PTBP1 promotes the progression of hepatocellular carcinoma by enhancing the oncogenic splicing switch of FGFR2.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer accounting for 90% of cases. It is a highly invasive and deadly cancer with a gradual onset. Polypyrimidine tract-binding protein 1 (PTBP1) is an important RNA-binding protein involved in RNA metabolism and has been linked to oncogenic splicing events. While the oncogenic role of PTBP1 in HCC cells has been established, the exact mechanism of action remains unclear. This study aimed to investigate the functional connection between PTBP1 and dysregulated splicing events in HCC. Through immunoprecipitation-mass spectrometry analyses, we discovered that the proteins bound to PTBP1 were significantly enriched in the complex responsible for the alternative splicing of FGFR2 (fibroblast growth factor receptor 2). Further RNA immunoprecipitation and quantitative PCR assays confirmed that PTBP1 down-regulated the FGFR2-IIIb isoform levels and up-regulated the FGFR2-IIIc isoform levels in HCC cells, leading to a switch from FGFR2-IIIb to FGFR2-IIIc isoforms. Subsequent functional evaluations using CCK-8, transwell, and plate clone formation assays in HCC cell lines HepG2 and Huh7 demonstrated that FGFR2-IIIb exhibited tumor-suppressive effects, while FGFR2-IIIc displayed tumor-promoting effects. In conclusion, this study provides insights into the PTBP1-mediated alternative splicing mechanism in HCC progression, offering a new theoretical basis for the prevention and treatment of this malignancy. Mechanistically, the isoform switch from FGFR2-IIIb to FGFR2-IIIc promoted epithelial-mesenchymal transformation (EMT) of HCC cells and activated the FGFR cascades ERK and AKT pathways.

Recombinant Neorudin for the Prevention of Deep-Vein Thrombosis After Spinal-Cord Injury.

Background: Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI. Methods: A rat model of SCI was developed by Allen's method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose-response and time-effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI. Results: EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose EH group compared with that in the normal-saline group, but were lower than those in the LMWH group. Conclusion: EH can reduce thrombus formation in a rat model of SCI, and bleeding is decreased significantly compared with that using LMWH. EH may prevent thrombosis after SCI or spinal surgery.

The application of CRISPR genome editing technologies in the pathogenesis studies, diagnosis, prevention and treatment of infectious diseases.

The CRISPR genome editing technology shows great application prospects in gene manipulation and infectious disease research, and is of great value for effective control and cure of infectious diseases. It has been utilized to generate specific disease models in cells, organoids and animals, which provide great convenience for research into the molecular mechanisms associated with infectious diseases. CRISPR screening technology enables high-throughput identification of risk factors. New molecular diagnostic tools based on CRISPR offer a more sensitive and faster method for detecting pathogens. The use of CRISPR tools to introduce resistance genes or to specifically destroy risk genes and virus genomes is intended to help prevent or treat infectious diseases. This review discusses the application of CRISPR genome editing technologies in the construction of disease models, screening of risk factors, pathogen diagnosis, and prevention and treatment of infectious diseases, thereby providing a reference for follow-up research in pathogenesis, diagnosis, prevention and treatment of infectious diseases.

Progresses on genetic susceptibility of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). Genetic factors might influence susceptibility to the SARS-CoV-2 infection or disease severity. Genome-wide association studies (GWASs) have identified multiple susceptible genes related to COVID-19 phenotypes, providing the scientific basis for the COVID-19 prevention and treatment. In this review, we summarize the recent progresses of COVID-19 susceptible genes, including the GWASs on multiple phenotypes of COVID-19, GWASs of COVID-19 in multiple ethnic populations, GWASs of COVID-19 based on multiple types of genetic variations, and the fine-mapping of the regions surrounding the susceptible genes.

