Anatomical modifications of the mid palatal suture during ageing: a radiographic study

In transverse maxillary deficiencies it is important to know if the mid palatal suture is obliterated or not, to decide which treatment to perform (orthodontic expansion or surgical disjunction of the suture). The maxillary sutures obliteration has been used in forensic medicine in estimating adult age at death. In order to determine the proportion of mid palatal suture obliteration in the elderly in man, we examined 100 consecutive CT scans of the palate. This study has shown that the age of mid palatal total obliteration was variable. The obliteration begins in the anterior and in the superior part of the palate. The inferior part of the junction between the palatal processes is the last part of the suture to be obliterated.     

A light microscopic investigation of the human midpalatal suture

Biopsy samples of the human midpalatal suture, obtained from patients (age range: 10 and 30 yrs), were embedded in resin, cut with ultramicrotome and analyzed at light microscopy. The sutural connective tissue was made up of fibroblasts, collagen fibers, capillaries and nerve fibers. The sutural bone was made up of lamellar and bundle bone which alternated along both sides of the sutural connective tissue. No osteoblasts or osteoclasts were found, no signs of synostosis were ever detected. Our findings suggest that the lamellar bone replaces bundle bone when the suture is no longer involved in the growth of the palatal bones. The absence of bone remodelling shows that the sutures, at the time of sampling, were in a resting stage. Tissue architecture and cell types, so similar in samples from patients of such different ages, lead us to suppose that the sutures under examination are subject in time to very slow bone turnover.     

Association of cytotoxic T‐lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high‐incidence region from northern China

The most important anti‐tumour immune response is mediated by T lymphocytes. Cytotoxic T lymphocyte‐associated protein 4 (CTLA4) plays a critical role in the immune surveillance against tumours as an inhibitory immune checkpoint molecule of T‐cell activation. This study was designed to explore the association of CTLA4 polymorphisms with the susceptibility to oesophageal squamous cell carcinoma (ESCC) and prognosis of patients with ESCC in a high‐incidence population from northern China. CTLA4 rs5742909 C/T and rs231775 G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase chain reaction–ligase detection reaction (PCR‐LDR) method in 577 ESCC patients and 580 controls. Upper gastrointestinal cancer family history increased the risk of ESCC (the sex‐, age‐ and smoking status‐adjusted OR = 1.383, 95%CI = 1.094–1.749). The genotype frequencies of these two SNPs in the patients with ESCC were similar to that in the controls. Survival analyses were conducted in 204 patients with ESCC with five‐year survival information. The mean survival time of ESCC patients with rs231775 SNP A/A genotype in age over 60 years group was 23.2 months, significantly shorter than that of those with G/G genotype (47.3 months). The A/A genotype was associated with increased death risk of patients with ESCC older than 60 years (adjusted HR = 4.544, 95%CI = 1.913–10.790). CTLA4 rs231775 SNP might be used as genetic marker of worse prognosis for patients with ESCC over 60 years in a high‐incidence population from northern China.     

DCE‐ and DW‐MRI as early imaging biomarkers of treatment response in a preclinical model of triple negative breast cancer

