Corrigendum to Acta Cryst. (2009), E65, o1824.
The title of the paper by Li, Li, Li, Zhang & Li [Acta Cryst. (2009), E65, o1824] is corrected.
The title compound, C25H19N3O2, crystallizes as discrete molecules which are well ordered through one intramolecular N—H⋯O hydrogen bond. Structural analysis indicates that the molecules exist as the amine–one form.
Female sex workers (FSWs) have become one of the key populations for HIV/STI control in China. Categorization of FSWs can help prioritize HIV/STI intervention efforts. We examined two possible categorizations of FSWs and the relationship with syphilis infection risk in Liuzhou City, China.
From October 2009 to February 2010, a total of 583 FSWs recruited by respondent-driven sampling in a cross-sectional survey were tested for syphilis and interviewed to collect socio-demographic and behavioural information. Respondents were categorized based on transaction price for vaginal sex and type of sex work location. The relationship between the two categorizations and syphilis infection risk was assessed using univariate and multivariate logistic regression analysis.
The prevalence rates of lifetime and active syphilis infection were 8.6% and 4.1% respectively. Lifetime and active syphilis prevalence were higher among FSWs in the lowest price category (52.7% and 25.4% respectively) and those working in streets (69.7% and 39.8% respectively) or through telephone (46.3% and 17.0% respectively). Multivariate analysis showed that lifetime syphilis prevalence was significantly higher among street-(Adjusted odds ratio AOR 38.7, 95% CI 10.7-139.9) and telephone-based FSWs (AOR 10.8, 95% CI 3.3-35.1), and that active syphilis prevalence was significantly higher among street-based FSWs (AOR 15.2, 95% CI 3.7-62.1) after adjusting for demographic and behavioural factors.
Categorization based on sex work location was more closely related to the risk of syphilis infection than the price classification. Street- and telephone-based FSWs had significantly higher risk of syphilis infection. Focused interventions among these particular high-risk FSWs subgroups are warranted.
female sex workers; syphilis; respondent-driven sampling; China
Polymorphisms in the TCRA and P2RY11, two immune related genes, are associated with narcolepsy in Caucasians and Asians. In contrast, CPT1B/CHKB polymorphisms have only been shown to be associated with narcolepsy in Japanese, with replication in a small group of Koreans. Our aim was to study whether these polymorphisms are associated with narcolepsy and its clinical characteristics in Chinese patients with narcolepsy.
We collected clinical data on 510 Chinese patients presenting with narcolepsy/hypocretin deficiency. Patients were included either when hypocretin deficiency was documented (CSF hypocretin-1 ≤110 pg/ml, n=91) or on the basis of the presence of clear cataplexy and HLA-DQB1*0602 positivity (n=419). Genetic data was compared to typing obtained in 452 controls matched for geographic origin within China. Clinical evaluations included demographics, the Stanford Sleep Inventory (presence and age of onset of each symptom), and Multiple Sleep Latency Test (MSLT) data.
Chinese narcolepsy was strongly and dose dependently associated with TCRA (rs1154155C) and P2RY11 (rs2305795A) but not CPT1B/CHKB (rs5770917C) polymorphisms. CPT1B/CHKB polymorphisms were not associated with any specific clinical characteristics. TCRA rs1154155A homozygotes (58 subjects) had a later disease onset, but this was not significant when corrected for multiple comparisons, thus replication is needed. CPT1B/CHKB or P2RY11 polymorphisms were not associated with any specific clinical characteristics.
The study extends on the observation of a strong multiethnic association of polymorphisms in the TCRA and P2RY11 with narcolepsy, but does not confirm the association of CPT1B/CHKB (rs5770917) in the Chinese population.
narcolepsy; TCR alpha; P2RY11; CPT1B/CHKB; hypocretin; orexin; MSLT; HLADQB1*0602
Video-assisted thoracoscopic surgery (VATS) has been developed for surgical treatment of thoracic spinal tuberculosis to overcome the problems associated with a formal thoracotomy. VATS, however, is technically demanding with a difficult learning curve.
Materials and methods
We conducted a retrospective long-term follow-up study of anterior debridement and reconstruction via a thoracoscopy-assisted mini-open approach for the surgical treatment of thoracic spinal tuberculosis. There were 50 patients collected with mean age 38.3 years with thoracic spinal tuberculosis.
