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Tricuspid regurgitation(TR)cases are widely distributed in China.Poor clinical drug efficacy,high surgical risk,and poor prognosis for right heart failure are found in patients with moderate or severe TR.In recent years,with the innovation of valve instruments and the development of technology,transcatheter tricuspid valve treatment could be a new choice for high-risk TR patients in surgery.Many TR animal models have emerged these years for the research of the mechanism of TR and for the clinical verification of instruments.Therefore,this review focuses on how to develop an animal model of TR and discusses the advantages and disadvantages of these techniques.
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OBJECTIVE@#To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL).@*METHODS@#A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant.@*RESULTS@#There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05).@*CONCLUSION@#The SNP of ARID5B gene is associated with MTX resistant in ALL children.
Subject(s)
Child , Humans , DNA-Binding Proteins/genetics , Gene Frequency , Genotype , Methotrexate , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Transcription Factors/genetics , Drug Resistance, NeoplasmABSTRACT
Objective: To explore the impact of transcatheter aortic valve replacement (TAVR) on renal function in patients with severe aortic stenosis. Methods: This is a single-center retrospective study. Consecutive patients with severe aortic valve stenosis and received TAVR in Zhongshan Hospital from December 2014 to December 2019 were included. The patients were divided into four groups according to the estimate glomerular filtration rate (eGFR) measured at one day before TAVR, namely eGFR>90 ml·min-1·1.73m-2 group, 60<eGFR≤90 ml·min-1·1.73m-2 group, 30<eGFR≤60 ml·min-1·1.73m-2 group and eGFR≤30 ml·min-1·1.73m-2 group. The patients were also divided into acute renal function recovery (AKR) group, acute kidney injury (AKI) group and no change in renal function group according to renal function changes at 72 hours after TAVR. AKR was defined as eGFR increased by more than 25% of the baseline value at 72 hours after TAVR, and AKI was defined as eGFR decreased more than 25% of the baseline value at 72 hours after TAVR. The clinical data of each group were compared, and multivariate logistic regression analysis was performed to analyze the determinants responsible for renal function changes after TAVR. Results: A total of 217 patients were enrolled in this study. The age was (76.7±7.4) years and there were 86 females. The Society of Thoracic Surgeons score was (9.5±5.8). The proportions achieved AKR after TAVR were 0, 30.2% (35/116), 58.6% (41/70) and 75.0% (9/12) respectively in eGFR>90 ml·min-1·1.73m-2 group, 60<eGFR≤90 ml·min-1·1.73m-2 group, 30<eGFR≤60 ml·min-1·1.73m-2 group and eGFR≤30 ml·min-1·1.73m-2 group. A total of 3 patients (1.4%) suffered AKI, including 2 patients in 30<eGFR≤60 ml·min-1·1.73m-2 group and 1 patient in 60<eGFR≤90 ml·min-1·1.73m-2 group. The incidence of AKI in eGFR<60 ml·min-1·1.73m-2 group was 2.4% (2/82). Among the 217 patients, AKR occurred in 85(39.2%) patients, 3(1.4%) experienced AKI and renal function remained unchanged in 129 (59.4%) patients post TAVR. Body mass index (BMI), left ventricular end diastolic dimension (LVEDD) and preoperative eGFR were statistically different between the 3 groups (P<0.05). Multivariate logistic regression analysis showed that BMI (OR=5.54, 95%CI 1.04-29.58, P=0.045), preoperative LVEDD (OR=1.22, 95%CI 1.09-1.38, P=0.001) and preoperative eGFR (OR=2.23, 95%CI 2.04-2.55, P=0.004) were associated with non-AKR post TAVR. Conclusions: After TAVR, most patients show no change or improvement of renal function. BMI, preoperative LVEDD and eGFR are related to renal function change after TAVR.
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OBJECTIVES@#To evaluate the ability of the ForenSeqTM DNA Signature Prep kit (ForenSeq kit) in analyzing the sequence information of STRs in Zhejiang She ethnic group and its forensic application efficacy.@*METHODS@#A total of 50 Zhejiang She ethnic group samples were sequenced with the ForenSeq kit on the MiSeq FGx platform. The data was analyzed using ForenSeqTM universal analysis software to obtain the motif structure and flank regions of the 58 STRs, then compared with PCR-CE typing results to test the consistency. At last, the allele frequency and population genetic parameters were calculated.@*RESULTS@#A total of 448 sequence polymorphic alleles were detected in 50 samples of Zhejiang She ethnic group. Compared with fragment length polymorphism detected by PCR-CE, 82 alleles were increased by MPS detection based on ForenSeq kit, and 7 SNPs variation were detected in the flanking regions of 6 loci. The 22 male individuals were genotyped, and total 19 haplotypes were detected in 24 Y chromosome STRs of these 22 males. The cumulative discrimination power of the 27 autosomal STRs was 1-8.87×10-30, the cumulative probability of exclusion of duo-testing was 0.999 999 962 640 657, the cumulative probability of exclusion of trios-testing was 0.999 999 999 999 633.@*CONCLUSIONS@#Based on MPS typing technology, using the ForenSeq kit greatly improves the detection efficiency. In addition, the 58 STRs have good genetic polymorphisms in Zhejiang She ethnic group, which are suitable for individual identification and paternity identification in forensic application.
Subject(s)
Humans , Male , DNA , DNA Fingerprinting/methods , Ethnicity/genetics , Gene Frequency , High-Throughput Nucleotide Sequencing/methods , Microsatellite Repeats , Polymorphism, Single Nucleotide , Sequence Analysis, DNA/methodsABSTRACT
Objective To assess the feasibility of the rbcL sequence of chloroplast DNA as a genetic marker to identify Cannabis sativa L. Methods The rbcL sequences in 62 Cannabis sativa L. samples, 10 Humulus lupulus samples and 10 Humulus scandens DNA samples were detected, and 96 rbcL sequences of the Cannabaceae family were downloaded from Genbank. Sequence alignment was performed by MEGA X software, the intraspecific and interspecific Kimura-2-Parameter (K2P) genetic distances were calculated, and the system clustering tree was constructed. Results The rbcL sequence length acquired by sequencing of Cannabis sativa L. and Humulus scandens were 617 bp and 649 bp, respectively, and two haplotypes of Cannabis sativa L. were observed in the samples. The BLAST similarity search results showed that the highest similarity between the sequences acquired by sequencing and Cannabis sativa L. rbcL sequences available from Genbank was 100%. The genetic distance analysis showed that the maximum intraspecific genetic distance (0.004 9) of Cannabis sativa L. was less than the minimum interspecific genetic distance (0.012 9). The results of median-joining network and system clustering tree analysis showed that Cannabis sativa L. and other members of the Cannabaceae family were located in different branches. Conclusion The rbcL sequence could be used as a DNA barcode for identifying Cannabis sativa L., and combined with comparative analysis of the rbcL sequence and system cluster analysis could be a reliable and effective detection method for Cannabis sativa L. identification in forensic investigation.
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Cannabis/genetics , Genetic Markers , Sequence Analysis, DNAABSTRACT
Objective To study the genetic polymorphism of whole mitochondrial DNA (mtDNA) genomes in She population in Zhejiang and to explore the maternal genetic structure of the She population. Methods Whole mtDNA genomes of 231 unrelated individuals from She population in Zhejiang Province were sequenced. The number of mutations and population genetics parameters such as, the haplotype diversity (HD), discrimination power (DP), and random match probabilities (RMP) were analyzed. The mtDNA haplogroups of Zhejiang She population were classified, and the maternal genetic relationships between She and nine other Chinese populations were estimated. Results In 231 Zhejiang She samples, 8 507 mutations (702 types) were observed and the samples were classified into 94 haplogroups. The HD, DP and RMP values were 0.998 6, 0.994 2 and 0.005 8, respectively. The lowest genetic differentiation degree (Fst=0.006 89) was detected between Zhejiang She population and southern Han population. Principal component analysis (PCA) and median-joining network analysis showed that the genetic distance of Zhejiang She population with Guangxi Yao, Yunnan Dai and Southern Han populations was relatively close, but the population still had some unique genetic characteristics. Conclusion The whole mtDNA genomes are highly polymorphic in Zhejiang She population. The Zhejiang She population contains complex and diverse genetic components and has a relatively close maternal genetic relationship with Guangxi Yao, Yunnan Dai and Southern Han populations. Meanwhile, Zhejiang She population has kept its unique maternal genetic components.
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Humans , Asian People/genetics , China , DNA, Mitochondrial/genetics , Ethnicity/genetics , Genetics, Population , Haplotypes , High-Throughput Nucleotide Sequencing , Polymorphism, GeneticABSTRACT
The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.
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Animals , Mice , 3T3 Cells , Adenylate Kinase , Adipocytes , Metabolism , Down-Regulation , Fibroblast Growth Factors , Metabolism , Leptin , Metabolism , MAP Kinase Signaling System , Phosphorylation , Signal TransductionABSTRACT
The scientificity and value of precision medicine are adequately reflected in the diagnosis and treatment of lung cancer. Numerous drugs for lung cancer are being developed and the therapeutic data constantly updated. Study of the targeted molecular therapy is concentrated on the optimal selection, combination and administration of drugs for common mutation targets after drug resistance, and that of the immunotherapy on more precise stratification. The clinical data on the targeted therapy and immunotherapy for lung cancer were updated at the European Conference on Lung Cancer (ECLC) in 2019. This paper focuses on the data from the ECLC on the studies of the targeted therapy for lung cancer, relating the epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1 fusion, and immunotherapy for elderly patients with lung cancer as well as for those with different PDL1 expression levels, aiming to provide some reference for more scientific, standardized and precise administration of drugs in clinical practice.
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OBJECTIVE@#To investigate the effect of lycium barbarum polysaccharide (LBP) alone or combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the apoptosis of leukemia cell lines with MLL gene-rearrangement, and to explore the cell apoptotic pathway after the combined action.@*METHODS@#MLL-ALL cell line KOCL44 and KOCL45 were selected as the research object, then the control and experimental groups were set up. The cell survival rate was measured by the trypan blue dye exclusion method, the cell early apoptosis and expression of death receptors on the cell surface were detected by flow cytometry with Annexin-V/PI double staining. The protein level of caspase-8, BID, caspase-3, caspase-9, BAD, BCL-2, as well as mitochondrial and cytosol Cyto-C were detected by Western blot.@*RESULTS@#LBF combined with TRAIL inhibited the growth of KOCL44 and KOCL-45 cells and showed the synergistic effect, the results of flow cytometry with Amnexiu V/PI double staining were consistent with above-mentioned results. After treatment of KOCL44 and KOCL45 cells with LBF plus TRAIL, the significant expression of DR4 on cell surface was not found, while the expression of DR4 receptor was enhanced significantly, the pro-apoptotic proteins including caspase-8, BID, caspase-3, caspase-9 and BAD were activated significantly and BCL-2 was suppressed significantly with time-dependent manner. The expression of mitochondria cyto-C in KOCL44 and KOCL45 decreased along with prolonging of treatment time (r=-0.95, r=-0.866), while the expression of cytosol cyto-C in KOCL44 and KOCL45 increased along with prolonging of treatment time (r=0.883, r=0.903).@*CONCLUSION@#The combination of LBP and TRAIL significantly increases the apoptosis of KOCL44 and KOCL45, and the LBP and TRAIL can up-regulate the expression of TRAIL death receptor-DR5 on the cell surface, activate the pathway of caspase and mito-chrondia mitachondria, thus enhance the sensitivity of KOCL44 and KOCL45 to TRAIL induced apoptosis through both mitochondrial and apoptotic pathway.