This work evaluates quantitative dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and diffusion‐weighted MRI (DW‐MRI) parameters as early biomarkers of response in a preclinical model of triple negative breast cancer (TNBC). The standard Tofts' model of DCE‐MRI returns estimates of the volume transfer constant (K^trans) and the extravascular extracellular volume fraction (v_e). DW‐MRI returns estimates of the apparent diffusion coefficient (ADC). Mice (n = 38) were injected subcutaneously with MDA‐MB‐231. Tumors were grown to approximately 275 mm³ and sorted into the following groups: saline controls, low‐dose Abraxane (15 mg/kg) and high‐dose Abraxane (25 mg/kg). Animals were imaged at days zero, one and three. On day three, tumors were extracted for immunohistochemistry. The positive percentage change in ADC on day one was significantly higher in both treatment groups relative to the control group (p < 0.05). In addition, the positive percentage change in K^trans was significantly higher than controls (p < 0.05) on day one for the high‐dose group and on days one and three for the low‐dose group. The percentage change in tumor volume was significantly different between the high‐dose and control groups on day three (p = 0.006). Histology confirmed differences at day three through reduced numbers of proliferating cells (Ki67 staining) in the high‐dose group (p = 0.03) and low‐dose group (p = 0.052) compared with the control group. Co‐immunofluorescent staining of vascular maturity [using von Willebrand Factor (vWF) and α‐smooth muscle actin (α‐SMA)] indicated significantly higher vascular maturation in the low‐dose group compared with the controls on day three (p = 0.03), and trending towards significance in the high‐dose group compared with controls on day three (p = 0.052). These results from quantitative imaging with histological validation indicate that ADC and K^trans have the potential to serve as early biomarkers of treatment response in murine studies of TNBC.     

Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis in Han Chinese from Hubei Province

We determined the high‐resolution allele and haplotype frequencies at the human leucocyte antigen (HLA)A, B and DRB1 loci in the Han population of Hubei province, the TB endemic area of Central China, with pulmonary tuberculosis (PTB), and established the relationship between HLA‐A, B and DRB1 alleles as well as haplotypes and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis (MDR/RR‐TB). Blood samples were drawn from 174 patients with MDR/RR‐TB and 838 patients with drug‐susceptible PTB in ethnic Han population from Hubei province (central China). Four‐digit allele genotyping of HLA‐ A, B and DRB1 loci was performed using polymerase chain reaction with sequence‐specific oligonucleotide probes (PCR‐ SSOP). The allele and haplotype frequencies of HLA‐A, B and DRB1 were determined and compared between patients with MDR/RR‐TB and patients with drug‐susceptible PTB. Statistical analysis of the generated data indicated no departure from expectation of Hardy–Weinberg equilibrium (HWE) at all loci of the control group. Multivariate analysis identified allele DRB1*08:01 (p < .0001; OR = 174.5, 95% CI 15.3–1987.2) as independent predictor of MDR/RR‐TB, except for old age (p < .0001; OR = 10. 9, 95% CI 7.6–15.8), previous treatment history (p < .0001; OR = 11.0, 95% CI 7.2–16.7) and poor compliance to treatment (p < .0001; OR = 12.9, 95% CI 8.4–20.0). While in the subgroup of new TB cases, DRB1*08:01 (p < .0001; OR = 80.3, 95% CI 7.0–917.1) and older age (p < .0001; OR = 3.9, 95% CI 2.4–6.4) were independent susceptibility factors for primary MDR/RR‐TB. Our results suggest that a combination of clinical and host genetic information about tuberculosis patients may contribute to prediction and early detection of MDR/RR‐TB.     

Cranial growth in isolated sagittal craniosynostosis compared with normal growth in the first 6 months of age

Sagittal craniosynostosis (SCS), the most common type of premature perinatal cranial suture fusion, results in abnormal head shape that requires extensive surgery to correct. It is important to find objective and repeatable measures of severity and surgical outcome to examine the effect of timing and technique on different SCS surgeries. The purpose of this study was to develop statistical models of infant (0–6 months old) skull growth in both normative and SCS subjects (prior to surgery). Our goal was to apply these models to the assessment of differences between these two groups in overall post-natal growth patterns and sutural growth rates as a first step to develop methods for predictive models of surgical outcome. We identified 81 patients with isolated, non-syndromic SCS from Seattle Children's Craniofacial Center patient database who had a preoperative CT exam before the age of 6 months. As a control group, we identified 117 CT exams without any craniofacial abnormalities or bone fractures in the same age group. We first created population-level templates from the CT images of the SCS and normal groups. All CT images from both groups, as well as the canonical templates of both cohorts, were annotated with anatomical landmarks, which were used in a growth model that predicted the locations of these landmarks at a given age based on each population. Using the template images and the landmark positions predicted by the growth models, we created 3D meshes for each week of age up to 6 months for both populations. To analyze the growth patterns at the suture sites, we annotated both templates with additional semi-landmarks equally spaced along the metopic, coronal, sagittal and lambdoidal cranial sutures. By transferring these semi-landmarks to meshes produced from the growth model, we measured the displacement of the bone borders and suture closure rates. We found that the growth at the metopic and coronal sutures were more rapid in the SCS cohort than in the normal cohort. The antero-posterior displacement of the semi-landmarks also indicated a more rapid growth in the sagittal plane in the SCS model than in the normal model. Statistical templates and geometric morphometrics are promising tools for understanding the growth patterns in normal and synostotic populations and to produce objective and reproducible measurements of severity and outcome. Our study is the first of its kind to quantify the bone growth for the first 6 months of life in both normal and sagittal synostosis patients.     