Analysis of the efficacy and safety of proton radiotherapy for primary hepatocellular carcinoma / 国际生物医学工程杂志

Objective:To study the efficacy, safety and prognostic factors affecting survival of proton radiation therapy for primary hepatocellular carcinoma (HCC).Methods:Forty-four patients with primary hepatocellular carcinoma treated at Zibo Wanjie Cancer Hospital in Shandong Province from June 15, 2005 to September 12, 2018 were enrolled and given proton radiation therapy with a single dose of 2-5 Gy and a total dose of 25-75 Gy. The overall and local control rates, factors influencing survival, and adverse effects were observed during a follow-up period of 12 to 120 months.Results:The overall survival rates of all patients were 79.5% at 1 year, 68.2% at 2 years, 50.0% at 3 years, and 45.5% at 5 years. The overall local control rate was 95.5%. Patients older than 50 years had a longer overall survival (Log Rank Chi-Square of 4.787, P = 0.029). Child-Pugh A classification had better overall survival compared with B classification (Log Rank Chi-Square 4.077, P = 0.043). The main adverse reactions were skin reactions and gastrointestinal reactions. Among the patients with adverse reactions, 23 patients had skin reactions and 9 patients had mild gastrointestinal reactions, and no serious adverse events were found. Conclusions:Proton radiation therapy has good efficacy and high safety in patients with HCC. Age and Child-Pugh classification are prognostic factors affecting survival after proton radiation therapy.

The Insertion in the 3' UTR of Pmel17 Is the Causal Variant for Golden Skin Color in Tilapia.

Understanding of the relationships between genotypes and phenotypes is a central problem in biology. Although teleosts have colorful phenotypes, not much is known about their underlying mechanisms. Our previous study showed that golden skin color in Mozambique tilapia was mapped in the major locus containing the Pmel gene, and an insertion in 3' UTR of Pmel17 was fully correlated with the golden color. However, the molecular mechanism of how Pmel17 determines the golden skin color is unknown. In this study, knockout of Pmel17 with CRISPR/Cas9 in blackish tilapias resulted in golden coloration, and rescue of Pmel17 in golden tilapias recovered the wild-type blackish color, indicating that Pmel17 is the gene determining the golden and blackish color. Functional analysis in vitro showed that the insertion in the 3' UTR of Pmel17 reduced the transcripts of Pmel17. Our data supplies more evidence to support that Pmel17 is the gene for blackish and golden colors, and highlights that the insertion in the 3' UTR of Pmel17 is the causative mutation for the golden coloration.

MCM2 promotes the proliferation, migration and invasion of cholangiocarcinoma cells by reducing the p53 signaling pathway.

The abnormal expressions of minichromosome maintenance protein 2 (MCM2) are closely related to the development of various kinds of cancers. We aimed to explore the functions and potential molecular mechanisms of MCM2 gene in cholangiocarcinoma (CCA) cell lines (Huh28 and RBE). First, the cell counting kit-8 (CCK-8), plate clone formation, transwell and invasion assays showed that MCM2 promotes the proliferation, migration and invasion of CCA cells. Flow cytometry assays showed that MCM2 significantly promotes the cell cycle, and inhibits the apoptosis of CCA cells. Further, by analyzing the RNA sequencing data of cholangiocarcinoma, we found that MCM2 gene is significantly negatively correlated with p53 signaling pathway. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting (WB) assays confirmed that MCM2 in CCA cells significantly down-regulated the mRNA and protein expression levels of p53 and BAX, and up-regulated the mRNA and protein expression levels of BCL2 and CCND1. Flow cytometry, qRT-PCR and WB assays confirmed that MCM2 promotes CCA through p53 pathway. Finally, we found that MCM2 is up-regulated in CCA tissues compared to the matched non-tumor cholangiocarcinoma tissues, and the high expressions of MCM2 are significantly associated with the poor clinical outcomes of CCA patients. In conclusion, this study revealed that MCM2 promotes the development of CCA by reducing the p53 pathway, and its high expression levels predict poor prognosis in CCA patients. These results provide a theoretical basis for the development of new clinical diagnosis and treatment of cholangiocarcinoma in the future.