The average operative time was 210 min (range 170–300 min), the average blood loss during operation was 550 ml (range 300–1,000 ml), and the mean chest drainage duration was 3.5 days (3–5 days). Complications occurred in 17 patients (34%). The mean follow-up was 6.5 years. There was statistically difference in VAS 3 months after surgery compared to preoperatively (P < 0.001), as well as final follow-up compared to 3 months post-op (P < 0.001). In patients with minor pulmonary impairment as measured by pulmonary function testing, 15 improved to normal and 5 had no change. In patients with moderate pulmonary impairment, 6 improved to normal and 2 improved to minor impairment at final follow-up. Neurological improvement of one to three grades had occurred in 26 patients by final follow-up. There was statistically difference in kyphotic angle 3 months after surgery compared to preoperatively (P < 0.05), as well as final follow-up compared to 3 months post-op (P < 0.001). The average correction rate of kyphotic angle was 38.7% and the loss of correction rate was 1.3% at final follow-up. No recurrent tuberculosis was found.
Thoracoscopy-assisted mini-open approach can provide a simple, safe, and practical treatment option with minimal invasiveness in cases of thoracic spinal tuberculosis. Successful clinical and radiographic outcomes can be achieved via anterior debridement and reconstruction at long-term follow-up.
Spinal thoracic vertebrae; Thoracoscopy; Tuberculosis
Subcutaneous (SC) delivery is a common route of administration for therapeutic monoclonal antibodies (mAbs) with pharmacokinetic (PK)/pharmacodynamic (PD) properties requiring long-term or frequent drug administration. An ideal in vivo preclinical model for predicting human PK following SC administration may be one in which the skin and overall physiological characteristics are similar to that of humans. In this study, the PK properties of a series of therapeutic mAbs following intravenous (IV) and SC administration in Göttingen minipigs were compared with data obtained previously from humans. The present studies demonstrated: (1) minipig is predictive of human linear clearance; (2) the SC bioavailabilities in minipigs are weakly correlated with those in human; (3) minipig mAb SC absorption rates are generally higher than those in human and (4) the SC bioavailability appears to correlate with systemic clearance in minipigs. Given the important role of the neonatal Fc-receptor (FcRn) in the PK of mAbs, the in vitro binding affinities of these IgGs against porcine, human and cynomolgus monkey FcRn were tested. The result showed comparable FcRn binding affinities across species. Further, mAbs with higher isoelectric point tended to have faster systemic clearance and lower SC bioavailability in both minipig and human. Taken together, these data lend increased support for the use of the minipig as an alternative predictive model for human IV and SC PK of mAbs.
mAb IgG; neonatal Fc receptor (FcRn); pharmacokinetics; subcutaneous bioavailability; animal model; minipig
Large-scale analysis of the transmission, mutation characteristics and the relationship between the reading frame and phenotype of the DMD gene has previously been performed in several countries, however, analogous studies have yet to be performed in Chinese populations.
Clinical data from 1053 Chinese patients with DMD/BMD were collected, and the DMD gene was tested by MLPA in all patients and 400 proband mothers. In 20 patients with negative MLPA, sequencing was also performed.
We found that 27.50% of cases had a family medical history of DMD/BMD, and large rearrangements were identified in 70.56% of the probands, of which 59.35% and 11.21% were deletions or duplications, respectively. The carrier status of the mothers in the study was determined to be 50.75%, and it was established that the DMD mutation was inherited from the mother in 51.72% of the probands. Exons 45–54 and 3–22 were the most frequently deleted regions, and exons 3–11 and 21–37 were the most prevalently duplicated regions of the gene. Breakpoints mainly occurred in introns 43–55 for deletion mutations and in introns 2 and 7 for duplication mutations. No breakpoints were found at the 5′ or 3′ end of introns 31, 35, 36, 40, 65, 68, and 74–78 in any of the deletion or duplication mutations. The reading frame rule held true for 86.4% of the DMD patients and 74.55% of the BMD patients.
