Novel Pathogenic Mutation of PNPLA1 Identified in Autosomal Recessive Congenital Ichthyosis: A Case Report / 中国医学科学杂志(英文版)

Autosomal recessive congenital ichthyosis (ARCI) is characterized by being born as collodion babies, hyperkeratosis, and skin scaling. We described a collodion baby at birth with mild ectropion, eclabium, and syndactyly. Whole exome sequencing showed a compound heterozygous variant c.[56C>A], p.(Ser19X) and c.[100G>A], p.(Ala34Thr) in the PNPLA1 gene [NM_001145717; exon 1]. The protein encoded by PNPLA1 acts as a unique transacylase that specifically transfers linoleic acid from triglyceride to ω-hydroxy fatty acid in ceramide, thus giving rise to ω-O-acylceramide, a particular class of sphingolipids that is essential for skin barrier function. The variant was located in the patatin core domain of PNPLA1 and resulted in a truncated protein which could disrupt the function of the protein. This case report highlights a novel compound heterozygous mutation in PNPLA1 identified in a Chinese child.

Molecular structures and functional exploration of NDA family genes respond tolerant to alkaline stress in Gossypium hirsutum L

BACKGROUND: The internal NAD(P)H dehydrogenase (NDA) gene family was a member of the NAD(P)H dehydrogenase (ND) gene family, mainly involved in the non-phosphorylated respiratory pathways in mitochondria and played crucial roles in response to abiotic stress. METHODS: The whole genome identification, structure analysis and expression pattern of NDA gene family were conducted to analyze the NDA gene family. RESULTS: There were 51, 52, 26, and 24 NDA genes identified in G. hirsutum, G. barbadense, G. arboreum and G. raimondii, respectively. According to the structural characteristics of genes and traits of phylogenetic tree, we divided the NDA gene family into 8 clades. Gene structure analysis showed that the NDA gene family was relatively conservative. The four Gossypium species had good collinearity, and segmental duplication played an important role in the evolution of the NDA gene family. Analysis of cis-elements showed that most GhNDA genes contained cis-elements related to light response and plant hormones (ABA, MeJA and GA). The analysis of the expression patterns of GhNDA genes under different alkaline stress showed that GhNDA genes were actively involved in the response to alkaline stress, possibly through different molecular mechanisms. By analyzing the existing RNA-Seq data after alkaline stress, it was found that an NDA family gene GhNDA32 was expressed, and then theGhNDA32 was silenced by virus-induced gene silencing (VIGS). By observing the phenotype, we found that the wilting degree of silenced plants was much higher than that of the control plant after alkaline treatment, suggesting that GhNDA32 gene was involved in the response to alkaline stress. CONCLUSIONS: In this study, GhNDAs participated in response to alkaline stress, especially NaHCO3 stress. It was of great significance for the future research on the molecular mechanism of NDA gene family in responding to abiotic stresses.

Modulation effect of Acanthopanax senticosus polysaccharides through inflammatory cytokines in protecting immunological liver-injured mice / 中国中药杂志

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1β) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1β and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.

MRI evaluation on morphology and function of iliococcygeal muscles in fertile and nulliparous women / 中国医学影像技术

Objective To observe the value of MRI in evaluation on the morphology and function of iliococcygeal muscles in fertile and nulliparous women.Methods Totally 50 healthy fertile women (fertile group,further divided into cesarean section subgroup and spontaneous delivery subgroup according to the mode of delivery) and 17 nulliparous healthy women (nulliparous group) underwent MR scanning in both natural and increased abdominal pressure state.Iliococcygeus thickness (ICT),coronal iliococcygeal angle (cICA) and sagittal iliococcygeal angle (sICA) of different states were measured and compared between the groups.Results In the natural state,the right and bilateral average sICA in the fertile group were larger than those in nulliparous group (both P＜0.05),while no statistical difference of ICT,right,left and bilateral average cICA and left sICA were found between two groups (all P＞0.05);the bilateral average sICA in spontaneous delivery subgroup was larger than that in cesarean section subgroup (P＜0.05).In increased abdominal pressure state,left,right sICA and bilateral average sICA in fertile group were larger than those in nulliparous group (all P＜0.05),while there was no statistical difference of ICT and cICA between two groups (all P＞0.05);no statistical difference of ICT,cICA nor sICA was found between spontaneous delivery subgroup and cesarean section subgroup (all P＞0.05).Conclusion MRI can accurately evaluate morphological and functional changes of iliococcygeal muscle in females.