Objectively measured night‐to‐night sleep variations are associated with body composition in very elderly women

This cross‐sectional study examined the association between objectively measured sleep patterns and body composition in very elderly community‐dwelling women. Participants included 191 community‐dwelling adults aged ≥ 80 years (mean age: 83.4 ± 2.6 years; age range: 80–92 years). Sleep and physical activity were monitored via accelerometer (ActiGraph GT3X+) during at least five consecutive 24‐h periods. Night‐to‐night sleep pattern variability across all nights of recording was assessed using standard deviations (SDs). Body composition was assessed using dual‐energy X‐ray absorptiometry. Simple and multivariable linear regression analyses were performed. The mean number of nights with usable actigraphy data was 7.3 ± 1.3. On average, participants went to bed at 22:57 hours (SD: 1.11 h) and rose from bed at 6:27 hours (SD: 1.01 h). Night‐to‐night bedtime, sleep duration and sleep timing mid‐point variations correlated slightly with the percentage body fat and percentage lean mass (P < 0.05). Multiple linear regression analysis revealed significant associations of night‐to‐night bedtime variations and inconsistent sleep–wake patterns with all body composition indices after adjusting for potential confounding factors, including mean nightly sleep duration, self‐reported nap duration and daily physical activity. After further adjusting for night‐to‐night wake time, sleep timing mid‐point and sleep duration variations, greater bedtime variability remained associated significantly with all body composition indices except lean/fat mass ratio. Inconsistent sleep–wake patterns were associated independently with an increased fat mass and decreased lean mass among very elderly women. These findings suggest that in most elderly individuals, sleep patterns might be an important modifiable factor associated with obesity and sarcopenia development.     

Size and shape of human cranial sutures–A new scoring method

A method for the differentiation of sutural patterns of the human cranial vault is introduced. Three criteria of differentiation are considered, one for size and two for shape: (1) maximal shape extension; (2) basic configuration; (3) secondary protrusion. The method is illustrated here for the coronal and lambdoid sutures of 70 recent Italian skulls (35 adult males and 35 adult females). Differences between coronal and lambdoid sutural size and shape can be detected analytically; for example, the coronal suture commonly shows lesser degrees of shape extension, a simpler basic configuration, and an absence of secondary protrusion. Heterogeneity within each suture, as well as a relationship among corresponding sections and between the three criteria adopted, have been also observed; symmetry predominates for both the sutures, and sexual differences are slight.     

Effect of tamoxifen on fibrosis,collagen content and transforming growth factor‐β1, ‐β2 and ‐β3 expression in common bile duct anastomosis of pigs

End‐to‐end anastomosis in the treatment for bile duct injury during laparoscopic cholecystectomy has been associated with stricture formation. The aim of this study was to experimentally investigate the effect of oral tamoxifen (tmx) treatment on fibrosis, collagen content and transforming growth factor‐β1, ‐β2 and ‐β3 expression in common bile duct anastomosis of pigs. Twenty‐six pigs were divided into three groups [sham (n = 8), control (n = 9) and tmx (n = 9)]. The common bile ducts were transected and anastomosed in the control and tmx groups. Tmx (40 mg/day) was administered orally to the tmx group, and the animals were euthanized after 60 days. Fibrosis was analysed by Masson's trichrome staining. Picrosirius red was used to quantify the total collagen content and collagen type I/III ratio. mRNA expression of transforming growth factor (TGF)‐β1, ‐β2 and ‐β3 was quantified using real‐time polymerase chain reaction (qRT‐PCR). The control and study groups exhibited higher fibrosis than the sham group, and the study group showed lower fibrosis than the control group (P = 0.011). The control and tmx groups had higher total collagen content than the sham group (P = 0.003). The collagen type I/III ratio was higher in the control group than in the sham and tmx groups (P = 0.015). There were no significant differences in the mRNA expression of TGF‐β1, ‐β2 and ‐β3 among the groups (P > 0.05). Tmx decreased fibrosis and prevented the change in collagen type I/III ratio caused by the procedure.     

Epstein–Barr virus patterns in US Burkitt lymphoma tumors from the SEER residual tissue repository during 1979–2009

Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein–Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV‐encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi‐squared statistics, and Student's t‐test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0–19, 20–34, 35–59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0–19 to 55% in age group 20–34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one‐third of tumors and it was strongly associated with race and HIV status, and marginally with age‐group.     

Sleep condition and cognitive decline in Japanese community‐dwelling older people: Data from a 4‐year longitudinal study

This study examined whether sleep duration and excessive daytime sleepiness (EDS) are related to cognitive decline among community‐dwelling older adults with intact cognition at baseline, using 4‐year longitudinal data. A total of 3,151 community‐dwelling older individuals aged ≥65 years were studied. They were assessed for cognitive function, including memory, attention, executive function and processing speed. Cognitive impairment was defined based on a score >1.5 standard deviations below the age‐ and education‐specific mean. Cognitive decline was defined in one or more cognitive tests at follow‐up. Self‐reported sleep duration (short, ≤6.0 hr; medium, 6.1–8.9 hr; long, ≥9.0 hr) and EDS at first‐wave examination were assessed and logistic regression analyses were used to examine the associations of sleep duration and EDS with cognitive status at second‐wave examination. The incidence of cognitive decline differed significantly among the sleep‐duration groups (short, 15.9%; medium, 11.9%; long, 20.1%; p = 0.001). The prevalence of having EDS was 13.1%, which was associated with a higher rate of cognitive decline than having no EDS (18.9% vs. 12.5%, p = 0.004). Long sleep duration compared with medium sleep duration (OR, 1.50; 95% CI, 1.05–2.13) and EDS (1.43; 1.01–2.03) independently impacted the incidence of cognitive decline. The results were similar after multiple imputations (long, 1.68, 1.12–2.52; EDS, 1.55, 1.05–2.29). In conclusion, our study revealed that both long sleep duration and EDS were independent risk factors associated with cognitive decline after 4 years among older adults.     

Insomnia as a mediating therapeutic target for depressive symptoms: A sub‐analysis of participant data from two large randomized controlled trials of a digital sleep intervention

