Studies have reported that interactions between keratins (KRTs) and other proteins initiate signaling cascades that regulate cell migration, invasion, and metastasis. In the current study, we found that expression of KRT19 was specifically high in breast cancers and significantly correlated with their invasiveness. Moreover, knockdown of KRT19 led to increased proliferation, migration, invasion, drug resistance, and sphere formation in breast cancer cells via an upregulated NOTCH signaling pathway. This was owing to reduced expression of NUMB, an inhibitory protein of the NOTCH signaling pathway. In addition, we found that KRT19 interacts with β-catenin/RAC1 complex and enhances the nuclear translocation of β-catenin. Concordantly, knockdown of KRT19 suppressed the nuclear translocation of β-catenin as well as β-catenin-mediated NUMB expression. Furthermore, modulation of KRT19-mediated regulation of NUMB and NOTCH1 expression led to the repression of the cancer stem cell properties of breast cancer patient-derived CD133high/CXCR4high/ALDH1high cancer stem-like cells (CSLCs), which showed very low KRT19 and high NOTCH1 expression. Taken together, our study suggests a novel function for KRT19 in the regulation of nuclear import of the β-catenin/RAC1 complex, thus modulating the NUMB-dependent NOTCH signaling pathway in breast cancers and CSLCs, which might bear potential clinical implications for cancer or CSLC treatment.

The objective of this study was to compare replacement of the radial head by metal prostheses with open reduction and internal fixation (ORIF) for the treatment of unstable, multi-fragmented radial head fractures. A prospective randomised controlled trial was employed to investigate 45 patients with unstable, multi-fragmented fractures of the radial head, from January 2004 to June 2007. The patients were randomised to two groups: the ORIF group and the radial head replacement group. Over the next two years, follow-up assessments recorded Broberg and Morrey scores and postoperative complication rate. Statistical analysis was performed. According to Broberg and Morrey scores, patients receiving radial head replacement achieved significantly better clinical results with 91% (20/22) good or excellent compared to patients assigned to the ORIF group with 65.2% (15/23) good or excellent results (P < 0.01). Postoperative complication rate of the radial head replacement group (13.6%) was significantly lower than that of the ORIF group (47.9%; P < 0.01). Compared with open reduction and internal fixation, radial head replacement with a metal prostheses resulted in favourable joint function for the unstable, multi-fragmented fractures of the radial head.

ObjectivePituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Due to the rarity of PSIS, clinical data are limited, especially in Chinese people. Herein, we analyzed the clinical characteristics of patients diagnosed with PSIS from our center over 10 years.Patients and MethodsWe retrospectively analyzed the clinical manifestations and laboratory and MRI findings in 55 patients with PSIS.ResultsOf the 55 patients with PSIS, 48 (87.3%) were male. The average age was 19.7±6.7 years and there was no familial case. A history of breech delivery was documented in 40 of 45 patients (88.9%) and 19 of 55 patients (34.5%) had a history of dystocia. Short stature was found in 47 of 55 patients (85.5%) and bone age delayed 7.26±5.37 years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone, gonadotropins, corticotropin, and thyrotropin were 100%, 95.8%, 81.8%, 76.3%, respectively. Hyperprolactinemia was found in 36.4% of patients. Three or more pituitary hormone deficiencies were found in 92.7% of the patients. All patients had normal posterior pituitary function and absent pituitary stalk on imaging. The average height of anterior pituitary was 28 mm, documented anterior pituitary hypoplasia. Midline abnormalities were presented in 9.1% of patients.ConclusionsThe clinical features of our Chinese PSIS patients seem to be different from other reported patients in regarding to the higher degree of hypopituitarism and lower prevalence of midline defects. In addition, our patients were older at the time of case detection and the bone age was markedly delayed. We also had no cases of familial PSIS.

The aims of this study were to investigate the prevalence of ED in Chinese men with type 2 diabetes mellitus, and evaluate the efficacy and safety of sildenafil citrate in these patients. Patients from 42 outpatient diabetes clinics with type 2 diabetes mellitus and ED as defined by the International Index of Erectile Function (IIEF)-5 were studied. Participants with ED received three doses (100 mg each) of sildenafil citrate for use over 3 months. Efficacy of sildenafil citrate was assessed using the IIEF-5 and the Global Efficacy Questionnaire (GEQ). Adverse events were recorded by patients in a daily diary. A total of 5477 participants were evaluated, and 75.2% had ED. Age, duration of diabetes and glycosylated hemoglobin (HbA 1 c) 46.5% were independently and significantly associated with the presence and degree of ED. Patients who received pharmacotherapy (N ¼ 389) reported significant improvements. The rate of erections as determined by the GEQ was also significantly improved following treatment. ED is a common complication in Chinese men with type 2 diabetes mellitus, and certain risk factors are associated with the presence of ED and severity. Sildenafil citrate is a safe and effective treatment for these patients.

