[The association of renalase single-nucleotide polymorphisms rs2576178 and rs10887800 with hypertension in patients with obstructive sleep apnea].

Objective: To evaluate the associations between the renalase single-nucleotide polymorphisms rs2576178 and rs10887800 and the risk of hypertension in OSA patients. Methods: A total of 3, 570 male OSA subjects diagnosed via standard polysomnography were included in this retrospective study. We recorded anthropometric, genomic, and polysomnographic parameters and blood pressure levels. All subjects were divided into four groups based on quartiles of the apnea-hypopnea index (AHI). The relationships between rs2576178 and rs10887800 and the risk of hypertension were evaluated using the binary logistic regression, and haplotype analysis. Results: In the bottom AHI quartile, rs10887800 was significantly associated with the risk of hypertension according to the dominant model [odds ratio(OR)=0.691, 95% confidence interval (CI)=0.483-0.990, P=0.044] even after adjustment for age, sex, and the body mass index. The G-A haplotype was associated with a co-effect of the two SNPs, namely, the risk of hypertension decreased (OR=0.879, 95%CI=0.784-0.986, P=0.028). Conclusions: We find no association between single rs2576178 or rs10887800 variants with the risk of hypertension in our OSA population. But, the synergistic effect of the two polymorphisms is associated with the risk of hypertension in OSA patients.

NF-κB inhibits the differentiation of hysteromyoma cells by reducing myocardin expression.

OBJECTIVE: To investigate the effect of nuclear factor-kappaB (NF-κB) on the myocardin-mediated differentiation of hysteromyoma cells. MATERIALS AND METHODS: Expression levels of myocardin in hysteromyoma cells from patients with hysteromyoma were detected. Normal uterine smooth muscle cells were used as control group. Overexpression of myocardin in hysteromyoma cells was achieved through lentivirus infection. Changes in expression levels of uterine smooth muscle cell maker p21, p57, Cyclin D1, PCNA, SM22α, and αSMA were detected. Hysteromyoma cells with lentivirus infection were stimulated by lipopolysaccharide (LPS), and changes in expression levels of myocardin were detected. RESULTS: Compared with normal uterine smooth muscle cells, the expression level of myocardin in hysteromyoma cells was extremely low, or even undetectable, and expression levels of smooth muscle cell differentiation markers were also minimal, and cells were in the de-differentiated state. Expression of exogenous myocardin can improve the expression of smooth muscle cell differentiation markers to induce cell re-differentiation. LPS stimulation can activate NF-κB to inhibit myocardin expression, thereby inducing cell dedifferentiation. CONCLUSIONS: NF-κB can inhibit the differentiation of hysteromyoma cells by decreasing the expression level of myocardin.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.

[Distribution and drug resistance of pathogens of blood stream infection in patients with hematological malignancies after chemotherapy].

Objective: To investigate the distribution and resistance of pathogens isolated from blood cultures in patients with hematological malignancies after chemotherapy in Union Hospital of Fujian Medical University so as to understand the real situation of blood stream infection (BSI) and provide the basis for rational use of antibiotics in clinic. Methods: The data of 657 strains isolated from blood culture specimens of patients with hematological malignancies from January 2013 to December 2016 were collected analyzed. Results: A total of 657 cases of blood culture positive bacterial strains were included in the study, involving 410 cases (62.4%) with single Gram-negative bacteria (G(-) bacteria) , 163 cases (24.8%) with single Gram-positive bacteria (G(+) bacteria) , 50 cases (7.6%) with single fungi. The most common 5 isolates in blood culture were Klebsiella pneumoniae (17.5%) , Escherichia coli (17.2%) , Coagulase negative staphylococci (CNS) (14.9%) , Pseudomonas aeruginosa (14.2%) and Staphylococcus aureus (3.5%) . The extended-spectrum beta-lactamase (ESBL) production rates of Klebsiella pneumoniae and Escherichia coli were 25.2% and 55.8%, respectively. ESBL producing strains were almost more resistant than non-ESBL producing strains. The resistance rates of Enterobacteriaceae to carbapenems, piperacillin/tazobactam and tigecycline were lower than 14.0%. The resistance rates of Pseudomonas aeruginosa to a variety of drugs were lower than 12.0%. Tigecycline-resistant Acinetobacter baumannii bacteria were not detected, and the resistance rates of Acinetobacter baumannii to cefixime and cefotaxime were 7.1%. Methicillin-resistant strains in CNS (MRCNS) and in Staphylococcus aureus (MRSA) accounted for 84.7% and 43.5%, respectively. Vancomycin, linezolid and tigecycline-resistant G(+) bacteria were not detected. Conclusion: The pathogens isolated from blood culture were widely distributed. Most of them were G(-) bacteria, and the resistance to antibiotics was quite common. Furhermore, vancomycin, linezolid and tigecycline can be chosen empirically to treat patiens who ar suspected to have G(+) bacterial BSI.

