Development and validation of a novel model to predict liver-related mortality in patients with idiosyncratic drug-induced liver injury.

BACKGROUND: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury (DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. METHODS: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve (AUC). A high-mortality-risk subgroup was identified according to the score. RESULTS: Three independent DILI cohorts, including one derivation cohort (n = 741) and two validation cohorts (n = 650, n = 617) were recruited. The DILI mortality predictive (DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin (mg/dL) + 0.439 × aspartate aminotransferase/alanine aminotransferase - 1.579 × albumin (g/dL) - 0.006 × platelet count (109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941 (95% CI: 0.922-0.957), 0.931 (0.908-0.949) and 0.960 (0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. CONCLUSIONS: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.

Association of PNPLA3 rs738409 G/C gene polymorphism with nonalcoholic fatty liver disease in children: a meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Current studies have shown that PNPLA3 (Patatin-like phospholipase domain containing 3) rs738409 G/C gene polymorphism is associated with adult nonalcoholic fatty liver disease [1, 2].But there is no consensus on the relationship between PNPLA3 rs738409 G/C gene polymorphism and children NAFLD due to differences in population samples. To this end, a meta-analysis of published research is conducted to comprehensively assess the relationship between PNPLA3 gene polymorphism and NAFLD in children. METHODS: We searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children's NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. The Stata 12.0 software was employed for data analysis. RESULTS: A total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children's NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR = 3.343, 95% CI = 1.524-7.334; GG + GC vs CC,OR = 3.157, 95% CI = 1.446-6.892;GG vs GC + CC,OR = 5.692, 95% CI = 1.941-16.689; GG + CC vs GC,OR = 2.756, 95% CI = 1.729-4.392). Four case-control studies compared Children with nonalcoholic fatty liver (NAFL) and children with nonalcoholic steatohepatitis (NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model (GG vs GC + CC,OR = 14.43, 95% CI = 5.985-34.997); The Egger's test revealed no significant publication bias. CONCLUSIONS: Meta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children.

Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth-most common malignancy worldwide. Multiple previous studies have assessed the relationship between TM6SF2 gene polymorphism and the risk of developing HCC, with discrepant conclusions reached. To assess the association of TM6SF2 rs58542926 T/C gene polymorphism with liver cancer, we performed the current meta-analysis. METHODS: This study queried the MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to April 2019. Case-control studies assessing the relationship between TM6SF2 rs5854292 locus polymorphism and liver cancer were selected according to inclusion and exclusion criteria. The Stata 12.0 software was employed for data analysis. RESULTS: A total of 5 articles, encompassing 6873 patients, met inclusion criteria and were included in the meta-analysis. Statistical analysis showed that the TM6SF2 gene polymorphism was significantly associated with liver cancer in the allele contrast, dominant, recessive and over dominant models (T vs C, OR = 1.621, 95%CI 1.379-1.905; CT + TT vs CC. OR = 1.541, 95%CI 1.351-1.758; TT vs CT + CC, OR = 2.897, 95%CI 1.690-4.966; CC + TT vs TC, OR = 0.693, 95%CI 0.576-0.834). The Egger's test revealed no significant publication bias. CONCLUSION: The present findings suggest a significant association of TM6SF2 gene polymorphism with HCC risk in the entire population studied.

Synthesis, Structure and Spectroscopy Study of a 1D Copper Coordination Polymer Based on a Carboxybenzyl Viologen Ligand and SCN-Anion.

A zwitterionic viologen derivative ligand, 1,1'-bis(4-carboxybenzyl)-4 4'-bipyridinium dichloride (H2BpybcCl2) as a multifunctional ligand, has been synthesized incorporating a 4,4'-bipyridine core with two carboxylate groups as a. building block, specifically designed for the rational construction of metal-organic frameworks. H2BpybcCl2 ligand is a multifunctional ligand that contains viologen's specific functions and carboxylate coordination groups. The coordination polymers of viologen carboxylate with copper thiocyanate are not reported to date. A novel copper coordination polymer, [Cu(SCN)2 (Bpybc)] (I) was by solution diffusion method and characterized by single-crystal X-ray diffraction, XRD, elemental analyses, IR spectroscopy, UV-Vis DRS, TG analysis and liquid-state luminescent properties. Compound I crystallized in the monoclinic system with C2/c space group. Crystal data for complex I is as follow: a=19. 508(4) A, b=9. 474(2) Å, c =16. 963(3) Å, α=90°, ß=124. 92(3)°, γ=90°. Two SCN-anions were coordinated to the Cu2+ cation forming a [Cu(SCN)2] unit. Complex I was built up by [Cu(SCN)2] units bridged sequentially by ladder-shaped Bpybc ligands to form one-dimensional zigzag chains running along the [203] direction. The chains were held together by π-π interaction between the pyridine rings and phenyl rings, thus yielding a 3-D extended supramolecular network. The UV-Visible absorption spectra show the absorption bands of π-π* transitions of Bpybc ligands and d-->d transition of Cu2+. The liquid-state luminescent property of compound I was investigated at room temperature. Attractively, the complex exhibits strong blue emission peak at 533 nm (λEx=360 nn) that can be assigned to intraligand transition of Bpybc ligand when it was excited at 360 nm.