Subject(s)
Apoptosis , Caspase 8 , Drugs, Chinese Herbal , Leukemia, Myeloid, Acute , Receptors, TNF-Related Apoptosis-Inducing Ligand , TNF-Related Apoptosis-Inducing Ligand , Tumor Necrosis Factor-alphaABSTRACT
Objective To evaluate the long-term efficacy of percutaneous pulmonary valve implantation (PPVI) and the durability of the home-made self-expanding pulmonary valve (Venus-P).Methods From May,2013 to Nov.,2015,14 patients who underwent percutaneous pulmonary valve implantation at Zhongshan Hospital,Fudan University and received at least 1 year follow-up were enrolled,including 3 males and 11 females,with an average age of (35.8 ± 7.8) years.All patients with tetralogy of Fallot received radical resection and developed severe pulmonary regurgitation.The longterm mortality,the operation related complications,the short term and long-term effect of PPVI,as well as the durability and effect of the self-expanding pulmonary valve were evaluated in the 14 patients.Results Over an average follow-up period of (2.3 ± 0.8) years (1.0-3.5 years),only 1 patient died (6.7 %).During the follow-up,no deterioration,infective endocarditis,malignant arrhythmia and other serious complications was observed,and nobody needed reoperation.There was no valve displacement,valve stent fracture,obvious circumferential leakage and pulmonary regurgitation.After PPVI,an acute improvement in pulmonary artery diastolic pressure was observed [(4.93 ± 3.37) mmHg vs.(11.47 ± 4.61) mmHg,P<0.05].Six month postoperatively,right ventricular end diastolic volume measured by cardiac nuclear magnetic resonance was significantly reduced [(139.29± 18.21)mL/m2 vs.(83.03 ± 20.0) mL/m2,P<0.05].At 1 year follow up,the across valve pressure difference were (20.85 ± 4.45) mmHg calculated by the echocardiography,and the NYHA cardiac function (Ⅰ-Ⅲ:4 cases;Ⅰ-Ⅱ:10 cases) was improved 1-2 degree and the distance of 6-minute walk test were significantly increased [(475.00 ± 55.06) m vs.(594.23 ± 194.51) m,P<0.05].Meanwhile,the QRS duration decreased was also observed.The changes of the QRS duration have statistical significance after 1 and 3 months of the PPVI when compared with the baseline [(169.93 ± 21.34) ms vs.(159.87 ± 24.4) ms or (160.00 ± 27.0 ms,P<0.05].Conclusions PPVI using home-made self-expanding pulmonary valve (Venus-P) for chronic pulmonary regurgitation has good long-term efficacy and low complication rate,and the valve is durable.
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<p><b>BACKGROUND</b>Right ventricular (RV) dysfunction ensues due to rheumatic mitral stenosis (RMS). The evaluation of RV function is clinically important for the diagnosis, treatment, and follow-up for patients with different degrees of RMS. The purpose of this study was to determine whether the 64-slice multi-detector row computed tomography (64-slice MDCT) can assess the RV function in RMS with high accuracy and reproducibility when compared to MR imaging (MRI).</p><p><b>METHODS</b>Right ventricular end-diastolic and end-systolic volumes (RV-EDV and RV-ESV), stroke volume (RV-SV), ejection fraction (RV-EF), cardiac output (RV-CO), and wall mass (RV-Mass) were measured with dedicated cardiac analysis software on 64-slice MDCT and compared with values measured with MRI in 43 consecutive patients with RMS. Agreement between MRI and 64-MDCT results were compared with Bland and Altman analysis and linear regression analysis. Repeated measurements were performed to determine intraobserver and interobserver variability.</p><p><b>RESULTS</b>No significant differences were revealed in calculated RV function parameters between the two methods. RV-EDV, RV-ESV, RV-SV, RV-EF, RV-CO, and RV-Mass by 64-slice MDCT were similar to those by MRI (P > 0.05). There were good correlations (r = 0.98, 0.97, 0.96, 0.96, 0.95 and 0.77, respectively) and close agreement (bias = -0.2 ml, -1.0 ml, 0.8 ml, 0.5%, 26.1 ml, and 0.5 g, respectively, P > 0.05). The variability in 64-slice MDCT measurements was similar to that in MRI values.