[Application of Diffusion-Weighted Imaging and Hepatobiliary-Specific Contrast Agent Gd-EOB-DTPA in the Diagnosis and Differential Diagnosis of Focal Liver Lesions].

There are many types of focal liver lesions (FLL) presenting different lesion signs and their diagnosis and differential diagnosis are relatively difficult. It is of great clinical significance to accurately detect, classify and characterize focal liver lesions as soon as possible. Diffusion-weighted imaging (DWI) provides information on liver cell density, microstructure, and microcirculation perfusion. Gadolinium-ethoxibenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is a hepatobiliary-specific contrast agent. Gd-EOB-DTPA-enhanced MRI examination of liver provides information on the blood perfusion of lesions and specific information on the uptake function of normal liver cells. The combined application of the two can significantly improve the sensitivity and diagnostic accuracy in the detection of FLL. Herein, we reviewed the research findings on the application of DWI and Gd-EOB-DTPA in FLL diagnosis in order to provide reference for further clinical application. Most of the existing studies only made comparison and discussion of the DWI image quality of different b values and their fitted apparent diffusion coefficient (ADC) values before and after Gd-EOB-DTPA enhancement, and the reported findings are not only varied, but also inconsistent. Whether Gd-EOB-DTPA will affect DWI images is still been debated. Future research should focus on quantitative comparison, discussion and verification of the enhancement effect after injection of Gd-EOB-DTPA, as well as the changes in the ADC value corresponding to different b values before and after enhancement, in order to provide more objective and consistent research results for clinical application.

Factors influencing mosaicism: a retrospective analysis.

RESEARCH QUESTION: What factors affect the incidence of mosaic embryos resulting from assisted reproductive technology? DESIGN: A retrospective analysis of data from preimplantation genetic testing for aneuploidies in 544 couples was conducted using data from an electronic medical record database. RESULTS: Of 1910 embryos studied, 127 (6.6%) were mosaic. In multivariable logistic regression analysis, mosaicism incidence increased in embryos from IVF versus intracytoplasmic sperm injection (ICSI) (odds ratio [OR] 4.560, 95% confidence interval [CI] 2.800-7.424, P < 0.001), and in embryos from abnormal versus normal semen (OR 3.496, 95% CI 2.455-4.979, P < 0.001). Embryos tested using SurePlex 24Sure had lower mosaicism percentages than those tested using MALBAC-NGS and PicoPLEX GenetiSure (OR 2.726, 95% CI 1.532-4.852, P = 0.001; OR 2.389, 95% CI 1.537-3.711, P < 0.001, respectively). CONCLUSIONS: Semen quality, fertilization method and detection system are independent factors associated with embryonic mosaicism.

Pathogenesis of acephalic spermatozoa syndrome caused by SUN5 variant.

Acephalic spermatozoa syndrome (ASS) is a rare teratozoospermia that leads to male infertility. Previous work suggested a genetic origin. Variants of Sad1 and UNC84 domain containing 5 (SUN5) are the main genetic cause of ASS; however, its pathogenesis remains unclear. Here, we performed whole-exome sequencing in 10 unrelated ASS and identified 2 homozygous variants, c.381delA[p.V128Sfs7*] and c.675C>A[p.Y225X], and 1 compound variant, c.88 C > T[p.R30X] and c.381 delA [p.V128Sfs7*], in SUN5 in 4 patients. The c.381delA variant had been identified as pathogenic in previous reports, while c.675C>A and c.88 C > T were two novel variants which could lead to a premature termination codon (PTC) and resulted in loss of SUN5, and may also be pathogenic. SUN5 mRNA and protein were present at very low levels in ASS patients with SUN5 nonsense mutation. Furthermore, the distribution of outer dense fiber protein 1 (ODF1) and Nesprin3 was altered in sperm of ASS patients with SUN5 variants. The co-immunoprecipitation analysis indicated that SUN5 and ODF1, SUN5 and Nesprin3, and ODF1 and Nesprin3 interacted with each other in transfected HEK293T cells. Thus, we propose that SUN5, Nesprin3, and ODF1 may form a 'triplet' structure through interactions at neck of sperm. When gene variants resulted in a loss of SUN5, the 'triplet' structure disappears and then the head-tail junction becomes fragile, leading to the occurrence of ASS.

