Cross-sectional study of the relationship of peripheral blood cell profiles with severity of infection by adenovirus type 55

BACKGROUND: The immunologic profiles of patients with human adenovirus serotype 55 (HAdV-55) infections were characterized in subjects diagnosed with silent infections (n = 30), minor infections (n = 27), severe infections (n = 34), and healthy controls (n = 30) during a recent outbreak among Chinese military trainees. METHODS: Blood was sampled at the disease peak and four weeks later, and samples were analyzed to measure changes in leukocyte and platelet profiles in patients with different severities of disease. Differential lymphocyte subsets and cytokine profiles were measured by flow cytometry and Luminex xMAP®, and serum antibodies were analyzed by ELISA and immunofluorescence staining. RESULTS: Patients with severe HAdV infections had higher proportions of neutrophils and reduced levels of lymphocytes (p < 0.005 for both). Patients with minor and severe infections had significantly lower platelet counts (p < 0.005 for both) than those with silent infections. The silent and minor infection groups had higher levels of dendritic cells than the severe infection group. Relative to patients with silent infections, patients with severe infections had significantly higher levels of IL-17(+)CD4(+) cells, decreased levels of IL-17(+)CD8(+) cells, and higher levels of IFN-γ, IL-4, IL-10, and IFN-α2 (p < 0.001 for all comparisons). CONCLUSIONS: Patients with different severities of disease due to HAdV-55 infection had significantly different immune responses. These data provide an initial step toward the identification of patients at risk for more severe disease and the development of treatments against HAdV-55 infection

Antidiabetic Activity of a Flavonoid-Rich Extract From Sophora davidii (Franch.) Skeels in KK-Ay Mice via Activation of AMP-Activated Protein Kinase

The present study was undertaken to investigate the hypoglycemic activity and potential mechanisms of action of a flavonoid-rich extract from Sophora davidii (Franch.) Skeels (SD-FRE) through in vitro and in vivo studies. Four main flavonoids of SD-FRE namely apigenin, maackiain, leachianone A and leachianone B were purified and identified. In vitro, SD-FRE significantly promoted the translocation and expression of glucose transporter 4 (GLUT4) in L6 cells, which was significantly inhibited by Compound C (AMPK inhibitor), but not by Wortmannin (PI3K inhibitor) or Gö6983 (PKC inhibitor). These results indicated that SD-FRE enhanced GLUT4 expression and translocation to the plasma membrane via the AMPK pathway and finally resulted in an increase of glucose uptake. In vivo, using a spontaneously type 2 diabetic model, KK-Ay mice received intragastric administration of SD-FRE for 4 weeks. As a consequence, SD-FRE significantly alleviated the hyperglycemia, glucose intolerance, insulin resistance and hyperlipidemia in these mice. Hepatic steatosis, islet hypertrophy and larger adipocyte size were observed in KK-Ay mice. However, these pathological changes were effectively relieved by SD-FRE treatment. SD-FRE promoted GLUT4 expression and activated AMPK phosphorylation in insulin target tissues (muscle, adipose tissue and liver) of KK-Ay mice, thus facilitating glucose utilization to ameliorate insulin resistance. Regulation of ACC phosphorylation and PPARγ were also involved in the antidiabetic effects of SD-FRE. Taken together, these findings indicated that SD-FRE has the potential to alleviate type 2 diabetes

Microsurgical vasovasostomy for the treatment of intractable chronic scrotal pain after vasectomy