It is essential to increase physicians’ understanding of DMD/BMD, to promote scientific information, and to increase awareness in regards to genetic counseling and prenatal diagnosis in pedigrees with a family history of the disease, particularly in families with small DMD lesions in China. In addition, such a large-scale analysis will prove to be instructive for leading translational studies between basic science and clinical medicine.
Duchenne muscular dystrophy; Becker muscular dystrophy; DMD gene; MLPA
Coupled with evaporative light scattering detection, a high-speed counter-current chromatography (HSCCC) method was developed for preparative isolation and purification of three glycine-conjugated cholic acids, glycochenodeoxycholic acid (GCDCA), glycohyodeoxycholic acid (GHDCA) and glycohyocholic acid (GHCA) from Pulvis Fellis Suis (Pig gallbladder bile) for the first time. The separation was performed with a two-phase solvent system consisted of chloroform-methanol-water-acetic acid (65:30:10:1.5, v/v/v/v) by eluting the lower phase in the head-to-tail elution mode. The revolution speed of the separation column, flow rate of the mobile phase and separation temperature were 800 rpm, 2 ml/min and 25 °C, respectively. In a single operation, 33 mg of GCDCA, 38 mg of GHDCA and 23 mg of GHCA were obtained from 200 mg of crude extract with the purity of 95.65%, 96.72% and 96.63%, respectively, in one step separation. The HSCCC fractions were analyzed by high-performance liquid chromatography (HPLC) and the structures of the three glycine-conjugated cholic acids were identified by ESI-MS, 1H NMR and 13C NMR.
High-speed countercurrent chromatography; Separation and purification; Two-phase solvent system; Pulvis Fellis Suis; Glycine-conjugated cholic acids
The mismatch of the elastic modulus between implants and bone tissue can lead to stress shielding, bone resorption and poor osseointegration. Compared with normal bone tissue, this problem is much more serious in osteoporosis. The purpose of this study was designed to find out whether the novel Ti-24Nb-4Zr-7.9Sn (TNZS) implant with low elastic modulus and high strength was suitable for biomedical material, especially in osteoporosis.
In vitro study, the viability and Alkaline phosphatase (ALP) activity of osteoblasts on the TNZS and Ti-6V-4V (TAV) were observed. In vivo study, 30 adult female New Zealand rabbits were selected and divided randomly into two groups: sham-operation (SHAM, n = 6) and ovariectomised in combination with methylprednisolone treatment (OVX+MP, n = 24). Two implants were then placed in the tibia of each OVX + MP group rabbit, one in each side (left: TAV; right: TNZS). The OVX + MP group rabbits were sacrificed at 4 and 12 weeks after the implantation. The osteoporotic bone responses to the TNZS and TAV implants were evaluated by pull-out test, Micro-CT analyses and histological observation.
Compared with the TAV group, the TNZS group showed a significant increase (P<0.05) in cell viability and ALP activity, new bone formation and pull-out force.
The novel TNZS implants show good biological performance both in vitro and in vivo, which suggests that the alloys are suitable for biomedical applications, especially in osteoporosis.
Antioxidant vitamin (vitamin E, beta-carotene, and vitamin C) are widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamin on cardiovascular events remains unclear.
Methodology and Principal Findings
We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant literature. Eligible studies were randomized controlled trials that reported on the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo. Outcomes analyzed were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any possible adverse events. We used the I2 statistic to measure heterogeneity between trials and calculated risk estimates for cardiovascular outcomes with random-effect meta-analysis. Independent extraction was performed by two reviewers and consensus was reached. Of 293 identified studies, we included 15 trials reporting data on 188209 participants. These studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation as compared to placebo had no effect on major cardiovascular events (RR, 1.00; 95%CI, 0.96–1.03), myocardial infarction (RR, 0.98; 95%CI, 0.92–1.04), stroke (RR, 0.99; 95%CI, 0.93–1.05), total death (RR, 1.03; 95%CI, 0.98–1.07), cardiac death (RR, 1.02; 95%CI, 0.97–1.07), revascularization (RR, 1.00; 95%CI, 0.95–1.05), total CHD (RR, 0.96; 95%CI, 0.87–1.05), angina (RR, 0.98; 95%CI, 0.90–1.07), and congestive heart failure (RR, 1.07; 95%CI, 0.96 to 1.19).
Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.
To explore the key regulatory genes associated with lung cancer in order to reduce its occurrence and progress through silencing these key genes.
To identify the key regulatory genes involved in lung cancer, we performed a combination of gene array and bioinformatics analyses to compare gene transcription profiles in 3 monoclonal cell strains with high, medium or low metastatic abilities, which were separated from the SPC-A-1sci and SPC-A-1 cell lines by limiting dilution monoclone assay. We then analyzed those genes’ biological activities by knocking down their expression in SPC-A-1sci cells using siRNA and lenti-viral shRNA vectors, followed by determinations of the invasion and migration capabilities of the resulting cell lines in vitro as well as their potential for inducing occurrence and metastasis of lung cancer in vivo. To examine the clinical relevance of these findings, we analyzed the expression levels of the identified genes in human lung cancer tissues (n = 135) and matched adjacent normal tissues by immunohistochemical (IHC) staining.
Three monoclonal cell strains characterized with high, medium or low metastatic abilities were successfully selected. Gene array and bioinformatics analyses implied that osteopontin, LAMB3 and ITGB1 were key genes involved in lung cancer. Knockdown of these genes suppressed human lung cancer cell invasion and metastasis in vitro and in vivo. Clinical sample analyses indicated that osteopontin, LAMB3 and ITGB1 protein expression levels were higher in lung cancer patients, compared to non-cancerous adjacent tissues, and correlated with lymphatic metastasis.
We confirmed that osteopontin, LAMB3 and ITGB1 played important roles in the occurrence and metastasis of lung cancer, thus provided important clues to understanding the molecular mechanism of metastasis and contributing to the therapeutic treatment of lung cancer.
Our previous work indicated that TWEAK is associated with various types of cutaneous vasculitis (CV). Herein, we investigate the effects of TWEAK on vascular injury and adhesion molecule expression in CV mice. We showed that TWEAK priming in mice induced a local CV. Furthermore, TWEAK priming also increased the extravasation of FITC-BSA, myeloperoxidase activity and the expression of E-selectin and ICAM-1. Conversely, TWEAK blockade ameliorated the LPS-induced vascular damage, leukocyte infiltrates and adhesion molecules expression in LPS-induced CV. In addition, TWEAK treatment of HDMECs up-regulated E-selectin and ICAM-1 expression at both mRNA and protein levels. TWEAK also enhanced the adhesion of PMNs to HDMECs. Finally, western blot data revealed that TWEAK can induce phosphorylation of p38, JNK and ERK in HDMECs. These data suggest that TWEAK acted as an inducer of E-selectin and ICAM-1 expression in CV mice and HDMECs, may contribute to the development of CV.
AIM: To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).
METHODS: Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN). Enteral nutrition was started within 48 h after admission in EEN group, whereas from the 8th day in DEN group. All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1, 3, 7 and 14 after admission. The clinical outcome variables were also recorded.
RESULTS: Sixty SAP patients were enrolled to this study. The CD4+ T-lymphocyte percentage, CD4+/CD8+ ratio, and the CRP levels in EEN group became significantly lower than in DEN group from the 7th day after admission. In contrast, the immunoglobulin G (IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7th day after admission. No difference of CD8+ T-lymphocyte percentage, IgM and IgA levels was found between the two groups. The incidences of multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group. However, there was no difference of hospital mortality between the two groups.
CONCLUSION: EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression. EEN can improve the clinical outcome, but not decrease the hospital mortality of SAP patients.
Early enteral nutrition; Immune; Severe acute pancreatitis
Environmental pollution and energy crisis restrict the development of China, and the utilization of renewable technology is an effective strategy to alleviate the damage. Biogas engineering has rapidly developed attributes to solve environmental problems and create a renewable energy product biogas. In this paper, two different biogas plants' materials were analyzed by emergy method. One of them is a biogas project whose degraded material is feces (BPF system), and the other is the one whose degraded material is corn straw (BPC system). As a result, the ecological-economic values of BPF and BPC are $28,300/yr and $8,100/yr, respectively. Considering currency, environment, and human inputs, both of the biogas projects have the ability of disposing waste and potential for development. The proportion of biogas output is much more than fertilizer output; so, fertilizer utilization should be emphasized in the future. In comparison, BPF is better than BPC in the aspects of ecological-economic benefits, environmental benefits, and sustainability. The reason is the difficulty of corn straw seasonal collection and degradation. Thus it is proposed that BPC should be combined with the other raw materials.