Sequential interval micro-droplet loading in closed hemi-straw carrier system: A convenient and efficient method for ultra-rapid cryopreservation in extreme oligozoospermia.

Cryopreservation of human spermatozoa with low concentration while maintaining adequate post-thawing motility remains a major challenge for male fertility preservation. A convenient and efficient ultra-rapid freezing method for small amounts of human spermatozoa in a closed Hemi-Straw carrier system (CHS) was developed. Spermatozoa from 60 healthy men were involved in a parameter refining test and another 15 extreme oligozoospermic specimens were assigned to a verification test. A commercialized sperm freezing medium, Quinn's Advantage® Sperm Freeze medium (glycerol and sucrose as the cryoprotective agent) was used in the study. The results showed that the highest recovery rates would be obtained via the method of 2 µl single droplet sequential interval loading, by placing the straw at 1 cm above the liquid nitrogen (LN2) surface for 60 s during freezing and 2 cm above the LN2 for 2 min during thawing. This method was applied in cryopreservation for the normozoospermic specimens and compared with a conventional slow freezing method. The results were better than those in the control group in the total motility recovery rate (77.8 ± 11.2% vs 56.6 ± 11.9%, P < 0.01), progressive motility recovery rate (77.6 ± 13.2% vs 47.7 ± 14.6%, P < 0.01), 24 h survival index (60.9 ± 13.4% vs 42.1 ± 14.1%, P < 0.01) and the sperm DNA fragment index (4.2 ± 3.7% vs 5.8 ± 3.7%, P = 0.126). This method was applied to the oligozoospermic specimens. Motile spermatozoa could be found in 12 of 15 cases in the ultra-rapid freezing group, while only in 7 cases in control group. The results indicated that this freezing method was simple, convenient and bio-safe for cryopreservation of severe oligozoospermic specimens.

Relationship between resistin and IL-23 levels in follicular fluid in infertile patients with endometriosis undergoing IVF-ET.

BACKGROUND: Endometriosis (EM) interferes with the reproductive process and affects the success rate of in vitro fertilization (IVF). Inflammatory cytokines are suggested to play a role in infertility in patients with EM. OBJECTIVES: In this study, we aimed to investigate the relationship between resistin and interleukin 23 (IL-23) levels in follicular fluid (FF) and serum together with the severity of endometriosis and in vitro fertilization/ embryo transfer (IVF-ET) outcome. MATERIAL AND METHODS: Samples from 116 infertile women were studied using enzyme-linked immunosorbent assay (ELISA). The study group consisted of 76 infertile patients diagnosed with EM (40 with stages I-II and 36 with stages III-IV) undergoing IVF-ET. The control group included 40 women with tubal factor infertility. FF and serum samples were collected on the day of follicle aspiration and hCG administration, respectively. RESULTS: The serum and FF resistin levels were significantly higher in the EM group than in the control group (p-value <0.05). The FF resistin and IL-23 levels were significantly higher in EM stages III-IV than in stages I-II (p-value <0.05), and the serum resistin and IL-23 levels were also significantly (p-value <0.01) higher in stages III-IV than in stages I-II. The E2 level on the day of hCG administration and the implantation rate were both significantly lower in the EM group than in the control group. However, there were no differences in the Gn duration and dose, and the cleavage, implantation and clinical pregnancy rates between the 2 groups. CONCLUSIONS: Our results suggest that patients with EM exhibit increased resistin level in FF and serum. Advanced EM may contribute to infertility via decreased embryo implantation rates because of inflammation and immune rejection. No influence was observed on pregnancy outcomes after IVF-ET.

Protective effects of traditional Tibetan medicine Zuo-Mu-A Decoction () on the blood parameters and myocardium of high altitude polycythemia model rats.

OBJECTIVE: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats. METHODS: Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy. RESULTS: Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group. CONCLUSION: ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.

Carnosic acid nanoparticles suppress liver ischemia/reperfusion injury by inhibition of ROS, Caspases and NF-κB signaling pathway in mice.