Dear Editor, We present herein two rare cases of intractable chronic scrotal pain after vasectomy. The patients were effectively treated with microsurgical vasovasostomy (MVV). We also discuss the possible aetiologies of the pain and other surgical options. Vasectomy was once the most common method of permanent contraception for men in both China and worldwide. One particularly distressing complication after vasectomy is chronic scrotal pain, which is defined as intermittent or constant, unilateral or bilateral scrotal pain for o3 months. The pain is intense enough to interfere with the patient&apos;s daily activities and prompts him to seek medical attention. 1 Although its aetiology remains unclear, epididymal congestion, painful sperm granulomas, vascular stasis and nerve impingement have been postulated as possible aetiologic factors. 2 Non-surgical options have been used successfully to treat chronic scrotal pain after vasectomy, including scrotal support, thermal therapy, limiting activity, non-steroidal anti-inflammatory drugs, narcotic analgesics, antibiotics, neuroleptics, spermatic cord nerve block, biofeedback and psychiatric evaluation. Surgical options include reversal of the vasectomy, microsurgical spermatic cord denervation, granuloma excision, epididymectomy and orchidectomy. The microsurgical techniques used for vasectomy reversal have changed significantly in the past decade, culminating in the standard surgical procedures used today, and its indications include a desire to have more children (remarriage or after the death of a child), treatment of post-vasectomy pain and treatment of obstructive azoospermia due to traumatic or iatrogenic injury of vas deferens. 3 To our knowledge, we report the first cases of the use of MVV for the treatment of intractable chronic scrotal pain after vasectomy in a Chinese hospital. The 72-year-old and 49-year-old men presented with a more than 20-year history of intractable, chronic scrotal pain after vasectomy. They had consulted various urologists and had undergone numerous attempted therapies in other hospitals. They reported a history of vasectomy more than 30 years and 20 years previously, respectively. They did not have any histories of haematuria, haematospermia, lower urinary tract symptoms, epididymitis, prostatitis or testicular trauma. Their physical examination was unremarkable, and both the secondary sexual characteristics and genital examination were normal. The testes were descended bilaterally and normal in size and consistency. The caput epididymides exhibited dilatation and tenderness. The vasa deferentia were palpated for painful lumps at the vasectomy sites. Digital rectal examination was unremarkable for prostatic abnormalities. Each patient underwent Doppler ultrasonography of the testes and urinary tract, urinalysis, urine culture and spermiogram to exclude primary or secondary causes of pain, including intratesticular infection, tumours and ureteral lithiasis. At our initial consultation, the patients were asked to complete a pain and psychological questionnaire, which included pain, depression and anxiety scores. The pain score (Visual Analogue Scale) was in the form of an 11-point numerical rating score with 0 representing &apos;no pain&apos; and 10 representing the &apos;worst possible pain&apos;. The patients&apos; preoperative pain scores were 5 and 6 points, respectively. The depression scores (Self-rating Depression Scale) were in the form of an 80-point numerical rating score; a score less than 50 indicated &apos;normal&apos;, and a score greater than 50 indicated &apos;depression&apos;. The depression scores of the two patients were 35 and 38 points, respectively. The anxiety scores (Self-rating Anxiety Scale) were in the form of an 80-point numerical rating score; scores less than 50 were considered to indicate &apos;normal&apos;, whereas scores greater than 50 indicated &apos;anxiety&apos;. The anxiety scores of the two patients were 33 and 32 points, respectively. Spermatic cord block was performed once for each patient with 6 ml of 1% lidocaine and 1 ml of methylprednisolone (40 mg). The patients had 3 and 7 days of complete pain relief after the blockade, respectively. The study protocol was approved by the Ethical Committee of the First Affiliated Hospital of Sun Yat-Sen University, and informed consent was signed by the patients. The patients were offered MVV as a more permanent solution in March and July 2012, respectively. Scrotal exploration was performed with the patients under combined spinal-epidural anaesthesia. The left-side incision (3 cm) of the scrotum through the tunica vaginalis was made, and the left vas deferens was delivered through this incision. The painful lumps and nerveimpinging tissue at the vasectomy site were thoroughly resected by electrocautery. Distal patency was confirmed by infusing diluted methylene blue through the abdominal side of the vas deferens, resulting in blue colouring of the urine. A 123 to 153 operating microscope (Leica Microsystems (Schweiz) AG, Heerbrugg, Switzerland) was use

R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome

<p>Abstract</p> <p>Background</p> <p>Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR) gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS) is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CA)_nrepeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and direct sequencing.</p> <p>Results</p> <p>There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The <it>Lys </it>allele had a significantly increased risk of ACS compared with the <it>Arg </it>allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted <it>P </it>= 0.006). However, no significant relationship between the number of (CA)_nrepeats of EGFR intron 1 (both alleles < 20 or any allele ≥ 20) and the risk of ACS was observed (adjusted OR = 0.97, 95% CI: 0.58–1.64, adjusted <it>P </it>= 0.911). Considering these two polymorphisms together, there was no statistically significant difference between the two groups.</p> <p>Conclusion</p> <p>R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.</p

Whole-genome resequencing of wild and domestic sheep identifies genes associated with morphological and agronomic traits

Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals

Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma

BACKGROUND: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma