Shear wave elastography for liver fibrosis in chronic hepatitis B: Adapting the cut-offs to alanine aminotransferase levels improves accuracy.

OBJECTIVES: To determine and validate alanine aminotransferase (ALT)-adapted dual cut-offs of liver stiffness measurements (LSMs) for assessing liver fibrosis with two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis B (CHB) infection. METHODS: Patients with CHB infection who underwent liver biopsy to assess liver fibrosis were consecutively included. 2D-SWE confirmation thresholds with a positive likelihood ratio ≥10 and 2D-SWE exclusion thresholds with a negative likelihood ratio ≤0.1 were identified to rule in or rule out significant fibrosis and cirrhosis, respectively. RESULTS: The first 515 patients (index cohort) and the next 421 patients (validation cohort) were included in the final analysis. The low and high cut-offs to rule out and rule in patients with significant fibrosis (≥ F2) were 5.4 kPa and 9.0 kPa, respectively, in patients with ALT levels ≤ 2 × the upper limit of normal (ULN) and 7.1 kPa and 11.2 kPa in patients with ALT levels > 2 × ULN. For cirrhosis (F4), the corresponding values were 8.1 kPa and 12.3 kPa in patients with ALT levels ≤ 2 × ULN and 11.9 kPa and 24.7 kPa in patients with ALT levels > 2 × ULN. The dual cut-off values showed an overall accuracy of more than 90% for diagnosis of the presence or absence of significant fibrosis and cirrhosis in the index and validation cohorts. There were no significant differences in the accuracy values between the cohorts (all p>0.05). CONCLUSION: The ALT-adapted dual cut-offs of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis in patients with CHB infection. KEY POINTS: • The ALT-adapted dual cut-off values of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis. • ALT levels did not influence the overall diagnostic accuracy for predicting significant fibrosis and cirrhosis. • The ALT-adapted dual cut-offs in patients with ALT levels > 2 × ULN were markedly higher than those in patients with ALT levels ≤ 2 × ULN.

2D shear wave elastography combined with MELD improved prognostic accuracy in patients with acute-on-chronic hepatitis B liver failure.

OBJECTIVES: To evaluate accuracy of two-dimensional shear wave elastography (2D SWE) and develop and validate a new prognostic score in predicting prognosis of acute-on-chronic liver failure (ACLF) patients. METHODS: From 1 October 2013 to 30 September 2015, we consecutively enrolled 290 patients, sequentially collected data (including 2D SWE, ultrasound parameters, laboratory data and prognostic scores) and recorded patients' outcome (recovering/steady or worsening) during a 90-day follow-up period. We evaluated ability of 2D SWE to predict outcomes of acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients. We developed a new score (MELD-SWE, combining MELD and SWE values) for predicting mortality risk of ACLF-HBV in 179 patients in a derivation group, and validated in 111 patients. RESULTS: 2D SWE values were higher in worsening patients than recovering/steady ones (p < 0.001). Accuracy of 2D SWE in predicting outcomes of ACLF-HBV was comparable to that of the MELD score (p = 0.441). MELD-SWE showed a significantly higher prognostic value than MELD in both derivation (AUROC, 0.80 vs. 0.76, p = 0.040) and validation (AUROC, 0.87 vs. 0.82, p = 0.018) group. CONCLUSIONS: The MELD-SWE score, combining MELD and SWE values, was superior to MELD alone for outcoming prediction in patients with ACLF-HBV. KEY POINTS: • 2D SWE is a simple prognostic evaluation tool in patients with ACLF-HBV. • MELD-SWE was created in this study: 1.3×MELD + 0.3×2D SWE (kPa). • MELD-SWE score was superior to MELD alone for outcoming prediction in ACLF-HBV. • In this study, 46.8 was the optimal cut-off value of MELD-SWE score.

Transcriptome microRNA profiling of bovine mammary glands infected with Staphylococcus aureus.