Racial/ethnic disparities in the prevalence and awareness of Hepatitis B virus infection and immunity in the United States.

Hepatitis B virus (HBV) infection in the United States is the most common among Asians followed by non-Hispanic blacks. However, there have been few studies that describe HBV infection and immunity by racial group. Our study aimed to assess racial/ethnic disparities in the prevalence and awareness of HBV infection and immunity using nationally representative data. In the National Health and Nutrition Examination Survey 2011-2014, 14 722 persons had HBV serology testing. We estimated the prevalence of HBV infection, past exposure, and immunity by selected characteristics and calculated adjusted odds ratios using survey-weighted generalized logistic regression. Awareness of infection and vaccination history was also investigated. The overall prevalence of chronic HBV infection, past exposure and vaccine-induced immunity was 0.34% [95%CI 0.24-0.43], 4.30% [95%CI 3.80-4.81], and 24.4% [95%CI 23.4-25.4], respectively. The prevalence of chronic infection was 2.74% [95% CI 1.72-3.76] in Asians, 0.64% [95% CI 0.35-0.92] in non-Hispanic blacks, and 0.15% [95% CI 0.06-0.24] in non-Asian, non-blacks. Only 26.2% of those with chronic infection were aware of their infection. The prevalence of the past exposure was 21.5% [95%CI 19.3-23.7] in Asians, 8.92% [95%CI 7.84-9.99] in non-Hispanic blacks, 2.05% [95%CI 1.49-2.63] in non-Hispanic whites and 4.47% [95%CI 3.25-5.70] in Hispanics. Prevalence of vaccine-induced immunity by each race was 34.1% [95%CI: 32.0-36.2] in Asians, 25.5% [95%CI: 24.0-27.0] in non-Hispanic blacks, 24.0% [95%CI: 22.6-25.4] in non-Hispanic whites and 22.2% [95%CI: 21.3-23.3] in Hispanics. There are considerable racial/ethnic disparities in HBV infection, exposure and immunity. More active and sophisticated healthcare policies on HBV management may be warranted.

Estimation of Right-Lobe Graft Weight From Computed Tomographic Volumetry for Living Donor Liver Transplantation.

BACKGROUND: The objective of the study was to establish a right-lobe graft weight (GW) estimation formula for living donor liver transplantation (LDLT) from right-lobe graft volume without veins (GVw/o_veins), including portal vein and hepatic vein measured by computed tomographic (CT) volumetry, and to compare its estimation accuracy with those of existing formulas. Right-lobe GW estimation formulas established with the use of graft volume with veins (GVw_veins) sacrifice accuracy because GW measured intra-operatively excludes the weight of blood in the veins. Right-lobe GW estimation formulas have been established with the use of right-lobe GVw/o_veins, but a more accurate formula must be developed. METHODS: The present study developed right-lobe GW estimation formulas based on GVw/o_veins as well as GVw_veins, using 40 cases of Korean donors: GW = 29.1 + 0.943 × GVw/o_veins (adjusted R2 = 0.94) and GW = 74.7 + 0.773 × GVw_veins (adjusted R2 = 0.87). The proposed GW estimation formulas were compared with existing GVw_veins- and GVw/o_veins-based models, using 43 cases additionally obtained from two medical centers for cross-validation. RESULTS: The GVw/o_veins-based formula developed in the present study was most preferred (absolute error = 21.5 ± 16.5 g and percentage of absolute error = 3.0 ± 2.3%). CONCLUSIONS: The GVw/o_veins-based formula is preferred to the GVw_veins-based formula in GW estimation. Accurate CT volumetry and alignment between planned and actual surgical cutting lines are crucial in the establishment of a better GW estimation formula.