Insomnia predicts the onset of depression, commonly co‐presents with depression and often persists following depression remission. However, these conditions can be challenging to treat concurrently using depression‐specific therapies. Cognitive behavioural therapy for insomnia may be an appropriate treatment to improve both insomnia and depressive symptoms. We examined the effects of a fully‐automated digital cognitive behavioural therapy intervention for insomnia (Sleepio) on insomnia and depressive symptoms, and the mediating role of sleep improvement on depressive symptoms in participants from two randomized controlled trials of digital cognitive behavioural therapy for insomnia. We also explored potential moderators of intervention effects. All participants met criteria for probable insomnia disorder and had clinically significant depressive symptomatology (PHQ‐9 ≥ 10; n = 3,352). Individuals allocated to treatment in both trials were provided access to digital cognitive behavioural therapy. Digital cognitive behavioural therapy significantly improved insomnia (p < .001; g = 0.76) and depressive symptoms (p < .001; g = 0.48) at post‐intervention (weeks 8–10), and increased the odds (OR = 2.9; 95% CI = 2.34, 3.65) of clinically significant improvement in depressive symptoms (PHQ‐9 < 10). Improvements in insomnia symptoms at mid‐intervention mediated 87% of the effects on depressive symptoms at post‐intervention. No variables moderated effectiveness outcomes, suggesting generalizability of these findings. Our results suggest that effects of digital cognitive behavioural therapy for insomnia extend to depressive symptoms in those with clinically significant depressive symptomatology. Insomnia may, therefore, be an important therapeutic target to assist management of depressive symptoms.     

IL‐17A[G197G]—Association between NOx and gestational age in a South African birth cohort

Interleukin (IL‐)17A, plays a role in pathogenic defence, but is implicated in chronic inflammatory diseases, and has recently been associated with variable pregnancy outcomes. We investigated the role of maternal IL‐17‐[G197A]‐specific effects of third‐trimester IL‐17 mRNA expression, NO_x exposure levels and other variables on gestational age, in the Mother and Child in the Environment (MACE) birth cohort in South Africa. A total of 327 participants were genotyped for IL‐17‐[G197A] by polymerase chain reaction restriction‐fragment length polymorphism (PCR‐RFLP). Quantitative real‐time PCR was used to quantitate IL‐17‐mRNA expression in whole blood. Multivariate linear regression analysis, stratified by IL‐17‐[G197A] genotype, was used to test for effects of NO_x, IL17A/GAPDH, haemoglobin, body mass index, HIV‐1 positivity, maternal education and income level on gestational age. Lower expression was associated with the IL‐17‐GG versus GA in the cohort and HIV‐1‐negative group (p = .0007, p = .0058), while no difference was observed in the HIV‐1 positives. Elevated IL‐17A expression was observed in the high NO_x exposure groups, within IL‐17[G197G] (p = .0004). IL‐17[G197G] was associated with PTB (p < .0001), and the PTB group had lower IL‐17A expression compared to the full‐term group (p = .0002). IL‐17 expression was associated with an increase in gestational age (p = .038), and NO_x was associated with a decrease in gestational age in the IL‐17[G197G] model (p = .046).     

Mechanism of skull suture maintenance and interdigitation

Skull sutures serve as growth centers whose function involves multiple molecular pathways. During periods of brain growth the sutures remain thin and straight, later developing complex fractal interdigitations that provide interlocking strength. The nature of the relationship between the molecular interactions and suture pattern formation is not understood. Here we show that by classifying the molecules involved into two groups, stabilizing factors and substrate molecules, complex molecular networks can be modeled by a simple two‐species reaction–diffusion model that recapitulates all the known behavior of suture pattern formation. This model reproduces the maintenance of thin sutural tissue at early stages, the later modification of the straight suture to form osseous interdigitations, and the formation of fractal structures. Predictions from the model are in good agreement with experimental observations, indicating that the model captures the essential nature of the interdigitation process.     

Rescue of coronal suture fusion using transforming growth factor-beta 3 (Tgf-beta 3) in rabbits with delayed-onset craniosynostosis