MicroRNAs are small non-coding RNA molecules that are important regulators of gene expression at the post-transcriptional level. miRNAs impact the processes of cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA expression profiles associated with mastitis will be conducive for its control. In this study, Staphylococcus aureus (S. aureus) was administered to the mammary gland of Chinese Holstein cows to construct a bacteria-type mastitis model. Total RNA was isolated from bovine mammary gland tissue samples from the S. aureus-induced mastitis group and controls. miRNAs were analyzed using Solexa sequencing and bioinformatics processing for the experimental group and control group. Two miRNA libraries were constructed respectively. A total of 370 known bovine miRNAs and 341 novel mi RNAs were detected for the S. aureus and 358 known bovine miRNAs and 232 novel miRNAs for control groups. A total of 77 miRNAs in the S. aureus group showed significant differences compared to the control group. GO (Gene Ontology) analysis showed these target genes were involved in the regulation of cells, binding, etc., while KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these genes were enriched in endocytosis, and olfactory transduction pathways involved in cancer. These results provide an experimental basis to reveal the cause and regulatory mechanism of mastitis and also suggest the potential of miRNAs to serve as biomarkers for the diagnosis of mastitis in dairy cows.

[Genetic polymorphism of the IL8 gene and its associations with milk traits and SCS in Chinese Holstein].

The polymorphism of Interleukin-8 (IL8) gene were investigated for 610 Chinese Holstein cows of 30 bull families from a dairy farm in Shanghai using Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) technique with a mixed animal model to verify the effects of the polymorphisms on some milk productive performance, tested day milk yield, tested day fat percentage, tested day milk protein percentage, 305 d corrected milk yield, 305 d milk fat yield, 305 d milk protein yield, and somatic cell score (SCS). The aim was to explore the significant molecular marker in practical dairy production. Three genotypes were identified and the genotypic frequencies of KK, KA, and AA were 0.187, 0.451, and 0.362, respectively. The gene frequencies of K and A were 0.412 and 0.588. The results showed highly significant (P < 0.01) association of IL8 mutations with tested day milk yield, 305 d milk protein yield, 305 d corrected milk yield and 305 d milk fat yield, SCS and tested day milk protein percentage (P < 0.05). However, no association (P > 0.05) with tested day milk fat percentage was recorded. The cows with KK genotype had higher tested day milk yield, 305 d milk protein yield, 305 d corrected milk yield and 305 d milk fat yield than those with AA and KA genotypes (P < 0.01). The least square mean of SCS for KK was significantly lower than that with AA and KA genotypes (P < 0.01). AA genotype was significant lower in tested day milk protein percentage than KK and KA genotypes (P < 0.05). The IL8 gene genetic diversity has a great genetic effect on milk traits and mastitis resistance and could be a useful genetic marker for Chinese Holstein breeding.

Pelvic floor biometry in asymptomatic primiparous women compared with nulliparous women: a single-center study in Southern China.

OBJECTIVE: This study aimed to investigate pelvic floor biometry of asymptomatic primiparous women compared with nulliparous women by using four-dimensional transperineal ultrasound (4D TPUS). METHODS: From July 2015 to February 2017, 722 women were enrolled and divided into the nulliparous group (n = 292), the vaginal delivery group (n = 272), and the elective cesarean section group (n = 158). The ultrasound parameters of 4D TPUS were compared among the groups. RESULTS: The vaginal delivery group had a significantly greater bladder neck descent (η2 = 0.04), retrovesical angles on Valsalva maneuver (η2 = 0.01), urethral rotation (η2 = 0.01), levator hiatus area on Valsalva maneuver (η2 = 0.02), urethral inclination angle (η2 = 0.02), and funneling of the proximal urethra (η2 = 0.11) than the other two groups. Comparison of the two modes of delivery (vaginal delivery and cesarean section) also showed significant differences in the above-mentioned ultrasound parameters. CONCLUSION: There are significant differences in pelvic floor biometry between asymptomatic primiparous women and nulliparous women, as well as between women with vaginal delivery and those with elective cesarean section.

Evaluation of the microcirculatory disturbance of biliary ischemia after liver transplantation with contrast-enhanced ultrasound: preliminary experience.

The aim of this study was to determine the efficacy of contrast-enhanced ultrasound for depicting the perfusion of hilar bile ducts in ischemic-type biliary lesions after orthotopic liver transplantation. Thirteen transplant recipients with ischemic-type biliary lesions and 12 patients without ischemic-type biliary lesions underwent ultrasound examinations after the injection of 1.5 mL of an intravenous contrast agent. The enhancement of the hilar bile duct wall in the arterial, portal venous, and late phases was qualitatively graded as higher, equal, lower, or none with respect to that of the adjacent liver parenchyma. No or low contrast enhancement was seen in 10 of 13 patients (76.90%) with biliary ischemia, whereas increased contrast enhancement with respect to the normal liver parenchyma was found in all 12 patients without biliary ischemia. The difference in the enhancement patterns between the 2 groups was significant (P = 0.0001). In conclusion, contrast-enhanced ultrasound is a new imaging modality to depict perfusion of the hilar bile duct. No or low contrast enhancement of the bile duct wall in the arterial phase may reflect the microcirculatory disturbance of biliary ischemia and may contribute to its early diagnosis.