Liver stiffness measurement is a potent predictor of histological fibrosis regression after hepatitis C virus clearance.

BACKGROUND: Most of the studies on fibrosis regression prediction were based on noninvasive fibrosis markers and differ greatly. The 'Beijing fibrosis classification' can use histological results to classify fibrosis into progressive or 'nonprogressive' according to fibrotic septal morphology. We use this standard which served as the gold standard in order to find fibrosis regression predictors. AIM: To study the predictors of fibrosis regression after hepatitis C virus clearance according to histological fibrosis staging by the 'Beijing fibrosis classification'. MATERIALS AND METHODS: This was a prospective cohort study. A total of 68 patients with advanced liver fibrosis or compensated cirrhosis who achieved sustained virological response were enrolled. Patients with the Ishak scores lower than 3 seemed to have fibrosis regression. The others were divided into the fibrosis progressive group and the nonprogressive group according to the 'Beijing fibrosis classification'. Predictors of fibrosis regression were studied by logistic regression using baseline factors and the dynamic change in noninvasive fibrosis factors. RESULTS: Eighteen patients were assigned to the progressive group, and the others were assigned to the nonprogressive group. The baseline liver stiffness measurements (LSMs) of the progressive and nonprogressive groups were 14.35 (11.3, 27.3) kPa and 11.3 (8.3, 14.2) kPa, respectively, P = 0.02. The baseline LSM was the only predictor of fibrosis progression. With a cutoff of 11.85 kPa, the AUC was 0.71 (0.5, 0.9), and the negative predictive value was 0.92. CONCLUSIONS: The baseline LSM was found to be the only predictor of fibrosis regression, 11.85 kPa is a possible 'hepatic fibrosis return point'.

Congenital syphilis: refining newborn evaluation and management in Shenzhen, southern China.

INTRODUCTION: Consistent definitions of congenital syphilis are critical for determining true incidences and setting up targets of elimination. This study aimed to assess the evaluation and management of infants at high risk of congenital syphilis with an antenatal syphilis-screening programme in the Shenzhen SEZ and to develop feasible definitions for the detection of congenital syphilis in China. METHODS: A retrospective study was conducted of all standardised records of pregnant women with positive syphilis between 2003 and 2007. Infants at high risk of congenital syphilis were evaluated by laboratory tests at birth and longitudinal follow-up. A screening test-positive congenital syphilis case was defined based on a positive 19S-IgM-FTA-ABS result at birth. Assuming that 19S-IgM-FTA-ABS was the gold standard, the sensitivity and specificity of the ascertainment methods were calculated. RESULTS: During the study period, 1010 live infants were born to women with active syphilis during pregnancy. 19S-IgM-FTA-ABS detected 42 screening-positive congenital syphilis cases and another nine cases were identified by longitudinal follow-up only. Using 19S-IgM-FTA-ABS as the gold standard, 'fourfold rapid plasma reagin (RPR) titres' had the highest sensitivity and specificity compared with the other two follow-up methods. DISCUSSION: 19S-IgM-FTA-ABS makes congenital syphilis case classification simpler and faster for newborns. In areas where 19S-IgM-FTA-ABS is not available, comparing newborn RPR titres with maternal titres can be an alternative method. Meanwhile, positive follow-up results act as treatment indicators for older infants. As congenital syphilis definitions vary over the country, the Shenzhen programme suggested a practical model for surveillance and treatment in areas with or without available 19S-IgM-FTA-ABS testing.

[Application of genetic algorithm in formulation optimization of microemulsion for transdermal delivery].

Using naproxen as model drug, the formulation of microemulsion vehicle for transdermal delivery was optimized by genetic algorithm. The ranges of microemulsion composed of Tween 80, IPM, alcohol and water, were defined through construction of the pseudo-ternary phase diagrams. Systematic model microemulsions containing naproxen 1.12% were prepared by a three-factor, three-level center design method, and their diffusion studies via excised rabbit skin were performed. Using the quadratic regression model of steady-state permeation rate (Js) of naproxen as objective function, the consequence of center design experiment was optimized by genetic algorithm, and the formulation of microemulsion with highest permeation rate for naproxen was screened. The optimum formulation was composed of 21.41% Tween 80, 15.17% alcohol, 4.14% IPM, and 59.28% water, and the anticipated Js was 183.57 microg x cm(-2) x h(-1). The results of back substitution test showed the steady-state permeation rate of naproxen microemulsion prepared according to optimum formulation was 189.43 microg x cm(-2) x h(-1), which was higher than anticipated value. This result demonstrated optimizing formulation of microemulsion for transdermal delivery by genetic algorithm is feasible, reliable and reasonable.