Prognostic and predictive value of the hypoxia-associated long non-coding RNA signature in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common cancer worldwide. Hypoxia is an important feature of solid tumors, including HCC, and is also an important factor involved in malignancy progression. However, the identification of hypoxia-related long non-coding RNA (lncRNAs) and their prognostic value in HCC have not been systematically investigated. The aim of this study is to identify the features based on the hypoxia-related lncRNAs and evaluate their predictive value for HCC prognosis. Based on the integrated analysis of HCC transcriptome data from The Cancer Genome Atlas (TCGA), we had identified 233 potential hypoxia-related lncRNAs. We further evaluated the prognostic value of these lncRNAs and optimally established a 12-lncRNA (AC012676.1, PRR7-AS1, AC020915.2, AC008622.2, AC026401.3, MAPKAPK5-AS1, MYG1-AS1, AC015908.3, AC009275.1, MIR210HG, CYTOR and SNHG3) prognostic risk model. The Cox proportional hazards regression analysis revealed that the hypoxia risk score is a novel independent prognostic predictor for HCC patients, which outperforms the traditional clinical pathological factors. Gene set enrichment analysis (GSEA) showed that the hypoxia risk score reflects the activation of biological features related to cell proliferation and the inactivation of lipid metabolism processes. In summary, we had constructed a risk score model based on 12 hypoxia-related lncRNAs, which might be a promising prognostic predictor for HCC patients and highlight their potential roles in the prevention and treatment of this malignancy.

PTBP1 Promotes Growth, Migration and Invasion of Cholangiocarcinoma Cells by Regulating mRNA Alternative Splicing / 中国生物化学与分子生物学报

Cholangiocarcinoma (CCA) is a highly invasive type of cancer with insidious onset and high mortality. Polypyrimidine tract-binding protein 1 (PTBP1) is highly over-expressed in various types of tumor tissues, which contributes to cancer progression. But the role of PTBP1 in CCA has not been explored yet. In this study, we aim to investigate the function of PTBP1 in CCA. Therefore, we used publicly available data from the cancer genome atlas (TCGA) to evaluate the dysregulation of PTBP1 in CCA. The results showed that the PTBP1 is significantly up-regulated in CCA tissues compared to the matched non-tumor tissues (P < 0. 05). We assessed the effects of PTBP1 on the growth of CCA cell lines RBE and HuH28 by performing CCK-8 and plate colony formation assays. The results showed that overexpression of PTBP1 significantly promoted the growth (P < 0. 01) of CCA cells, whereas knockdown of PTBP1 exhibited opposite effects. Transwell and Invasion assays revealed that overexpression of PTBP1 significantly promotes the migration and invasion of CCA cells (P < 0. 001), whereas knockdown of PTBP1 exhibited opposite effects (P < 0. 001). The RNA sequencing (RNA-seq) analysis in PTBP1-depleted cells showed that the up-regulated genes are significantly enriched in p53 signaling pathway, while the down-regulated genes are represented by cholesterol metabolism, Rho GTPase and TGF-β pathways. Then, the alternative splicing analysis revealed that inhibition of PTBP1 led to series of aberrant alternative splicing events, including several cancer-associated ones, such as splicing events within the TGF-β regulator TGIF1 and the p53 activity-correlated gene GNAS. These results indicate that PTBP1 promotes the progression of CCA likely by regulating the transcriptome alternative splicing to influence multiple cancer-associated signaling pathways.