Cerebral Abscesses and Osteomyelitis Caused by Fish Bone Impaction on FDG PET/CT Imaging.

A 50-year-old woman complained postprandial vomiting for 5 days and drowsiness for 3 days. Possible central nervous pathology was suspected clinically. Brain MRI suggested likely brain metastases. For this reason, FDG PET/CT was performed to search the primary malignancy. The images showed abnormal activity not only in the brain, but also in the retropharyngeal region and in the thoracic vertebral body. The lesions were eventually confirmed as infection caused by fish bone impaction that occurred 1 month earlier.

Heme oxygenase-2 suppress TNF-α and IL6 expression via TLR4/MyD88-dependent signaling pathway in mouse cerebral vascular endothelial cells.

Heme oxygenase (HO) represents an intrinsic antiinflammatory system based on its ability to inhibit expression of proinflammatory cytokines. The constitutive isoform heme oxygenase-2 (HO-2) has high expression and activity in cerebral microvascular endothelial cells (CMVEC). This study was undertaken to evaluate the role of HO-2 in regulation of TLR4/MyD88-dependent signaling and to study the effect of HO-2 on the expression and secretion of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and Interleukin-6 (IL6) in CMVEC. HO-2 short hairpin RNA (shRNA) and HO-2 overexpression plasmids were used to observe the effect of HO-2 on proinflammatory cytokines in CMVEC in vitro, and the results showed that the messenger RNA (mRNA) and protein levels of TNF-α and IL6 were increased and decreased, respectively, compared with control groups. LPS-stimulated TNF-α and IL6 mRNA and protein were also reduced in CMVEC treated with an inhibitor of TLR4 signaling, CLI-095, or HO-2 overexpression. CLI-095 and HO-2 overexpression both reduced TLR4 expression in CMVEC, and HO-2 shRNA blocked these effects of CLI-095. CLI-095 and HO-2 overexpression potently suppressed TLR4/MyD88-dependent proinflammatory cytokine expression in CMVEC. These results suggest that HO-2 plays an important role in protecting CMVEC against cytokine-mediated inflammation.

The use of contrast-enhanced ultrasound in uterine leiomyomas.

BACKGROUND: Ultrasound (US) is a popular method in the diagnosis and treatment of uterine leiomyomas, but the lack of accuracy greatly limits its application. Recently, microbubble enhancement technique affords direct depiction of tumor neovascularity and establishes a more precise vascular map of the tumor. This study was undertaken to describe the distribution patterns of SonoVue, a second-generation contrast agent, in the microcirculation of uterine leiomyomas, and to investigate the potential use of contrast-enhanced ultrasound (CEUS) in the characterization and treatment of uterine leiomyomas. METHODS: Ninety-six patients with uterine leiomyomas were enrolled in this study. The CEUS was performed using cadence pulse sequencing technique (CPS) and SonoVue. Enhancement patterns of different lesions were observed. The diagnostic accuracy of CEUS was compared with that of conventional ultrasound. RESULTS: After contrast injection, vessels of macro- and micro-circulation of the myoma first appeared, followed by the normal myometrium and finally the endometrium. During the washout phase, the myoma exhibited homogeneous enhancement followed by apparent hypoenhancement. The margin of the tumor was depicted clearly. There was no agent perfusion in the benign degenerative or necrotic area. However in sarcomas degeneration, the feeding vessels appeared markedly earlier than those in myometrium. In addition, the tumor exhibited heterogeneous hyperenhancment with no agent perfusion in the center and no membraniform sign was observed in the late phase. In subserous and submucous leiomyomas, the feeding arteries in the pedicle arising from the uterine could be seen. In this study, the diagnostic accuracy of CEUS and conventional US for uterine leiomyomas was 96.7% (160/165) and 82.4% (136/165) respectively. CONCLUSIONS: CEUS can provide a precise description of the leiomyomas vascularization. The specific enhancement pattern may be helpful for the characterization, treatment choice and therapeutic monitoring of leiomyomas.