Craniosynostosis results in cranial deformities and increased intracranial pressure, which pose extensive and recurrent surgical management problems. Developmental studies in rodents have shown that low levels of transforming growth factor-beta 3 (Tgf-beta 3) are associated with normal fusion of the interfrontal (IF) suture, and that Tgf-beta 3 prevents IF suture fusion in a dose-dependent fashion. The present study was designed to test the hypothesis that Tgf-beta 3 can also prevent or "rescue" fusing sutures in a rabbit model with familial craniosynostosis. One hundred coronal sutures from 50 rabbits with delayed-onset, coronal suture synostosis were examined in the present study. The rabbits were divided into five groups of 10 rabbits each: 1) sham controls, 2) bovine serum albumin (BSA, 500 ng) low-dose protein controls, 3) low-dose Tgf-beta 3 (500 ng), 4) high-dose BSA (1,000 ng) controls, and 5) high-dose Tgf-beta 3 (1,000 ng). At 10 days of age, radiopaque amalgam markers were implanted in all of the rabbits on either side of the coronal suture to monitor sutural growth. At 25 days of age, the BSA or Tgf-beta 3 was combined with a slow-absorbing collagen vehicle and injected subperiosteally above the coronal suture. Radiographic results revealed that high-dose Tgf-beta 3 rabbits had significantly greater (P < 0.05) coronal suture marker separation than the other groups. Histomorphometric analysis revealed that high-dose Tgf-beta 3 rabbits also had patent coronal sutures and significantly (P < 0.01) greater sutural widths and areas than the other groups. The results suggest that there is a dose-dependent effect of TGF-beta 3 on suture morphology and area in these rabbits, and that the manipulation of such growth factors may have clinical applications in the treatment of craniosynostosis.     

Diagnostic Yield of Heat Shock Protein 70 (HSP‐70) and Anti‐HSP‐70 in Behcet‐Induced Uveitis

Heat shock proteins (HSPs) are intracellular proteins with pro‐ and anti‐inflammatory actions, playing an important role in the pathogenesis of Behcet's disease (BD). Diagnosis of BD uveitis in early stages is still problematic, thus this study was undertaken to determine diagnostic values of serum HSP‐ and anti‐HSP‐70 in BD uveitis. Serum levels of HSP‐ and anti‐HSP‐70 were measured in 53 patients with BD (26 with and 27 without uveitis). In control group, 25 age‐ and sex‐matched idiopathic uveitis patients were enrolled consecutively. Both groups had no medical problems save uveitis at the time of sampling. Confounders like medications were analysed subsequently. HSP‐ and anti‐HSP‐70 values were measured by commercial ELISA kits. Data were analysed by spss 11.5 and medcalc 11.5.1 software. The Mean HSP‐70 serum levels were different among aforementioned subgroups (P = 0.001, anova ). They were elevated in BD uveitis compared with BD without uveitis (4.84 ± 4.21 versus 2.24 ± 2.08 ng/ml; P = 0.045). HSP‐70 in sera of BD uveitis was also higher than that parameter in patients with idiopathic uveitis (4.84 ± 4.21 versus 2.37 ± 3.30 ng/ml; P = 0.001; cut‐off point value 1.0 9 ng/ml, 95% CI 0.61–0.86, P = 0.0002, ß = 0.06). However, there was not any statistical difference among those groups in the serum anti‐HSP‐70 levels (P = 0.63, anova ). Multiple regression analysis demonstrated that among different confounders, only prednisolone increases and BD uveitis decreases HSP‐70 levels independently. This prospective cross‐sectional study suggested that HSP‐70 serum level is impressed over the course of BD uveitis, and it could be utilized to diagnose or predict developing it.     

Four years comparative follow‐up evaluation of community‐based,step‐down,and residential specialist psychodynamic programmes for personality disorders