The effect of montelukast and antiadhesion barrier solution on the capsule formation after insertion of silicone implants in a white rat model.

BACKGROUND AND PURPOSES: Capsular contracture is one of the most severe complications that can occur in breast surgery following silicone implant insertion. The purpose of this study was to investigate the effect of montelukast and antiadhesion barrier solution (AABS) on reducing capsular formation and their possible synergism. MATERIALS AND METHODS: This study was approved by the Animal Ethics Committee (Reference No. KNU 2012-33) and was conducted in accordance with the Kyungpook National University - Institutional Animal Care and Use Committee, Animal Ethics Committee. The experiments in this study were conducted in vivo in 4 groups of 24 rats. Following silicone implant insertion, the pocket was injected with different agents. Group I (control group) was given normal saline injections into the pocket and fed with pure water. Group II was given injections of AABS and fed with pure water. Group III was given injections of normal saline and the medication montelukast during the experimental period. Group IV was given injections of AABS and montelukast as postoperative medication. Peri-implant capsules were excised after 8 weeks and were evaluated for transparency, inflammatory cell content, capsule thickness, collagen pattern and TGF-ß expression. RESULTS: The capsules in the experimental groups (i.e., groups II-IV) were significantly more transparent than those in group I (controls; p < 0.05, Student's t test). The mean capsule thickness of the experimental groups II (296 ± 14.76 µm), III (280 ± 14.77 µm) and IV (276 ± 39.28 µm) was smaller than that of the control group I (361 ± 35.43 µm). Compared to the control group, the histologic findings in the experimental groups suggested a decreased inflammatory response occurring in the peri-implant capsules as they exhibited minor vascularization and a reduced number of mast cells and macrophages. The collagen patterns in the experimental groups were of a lower density than in the control group with the former showing a loose, tidy collagen pattern. The amounts of TGF-ß and collagen I were higher in the control group than in the experimental groups. Group IV (the synergic effect group) had a more pronounced effect on all the parameters examined than that in groups II and III with separate drug administration. CONCLUSIONS: Montelukast and AABS reduced the thickness, the inflammatory cell infiltrate and the myofibroblast content of the peri-implant capsules around silicone implants in this white rat model. They lowered the expression of the fibrotic mediator, TGF-ß, and inhibited the peri-implant capsular fibrosis. Therefore, montelukast and AABS are effective in the reduction of silicone-induced peri-implant capsular formation.

Factors predicting the usefulness of deceased donors.

BACKGROUND: Preoperative management for deceased donation is important. Deceased donation can failed for several reasons. We analyzed the clinical data of deceased donation after consent for cadaveric donation to evaluate the reasons of failure of organ procurement. MATERIAL AND METHODS: We retrospectively reviewed the medical records of 112 deceased donors in a single institution between January 1998 and September 2012. There were no organs from cardiac death donors. RESULTS: Of 112 deceased donors, 51 (45.5%) were traumatic brain deaths and 33 (29.5%), nontraumatic brain hemorrhages. The overall mean age was 37.2 (±16.6) years with 35 (30.7%) of female gender. There were 15 (13.3%) donation failures for all organs. Significant factors for failure were histories of cardiopulmonary resuscitation (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05-0.58; P = .005), cardiac arrest (OR, 0.03; 95% CI, 0.006-0.14; P < .001), or acute renal failure (OR, 0.05; 95% CI, 0.006-0.42; P = .006). The nonsignificant factors included the time from intensive care unit to brain death (mean time, 105.1 ± 153.4); diabetes insipidus; hypotension despite inotrophic therapy, hypothermia (<35°C), arrhythmia, infection, metabolic acidosis, disseminated intravascular coagulopathy, and brain death cause. CONCLUSIONS: Failure of deceased donation was associated with cardiac arrest while awaiting organ procurement and the presence of an history of cardiopulmonary resuscitation or presence of acute renal failure.