Efficacy and safety of total aortic arch replacement in elderly patients with Stanford type A aortic dissection / 中华老年医学杂志

Objective:To evaluate the efficacy and safety of total aortic arch replacement in elderly patients with Stanford type A aortic dissection(TAAD).Methods:In this retrospective study, a total of 481 TAAD patients treated with total arch replacement in our hospital from January 2016 to January 2020 were divided into three groups: aged≤59 years, 60-69 years and ≥70 years.The differences between three groups in surgical method, extracorporeal circulation time, blocking time, circulatory time, stopping time, surgical time, ventilator use time, ICU time, hospitalization time, treatment rate of continued renal replacement, fatality rate, and cause of death were statistically analyzed and compared.Results:There were statistically significant differences in the stopping time between any two groups of the three groups(all P<0.05). The older the age, the shorter the circulatory arrest time.The difference of ventilator time and ICU time between ≤59 and 60-69 years was statistically significant( P<0.01). Patients with continuous renal replacement(CRRT)were 19.0%(71/373)in ≤59 years, 23.1%(18/78)in 60~69 years, and 26.7%(8/30)over 70 years.In-hospital mortality was 35/373(9.4%)in the group of ≤59 years old, 11/78(14.1%)in the group of 60~69 years old, and 5/30(16.7%)in the group of ≥70 years old.There was no death in patients undergoing type Ⅱ hybrid surgery. Conclusions:Age is one of the important death factors after total aortic arch replacement in TAAD patients.Total aortic arch replacement is an acceptable surgical method for elderly patients with TAAD.Hybridization may reduce hospitalization death in elderly patients.

Prognostic and predictive value of a DNA methylation-driven transcriptional signature in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. DNA methylation alterations are frequently observed in malignant tumours and play critical roles in the development of cancers, including HCC. To provide novel clinical prognosis biomarkers for HCC patients, we first performed a comprehensive analysis and identified a collection of prognosis-associated genes with DNA methylation-driven expression dysregulation in HCCs. Then, we optimally established a 10-gene prognostic risk score model using the least absolute shrinkage and selection operator (LASSO) analysis. Cox's proportional hazards regression analysis revealed that the high-risk score is significantly associated with poor prognosis after being adjusted by clinical parameters, indicating its potential prognostic value. The receiver operating characteristic curve (ROC) analysis showed that this 10-gene prognostic risk score model outperformed several other publicly available models in predicting both short- and long-term prognosis. Gene set enrichment analysis revealed that the high-risk score is relevantly associated with pathways involved in cell cycle and DNA damage repair. The above results indicate that we have constructed a 10-DNA-methylation-driven-gene prognostic risk score model, which might serve as a potential prognostic biomarker for HCC patients and guide treatment decisions for patients at high risk of tumour progression.

Application of posterior scleral reinforcement in the treatment of retinal detachment due to macular hole with over-long axial length / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To evaluate the clinical effect of the auxiliary application of posterior scleral reinforcement(PSR)in the vitrectomy of macular hole retinal detachment with over-long axial length.<p>METHODS:A clinical randomized controlled trial was conducted. Patients of macular hole retinal detachment with over-long axial length ≥29mm were randomly divided into two groups. Group A accepted PSR + PPV + silicone oil injection, group B accepted PPV + silicone oil injection. After followed-up one year, the BCVA, the percentage of macular hole closure, cure rate of retinal detachment and reoperation rate were analyzed.<p>RESULTS:Totally 46 eyes were included in the study. The average BCVA of the two groups after treatment was improved. The BCVA of group A changed from 1.61±0.02 to 0.85±0.22(<i>t</i>=10.36, <i>P</i><0.01), and that of group B increased from 1.59±0.04 to 1.08±0.16(<i>t</i>=7.92, <i>P</i><0.01). The improvement of group A was greater than that of group B(<i>t</i>= -2.38, <i>P</i>=0.03). There was no significant change of the axial length before and after operation in both groups(<i>P</i>>0.05). In group A, the healing rate of macular hole was 91%(21/23), and the reoperation rate was 4%(1/23)before silicone oil removal. After silicone oil removal, no patients recurred to retinal detachment. During the follow-up period, silicone oil removal was completed in all eyes. In group B, the closure rate of macular hole was 65%(15/23), the rate of reoperation before silicone oil removal was 35%(8/23), the redetachment rate after silicone oil removal was 26%(6/23), and the rate of the silicone oil removal throughout the follow-up period was 74%(17/23).<p>CONCLUSION: PSR can effectively improve the successful rate of pathological myopic macular holes with retinal detachment and reduce the recurrence and reoperation.