Clinical investigation of percutaneous closure of patent ductus arteriosus under echocardiography guidance / 中国胸心血管外科临床杂志

@#Objective    To assess the efficacy and safety of percutaneous closure of patent ductus arteriosus (PDA) solely under echocardiography guidance. Methods    We retrospectively analyzed the clinical data of 200 patients who received the percutaneous closure of PDA under echocardiography guidance in Fuwai Hospital from August 2013 to April 2016. According the different approach, they were divided into 2 groups: a femoral artery approach group (n=143) and a femoral vein approach group (n=57). In the femoral artery approach group, there were 42 males and 101 females aged 3.20±5.63 years. In the femoral vein group, there were 10 males and 47 females aged 7.30±11.36 years. All Patients were treated by percutaneous PDA closure solely under echocardiography guidance. The follow-up was performed at one month after the operation by echocardiography, chest radiograph and electrocardiogram. Results    All 200 patients were successfully treated with percutaneous closure of PDA. The patients’ gender, in-hospital stay, rates of occluder  detachment were similar between the two groups (P>0.05). Compared with the femoral vein approach group, the femoral artery approach group had a younger age (3.20±5.63 years vs. 7.30±11.36 years, P<0.001), less body weight (14.25±11.54 kg vs. 24.25±19.14 kg, P<0.001) and shorter diameter of PDA (3.06±0.79 mm vs. 5.93±0.68 mm, P<0.001) and PDA occluders (5.43±1.00 mm vs. 12.14±0.54 mm, P<0.001), but had higher hospitalization expenses (32 108.2±3 100.2 yuan vs. 25 120.7±3 534.1 yuan, P<0.001). In the femoral vein approach group, one patient was closed under radiation guidance because guide wires could not pass through PDA. One patient in the femoral artery approach group suffered from occluder detachment at one day after operation and was cured by transthoracic minimally invasive PDA occlusion. There were no complications of occluder detachment, residual shunt, pericardial effusion or left pulmonary stenosis during the follow-up. Conclusion    Echocardiography-guided percutaneous PDA closure is safe and effective, while the proper interventional approach should be chosen by the anatomical features of PDA.

Structure-activity relationship of annonaceous acetogenins against multidrug resistant human hepatic carcinoma cell line SMMC-7721/ADR / 中国中药杂志

The present research was launched to investigate the effects of 12 annonaceous acetogenins (ACGs) on human hepatic carcinoma cell line SMMC-7721/ADR, and to find out their structure-activity relationship. SMMC-7721/ADR cells were treated with 12 ACGs including annosquamin A(1)，annosquamin B(2)，annotemoyin-1(3)，uvariamicin Ⅱ(4)，annosquacin D(5)，annosquacin B(6)，isodesacetyluvaricin(7)，uvarigrandin A(8)，squamostatin D(9)，squamostatin E(10)，squamostatin A(11)，and 12,15-cis-squamostatin A(12) for 24 h, and the different expression of the target gene NDUFV2 were detected by quantitative real-time PCR. All the tested compounds made the expression of the target gene NDUFV2 decreased on human hepatic carcinoma cell line SMMC-7721/ADR, of which the bistetrahydrofuran ACGs showed the best activity,which the non-adjacent bistetrahydrofuran ACGs displayed the worst activity.The ACGs with the reducing number of carbons between γ-unsaturated lactone and the close tetrahydrofuran (THF) ring are more potent. For bistetrahydrofuran ACGs with the same nucleus skeleton,they would be more active as more hydroxyls on aliphatic chain, which for the non-adjacent bistetrahydrofuran ACGs with less hydroxyls on aliphatic chain that would be more active. ACGs with 3 hydroxyls on aliphatic chain would be more active. ACGs with threo configuration are more active than erythro configurotion, and the compounds with cis THF ring seem to be superior to those of trans THF ring. Furthermore, the ACGs with the reducing number of carbons between terminal methyl and the close tetrahydrofuran (THF) ring are more potent.