In the title compound, C10H6F2N4, the Car—N bonds are slightly shortened with respect to a standard aniline C—N bond [1.3580 (16) and 1.3618 (16) versus 1.39 Å], thus indicating some π–π conjgation with the electron-acceptor CN groups. The molecule, except for two C atom of the ethylene bridge, is nearly planar, the largest deviation of the other non-H atoms from the mean plane being 0.309 (2) Å. The N—C—C—N torsion angle involving the ethylene bridge is 50.23 (18)°. In the crystal, molecules are connected by pairs of N—H⋯N hydrogen bonds into chains along [21-1].
Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.
Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93–1.26; additive model: OR = 1.33, 95%CI = 0.81–2.17; dominant model: OR = 1.00, 95%CI = 0.86–1.15; recessive model: OR = 1.06, 95%CI = 0.77–1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88–1.41; additive model: OR = 1.36, 95%CI = 0.60–3.09; dominant model: OR = 1.25, 95%CI = 0.74–2.11; recessive model: OR = 2.17, 95%CI = 1.11–4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.
This meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.
Postmenopausal osteoporosis is a complicated and multi-factorial disease. To study the metabolic profiles and pathways activated in osteoporosis, Eight rats were oophorectomized (OVX group) to represent postmenopausal osteoporosis and the other eight rats were sham operated (Sham group) to be the control. The biochemical changes were assessed with metabolomics using a gas chromatography/time-of-flight mass spectrometry. Metabolomic profile using serial blood samples obtained prior to and at different time intervals after OVX were analyzed by principal component analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA). The conventional indicators (bone mineral density, serum Bone alkaline phosphatase (B-ALP) and N-telopeptide of type I collagen (NTx) of osteoporosis in rats were also determined simultaneously. In OVX group, the metabolomics method could describe the endogenous changes of the disease more sensitively and systematically than the conventional criteria during the progression of osteoporosis. Significant metabolomic difference was also observed between the OVX and Sham groups. The metabolomic analyses of rat plasma showed that levels of arachidonic acid, octadecadienoic acid, branched-chain amino acids (valine, leucine and isoleucine), homocysteine, hydroxyproline and ketone bodies (3-Hydroxybutyric Acid) significantly elevated, while levels of docosahexaenoic acid, dodecanoic acid and lysine significantly decreased in OVX group compared with those in the homeochronous Sham group. Considering such metabolites are closely related to the pathology of the postmenopausal osteoporosis, the results suggest that potential biomarkers for the early diagnosis or the pathogenesis of osteoporosis might be identified via metabolomic study.
Phosphoribosylglycinamide formyltransferase (PurN) from Streptococcus mutans was expressed in E. coli, purified and studied crystallographically.
Phosphoribosylglycinamide formyltransferase (PurN) from Streptococcus mutans was recombinantly expressed in Escherichia coli. An effective purification protocol was established. The purified protein, which had a purity of >95%, was identified by SDS–PAGE and MALDI–TOF MS. The protein was crystallized using the vapour-diffusion method in hanging-drop mode with PEG 3350 as the primary precipitant. X-ray diffraction data were collected to 2.1 Å resolution. Preliminary X-ray analysis indicated that the crystal belonged to space group P212121, with unit-cell parameters a = 52.25, b = 63.29, c = 131.81 Å.