Experience for 107 patients with acute type A aortic dissection involving coronary arteries / 中国胸心血管外科临床杂志

@#Objective    To summarize the clinical feature and treatment experience of patients with acute type A aortic dissection involving coronary arteries. Methods    The clinical data of 107 patients with acute type A aortic dissection involving coronary arteries, who received operation between June 5, 2012 and December 31, 2019 in our hospital, were analyzed retrospectively. There were 80 males and 27 females at age of 24-83 (49.8±11.2) years. Results    The right coronary artery was involved in 65 patients, the left in 17 patients, and both coronary arteries in 25 patients. There were 48 (44.9%) patients undergoing coronary artery bypass grafting, 49 (45.8%) patients undergoing coronary artery plasty. Fifteen patients died 30 d after the operation, with a mortality rate of 14.0%. Patients with preoperative cardiogenic shock and postoperative acute renal failure had increased risk of death (P<0.05). Eighty-two (88.2%) patients were followed up for 2 to 71 months, and 1 patient had sudden cardiac death during the follow-up period. Conclusion    Acute type A aortic dissection with coronary involvement is associated with high misdiagnosis rate and mortality rate. Taking proper strategies for surgical treatment of involved coronary arteries based on precise diagnosis may improve the prognosis of patients.

Clinical study of macular edema secondary to ischemic branch retinal vein occlusion treated by dual laser and single intravitreal injection with Conbercept / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To appraise the therapeutic effect of dual laser(micro-pulse laser and traditional laser)and single intravitreal injection with conberceptin on macular edema secondary to ischemic branch retinal vein occlusion.<p>METHODS: A prospective cohort study was conducted. 83 patients(83 eyes)participated in the study from November 2017 to November 2018. They were randomly divided into two groups. Group A(42 eyes)accepted the treatment of dual laser and single intravitreal injection with conbercept and group B(41 eyes)accepted only traditional laser treatment and single intravitreal injection with anti-VEGF, and the aim is to analysis the data including BCVA, CMT in follow-up visit after treatment 1, 3, 6mo.<p>RESULTS: After 1mo: in group A, BCVA improved from 0.88±0.11 to 0.43±0.19(<i>P</i><0.01), CMT changed from 595.00±61.12 to 379.8±76.08μm(<i>P</i><0.01). In group B, BCVA changed from 0.82±0.19 to 0.39±0.16(<i>P</i><0.01)while CMT changed from 601.70±81.37 to 381.50±70.92 μm(<i>P</i><0.01). There were no difference between two groups(<i>P</i>>0.05). After 3mo: in group A, BCVA raised to 0.13±0.07(<i>P</i><0.01), CMT reduced to 282.80±31.93μm(<i>P</i><0.01); in group B, BCVA hold on 0.41±0.09(<i>P</i>=1.00), CMT retained 395.80±34.53μm(<i>P</i>=0.99). The improvement of BCVA and CMT were better in group A(<i>P</i><0.01). After 6mo: in group A, BCVA maintained 0.28±0.12(<i>P</i><0.01), CMT keeped 335.60±33.98μm(<i>P</i>=0.02); in group B, BCVA rebounded to 0.77±0.15(<i>P</i><0.01), CMT was 579.60±19.61μm(<i>P</i><0.01). Both BCVA and CMT were better in group A than group B(<i>P</i><0.01). No serious complications happened in all phases.<p>CONCLUSION: The treatment of dual laser and single intravitreal injection with conbercept for macular edema secondary to ischemic branch retinal vein occlusion can maintain good effect more than 3mo.