Reappraisal of the ligament of Henle (ligamentum inguinale internum mediale; Henle, 1871): a topohistological study using Korean foetuses.

Ligament of Henle is one of muscle-associated connective tissues of the rectus abdominis muscle, but it has been confused with the conjoint tendon (a common aponeurosis for insertion of the inferomedial end of the obliquus internus and transversus abdominis muscles). To reconsider the inguinal connective tissue structures, we examined 20 mid-term foetuses (10 males and 10 females) at approximately 14-20 weeks of gestation (crown rump length 100-170 mm). In female horizontal sections, we consistently found the ligament of Henle asa wing-like aponeurosis extending from the lateral margin of the rectus tendon behind the superficial inguinal ring. The ligament was separated from and located behind the conjoint tendon. In all male foetuses, instead of the ligament, the conjoint tendon was evident behind the superficial ring and it winded around the posterior aspect of the spermatic cord. Therefore, although a limited number of specimens were examined, the ligament of Henle was likely to be a female-specific structure. The ligament of Henle, if developed well, may provide an arch-like structure suitable for a name "falx inguinalis" instead of the inferomedial end ofthe conjoint tendon. In addition, a covering fascia of the iliopsoas muscle joined the posterior wall of the inguinal canal in male, but not in female, specimens.

Insulin-degrading enzyme and Alzheimer disease: a genetic association study in the Han Chinese.

BACKGROUND: The gene for insulin-degrading enzyme (IDE) represents a strong positional and biologic candidate for late-onset Alzheimer disease (LOAD) susceptibility. IDE is located on chromosome 10q23.3 close to a region of linkage for LOAD. In addition, many studies have identified a possible role of IDE in the degradation of amyloid beta-protein and the intracellular amyloid precursor protein (APP) domain released by gamma-secretase processing. OBJECTIVE: To examine the association of IDE with AD in the Han Chinese. METHODS: Four IDE polymorphisms (three in 5'-untranslated region and one in intron 21) were analyzed, using a population of 210 patients with LOAD and 200 control subjects well matched for age, sex, and ethnic background. RESULTS: Among the four polymorphisms studied, only the C allele of single-nucleotide polymorphism (SNP) IDE2 showed association with AD (p = 0.005). Stratification of the data by APOE epsilon4 status indicated that the association between IDE2 and AD was confined to APOE epsilon4 carriers only. No association was found between all variants studied and AD within APOE epsilon4-negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, overrepresentation of GCTG haplotype in the AD group was found. It may be a risk haplotype for AD. CONCLUSIONS: These results suggest a possible synergic interaction between IDE and APOE epsilon4 in the risk to develop late-onset sporadic AD. IDE might modify the effect of the APOE epsilon4 risk factor in the Han Chinese population.

Apolipoprotein E -491 promoter polymorphism is an independent risk factor for Alzheimer's disease in the Chinese population.

