Liver Transplantation in China

Liver transplantation has been developed in Mainland China for about 40 years, from clinical trials to maturity. Its number has become the second in the world, its quality is also in line with the international level, and the source of donors has gradually transitioned to donation after citizen’s death (DCD). This chapter is aimed to elaborate the liver transplant work in China from the history and current status of liver transplantation, the main operating methods, major indications, donor maintenance and donor quality assessment, postoperative major complications, and application of immunosuppressive agents to the postoperative follow-up. Liver transplantation is a meaningful and challenging work currently in China; all the Chinese transplant surgeons and scholars are devoting themselves to this work in order to give more effective help to the patients

Association Between Vitamin D Receptor Gene Polymorphisms and Polycystic Ovary Syndrome Risk: A Meta-Analysis

Objective: Published studies have demonstrated a closer association between vitamin D receptor (VDR) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We therefore performed this meta-analysis to explore the precise associations between VDR gene polymorphisms and PCOS risk.Methods: Five online electronic databases (PubMed, Embase, SCI index, CNKI and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between VDR Fok I C/T (rs10735810), BsmI A/G (rs1544410), ApaI A/C (rs7975232), and TaqI T/C (rs731236) polymorphisms and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis and publication bias were conducted to check the statistical power.Results: Overall, 10 publications (31 independent case-control studies) involving 1,531 patients and 1,174 controls were identified. We found that the C mutation of ApaI A/C was a risk factor for PCOS (C vs. A: OR = 1.20, 95%CI = 1.06–1.35, P < 0.01, I2 = 29.7%; CC vs. AA: OR = 1.49, 95%CI = 1.17–1.91, P < 0.01, I2 = 0%; CC vs. AA+AC: OR = 1.36, 95%CI = 1.09–1.69, P = 0.01, I2 = 12.8%). Moreover, the BsmI A/G polymorphism also showed a dangerous risk for PCOS in Asian population (G vs. A: OR = 1.62, 95%CI = 1.24–2.11, P < 0.01, I2 = 0%; AG vs. AA: OR = 2.08, 95%CI = 1.26–3.20, P < 0.01, I2 = 0%; GG vs. AA: OR = 2.21, 95%CI = 1.29–3.77, P < 0.01, I2 = 0%; AG+GG vs. AA: OR = 2.12, 95%CI = 1.42–3.16, P < 0.01, I2 = 0%). In addition, no significant association of Fok I C/T, and TaqI T/C polymorphisms was observed.Conclusions: In summary, our meta-analysis suggested that VDR gene polymorphisms contribute to PCOS development, especially in Asian populations

Transcriptional regulation of BRD7 expression by Sp1 and c-Myc

<p>Abstract</p> <p>Background</p> <p>Bromodomain is an evolutionally conserved domain that is found in proteins strongly implicated in signal-dependent transcriptional regulation. Genetic alterations of bromodomain genes contributed to the development of many human cancers and other disorders. BRD7 is a recently identified bromodomain gene. It plays a critical role in cellular growth, cell cycle progression, and signal-dependent gene expression. Previous studies showed that BRD7 gene exhibited much higher-level of mRNA expression in normal nasopharyngeal epithelia than in nasopharyngeal carcinoma (NPC) biopsies and cell lines. However, little is known about its transcriptional regulation. In this study, we explored the transcriptional regulation of BRD7 gene.</p> <p>Method</p> <p>Potential binding sites of transcription factors within the promoter region of BRD7 gene were predicted with MatInspector Professional <url>http://genomatix.de/cgi-bin/matinspector_prof/mat_fam.pl</url>. Mutation construct methods and luciferase assays were performed to define the minimal promoter of BRD7 gene. RT-PCR and western blot assays were used to detect the endogenous expression of transcription factor Sp1, c-Myc and E2F6 in all cell lines used in this study. Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) were used to detect the direct transcription factors that are responsible for the promoter activity of BRD7 gene. DNA vector-based siRNA technology and cell transfection methods were employed to establish clone pools that stably expresses SiRNA against c-Myc expression in nasopharyngeal carcinoma 5-8F cells. Real-time PCR was used to detect mRNA expression of BRD7 gene in 5-8F/Si-c-Myc cells.</p> <p>Results</p> <p>We defined the minimal promoter of BRD7 gene in a 55-bp region (from -266 to -212bp), and identified that its promoter activity is inversely related to c-Myc expression. Sp1 binds to the Sp1/Myc-Max overlapping site of BRD7 minimal promoter, and slightly positively regulate its promoter activity. c-Myc binds to this Sp1/Myc-Max overlapping site as well, and negatively regulates the promoter activity and endogenous mRNA expression of BRD7 gene. Knock-down of c-Myc increases the promoter activity and mRNA level of BRD7 gene. The luciferase activity of the mutated promoter constructs showed that Sp1/Myc-Max overlapping site is a positive regulation element of BRD7 promoter.</p> <p>Conclusion</p> <p>These studies provide for the first time the evidence that c-Myc is indeed a negative regulator of BRD7 gene. These findings will help to further understand and uncover the bio-functions of BRD7 gene involved in the pathogenesis of NPC.</p

Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats

<p>Abstract</p> <p>Background</p> <p>Pulmonary vascular structure remodeling (PVSR) is a hallmark of pulmonary hypertension. P27^kip1, one of critical cyclin-dependent kinase inhibitors, has been shown to mediate anti-proliferation effects on various vascular cells. Beta-estradiol (β-E2) has numerous biological protective effects including attenuation of hypoxic pulmonary hypertension (HPH). In the present study, we employed β-E2 to investigate the roles of p27^kip1and its closely-related kinase (Skp-2) in the progression of PVSR and HPH.</p> <p>Methods</p> <p>Sprague-Dawley rats treated with or without β-E2 were challenged by intermittent chronic hypoxia exposure for 4 weeks to establish hypoxic pulmonary hypertension models, which resemble moderate severity of hypoxia-induced PH in humans. Subsequently, hemodynamic and pulmonary pathomorphology data were gathered. Additionally, pulmonary artery smooth muscle cells (PASMCs) were cultured to determine the anti-proliferation effect of β-E2 under hypoxia exposure. Western blotting or reverse transcriptional polymerase chain reaction (RT-PCR) were adopted to test p27^kip1, Skp-2 and Akt-P changes in rat lung tissue and cultured PASMCs.</p> <p>Results</p> <p>Chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of right ventricle/left ventricle plus septum (RV/LV+S) ratio, medial width of pulmonary arterioles, accompanied with decreased expression of p27^kip1in rats. Whereas, β-E2 treatment repressed the elevation of RVSP, RV/LV+S, attenuated the PVSR of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of p27^kip1. Study also showed that β-E2 application suppressed the proliferation of PASMCs and elevated the expression of p27^kip1under hypoxia exposure. In addition, experiments both <it>in vivo </it>and <it>in vitro </it>consistently indicated an escalation of Skp-2 and phosphorylated Akt under hypoxia condition. Besides, all these changes were alleviated in the presence of β-E2.</p> <p>Conclusions</p> <p>Our results suggest that β-E2 can effectively attenuate PVSR and HPH. The underlying mechanism may partially be through the increased p27^kip1by inhibiting Skp-2 through Akt signal pathway. Therefore, targeting up-regulation of p27^kip1or down-regulation of Skp-2 might provide new strategies for treatment of HPH.</p

Comparative Efficacy of Ivermectin and Levamisole for Reduction of Migrating and Encapsulated Larvae of Baylisascaris transfuga in Mice

The comparative efficacy of 2 anthelmintics (ivermectin and levamisole) against Baylisascaris transfuga migrating and encapsulated larvae was studied in mice. A total of 60 BALB/c mice inoculated each with about 1,000 embryonated B. transfuga eggs were equally divided into 6 groups (A-F) randomly. Mice of groups A and B were treated with ivermectin and levamisole, respectively, on day 3 post-infection (PI). Mice of groups A-C were killed on day 13 PI. Similarly, groups D and E were treated with ivermectin and levamisole, respectively, on day 14 PI, and all mice of groups D-F were treated on day 24 PI. The groups C and F were controls. Microexamination was conducted to count the larvae recovering from each mouse. The percentages of reduction in the number of migrating larvae recovered from group A (ivermectin) and B (levamisole) were 88.3% and 81.1%, respectively. In addition, the reduction in encapsulated larvae counts achieved by ivermectin (group D) and levamisole (group E) was 75.0% and 49.2%, respectively. The results suggested that, to a certain extent, both anthelmintics appeared to be more effective against migrating larvae than encapsulated larvae. However, in the incipient stage of infection, ivermectin may be more competent than levamisole as a larvicidal drug for B. transfuga