Growing evidence has shown that gut microbiome is a key factor involved in liver health. Therefore, gut microbiota modulation with probiotic bacteria, such as Saccharomyces boulardii, constitutes a promising therapy for hepatosis. In this study, we aimed to investigate the protective effects of S. boulardii on D-Galactosamine-induced liver injury in mice. Liver function test and histopathological analysis both suggested that the liver injury can be effectively attenuated by S. boulardii administration. In the meantime, S. boulardii induced dramatic changes in the gut microbial composition. At the phylum level, we found that S. boulardii significantly increased in the relative abundance of Bacteroidetes, and decreased the relative abundance of Firmicutes and Proteobacteria, which may explain the hepatic protective effects of S. boulardii. Taken together, our results demonstrated that S. boulardii administration could change the gut microbiota in mice and alleviate acute liver failure, indicating a potential protective and therapeutic role of S. boulardii.

Pregnancies complicated by pre-gestational diabetes (PGD) are associated with a higher rate of adverse outcomes, including an increased rage of preterm delivery, pregnancy-induced hypertension, pre-eclampsia, caesarean section, perinatal mortality, stillbirth, shoulder dystocia, macrosomia, small for gestational age, large for gestational age, low birth weight, neonatal hypoglycemia, neonatal death, low Apgar score, NICU admission, jaundice and respiratory distress. In the past two decades, numerous reports have been published regarding associations between PGD and risk of adverse outcomes. However, study results are inconsistent. To provide a synopsis of the current understanding of PGD for risk of adverse pregnancy outcomes, a random-effects meta-analysis over 40 million subjects from 100 studies was performed to calculate the pooled ORs. Potential sources of heterogeneity were systematically explored by multiple strata analyses and meta-regression. Overall, PGD were significantly associated with increased risk of preterm delivery (OR=3.48), LGA (OR=3.90), perinatal mortality (OR=3.39), stillbirth (OR=3.52), pre-eclampsia (OR=3.48), caesarean section (OR=3.52), NICU admission (OR=3.92), and neonatal hypoglycemia (OR=26.62). Significant results were also observed for 7 adverse outcomes with OR range from 1.54 to 2.82, while no association was found for SGA and respiratory distress after Bonferroni correction. We found that women with T1DM had higher risks for most of adverse pregnancy outcomes compared with women with T2DM. When stratified by study design, sample size, type of diabetes, geographic region, and study quality, significant associations remains. Our findings demonstrated that PGD is a strong risk-conferring factor for adverse maternal, perinatal and neonatal outcomes.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The mechanism of susceptibility to chronic persistent HBV infection is not well clarified, while the outcome of HBV infection mainly depends on the host immune response. Human leukocyte antigen (HLA) class II molecule is an integral component of the immune response on which majority of host genetic studies have concentrated. Many different HLA class II alleles have been demonstrated to play roles in HBV infection. In this study, the association between HBV infection and HLA-DRB1 alleles in Han individuals in northwestern China was studied for the first time. Two hundred and fifty Shaanxi Han individuals were categorized into three different groups: the HBV-infected patient group (n = 108), the spontaneously cleared control group (n = 108) and the unexposed group (n = 34). DRB1*04, DRB1*09, DRB1*12 and DRB1*15 were the most common genotypes in all the groups. The allele frequencies of HLA-DRB1*03 [10.6% of HBV-infected patients vs 3.7% of spontaneously cleared controls, odds ratios (OR) = 3.10, Pc = 0.008, P < 0.05] and HLA-DRB1*07 (17.6% of HBV-infected patients vs 9.3% of spontaneously cleared controls, Pc = 0.016, OR = 2.09, P < 0.05) were markedly higher in the HBV-infected group. But the allele frequencies of HLA-DRB1*15 (6.9% of HBV-infected patients vs 13.4% of spontaneously cleared controls Pc = 0.039, OR = 0.48, P < 0.05) were obviously lower than that of the spontaneously cleared controls. The above data indicate that HLA-DRB1*03 and HLA-DRB1*07 are related to susceptibility to chronic HBV infection, and DRB1*15 is negatively related to persistence to chronic HBV infection among people in northwestern China. Similar results were got for DRB1*03 and 15 alleles between the HBV-infected patients (n = 108) and 46 HBV seronegative spouses of the HBV patients, who were high-risk group for HBV infection. The above results suggest that host HLA class II gene is an important factor in determination of the outcome of HBV infection.

Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Recently, genome-wide association studies have identified human leukocyte antigen (HLA)-DP polymorphisms (rs3077 and rs9277535) as a new chronic HBV infection susceptibility locus. Since then, the relationship between HLA-DP polymorphisms and various outcomes of HBV infection has been reported. However, the results have been inconclusive. To derive a more precise estimation of the relationship between HLA-DP polymorphisms and various outcomes of HBV infection, a meta-analysis of 62,050 subjects from 29 case-control studies was performed. We found that rs3077 and rs9277535 in HLA-DP significantly decreased HBV infection risks and increased HBV clearance possibility in a dose-dependent manner. In the subgroup analysis by ethnicity, study design and sample size, significant associations were found for these polymorphisms in almost all comparisons. Meanwhile, haplotype analyses of the two polymorphisms revealed a significant association between the combination of these alleles and HBV infection outcomes. However, no significant results were observed in HCC development. Our results further confirm that genetic variants in the HLA-DP locus are strongly associated with reduced HBV infection and increased the likelihood of spontaneous viral clearance.