Polymorphisms at positions -491, -427 and -219 in the promoter region of the Apolipoprotein E APOE gene have been variously reported to confer an increased risk of developing Alzheimer's disease (AD) independent of the effect of epsilon 2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in AD we have compared results in 183 definite or probable AD cases with 133 controls. We assayed markers at sites -491, -427, -219, and +113 in APOE gene and a polymorphic Hha1 site in the nearby APOC1 gene. We found that APOE promoter polymorphisms and APOC1 insertion alleles were significantly associated with AD. However, after stratification for epsilon 4 allele, only the A allele at -491 in APOE remained significantly associated with AD. The effects of the other markers depended almost entirely upon linkage disequilibrium with epsilon 4 allele, and only trends remained when cases and controls were stratified for the presence or absence of epsilon 4 allele. This occurred irrespective of whether markers were examined separately or together as haplotypes. So in the Chinese population only APOE -491 promoter alleles confer significant risk of AD independent of epsilon 4 status.

Selective oxidation of allylic sulfides by hydrogen peroxide with the trirutile-type solid oxide catalyst LiNbMoO(6).

Chemoselective sulfur oxidation of allylic sulfides containing double bonds of high electron density due to multiple alkyl substituents or extended conjugation was developed using the composite metal oxide catalyst, LiNbMoO(6), without any epoxidation of the electron-rich double bond(s). Selective oxidation to either the corresponding sulfoxides or the sulfones was realized by controlling the stoichiometry of the quantitative oxidant, H(2)O(2). This new oxidant system had general applicability for chemoselective oxidation of various allylic, benzylic, or propargylic sulfides containing unsaturated carbon-carbon bonds with different electron properties. Various functional groups including hydroxy, formyl, and ethers of THP or TBDMS are compatible under this mild oxidation reaction condition.

[The experimental study of the delayed replantation after cryopreservation of mature tooth in dogs].

OBJECTIVE: To study the conditions of healing of mature tooth in dogs after long cryopreservation followed by replantation. METHODS: The tooth was extracted after filling the root canals and then preserved for one week and three months respectively by Schwartz's method of cryopreservation of periodontal membrane. The specimens were took out eight weeks after replantation. It was demineralized in a 5% solution of formic acid,and then sectioned perpendicular to the long axes of tooth at a thickness of 5microm. The tooth were sectioned in step-serial sections at 500 microm intervals. The sections were stained with hematoxylin-eosin and followed by evaluation according to Andreasen. RESULTS: The percentage of healing of periodontal membrane (PHPM) of the group of cryopreservation for one week was 64.53%. It was lower than the PHPM of the group of immediate replantation (85%), but the difference demonstrated no significance (P>0.05). The PHPM of the group of cryopreservation for three months was 50.3%. It was lower than the PHPM of the group of immediate replantation significantly (P<0.05). CONCLUSION: The human's periodontal membrane may be cryopreserved longly and heals after the replantation of tooth as the human's tissues of corneas, skin, islets, et al may be done. The alveolar cavities to be newly made affect the healing of periodontal membrane in some degree.

Association between angiotensin-converting enzyme gene and late onset Alzheimer's disease in Han chinese.

There is now overwhelming evidence that the varepsilon4 allele of apolipoprotein (APOE) gene is a major risk factor for late-onset Alzheimer's disease (AD). However, the APOE locus only accounts for a proportion of the overall genetic risk for AD. The angiotensin-converting enzyme (ACE) is widely expressed in the brain and may have a role in AD. Recently an insertion/deletion (I/D) DNA polymorphism at the intron 16 of ACE gene has been found associated with late-onset AD, but the results are not consistent. We have examined ACE gene in a cohort of Han Chinese AD cases and controls. We have found the ACE-I allele was enriched in our cases compared to controls (odds ratio (OR)=2.09, P=0.0043). The phenomenon was restricted to cases presenting with AD after the age of 70 years (P<0.0005), and was independent of APOE genotype. We conclude that ACE genotype is a risk factor for late onset AD.

Achievement of high cell density and high antibody productivity by a controlled-fed perfusion bioreactor process.

