.</p>

Expression of von willebrand factor-A3 domain in E coli and its biological function / 中国实验血液学杂志

The interaction among collagen, von Willebrand factor (vWF) and glycoprotein Ib axis is the first step in hemostasis and thrombosis, especially under high shear condition. To develop a new remedy of anti-thrombosis, mRNA from endothelial cells was extracted, and reverse transcription PCR was adopted to amplify DNA of interest. After sequencing, recombinant expression vector was constructed. The amplified DNA fragment of vWF domain A3 was inserted into expression vector with 6 x his taq, pET20b(+), the recombinant was transformed into E coli (strain DE3) and induced by IPTG. Recombinant vWF-A3 was designated as a recombinant fragment comprising residues 918 - 1114 of mature vWF subunit. It was purified through Ni-NTA resin column and refolded in Tris buffer containing GSH and GSSG. The results showed that rvWF-A3 was expressed successfully in E coli (strain DE3), accounting for 46% of total bacterial protein with its purity of over 95%. It was identified that rvWF-A3 is capable to bind collagen and inhibit the wild vWF binding to collagen by competition. It is concluded that rvWF-A3 fragment might be an effective antithrombotic agent for preventing arterial thrombosis.

Molecular cloning of human vWF/A1 gene and its expression / 中国实验血液学杂志

To study the mechanism of thrombogenesis and search new anti-thrombotic agent, the cDNA for human vWF A1 domain was high-level expressed in E. coli and recombinant protein of vWF A1 with biologic activity was obtained. The gene encoding A1 domain was amplified by PCR from plasmid containing full length cDNA of human vWF. After confirming by DNA sequencing analysis, the recombinant expression plasmid pQE31-vWF/A1 was constructed and introduced into E. coli M15 strain, then induced by IPTG; the expressed protein was purified with Ni-NTA agarose, identified by Western blotting. The results showed that the 854 bp DNA fragment was obtained by PCR from the plasmid containing full length cDNA for human vWF and its sequence was identical to the published sequence. High level expression of A1 protein was yielded after 5 hour-induction, which amounted to 30% of total bacteria protein in inclusion body. Western blot demonstrated it possessed good antigenicity and high specificity. It is concluded that cDNA for vWF/A1 had been cloned successfully, high level expression of A1 protein was achieved in E. oli. This study will provide a basis for the further clinical and basic research on the role of vWF in thrombosis and hemostasis.