Effect of platelet level and platelet parameters on the prognosis of patients with acute-on-chronic liver failure / 临床肝胆病杂志

Objective To investigate the differences in platelet and platelet parameters between patients with different types and etiologies of acute-on-chronic liver failure (ACLF) and the influence of platelet and its dynamic change on the prognosis of ACLF patients. Methods Clinical data, liver function parameters, platelet, and platelet parameters were collected from 364 patients with ACLF who attended Tianjin Third Central Hospital from January 2014 to December 2018. Platelet level and platelet parameters (platelet distribution width and mean platelet volume) were compared between the patients with different types and etiologies of ACLF, and their influence on the 90-day mortality rate of ACLF patients was analyzed, as well as the association of the dynamic change of platelet at baseline and on days 7 and 14 after admission with the prognosis of patients. The chi-square test was used for comparison of categorical data between groups; the Kruskal-Wallis H test or Mann-Whitney U test was used for comparison of continuous data between groups; the Kaplan-Meier method was used for survival analysis; the univariate and multivariate Cox regression analyses were used to analyze the parameters associated with prognosis; the repeated measures analysis of variance was used to analyze the dynamic change of platelet; receiver operating characteristic (ROC) curve was plotted based on platelet level and overall survival. Results The patients with type C ACLF had a significantly lower platelet level than those with type A/B ACLF (all P < 0.001). Compared with the ACLF patients with hepatitis B, the ACLF patients with autoimmune liver diseases had a significant reduction in mean platelet volume ( P =0.035). Based on the cut-off value obtained by the ROC curve analysis, the patients with a platelet level of < 60.5×10 9 /L had a significantly higher mortality rate than those with a platelet level of ≥60.5×10 9 /L ( P =0.006). Platelet level was an independent protective factor against 90-day death in ACLF patients (hazard ratio=0.995, 95% confidence interval: 0.990-0.999, P =0.026), and the mortality rate increased with the reduction in platelet level. The patients with type C ACLF had a significantly higher mortality rate than those with type A ACLF ( P < 0.05), and the death group tended to have a significantly greater reduction in platelet level ( P < 0.05). Compared with the survival group, the 90-day death group had a significantly greater reduction in platelet ( P =0.032). Conclusion There is a difference in platelet level between ACLF patients with different types. Platelet level is an important indicator for the 90-day prognosis of ACLF patients, and patients with a greater dynamic reduction in platelet tend to have a higher 90-day mortality rate.

Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression / 医学前沿

Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in γ-secretase component genes. We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In Ncstn;K5-Cre mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF-α, IL-23A, IL-1β, and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the Ncstn;K5-Cre mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.

Screening of LDLR gene mutations in nine patients with familial hypercholesterolemia / 中华医学遗传学杂志

OBJECTIVE@#To screen for LDLR gene mutations in 9 patients with familial hypercholesterolemia (FH).@*METHODS@#All exons of the LDLR gene and flanking intronic sequences were amplified by PCR and subjected to automatic DNA sequencing. For patients with homozygous or compound heterozygous mutations, parental DNA sequencing or T cloning sequencing was carried out to determine the parental origin of the mutant alleles.@*RESULTS@#Direct sequencing of PCR products revealed 8 LDLR variants in 7 patients, which included c.259T>G, c.513delC, c.530C>T, c.682G>T, c.763C>T, c.1187-10G>A, c.1948delG, and c.1730G>A, among which c.1948delG was novel. Four patients have carried heterozygous mutations, two carried homozygous mutations, and one carried compound heterozygous mutations. The patients with biallelic mutations presented with a more severe phenotype compared those carrying heterozygous mutations.@*CONCLUSION@#LDLR mutations were identified in 7 out of 9 patients with FH. Among the 8 identified LDLR mutations, c.1948delG was firstly reported. Above findings have expanded the mutation spectrum of LDLR gene.

The 463rd case: rhabdomyolysis, acute kidney failure and acute hepatic failure / 中华内科杂志

We represented a 22-year-old male patient who developed rhabdomyolysis,acute kidney failure and acute hepatic failure and was finally diagnosed as multiple acyl-CoA dehydrogenase deficiency.The patient appeared temporary stable status after high dose vitamine-B2 supplement whereas deterioration was still fatal with pulmonary infection,acute respiratory failure and acute heart failure.

Genetic Testing of the mucin 1 gene-Variable Number Tandem Repeat Single Cytosine Insertion Mutation in a Chinese Family with Medullary Cystic Kidney Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Medullary cystic kidney disease (MCKD) is clinically indistinguishable from several other autosomal-dominant renal diseases; thus, molecular genetic testing is needed to establish a definitive diagnosis. A specific type of single cytosine insertion in the variable number tandem repeat (VNTR) of the mucin 1 (MUC1) gene is the only known cause of MCKD1; however, genetic analysis of this mutation is difficult and not yet offered routinely. To identify the causative mutation/s and establish a definitive diagnosis in a Chinese family with chronic kidney disease, clinical assessments and genetic analysis were performed, including using a modified genotyping method to identify the MUC1- VNTR single cytosine insertion.</p><p><b>METHODS</b>Clinical data from three patients in a Chinese family with chronic kidney disease were collected and evaluated. Linkage analysis was used to map the causative locus. Mutation analysis of uromodulin (UMOD) gene was performed using polymerase chain reaction (PCR) and direct sequencing. For MUC1 genotyping, the mutant repeat units were enriched by MwoI restriction, and then were amplified and introduced into pMD-18T vectors. The 192 clones per transformant were picked up and tested by colony PCR and second round of MwoI digestion. Finally, Sanger sequencing was used to confirm the MUC1 mutation.</p><p><b>RESULTS</b>Clinical findings and laboratory results were consistent with a tubulointerstitial lesion. Linkage analysis indicated that the family was compatible with the MCKD1 locus. No mutations were found in UMOD gene. Using the modified MUC1 genotyping method, we detected the MUC1-VNTR single cytosine insertion events in three patients of the family; and mutation-containing clones were 12/192, 14/192, and 5/96, respectively, in the three patients.</p><p><b>CONCLUSIONS</b>Clinical and genetic findings could support the MCKD1 diagnosis. The modified strategy has been demonstrated to be a practical way to detect MUC1 mutation.</p>

Identification of a novel mutation in solute carrier family 29, member 3 in a Chinese patient with H syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>H syndrome (OMIM 612391) is a recently described autosomal recessive genodermatosis characterized by indurated hyperpigmented and hypertrichotic skin, as well as other systemic manifestations. Most of the cases occurred in the Middle East areas or nearby countries such as Spain or India. The syndrome is caused by mutations in solute carrier family 29, member 3 (SLC29A3), the gene encoding equilibrative nucleoside transporter 3. The aim of this study was to identify pathogenic SLC29A3 mutations in a Chinese patient clinically diagnosed with H syndrome.</p><p><b>METHODS</b>Peripheral blood samples were collected from the patient and his parents. Genomic DNA was isolated by the standard method. All six SLC29A3 exons and their flanking intronic sequences were polymerase chain reaction (PCR)-amplified and the PCR products were subjected to direct sequencing.</p><p><b>RESULTS</b>The patient, an 18-year-old man born to a nonconsanguineous Chinese couple, had more extensive cutaneous lesions, involving both buttocks and knee. In his genomic DNA, we identified a novel homozygous insertion-deletion, c. 1269_1270delinsA, in SLC29A3. Both of his parents were carriers of the mutation.</p><p><b>CONCLUSIONS</b>We have identified a pathogenic mutation in a Chinese patient with H syndrome.</p>