Streptococcus mutans; PurN; phosphoribosylglycinamide formyltransferases
Employing molecular dynamics (MD) simulations, the pathway and mechanism of substrate unbinding from the inward-facing state of the Na+–coupled galactose transporter, vSGLT, have been investigated. During a 200–ns equilibrium simulation, repeated spontaneous unbinding events of the substrate from its binding site have been observed. In contrast to the previously proposed gating role of a tyrosine residue (Y263), the unbinding mechanism captured in the present equilibrium simulation does not rely on the displacement and/or rotation of this side chain. Rather, the unbinding involves an initial lateral displacement of the substrate out of the binding site which allows the substrate to completely emerge from the region covered by the side chain of Y263 without any noticeable conformational changes of the latter. Starting with the snapshots taken from this equilibrium simulation with the substrate outside the binding site, steered MD (SMD) simulations were then used to probe the translocation of the substrate along the remaining of the release pathway within the protein’s lumen and to characterize the nature of protein-substrate interactions involved in the process. Combining the results of the equilibrium and SMD simulations, we provide a description of the full translocation pathway for the substrate release from the binding site into the cytoplasm. Residues E68, N142, T431, and N267 facilitate the initial substrate’s displacement out of the binding site, while the translocation of the substrate along the remainder of the exit pathway formed between TM6 and TM8 is facilitated by H–bond interactions between the substrate and a series of conserved, polar residues (Y138, N267, R273, S365, S368, N371, S372, and T375). The observed molecular events indicate that no gating is required for the release of the substrate from the crystallographically captured structure of the inward-facing state of SGLT, suggesting that this conformation might represent an open, rather than occluded, state of the transporter.
The purpose of this study was to validate the efficacy and safety of single-stage posterior instrumentation and anterior debridement for treatment of active spinal tuberculosis with kyphotic deformity.
From January 2005 to January 2009, 13 males and 24 females were enrolled in this retrospective study. All patients underwent single-stage posterior instrumentation and fusion, combined with anterior radical debridement and bone grafting. Clinical and radiographic results were analysed.
Patients were followed-up for 33.6 months on average. Bony fusion was achieved at six- to nine-month follow-up in all patients. The respective average kyphosis at the pre-operative and the last follow-up was 53.5° and 12.6°, with a mean correction of 40.9° (78.5%). Neurologic recovery averaged 1.5 grades on the Frankel scale. No recurrence of tuberculosis or instrumentation failure occurred.
Single-stage posterior instrumentation and anterior debridement with fusion was demonstrated to be a safe and effective method to achieve spinal decompression and kyphosis correction in patients with Pott’s disease.
Hepatic enzymes, CYP2B6 and UGT2B7 play a major role in the metabolism of the widely used antiretroviral drugs efavirenz, nevirapine and zidovudine. In the present study, we provide a view of UGT2B7 haplotype structure, and quantify the genetic diversity and differentiation at both CYP2B6 and UGT2B7 genes on a worldwide scale.
Materials & methods
We genotyped one intronic and three promoter SNPs, and together with three nonsynonymous SNPs, inferred UGT2B7 alleles in north American (n = 326), west African (n = 133) and Papua New Guinean (n = 142) populations. We also included genotype data for five CYP2B6 and six UGT2B7 SNPs from an additional 12 worldwide populations (n = 629) analyzed in the 1000 Genomes Project.
We observed significant differences in certain SNP and allele frequencies of CYP2B6 and UGT2B7 among worldwide populations. Diversity values were higher for UGT2B7 than for CYP2B6, although there was more diversity between populations for CYP2B6. For both genes, most of the genetic variation was observed among individuals within populations, with the Papua New Guinean population showing the highest pairwise differentiation values for CYP2B6, and the Asian and European populations showing higher pairwise differentiation values for UGT2B7.
These new genetic distinctions provide additional insights for investigating differences in antiretroviral pharmacokinetics and therapy outcomes among ethnically and geographically diverse populations.
1000 Genomes Project; CYP2B6; efavirenz; HIV/AIDS; nevirapine; Papua New Guinea; UGT2B7; zidovudine
Inflammasomes are multi-protein complexes that trigger the activation of caspase-1 and the maturation of interleukin-1β (IL-1β), yet the regulation of these complexes remains poorly characterized. Here we show that nitric oxide (NO) inhibited the NLRP3-mediated ASC pyroptosome formation, caspase-1 activation and IL-1β secretion in myeloid cells from both mice and humans. Meanwhile, endogenous NO derived from iNOS (inducible form of NO synthase) also negatively regulated NLRP3 inflammasome activation. Depletion of iNOS resulted in increased accumulation of dysfunctional mitochondria in response to LPS and ATP, which was responsible for the increased IL-1β production and caspase-1 activation. iNOS deficiency or pharmacological inhibition of NO production enhanced NLRP3-dependent cytokine production in vivo, thus increasing mortality from LPS-induced sepsis in mice, which was prevented by NLRP3 deficiency. Our results thus identify NO as a critical negative regulator of the NLRP3 inflammasome via the stabilization of mitochondria. This study has important implications for the design of new strategies to control NLRP3-related diseases.
