Prognostic Factors Related to In-hospital Death in Children with Biliary Atresia: Analysis of a Nationwide Inpatient Database.

Background and Aims: Patients with biliary atresia (BA) are prone to hepatic decompensation, which might eventually lead to death. This study aimed to identify the possible risk factors affecting in-hospital death in BA patients in China. Methods: We collected data from the Hospital Quality Monitoring System, a national inpatient database. All patients aged up to 2 years old with a diagnosis of BA were included. The subjects were divided to three groups, including Kasai portoenterostomy (KP), liver transplantation (LT), and no surgery. Logistic regression with Firth's method was performed to identify potential influencing variables associated with in-hospital death. Results: During the year 2013 to 2017, there were 14,038 pediatric admissions with a diagnosis of BA. The proportion of in-hospital death in pediatric BA admissions was 1.08%. Compared with patients under six months, there was a higher risk of in-hospital death for children aged six months to 1 year and 1-2 years old. Clinical signs, including cirrhosis, variceal bleeding, and hepatic encephalopathy, were significantly associated with the risk of in-hospital death. In no surgery group, compared to those in Beijing and Shanghai, BA patients admitted in other districts had a lower risk of in-hospital death (OR=0.39, 95% CI: 0.21, 0.70). However, in the LT group, patients admitted in other districts had a higher risk of in-hospital death (OR=9.13, 95% CI: 3.99, 20.87). Conclusions: In-hospital survival remains unsatisfactory for pediatric BA patients with severe complications. Furthermore, more resources and training for BA treatment, especially LT, are essential for districts with poor medical care in the future.

Whole-exome sequencing reveals POLR3B variants associated with progeria-related Wiedemann-Rautenstrauch syndrome.

BACKGROUND: Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive neonatal progeroid disorder characterized by prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, and mental impairment. CASE PRESENTATION: A 6-year-old patient, who initially presented with multiple postnatal abnormalities, facial dysplasia, micrognathia, skull appearance, hallux valgus, and congenital dislocation of the hip, was recruited in this study. The patient was initially diagnosed with progeria. The mother of the patient had abnormal fetal development during her second pregnancy check-up, and the clinical phenotype of the fetus was similar to that of the patient. Whole-exome sequencing (WES) of the patient was performed, and POLR3B compound heterozygous variants-c.2191G > C:p.E731Q and c.3046G > A:p.V1016M-were identified in the patient. Using Sanger sequencing, we found that the phenotypes and genotypes were segregated within the pedigree. These two variants are novel and not found in the gnomAD and 1000 Genomes databases. The two mutation sites are highly conserved between humans and zebrafish. CONCLUSIONS: Our study not only identified a novel WRS-associated gene, POLR3B, but also broadened the mutational and phenotypic spectra of POLR3B. Furthermore, WES may be useful for identifying rare disease-related genetic variants.

Multicenter prospective study to validate a new transient elastography device for staging liver fibrosis in patients with chronic hepatitis B.

OBJECTIVES: To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS: In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to < 0.0001). Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively. CONCLUSION: FibroTouch has a high success rate and good reliability in staging liver fibrosis in patients with CHB.

Non-obese patients with nonalcoholic fatty liver disease may use a lower liver stiffness cut-off to assess fibrosis stages.

OBJECTIVE: We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). METHODS: NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. RESULTS: A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. CONCLUSIONS: Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

Nicotinamide phosphoribosyltransferase aggravates inflammation and promotes atherosclerosis in ApoE knockout mice.

Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme of nicotinamide adenine dinucleotide (NAD) salvage biosynthesis in mammals, and is involved in fundamental physiological processes and pathophysiology of many diseases. Thus far, however, the role of Nampt in atherosclerosis development is still in debate. In this study, we crossed global Nampt transgenic mice (Nampt-Tg) with a well-established atherosclerosis animal model (ApoE knockout mice, ApoE-/-) to generate ApoE-/-;Nampt-Tg mice and investigated the effects of Nampt overexpression on atherosclerosis development in ApoE-/- mice. Both ApoE-/- and ApoE-/-;Nampt-Tg mice were fed with a pro-atherosclerotic high-fat diet (HFD) for 16 weeks. Their serum lipid contents and atherosclerotic lesion were assessed. The results showed that there was no significant difference in body weight or serum levels of glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol between the two strains of mice, but ApoE-/-;Nampt-Tg mice had a significantly higher level of serum non-esterified fatty acid. Compared with ApoE-/- mice, ApoE-/-;Nampt-Tg mice displayed significantly increased atherosclerotic lesion area and thickness, lower collagen content, decreased collagen I/III ratio (collagen immaturation), increased number of apoptotic cells, and enhanced activities of caspase-3, caspase-8, and caspase-9. Moreover, macrophage infiltration (F4/80 staining), tumor necrosis factor signaling, and chemokines expression (ICAM-1 and CXCR-4) were all activated in aortic atherosclerotic plaque of ApoE-/-;Nampt-Tg mice compared with ApoE-/- mice. Our results provide in vivo evidence that Nampt transgene aggravates atherosclerotic inflammation and promotes atherosclerosis development in ApoE-/- mice.

MagT1 regulated the odontogenic differentiation of BMMSCs induced byTGC-CM via ERK signaling pathway.

BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) are suitable cell sources for dental pulp regeneration, but the mechanism of BMMSCs differentiation into odontogenic lineage remains unknown. The aim of the present study was to reveal the role of magnesium transporter protein 1 (MagT1) and MAPK pathways in the odontogenic differentiation of BMMSCs. METHODS: The RNA sequencing (RNA-seq) was performed to explore the altered transcriptome of BMMSCs undergoing odontogenic differentiation induced by tooth germ cell-condition medium (TGC-CM). Pathway analysis was conducted to explore enriched pathways of the differential expression signature. Automated western blot, real-time PCR, shRNA lentivirus, and flow cytometry were used to detect the function of MagTl and MAPK pathway in odontogenic differentiation of BMMSCs. RESULTS: RNA-seq identified 622 differentially expressed genes associated with odontogenic differentiation of BMMSCs induced by TGC-CM, some of which were responsible for MAPK pathway. Consistently, we verified that TGC-CM induced odontogenic differentiation of BMMSCs through activating ERK/MAPK pathway, and the inactivation of ERK/MAPK pathway inhibited the odontogenic differentiation induced by TGC-CM. We also found MagT1 protein was significantly increased during odontogenic differentiation of BMMSCs induced by TGC-CMM, in accordance, MagT1 knockdown significantly decreased the extent of mineralized nodules and the protein levels of alkaline phosphatase (ALP), dentin matrix protein 1 (DMP-1), and dentin sialophosphoprotein (DSP). Flow cytometry showed that intracellular Mg2+ was significantly reduced in MagT1-knockdown BMMSCs, indicating the suppression of MagT1 inhibited odontogenic differentiation of BMMSCs by decreasing intracellular Mg2+. Finally, we performed RNA-seq to explore the altered transcriptome of MagT1-knockdown BMMSCs undergoing odontogenic differentiation and identified 281 differentially expressed genes, some of which were involved in MAPK pathway. Consistently, automated western blot analysis found the ERK/MAPK pathway was inhibited in MagT1-knockdown BMMSCs during odontogenic differentiation, indicating that suppression of MagT1 inhibited odontogenic differentiation of BMMSCs via ERK/MAPK pathway. CONCLUSIONS: This study identified the significant alteration of transcriptome in BMMSCs undergoing odontogenic differentiation induced by TGC-CM. We clarified the pivotal role of MagT1 and ERK/MAPK pathway in odontogenic differentiation of BMMSCs, and suppression of MagT1 inhibited the odontogenic differentiation of BMMSCs by decreasing the intracellular Mg2+ and inactivating ERK/MAPK pathway.

Influence of thermocycling on shear bond strength of glass ionomer cement to Er:YAG laser-prepared enamel.

PURPOSE: To evaluate the long-term influence of the shear bond strength (SBS) on glass-ionomer cement (GIC) to Er:YAG-irradiated and bur-prepared enamel. MATERIALS AND METHODS: One hundred and ninety human premolar and molars were selected and the crowns were sectioned. Samples were divided into five groups, according to surface treatments: bur preparation (B); bur preparation, etching with 37% phosphoric acid (BA); laser preparation (L); laser preparation, etching with 37% phosphoric acid (LA); laser preparation, twice irradiating with laser at low (150 mJ, 10 Hz; water spray 10 ml/min) (LL). Samples were subdivided according to the number of thermo-cycles (TCs)-500 TCs, 1,000 TCs, 3,000 TCs, and 5,000 TCs. The SBS between GIC and enamel was measured using a universal testing machine; failure patterns were analyzed with stereomicroscope. The enamel surfaces and the patterns of the junction between GIC and enamel were observed by scanning electronic microscopy (SEM). RESULTS: The SBS of L group was higher than that for the B group (P < 0.05). The failure mode analysis demonstrated a cohesive failure within the cement in BA and LA groups, but the SBS of LA group was higher than that for the BA group (P < 0.05). LL had a similar effect on SBS compared with LA. Thirty-seven percent phosphoric acid had greatly increased SBS of GIC to enamel (P < 0.05). The SBS was significantly affected by thermocycling (TC) (P < 0.05). CONCLUSION: Our results showed that Er:YAG irradiated significantly increased the SBS on GIC to enamel than bur-prepared enamel. In addition, 37% phosphoric acid pretreated also significantly increased the SBS on GIC to enamel. However, the results of these in vitro tests were limited, and extrapolation to the clinical situation was difficult. Thus, further studies were needed on this subject to simulate the highly complex and dynamic environment in the analysis. Lasers Surg. Med. 48:978-984, 2016. © 2015 Wiley Periodicals, Inc.

[Effect of Chinese herbs for nourishing shen-yin and removing xiang-fire on estrogen receptor expression in reproductive organ of rats contaminated with environmental endocrine disruptor].

OBJECTIVE: To investigate the effect of Chinese herbs for nourishing Shen-yin and removing Xiang-fire (NYRF) on estrogen receptor (ER) expression in uterus and ovary of rats contaminated with nonylphenol (NP) or its bisphenol A (BPA) mixture, for exploring the action mechanism of NYRF in antagonizing the estrogen-mimetic activity of environmental endocrine disruptors (EEDs). METHODS: EEDs contaminated female SD rats, 3-week old, were divided into two groups, the treated group fed with NYRF and the control group with corn oil during the same period of contaminating for 15 days. The wet weight (WW) and organ coefficient (OC) of uterus in rats, as well as the ER protein and mRNA expressions in rat's uterus and ovary were detected and compared. RESULTS: As compared with normal range, WW and OC increased significantly in the contaminated rats of the control group, with significantly down-regulated ER protein expression in uterus, and expressions of ER alpha and ER beta gene and protein in ovary (P<0.05). While in the treated group, the above-mentioned abnormalities of various indicators were markedly reversed to a certain extent (P<0.05). CONCLUSION: EEDs show estrogenic-mimetic action on productive organs, which could be antagonized by NYRF, resulting in the down-regulated mRNA and protein expressions of ER in reproductive organs, so as to reduce the sensibility of reproductive organs to EEDs, which is probably one of the acting mechanisms of NYRF.