Controlled feeding of nutrient supplements to a cell culture to enhance monoclonal antibody productivity has been practiced widely in high-yield, fed-batch processes. In this study, a similar feeding concept has been applied to a perfused culture and evaluated for the effects on bioreactor productivity and product quality. Our experimental results show that, by using such a "controlled-fed perfusion" approach, the volumetric antibody productivity (antibody per liter per day) was significantly increased by nearly twofold over the perfusion process, and surpassed fed-batch and batch processes by almost tenfold. The substantial boost in the overall productivity is attributable primarily to the combined effects of increased cell density as well as reduced product dilution. Both were achieved through careful nutrient supplementation in conjunction with metabolite minimization. As the manufacturing process evolved from roller bottles to the controlled-fed perfusion bioreactor system, the immunoreactivity and the cDNA sequences of the antibody were well preserved. However, the product glycosylation distribution patterns did alter. The controlled-feed perfusion process demonstrated a unique encompassment of the advantages of fed-batch and perfusion methods; that is, high product concentration with high volume throughput. Therefore, it may be very suitable for large-scale production of monoclonal antibodies.

Synthesis and antimalarial activity of artemisinin derivatives containing an amino group.

In search of water-soluble artemisinin derivatives that are more stable than sodium artesunate, over 30 derivatives containing an amino group (compounds 3-5) were synthesized and tested in mice. All products tested (except 5a and 5b) are the beta isomers. These basic compounds combined with organic acids (oxalic acid, maleic acid, etc. ) to yield the corresponding salts. Generally, the maleates have better solubility in water than the corresponding oxalates. The aqueous solutions of these salts can be kept at room temperature for several weeks without any discernible decomposition. Compounds 3f, 3h, and 3r are much more active against P. berghei than artesunic acid by oral administration and therefore were further tested in monkeys. However, their oral efficacies are poorer than that of artesunic acid against P. knowlesi in rhesus monkeys. It is interesting to note that 3f, 3h, and 3r showed much lower efficacies against P. berghei when they were administered subcutaneously than orally.

Schizontocidal effects of oral artesunate on Plasmodium berghei in mice and P knowlesi in monkeys.

AIM: To study the blood schizontocidal effect of oral artesunate on P berghei in mice and P knowlesi in monkey. METHODS: Effects of artesunate and chloroquine were detected with "4-day test" and "28-day test" on P berghei in mice and "7-day test" on P knowlesi in Macaca mudatta. RESULTS: The suppressive efficacy of oral artesunate was inferior to chloroquine on P berghei K173 strain but the time for 50% and 90% reduction and the time of clearance of parasitemia was 10-15 h shorter than that of chloroquine. Its curative effect on RC/K173 line was markedly superior to that of chloroquine. Moreover, artesunate showed no cross-resistance with chloroquine, index of resistance I90 was only 1.4. At 31.6, 10.0, and 3.16 mg.kg-1, artesunate and chloroquine oral administrations cured P knowlesi in all monkeys. Recrudescence did not occur in 105 d. CONCLUSION: The study of effects of oral artesunate in P berghei/mice and P knowlesi/Macaca mulatta model provided a useful index for clinical trial.

Single-chain Fv with manifold N-glycans as bifunctional scaffolds for immunomolecules.

Unlike natural antibodies, single-chain Fv (sFv) proteins normally lack asparagine-linked glycosylation. Many designed immunoconjugates and other therapeutics currently employ the advantageous conjugation chemistry or targeting properties provided by the glycoprotein oligosaccharide domain. sFv proteins with engineered N-glycan designs were evaluated in Pichia pastoris for glycosylation efficiency, expression level, oligosaccharide chain length and composition, and affinity. In contrast to nearly all natural glycoproteins, the engineered attachment of N-glycans conveniently near the polypeptide C-terminus was found to produce the optimal results. Furthermore, the percentage modification and chain length of the attached mannose chains were controllable by the use of tandem and overlapping Asn-X-Thr tripeptide sites. The glycosylated sFv mannose chains could be effectively conjugated to polyethylene glycol and the resulting conjugate displayed a 10-fold increased circulating life in mice. The potential to control polymer:sFv or drug:sFv molar ratios by site-specific conjugation may substantially improve the therapeutic efficacy of these minimal antigen-binding molecules.