OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a Chinese pedigree affected with Hereditary dentin dysplasia type II (DD-II) due to variant of dentin sialophosphoprotein (DSPP) gene. METHODS: A child diagnosed with DD- II at the Third Clinical Division of Peking University Hospital of Stomatology in December 2021 and her family members were selected as study subjects. Clinical data were retrospectively analyzed. Saliva samples were collected from the proband, her parents and sister for genomic DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and TOPO-TA cloning sequencing. The candidate variant was also subjected to bioinformatics analysis using Mutation Taster v2021. Secondary and tertiary structures of the wild-type and variant DSPP proteins were predicted with psipred v4.0 and PyMOL v2.3 software, respectively. The pathogenicity of the variant was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Peking University Hospital of Stomatology (Ethics No.: PKUSSIRB-202162021). RESULTS: The proband and her mother and sister had all exhibited typical clinical manifestations of hereditary DD-II. The primary dentition of the proband displayed yellowish brown discoloration, wear, and obliteration in the chamber and root canal, while the permanent teeth of the proband's sister and mother appeared nearly normal in both color and appearance, though with obliteration in the chamber and root canal. Her father showed normal dentition. WES identified a heterozygous c.1915_1918delAAGT, p.(Lys639Glnfs*674) frameshift variant in the DSPP gene. Sanger sequencing and TOPO-TA cloning sequencing confirmed the presence of this variant in the proband, the proband's sister, and the mother, while the proband's father was negative for the variant, indicating an autosomal dominant inheritance pattern. The variant was predicted to be pathogenic by Mutation Taster v2021. Prediction of the secondary structure of the DSPP protein showed that the variant has changed it from coil to helix. The tertiary structure prediction of the DSPP protein showed change of the spatial structure of the variant DSPP, with the loops in the variant region replaced by helices at multiple sites. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP1+PP4). CONCLUSION Phenotypic analysis and genetic testing of this family has clarified the clinical diagnosis of hereditary DD- II. The c.1915_1918delAAGT variant probably underlay the pathogenesis of DD-II in this family. Above results have expanded the phenotypic spectrum of the disease and may contribute to further clinical and genetic research on this disease.
Humans ; Pedigree ; Female ; Extracellular Matrix Proteins/chemistry* ; Male ; Sialoglycoproteins/chemistry* ; Dentin Dysplasia/genetics* ; Asian People/genetics* ; Phosphoproteins/chemistry* ; Child ; Mutation ; China ; Exome Sequencing ; Adult ; East Asian People

Objective:To evaluate the efficacy and safety of θ short burst rapid pulse stimulation(TBS)in treating schizophrenia by meta-analysis.Methods:Randomized controlled trials(RCTS)on TBS in the treatment of schizophrenia were searched from CNKI,Wanfang,VIP,China Biomedicine,Web of science,PubMed,Embase and Cochrane Library databases to December 2022.The main study indicator was the Positive and Negative Symptoms Scale(PANSS).Risk quality assessment of the included literatures was performed by two reviewers and statistical analysis was performed using RevMan5.3.Results:A total of 13 RCTS with 641 patients were included.Meta-anal-ysis showed that TBS targeting the left dorsolateral prefrontal cortex(DLPFC)with intervention duration longer than 2 weeks decreased the PANSS total scores(WMD=-4.63,95％CI:-5.75--3.51,P＜0.001),positive symptom scores(WMD=-1.13,95％CI:-2.00--0.26,P＜0.05),negative symptom scores(WMD=-2.51,95％CI:-2.77--1.53,P＜0.001)and general psychopathological symptom scores(WMD=-1.20,95％CI:-1.80--0.60,P＜0.001).The adverse reactions of TBS included dizziness,and no serious adverse e-vents were reported.Conclusion:TBS has high safety,and stimulation of left dorsolateral prefrontal cortex targets for more than 2 weeks could effectively improve psychiatric symptoms in patients with schizophrenia.

Objective: To evaluate the effects and partly mechanism of Qileng decoction(QLD,芪棱汤) resisting focal cerebral ischemia/reperfusion(I/R) injury in rats by apoptosis and signal transduction pathway.Methods: The rats were randomly divided into three groups including sham operation group,normal saline(NS) control group and QLD group.The model of focal cerebral I/R injury was induced by using modified thread embolizing in rats.Rats were evaluated by neurologic function score at 2 hours after ischemia and 2,4,6,12,24 and 48 hours after cerebral reperfusion,and the pathological changes of nerve cells and mitochondria ultrastructure at pallium and hippocampus CA1 region were observed at 24 hours after reperfusion.Immunohistochemical method was performed to examine the expression of cytochrome C(cyt C) and caspase-9 at different time points after reperfusion.Apoptosis of nerve cells in ischemic penumbra(IP) was also characterized by terminal deoxynucleotidyl-transferase mediated dUTP-biotin nick end labeling(TUNEL) method.Results: Compared with NS control group,neurologic function scores at different reperfusion time points were improved and the pathological changes were ameliorated at 24 hours after cerebral I/R in QLD group.Mitochondria hydropsia was alleviated,mitochondrial cristae fragmentation and granulum basale shedding were diminished,and mitochondrial basical morphology was retained.Meanwhile,apoptosis index(AI) was decreased and the expressions of cyt C and caspase-9 were reduced in IP in QLD group.Conclusion: QLD intervenes in mitochondria mediated and caspase-9 dependent apoptopic pathway.QLD lowers AI and plays a role of protecting nerve by maintaining mitochondrial basical form,stabilizing mitochondrial membrane and inhibiting the release of cyt C and activation of caspase-9.The above actions are possibly some parts of mechanisms of QLD resisting focal cerebral I/R injury.

AIM: To investigate effects of different therapeutic methods and typical recipes on activation of ERK1/2 in Kupffer cells of rats with fatty liver.METHODS: The rat model of fatty liver was established by feeding high fat diet combinated with distillate spirit.Meanwhile Chinese medicines Shugan fang,Jianpi fang,Huoxue fang,Qushi fang,and Zonghe fang were given to treat different groups respectively.12 weeks later,the Kupffer cells were isolated from livers of control group,model group and different treatment groups by sequential in situ perfusion with collagenaseⅣ and pronase E,density gradient centrifugation,selective adherence.The expression of total ERK1/2 and phospho-ERK1/2 in Kupffer cells of control group,model group and different treatment groups were detected by Western blotting.RESULTS: The expressions of total ERK1/2 and phospho-ERK1/2 were higher in Kupffer cells from model group than those in control group(P

The antagonistic effects of ruthenium red (RuR) on the biological activi-ties of endotoxin (ET) which included the limulus amebocytes lysate test, the local Shw-artzman reaction, decreasing the white blood cell counts, and increase of zinc in periphe-ral blood were observed. The destroyed meshes of endotoxin have been seen under electronmicroscope. The amino-groups of endotoxin increased markedly, which it was treated withRuR. These results indicated that the polycationic residues of RuR may be the effectiveunits of antiendotoxin activity.

The significant changes in morphology and nitric oxide synthase (NOS) activity in cultured human aortic endothelial cells (HAEC) were observed when these cells were exposed to LPS, IL-1? and IFN-?. NOS activity increased at 6h of treatment, the time point that HAEC began to change and elongate. The cell shape became fibroblast like and the length to width ratio of the cells increased 2 times of that of the control at 20h treatment, the time point that NOS activity returned to control level.