[Analysis of the prognosis of isolated ventriculomegaly and outcome of imaging follow-up].

Objective: To evaluate the clinical outcome of fetus diagnosed as mild and moderate isolated ventriculomegaly (IVM) and its correlation with imaging follow-up. Methods: Totally, 161 cases of single pregnancy whose fetus was diagnosed as mild or moderate IVM by ultrasound were administrated. Data of prenatal ultrasound examination, pregnancy outcomes, and the postnatal MRI results were collected. New borns' growth and development, language expression, movement coordination, auditory and visual function were followed up to evaluate the neurodevelopment. Results: (1) Before birth: 80.1% (129/161) of IVM disappeared before the delivery, 16.1% (26/161) remained stable, and 3.7% (6/161) continued to deteriorate. (2) Postnatal MRI: 8 cases (9.6%, 8/83) were diagnosed IVM, of which 3 cases were found additional abnormalities (1 case was the corpus callosum dysplasia and 2 cases were leukodystrophy) . The additional abnormal detection rate was 3/8. (3) Postnatal assessments: There were 7 cases (8.9%, 7/79) neunatal behavioral neurological assessment (NBNA) , 6 cases (7.6%, 6/79) Bayley scales of infant development (BSID) -psychomotor developmental index (PDI) and 3 cases (3.8%, 3/79) BSID-mental development index (MDI) whose scores were low. There was no significant difference of the NBNA and BSID scores between mild and moderate IVM (NBNA: χ(2)=2.042, P=0.210; BSID-PDI: χ(2)=-1.359, P=0.174; BSID-MDI: χ(2)=-1.205, P=0.228) . Follow-up of 9 cases (11.4%, 9/79) with low BSID score, 6 of them were found to be stable in the medial ventricle of the uterus, and the size of the lateral ventricle was normal after birth by ultrasound and MRI. Conclusions: The majority of IVM fetuses have good prognosis, but there is also a risk of neurodevelopmental dysplasia. The postnatal follow-up should be paid attention to, and MRI should be performed as the postnatal imaging evaluation.

Significant impacts of CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the pharmacokinetics of diltiazem and its main metabolites in Chinese adult kidney transplant patients.

WHAT IS KNOWN AND OBJECTIVE: The calcium channel blocker diltiazem has been used widely as a cyclosporine (CsA)/tacrolimus-sparing agent. However, considerable interpatient variability in diltiazem's CsA/tacrolimus-sparing effect has been observed in many clinical studies. This study was carried out to investigate the impacts of the CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients. METHODS: Two hundred and twenty-five Chinese renal transplant patients were genotyped for CYP3A4*1G and CYP3A5*3. The predose and post-dose plasma concentrations of diltiazem and its main metabolisms were determined by HPLC. The relationships between the genotypes and pharmacokinetics were investigated. RESULTS AND DISCUSSION: The dose-adjusted concentrations and pharmacokinetics of diltiazem and its main metabolites were significantly affected by CYP3A4 *1G and CYP3A5*3 alleles. Patients with a CYP3A4*1/*1 genotype were found to have a higher dose-adjusted trough concentration and AUC of diltiazem and its main metabolites compared with those with CYP3A4*1G*1G(P<0·05). The dose-adjusted trough levels and AUC of diltiazem and its main metabolites were significantly lower in CYP3A5*1*1 carriers than in CYP3A5*3 carriers (P < 0·05). WHAT IS NEW AND CONCLUSION: The CYP3A4*1G and CYP3A5*3 genetic polymorphisms are closely related to the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients.

The Scar-in-a-Jar: studying potential antifibrotic compounds from the epigenetic to extracellular level in a single well.

BACKGROUND AND PURPOSE: Fibrosis, a pathological accumulation of collagen in tissues, represents a major global disease burden. Effective characterization of potential antifibrotic drugs has been constrained by poor formation of the extracellular matrix in vitro, due to tardy procollagen processing by collagen C-proteinase/BMP-1, and difficulties in relating this matrix to cell numbers in experimental samples. EXPERIMENTAL APPROACH: The Scar-in-a-Jar model provided, in vitro, the complete biosynthetic cascade of collagen matrix formation including complete conversion of procollagen by C-proteinase/BMP-1, its subsequent extracellular deposition and lysyl oxidase-mediated cross-linking, achieved by applying the biophysical principle of macromolecular 'crowding'. Collagen matrix deposition, velocity and morphology can be controlled using negatively charged 'crowders' in a rapid (2 days) mode or a mixture of neutral 'crowders' in an accelerated (6 days) mode. Combined with quantitative optical bioimaging, this novel system allows for in situ assessment of the area of deposited collagen(s) per cell. KEY RESULTS: Optical evaluation of known and novel antifibrotic compounds effective at the epigenetic, post-transcriptional/translational/secretional level correlated excellently with corresponding biochemical analyses. Focusing on quantitation of deposited collagen, the Scar-in-a-Jar was most effective in assessing novel inhibitors that may have multiple targets, such as microRNA29c, found to be a promising antifibrotic agent. CONCLUSIONS AND IMPLICATIONS: This novel screening system supersedes current in vitro fibroplasia models, as a fast, quantitative and non-destructive technique. This method distinguishes a reduction in collagen I deposition, excluding collagen cross-linking, and allows full evaluation of inhibitors of C-proteinase/BMP-1 and other matrix metalloproteinases.