Metabolomic Analysis Uncovers Energy Supply Disturbance as an Underlying Mechanism of the Development of Alcohol‐Associated Liver Cirrhosis

Alcohol-associated liver disease (ALD) is caused by alcohol metabolism's effects on the liver. The underlying mechanisms from a metabolic view in the development of alcohol-associated liver cirrhosis (ALC) are still elusive. We performed an untargeted serum metabolomic analysis in 14 controls, 16 patients with ALD without cirrhosis (NC), 27 patients with compensated cirrhosis, and 79 patients with decompensated ALC. We identified two metabolic fingerprints associated with ALC development (38 metabolites) and those associated with hepatic decompensation (64 metabolites) in ALC. The cirrhosis-associated fingerprint (eigenmetabolite) showed a better capability to differentiate ALC from NC than the aspartate aminotransferase-to-platelet ratio index score. The eigenmetabolite associated with hepatic decompensation showed an increasing trend during the disease progression and was positively correlated with the Model for End-Stage Liver Disease score. These metabolic fingerprints belong to the metabolites in lipid metabolism, amino acid pathway, and intermediary metabolites in the tricarboxylic acid cycle. Conclusion: The metabolomic fingerprints suggest the disturbance of the metabolites associated with cellular energy supply as an underlying mechanism in the development and progression of alcoholic cirrhosis

Sex Differences in Abnormal Intrinsic Functional Connectivity After Acute Mild Traumatic Brain Injury

Mild traumatic brain injury (TBI) is considered to induce abnormal intrinsic functional connectivity within resting-state networks (RSNs). The objective of this study was to estimate the role of sex in intrinsic functional connectivity after acute mild TBI. We recruited a cohort of 54 patients (27 males and 27 females with mild TBI within 7 days post-injury) from the emergency department (ED) and 34 age-, education-matched healthy controls (HCs; 17 males and 17 females). On the clinical scales, there were no statistically significant differences between males and females in either control group or mild TBI group. To detect whether there was abnormal sex difference on functional connectivity in RSNs, we performed independent component analysis (ICA) and a dual regression approach to investigate the between-subject voxel-wise comparisons of functional connectivity within seven selected RSNs. Compared to female patients, male patients showed increased intrinsic functional connectivity in motor network, ventral stream network, executive function network, cerebellum network and decreased connectivity in visual network. Further analysis demonstrated a positive correlation between the functional connectivity in executive function network and insomnia severity index (ISI) scores in male patients (r = 0.515, P = 0.006). The abnormality of the functional connectivity of RSNs in acute mild TBI showed the possibility of brain recombination after trauma, mainly concerning male-specific

Breast cancer detection based on simplified deep learning technique with histopathological image using BreaKHis database

Presented here are the results of an investigation conducted to determine the effectiveness of deep learning (DL)-based systems utilizing the power of transfer learning for detecting breast cancer in histopathological images. It is shown that DL models that are not specifically developed for breast cancer detection can be trained using transfer learning to effectively detect breast cancer in histopathological images. The outcome of the analysis enables the selection of the best DL architecture for detecting cancer with high accuracy. This should facilitate pathologists to achieve early diagnoses of breast cancer and administer appropriate treatment to the patient. The experimental work here used the BreaKHis database consisting of 7909 histopathological pictures from 82 clinical breast cancer patients. The strategy presented for DL training uses various image processing techniques for extracting various feature patterns. This is followed by applying transfer learning techniques in the deep convolutional networks like ResNet, ResNeXt, SENet, Dual Path Net, DenseNet, NASNet, and Wide ResNet. Comparison with recent literature shows that ResNext-50, ResNext-101, DPN131, DenseNet-169 and NASNet-A provide an accuracy of 99.8%, 99.5%, 99.675%, 99.725%, and 99.4%, respectively, and outperform previous studies