Association between N-terminal proB-type Natriuretic Peptide and Depressive Symptoms in Patients with Acute Myocardial Infarction.

BACKGROUND: While depression and certain cardiac biomarkers are associated with acute myocardial infarction (AMI), the relationship between them remains largely unexplored. We examined the association between depressive symptoms and biomarkers in patients with AMI. METHODS: We performed a cross-sectional study using data from 103 patients with AMI between March 2013 and September 2014. The levels of depression, N-terminal proB-type natriuretic peptide (NT-proBNP), and troponin I (TnI) were measured at baseline. The patients were divided into two groups: those with depressive symptoms and those without depressive symptoms according to Zung Self-rating Depression Scale (SDS) score. Baseline comparisons between two groups were made using Student's t-test for continuous variables, Chi-square or Fisher's exact test for categorical variables, and Wilcoxon test for variables in skewed distribution. Binomial logistic regression and multivariate linear regression were performed to assess the association between depressive symptoms and biomarkers while adjusting for demographic and clinical variables. RESULTS: Patients with depressive symptoms had significantly higher NT-proBNP levels as compared to patients without depressive symptoms (1135.0 [131.5, 2474.0] vs. 384.0 [133.0, 990.0], Z = -2.470, P = 0.013). Depressive symptoms were associated with higher NT-proBNP levels (odds ratio [OR] = 2.348, 95% CI: 1.344 to 4.103, P = 0.003) and higher body mass index (OR = 1.169, 95% confidence interval [CI]: 1.016 to 1.345, P = 0.029). The total SDS score was associated with the NT-proBNP level (ß= 0.327, 95% CI: 1.674 to 6.119, P = 0.001) after multivariable adjustment. In particular, NT-proBNP was associated with three of the depressive dimensions, including core depression (ß = 0.299, 95% CI: 0.551 to 2.428, P = 0.002), cognitive depression (ß = 0.320, 95% CI: 0.476 to 1.811, P = 0.001), and somatic depression (ß = 0.333, 95% CI: 0.240 to 0.847, P = 0.001). Neither the overall depressive symptomatology nor the individual depressive dimensions were associated with TnI levels. CONCLUSIONS: Depressive symptoms, especially core depression, cognitive depression, and somatic depression, were related to high NT-proBNP levels in patients with AMI.

Spatial transmission and meteorological determinants of tuberculosis incidence in Qinghai Province, China: a spatial clustering panel analysis.

BACKGROUND: Tuberculosis (TB) is the notifiable infectious disease with the second highest incidence in the Qinghai province, a province with poor primary health care infrastructure. Understanding the spatial distribution of TB and related environmental factors is necessary for developing effective strategies to control and further eliminate TB. METHODS: Our TB incidence data and meteorological data were extracted from the China Information System of Disease Control and Prevention and statistical yearbooks, respectively. We calculated the global and local Moran's I by using spatial autocorrelation analysis to detect the spatial clustering of TB incidence each year. A spatial panel data model was applied to examine the associations of meteorological factors with TB incidence after adjustment of spatial individual effects and spatial autocorrelation. RESULTS: The Local Moran's I method detected 11 counties with a significantly high-high spatial clustering (average annual incidence: 294/100 000) and 17 counties with a significantly low-low spatial clustering (average annual incidence: 68/100 000) of TB annual incidence within the examined five-year period; the global Moran's I values ranged from 0.40 to 0.58 (all P-values < 0.05). The TB incidence was positively associated with the temperature, precipitation, and wind speed (all P-values < 0.05), which were confirmed by the spatial panel data model. Each 10 °C, 2 cm, and 1 m/s increase in temperature, precipitation, and wind speed associated with 9 % and 3 % decrements and a 7 % increment in the TB incidence, respectively. CONCLUSIONS: High TB incidence areas were mainly concentrated in south-western Qinghai, while low TB incidence areas clustered in eastern and north-western Qinghai. Areas with low temperature and precipitation and with strong wind speeds tended to have higher TB incidences.

A fluorescent, photochromic and thermochromic trifunctional material based on a layered metal-viologen complex.

The azide anion as an energy acceptor and an electron donor has been introduced into a metal-viologen compound to form a 2D layered viologen-based trifunctional material, which exhibits the rare discolored function of reversible photochromism and thermochromism. Interestingly, its fluorescence can be switched by visible light irradiation and heating in air.