</p><p><b>CONCLUSION</b>ECG-gated 64-slice MDCT could assess the RV function in RMS with high accuracy and reproducibility when compared to MRI.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Magnetic Resonance Imaging , Methods , Mitral Valve Stenosis , Multidetector Computed Tomography , Methods , Prospective Studies , Rheumatic Heart Disease , Ventricular Function, RightABSTRACT
Objective To systematically review the efficiency of 18 F-FDG PET in glioma grading by using Meta-analysis. Methods Retrieval in PubMed and China National Knowledge Infrastructure (CNKI)was performed. Relevant papers concerning with glioma diagnoses with 18 F- FDG PET were selected. Paper quality was evaluated according to the standard of diagnostic test recommended by Cochrane Workshop. The data of glioma malignancy degree defined as semi-quantitatively and qualitatively were extracted from the papers. Meta-analysis was conducted with the Meta-Disc software to calculate pooled weighted sensitivity and specificity with 95% confidence interval (CI). Summary receiver operating characteristic (SROC) curve was performed and the areas under the curve (AUC) were calculated. Results Seven hundred and fifty-three patients from 17 papers ( 16 in English, 1 in Chinese) were included. Two hundred and seventy-two patients from 11 papers were using semi-quantitative (tumor to cortex ratio, T/C; tumor to white matter ratio,T/W) method and 481 patients from 9 papers were using qualitative method (visual observation, some of the papers had 2 or more methods). After heterogeneity test was done, different effect models were selected. The pooled weighted sensitivity, specificity and diagnostic odds ratio (DOR) with 95% CI for T/C group was 0. 952 (95% CI: 0. 903 -0. 980), 0. 409 (95% CI: 0. 318-0. 504) and 11. 746 (95% CI:5. 368-25. 702) respectively. The pooled weighted sensitivity, specificity and DOR with 95% CI for T/W group was 0. 857 (95% CI: 0. 768-0. 922), 0. 538 (95% CI: 0. 431 -0. 642) and 22. 066 (95% CI:7. 077-68. 800) respectively. The pooled weighted sensitivity, specificity and diagnostic odds ratio (DOR)with 95% CI for qualitative method was 0.810 (95%CI: 0.757-0.855), 0.870 (95%CI: 0. 819-0.911 ) and 15.282 (95% CI: 3. 716-62. 851 ) respectively. The AUC for T/C group, T/W group and qualitative method was 0.8604, 0. 8373 and 0. 8724 respectively. Conclusions Grading glioma by 18 F-FDG PET with semi-quantitative method may provide high diagnostic sensitivity. If qualitative method is used, the diagnostic specificity may be higher.
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<p><b>OBJECTIVE</b>To investigate the clinicopathological features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC).</p><p><b>METHODS</b>Patients who met the Amsterdam criteria were enrolled in this study from several hospitals in China. Clinicopathological features of patients with HNPCC were compared between the patients with suspected HNPCC and sporadic colorectal cancer.</p><p><b>RESULTS</b>One hundred and sixty-seven individuals from 31 families met the Amsterdam criteria. The average age was 48.6 (22-78) years old. There were 43 cases (31.9%) with ascending colon cancer and 52 cases (38.5%) with rectal cancer. The 3-, 5-, 10- years survival rate was 70.3%, 49.9% and 39.7% respectively. The incidence of multiple primary neoplasms was 20.4% .</p><p><b>CONCLUSIONS</b>Chinese HNPCC is characterized by early disease onset. Rectal cancer and ascending colon cancer are the first and the secondly common cancer for Chinese HNPCC. Gastric cancer is the most common parenteral cancer in Chinese HNPCC families.</p>