Clinicopathological analysis of nine cases of hypopigmented mycosis fungoides / 中华皮肤科杂志

Objective:To analyze clinical and pathological characteristics of 9 cases of hypopigmented mycosis fungoides (HMF) .Methods:Nine patients with clinically and histopathologically confirmed HMF were collected at Department of Dermatology, Hangzhou Third People's Hospital from 2014 to 2018, and their clinical and pathological manifestations and follow-up findings were retrospectively analyzed.Results:Among the 9 patients, there were 7 males and 2 females; the age ranged from 6 to 29 years (average, 12.4 years) ; the duration of disease varied from 6 months to 3 years (average, 20.7 months) . All skin lesions manifested as poorly demarcated, irregular, hypopigmented patches, some hypopigmented patches were confluent, and hypopigmented patches were covered with scales in 2 cases. Wood′s lamp examination of hypopigmented patches showed a grayish-white color with weak fluorescence. Dermoscopic images showed white scales on the lesions and blood vessels distributed in spermatozoa-like, punctiform or short linear patterns. Reflectance confocal microscopy showed mild hypopigmentation in the basal layer without obvious depigmentation, and highly-refractive atypical cells at the dermo-epidermal junction. Histopathological examination of the 9 cases showed epidermotropic phenomenon of atypical lymphocytes, and some cells clustered and formed Pautrier′s microabscess, immunohistochemical staining revealed that all the cells expressed T cell phenotypes, and were mainly infiltrating CD8 + T cells. The 9 patients were treated with narrow-band ultraviolet B (NB-UVB) , and all of them achieved clinical complete response. During a follow-up of 23.8 months on average, 2 patients experienced recurrence, and they achieved clinical complete response again after NB-UVB treatment. Conclusions:HMF progresses slowly, and NB-UVB treatment is effective. There is the possibility of recurrence after clinical recovery in patients with HMF, and a long-term follow-up is needed.

[Genetic association of MKL1 gene polymorphisms with the high-altitude adaptation].

Genetic factors are closely related to the high-altitude adaptation. Several candidate genes have been reported to be significantly associated with high-altitude adaptation. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator, which plays crucial roles in the phenotypic modulation of smooth muscle cells. To explore whether MKL1 gene is involved in high-altitude adaptation, we performed genetic association study between MKL1 gene polymorphisms and high-altitude adaptation. We recruited 595 Tibetans from the Qinghai-Tibet plateau and 442 Hans living at low altitude. The SNP rs59098711 locus in the MKL1 gene was genotyped using the MassARRAY assays. We compared the genotypes and allele frequency distributions of rs59098711 between the Hans and Tibetans. The results showed that the genotypes of rs59098711 are significantly different between these two populations (P<0.05). We further compared the genotypes of rs59098711 between Tibetans and other ethnic groups using data from various public databases. We also observed that the genotypes of rs59098711 are significantly different between Tibetans and these other populations (P<0.05). Bioinformatics analyses suggested that rs59098711 could be located at the enhancer region and regulate the expression of the MKL1 gene. Additional study of gene expression data from available public datasets showed that MKL1 gene was up-regulated in a hypobaric hypoxic environment. Our results suggested that the genetic polymorphism rs59098711 locus of the MKL1 gene is associated with high-altitude adaption.

Analysis of chloroplast genome and its characteristics of medicinal plant Sophora flavescens / 药学学报

In order to explore the chloroplast genome characteristics of Sophora flavescens and the phylogenetic relationship of the genus, this study used high-throughput sequencing technology to sequence and functionally annotate the chloroplast genome of Sophora flavescens. The results showed that the full length 154 165 bp of Sophora flavescens chloroplast genome showed a typical four-stage structure. The chloroplast genome contains 123 genes, including 77 protein-coding genes, 38 tRNA genes and 8 rRNA genes. Sequence analysis revealed 104 SSR loci, most of which consisted of A and T. In addition, the chloroplast genome codon preference is weak, and the coding region is biased towards the use of A and T bases. A comparative analysis of two different regions of Sophora flavescens chloroplast genome revealed four differential genes. Based on the maximum likelihood method (ML) for phylogenetic analysis of Sophora flavescens and 16 other leguminous, it was found that the relationship between Sophora flavescens and the genus Sophora alopecuroides is the closest. This study provides an important theoretical basis for the genetic variation, breeding and phylogenetic analysis of Sophora flavescens, and has certain reference value.