Although the fulcrum of service provision for personality disorder (PD) has shifted from hospital‐based to psychodynamically‐ and cognitively‐oriented outpatient programmes, very few studies have attempted to compare specialist moderate intensity outpatient programmes with specialist high‐intensity residential models, or to explore whether a period of inpatient treatment may be necessary to improve outcome and prognosis. In this article, we prospectively compare changes over a 4‐year period in 3 groups of patients with personality disorders (N  = 162) treated in a specialist community‐based (CBP, N  = 30), a step‐down (RT‐CBP, N  = 87), and a specialist residential programme (RT, N  = 45) in psychiatric distress, deliberate self‐injury, and suicide attempt using multilevel modelling and multivariate logistic regression analyses. The results showed that percentages of early‐dropout were significantly different (p  = .0001) for the 3 programmes (CBP = 13.4%, RT‐CBP = 10.2%, and RT = 41.4%). A significant interaction between treatment model and time was found for psychiatric distress (p  = .001), with CBP and RT‐CBP achieving more marked changes (g  = 1.20 and g  = 0.68, respectively) compared to RT (g  = 0.30) at 48‐month follow‐up. CBP and RT‐CBP were found to significantly reduce impulsive behaviour (deliberate self‐injury and suicide attempt) compared to RT. Severity of presentation was not found to be a significant predictor of outcome. Long‐term RT showed no advantage over long‐term CBP, either as stand‐alone or as step‐down treatment. Replication may be needed to confirm generalizability of results, and a number of limitations in the study design may moderate the inferences that can be drawn from the results.     

Association of interleukin‐18 promoter polymorphisms with chronic obstructive pulmonary disease in male smokers

Chronic obstructive pulmonary disease (COPD) is considered a complex genetic disorder and it is expected that many genes play a role in the pathogenesis of this disease. Previous studies have reported that several variations within the interleukin (IL)‐18 gene promoter region have been associated with different inflammatory diseases such as asthma. However, the association of IL‐18 promoter polymorphisms with COPD has not been studied yet. We then performed a prospective case–control study to explore this association in male smokers of Chinese Han people. Our study recruited 112 COPD cases and 105 healthy controls matched for age. The genotyping of IL‐18 promoter polymorphisms (‐607 C/A and ‐137 G/C) was performed using TaqMan single nucleotide polymorphism genotyping assays. The frequencies of the alleles and genotypes in patients and controls were compared. We found that the frequency of IL‐18 ‐607 C allele was significantly increased in patients with COPD (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.01–2.15, P = 0.04). The frequency of IL‐18 ‐607 C allele was significantly higher in the GOLD (Global initiative for Obstructive Lung Disease) 3–4 group compared with the GOLD 1–2 group (OR=2.06, 95% CI = 1.21–3.51, P = 0.01). There were no significant differences in the frequencies of the alleles and genotypes of IL‐18 ‐137 G/C polymorphism between the patients and healthy smokers or between GOLD 3–4 group and GOLD 1–2 group. Our study revealed that the IL‐18 ‐607 C/A polymorphism was associated with COPD susceptibility and severity of airflow limitation in male smokers of Chinese Han people.     

Association between interleukin‐21 gene polymorphisms (rs12508721) and HBV‐related hepatocellular carcinoma

Interleukin‐21 (IL‐21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL‐21 gene and susceptibility of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV‐related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction–ligase detection reaction (PCR‐LDR) method was used to genotype the SNPs (rs2221903, rs907715 and rs12508721) within IL‐21 gene. Our results showed that IL‐21 polymorphisms were associated with the risk of HCC and chronic HBV infection when compared with healthy controls. The rs2221903A/G AG genotype was associated with a higher risk of chronic HBV infection when compared with healthy controls [AG versus AA + GG, P = 0.036, OR = 1.898, 95%CI = 1.038–3.471]. The rs12508721C/T TT genotype was related with a lower risk of chronic HBV infection and HBV‐related HCC than in healthy controls [TT versus CT + CC, P = 0.026, OR = 0.451, 95%CI = 0.221–0.920; P = 0.049, OR = 0.482, 95%CI = 0.231–1.005]. No significant difference in the genotype and allele distrubutions of rs907715G/A SNP was observed in the HBV‐related HCC group, chronic HBV‐infected group and the healthy control group when compared to each other. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL‐21 gene are associated with the susceptibility of HBV‐related HCC and chronic HBV infection. The genetic variant may in fact cause protection against the HBV‐related HCC. However, the function in these SNPs of IL‐21 gene needs to clarify the mechanisms involved in the pathogenesis of HBV‐related HCC further.