nitric oxide; NLRP3 inflammasome; septic shock
Human enterovirus 85 (HEV85), whose prototype strain (Strain BAN00-10353/BAN/2000) was isolated in Bangladesh in 2000, is a recently identified serotype within the human enterovirus B (HEV-B) species. At present, only one nucleotide sequence of HEV85 (the complete genome sequence of the prototype strain) is available in the GenBank database.
In this study, we report the genetic characteristics of 33 HEV85 isolates that circulated in the Xinjiang Uighur autonomous region of China in 2011. Sequence analysis revealed that all these Chinese HEV85 isolates belong to 2 transmission chains, and intertypic recombination was found with the new unknown serotype HEV-B donor sequences. Two HEV85 isolates recovered from a patient presenting acute flaccid paralysis and one of his contacts were temperature-insensitive strains, and some nucleotide substitutions in the non-coding regions and in the 2C or 3D coding regions may have affected the temperature sensitivity of HEV85 strains.
The Chinese HEV85 recombinant described in this study trapped a new unknown serotype HEV-B donor sequence, indicating that new unknown HEV-B serotypes exist or circulate in Xinjiang of China. Our study also indicated that HEV85 is a prevalent and common enterovirus serotype in Xinjiang.
The superconducting magnet generates a field and field gradient product that can levitate diamagnetic materials. In this study a specially designed superconducting magnet with a large gradient high magnetic field (LG-HMF), which can provide three apparent gravity levels (μ-g, 1-g, and 2-g), was used to simulate a space-like gravity environment. The effects of LG-HMF on the ultrastructure and function of osteoblast-like cells (MG-63 and MC3T3-E1) and the underlying mechanism were investigated by transmission electromicroscopy (TEM), MTT, and cell western (ICW) assays. Under LG-HMF significant morphologic changes in osteoblast-like cells occurred, including expansion of endoplasmic reticulum and mitochondria, an increased number of lysosomes, distorted microvilli, and aggregates of actin filaments. Compared to controls, cell viability and alkaline phosphatase (ALP) secretion were significantly increased, and collagen I (col I), fibronectin (FN), vinculin, integrin α3, αv, and β1 expression were changed under LG-HMF conditions. In conclusion, LG-HMF affects osteoblast ultrastructure, cell viability, and ALP secretion, and the changes caused by LG-HMF may be related to disrupting col I or FN/αβ1 integrin.
AIM: To explore the optimal steroid therapeutic strategy for autoimmune pancreatitis (AIP).
METHODS: This study was conducted retrospectively in two large institutions in China. Patients with clinically, radiologically and biochemically diagnosed AIP were enrolled. The performed radiological investigations and biochemical tests, the regimen of the given steroid treatment, remission and relapse whether with and without steroid therapy were analyzed.
RESULTS: Twenty-eight patients with AIP received steroid treatment, while 40 patients were treated surgically by pancreatoduodenectomy, distal pancreatectomy and choledochojejunostomy, radiofrequency ablation for the enlarged pancreatic head, percutaneous transhepatic biliary drainage and endoscopic biliary drainage. The starting oral prednisolone dose was 30 mg/d in 18 (64.3%) patients and 40 mg/d in 10 (35.7%) patients administered for 3 wk. The remission rate of AIP patients with steroid treatment (96.4%) was significantly higher than in those without steroid treatment (75%). Maintenance therapy (oral prednisolone dose 5 mg/d) was performed after remission for at least 6-12 mo to complete the treatment course. Similarly, the relapse rate was significantly lower in AIP patients with steroid treatment (28.6%) than in those without steroid treatment (42.5%). Steroid re-treatment was effective in all relapsed patients with or without steroid therapy.
CONCLUSION: Steroid therapy should be considered in all patients with active inflammatory phase of AIP. However, the optimal regimen still should be trailed in larger numbers of patients with AIP.
Autoimmune pancreatitis; Chinese population; Steroid therapy; Remission; Relapse