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can lead to early graft injury. However, the detailed molecular mechanism of I/R injury remains unclear. Carnosic acid, as a phenolic diterpene with function of anti-inflammation, anti-cancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, is produced by many species from Lamiaceae family. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of carnosic acid nanoparticles was thought to be sufficient to lead to considerable inhibition of liver injury progression induced by ischemia/reperfusion. In our study, liver ischemia/reperfusion injury was established successfully with C57BL/6 animal model. 10 and 20mg/kg carnosic acid nanoparticles were injected to mice for five days prior to ischemia. After liver ischemia/reperfusion, the levels of serum AST, ALT and APL were increased, which was attenuated by pre-treatment with carnosic acid nanoparticles. In addition, carnosic acid nanoparticles inhibited ROS production via its related signals regulation. And carnosic acid nanoparticles also suppressed the ischemia/reperfusion-induced up-regulation in the pro-apoptotic protein and mRNA levels of Bax, Cyto-c, Apaf-1 and Caspase-9/3 while increased ischemia/reperfusion-induced decrease of anti-apoptotic factor of Bcl-2. Further, ischemia/reperfusion-induced inflammation was also inhibited for carnosic acid nanoparticles administration via inactivating NF-κB signaling pathway, leading to down-regulation of pro-inflammatory cytokines releasing. In conclusion, our study suggested that carnosic acid nanoparticles protected against liver ischemia/reperfusion injury via its role of anti-oxidative, anti-apoptotic and anti-inflammatory bioactivity.

MicroRNA-361-5p Inhibits Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma.

BACKGROUND/AIMS: A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC). METHODS: Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo. RESULTS: miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice. CONCLUSION: Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients.

Left Lateral Sectionectomy of the Native Liver and Combined Living-Related Liver-Kidney Transplantation for Primary Hyperoxaluria Type 1.

Primary hyperoxaluria type I (PH1), the most severe form of primary hyperoxalurias, is a liver disease of the metabolic defect in glyoxylate detoxification that can be corrected by liver transplantation. A 21-year-old man presented to our center after 4 months of regular hemodialysis for kidney failure caused by nephrolithiasis. A diagnosis of PH1 was confirmed by mutations of the AGXT gene. Left lateral sectionectomy of the native liver was performed; and auxiliary partial orthotopic liver transplantation (APOLT) and kidney transplantation were carried out synchronously using a living donor. After transplantation, the patient's plasma oxalate and creatinine levels substantially decreased and the patient recovered well with good dual grafts function. APOLT and kidney transplantation can compensate the liver deficient in liver enzyme production and aid the renal elimination of oxalate, thus serving as an effective treatment option for patients with PH1. In conclusion, left lateral sectionectomy of the native liver and combined living-related liver-kidney transplantation can be a surgical option for PH1.

[Study on indicator system for evaluating the adult health literacy in China].

OBJECTIVE: To establish a comprehensive evaluation indicator system for healthy literacy based on national survey data. METHOD: A multi-stage stratified sampling method was carried out to select the sample population in six provinces of China, which were adults aged 18 - 69 years old. The national health literacy questionnaire was used to investigate the sample populations. The answers were scored according to the error answer of 0, uncertain answer of 1 and the correct answer of 2. The degrees of difficulty and difference were calculated and be used to screen the indicators from the questionnaire as to establishing the comprehensive evaluation indicator system of the health literacy. The Cronbach alpha coefficient, correlation analysis, regression analysis and cluster analysis methods were used to assess the reliability and validity of the indicator system. RESULTS: The samples were 11 759 people, the valid questionnaires were 11 693 and the effective recovery rate was 99.4%, the Myer' index of sample was 4.92. There were 40 indexes selected to establish the comprehensive evaluation indicator system of health literacy. The correlation coefficient between indicator system and the questionnaire scores was 0.948 (P < 0.01), there were the significant differences between groups of being clustered by Q cluster analysis method (P < 0.01). The VIF of these four dimensions was less than 5. CONCLUSION: In this study, the comprehensive evaluation indicator system had a good reliability and validity, and there existed no collinearity among four dimensions of indicator system, it should be the foundation for developing comprehensive evaluation index of health literacy.

[Toxicological study of fresh water microcystins].

Microcystins are a group of toxins that are produced by fresh water cyanobacteria. They are bioactive materials which are hepatotoxic. They can inhibit serine/threonine protein phosphatase (PP1 and PP2A), breaking the balance between protein phosporylation and phosphorylysis. They present a wide range of harmful effects to human body, such as hepatotoxicity and tumor promotion. They also affect other organs like kidney and intestines. Recently, more and more attention is being paid to microcystins worldwide. This review summarizes the progress in the toxicological study of fresh water microcystins.