Research of autophagy marker molecular LC3-Ⅱ in hepatic ischemia-reperfusion injury / 国际外科学杂志

Surgical resection of liver diseases such as liver cancer,traumatic hepatic rupture,it was often faced with ischemia-reperfusion injury of the residual liver,which significantly increased the risk of surgical treatment and impact the postoperative recovery of patients.Autophagy was a way of programmed cell death after hepatic ischemia reperfusion.When researching hepatic ischemia-reperfusion injury simulated by animal experiments,it ofen detected the level change of autophagy marker molecular LC3-Ⅱ representing the activity of cell autophagy.Now the authors write the research progress of LC3-Ⅱ in hepatic ischemia-reperfusion injury.

Mechanism research of alleviating rat liver ischemia-reperfusion injury by Astilbin / 国际外科学杂志

Objective To explore the protective effect of astilbin in hepatic ischemia-reperfusion injury (HIRI).Methods SD rats were divided into Sham group (control group),HIRI group (ischemia-reperfusion group),astilbe (low dose group,middle dose group,high dose group),and estabilished the model of rat HIRI.After liver were reperfused with blood (in 4 h,8 h,16 h),collecting the specimens of blood and liver tissues.Detection of serum alanine aminotransferase (ALT),aspertate aminotransferase (AST);Then observed the changes of liver cell microstructure;Western blot analysised the expression of HMGB1,TLR4,NF-kB,TNF-α in liver tissue.Results The serum ALT levels of Sham group in 4 h,8 h,16 h were (58.11 ±4.81) U/L,(57.12 ± 5.33) U/L,(57.63 ±4.54) U/L,the serum ALT levels of HIRI group in 4 h,8 h,16 h were (540.38 ± 21.41) U/L,(831.21 ± 20.11) U/L,(191.95 ± 15.35) U/L.Compared with Sham group,the serum ALT levels of HIRI group were significantly increased(P ＜ 0.01).Compared with HIRI group,The serum ALT levels of three dose groups in 4 h,8 h,16 h were significantly declined,including high dose group lower the most obvious (The serum ALT levels of high dose group in 4 h,8 h,16 h were (223.75 ± 10.53) U/L,(412.14 ±23.59) U/L,(205.25 ± 15.48) U/L (P ＜0.01).The results of light microscope indicated that drug groups significantly reduce the liver cell damage.The results of Western blot displayed that High dose group of HMGB1,TLR4 protein expression in 4 h,8 h,16 h drop significantly than HIRI group(P ＜0.05).High dose group of NFkB,TNF-α protein expression in postoperative 8 h,16 h decrease significantly than HIRI group (P ＜ 0.05),but in postoperative 8 h,there was no statistically significant difference compared with group HIRI (P＞0.05).Conclusion Astilbe pretreatment can reduce HIRI and its mechanism may be associated with downregulating the axis of HMGB1/TLR4/NF-kB/TNF-α,proceed to the next inhibiting the inflammatory response.

Mutation detection of type II hair cortex keratin gene KRT86 in a Chinese Han family with congenital monilethrix / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Monilethrix is an autosomal dominant hair disorder characterized clinically by alopecia and follicular papules. In this study, we collected a Han monilethrix family to detect the mutations in patients and investigated the correlation between the genotype and phenotype of monilethrix.</p><p><b>METHODS</b>In this study, we identified a Chinese family with monilethrix through light microscopic and scanning electron microscopic (SEM) examination. Genomic DNA from peripheral blood samples was prepared. DNA samples from controls and monilethrix patients were subject to polymerase chain reaction (PCR) amplification. Two pairs of primers were used to amplify the seventh exon of KRT86. Mutation screening of the PCR products was detected using direct sequencing.</p><p><b>RESULTS</b>Light microscopic examination showed a regular alternate enlargement and narrow area. SEM examination showed that part of the cuticle of the nodules shed and disappeared gradually in the narrow area with granular protrusions on the surface similar to the erosion-like structure. Parallel longitudinal ridge and groovepattern appeared, and the ridges varied in width, like dead wood. A heterozygous transversion mutation c.1204G > A (p.E402K) in the seventh exon of KRT86 was identified in both patients.</p><p><b>CONCLUSIONS</b>The mutation of extron 7 of KRT86 identified plays a major role in the pathogenesis of this pedigree with monilethrix, and is a mutation hot spot of KRT86. Further research is needed to explore the relationship between the phenotype and the mutation of the type II hair keratin gene KRT86 of monilethrix.</p>