The critical roles of TBC proteins in human diseases.

The Tre-2/Bub2/Cdc16 (TBC) domain is a conserved protein motif consisting of approximately 200 amino acids, and is present in many eukaryotic proteins. TBC domain-containing proteins (TBC proteins) function as GTPase activating proteins (GAPs) for the small GTPase Rab, which can promote the hydrolysis of Rab-GTP to Rab-GDP in regulation of specific intracellular trafficking pathways. Several TBC proteins play important roles in cellular functions in mammals, and defects of which are closely associated with numerous disease processes. In this review, we summarize the structures and functions of the mammalian TBC proteins and recent advances in understanding their critical roles in the development of human diseases. This review serves as a reference for further investigations on the functions of TBC proteins in disease pathogeneses.

Clinical efficacy of two different tricuspid annuloplasty techniques in left cardiac valve surgery

Objective:To investigate the mid-and long-term clinical effects of tricuspid valvuloplasty with the implantation of an artificial plastic ring.Methods:Data of 677 patients who had functional tricuspid regurgitation and left cardiac valve disease and underwent tricuspid valvuloplasty and left cardiac valve surgery were retrospectively. Among these patients, 353 underwent simple suture annuloplasty (group A) while the rest 324 patients underwent artificial plastic ring annuloplasty (group B). The two-year and more-than-two-year clinical and ultrasonocardiograph (UCG) follow-up data of the two groups were obtained and compared.Results:A total of 600 patients (88.6%) completed the long-term follow-up (more than two years). The two-year follow-up showed no significant difference in the incidence of mild tricuspid regurgitation between the two groups (82.2% vs. 92.7%, P=0.37). However, there were significantly more cases that developed into moderate to severe tricuspid regurgitation in group A than in group B (17.8% vs. 7.3%, P=0.031). The long-term follow-up revealed that the recurrence rate of tricuspid regurgitation in group B was significantly lower than that in group A (11.0% vs. 25.0%, P=0.029), and the ratio of cases developing into moderate to severe tricuspid regurgitation in group A was significantly higher than that in group B (28.9% vs. 9.9%, P=0.007). The comparison between the two intra-group time segments showed that the development of tricuspid regurgitation in group A was significantly increased (28.9% vs. 17.8%, P=0.022), but in group B it was relatively stable (9.9% vs. 7.3%, P=0.52).Conclusions:Artificial ring annuloplasty is associated with significantly less tricuspid regurgitation than simple suture annuloplasty.

Effect of MCUR1 on proliferation,cell cycle and apoptosis of K562 cells / 军事医学

Objective To investigate the effect of mitochondrial calcium uniporter(MCU)regulator 1(MCUR1)on proliferation,cell cycle and apoptosis of K562 cells and the possible molecular mechanism.Methods Recombinant plasmid vectors containing short hairpin RNAs(shRNAs)targeting MCUR1 were transfected into K562 cells,before the K562 cells stably expressing low MCUR1 were selected with G418.The expression of MCUR1 mRNA was detected by quantitative real-time polymerase chain reaction(qRT-PCR)assays.Western blotting(WB)assays were used to detect the expressions of MCUR1,P53,BAX and BCL2.The proliferation,cell cycle and apoptosis of K562 cells were detected by cell counting kit-8(CCK-8)assays and flow cytometry, respectively.Results The results of qRT-PCR and WB assays revealed that MCUR1 was stably down-regulated at mRNA and protein levels in the K562 cells transfected with shRNAs targeting MCUR1.Knockdown of MCUR1 significantly inhibited the cell proliferation, induced the cell apoptosis, but did not influence the cells cycle.Meanwhile, knockdown of MCUR1 increased the expression of P53 protein and the ratio of protein BAX/BCL2 in K562 cells.Conclusion MCUR1 promotes cell proliferation and inhibits cell apoptosis in K 562 cells.