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Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide. However, unlike that in female infertility, the role of CT infection in male infertility remains controversial. The objective of this retrospective study was to explore the impacts of CT infection in the genital tract on sperm quality, sperm acrosin activity, antisperm antibody levels, and inflammation in a large cohort of infertile males in China. A total of 7154 semen samples were collected from infertile male subjects, 416 of whom were CT positive (CT+ group) and 6738 of whom were CT negative (CT- group), in our hospital between January 2016 and December 2018. Routine semen parameters (semen volume, pH, sperm concentration, viability, motility, morphology, etc.), granulocyte elastase levels, antisperm antibody levels, and sperm acrosin activity were compared between the CT+ and CT- groups. Our results showed that CT infection was significantly correlated with an abnormally low semen volume, as well as an increased white blood cell count and granulocyte elastase level (all P < 0.05) in the semen of infertile males; other routine semen parameters were not negatively impacted. The antisperm antibody level and sperm acrosin activity were not affected by CT infection. These findings suggested that CT infection might contribute to inflammation and hypospermia but does not impair sperm viability, motility morphology, and acrosin activity or generate antisperm antibodies in the infertile males of China.
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Female , Humans , Male , Chlamydia trachomatis , Genitalia , Infertility, Male/epidemiology , Inflammation/epidemiology , Retrospective Studies , Semen , SpermatozoaABSTRACT
Objective:To detect the incidence and analyze the clinical significance of regions of homozygosity (ROH) through the single nucleotide polymorphism array (SNP array).Methods:The SNP array detection results of 5 116 pregnant women in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2020 were retrospectively analyzed. The pregnant women with ROH (5 Mb as the threshold) were followed up to analyze the relationship between ROH and abnormal fetal phenotype. Whole exon sequencing was performed in 4 cases of consanguineous marriage to detect potential recessive causative genes in the ROH region.Results:(1) A total of 39 cases of ROH were detected, with a positive rate of 0.76% (39/5 116). Among them, 25 cases (64%, 25/39) were detected only on single chromosome, and chromosome 11 had the highest detection rate, suggesting the risk of uniparental disomy; fourteen cases (36%,14/39) were detected on multiple chromosomes, most commonly on chromosomes 11, 1, 3, 4 and 8. (2) The number of cases and detection rate of ROH detected by different prenatal diagnosis indicators were as follows: 12 cases (1.78%, 12/676) in pregnant women with abnormal non-invasive prenatal testing result, 12 cases (0.37%, 12/3 284) in pregnant women with ultrasound abnormality, 4 cases (4/4) in pregnant women with consanguineous marriage, 3 cases (0.92%, 3/326) in pregnant women with previous adverse pregnancy, 2 cases (1.15%, 2/174) in pregnant women with high risk of serology in screening, 2 cases (4.00%, 2/50) in pregnant women with abnormal fetal chromosomal karyotype, 2 cases (0.79%, 2/253) in pregnant women with advanced maternal age, 1 case (0.56%, 1/178) in pregnant women with related parental genetic factors and 1 case (0.58%, 1/171) in pregnant women with the other factors. (3) The follow-up results of 39 cases of prenatal ROH showed that there were 16 cases of term birth, 15 cases of termination of pregnancy, 2 cases of preterm births, 1 case of fetal death and 5 cases lost to follow-up.Conclusions:Chromosomal ROH phenomenon is not rare. By analyzing the detection rate of ROH in prenatal diagnosis, combined with the results of fetal phenotype and postpartum follow-up, the clinical characteristics of ROH are discussed, so as to better understand the relationship between ROH and its phenotype.
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Objective:To investigate the effects of Tongxinluo capsule on the improvement of cardiac function and the expression of myocardial enzyme spectrum in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:One hundred patients with coronary heart disease after PCI who received treatment in Hebei Xianghe County People′s Hospitalfrom April 2018 to April 2020 were enrolled and randomly divided into the observation group and the control group. The control group was given conventional treatment, while the observation group was treated with Tongxinluo capsule on the basis of the control group. Patients in both groups were treated for 3 months. The normal clinical remission after treatment was observed in the two groups. The improvement of cardiac function index left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and myocardial enzyme index aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzyme - MB (CK - MB), lactate dehydrogenase (LDH), troponin T (TnT) were compared between the two groups before and after the treatment.Results:After treated for 3 months, the total effective rate in the observation group was higher than that in the control group: 92.0%(46/50) vs. 76.0%(38/50), the difference was statistically significant ( χ2 = 4.76, P<0.05). After treated for 3 months, the levels of LVEDV and LVESV in two groups were decreased, and the level of LVEF in two groups was increased, and the levels of LVEDV and LVESV in the observation group were lower than those in the control group: (153.39 ± 8.35) ml/m 2 vs. (155.57 ± 9.32) ml/m 2, (103.49 ± 9.25) ml/m 2 vs. (109.65 ± 10.46) ml/m 2; the levels of LVEF in the observation group was higher than that in the control group: (58.14 ± 7.41)% vs. (54.59 ± 6.92)%, the differences were statistically significant ( P<0.05). After treated for 3 months, the levels of AST, CK, CK-MB, LDH, TnT in two groups were decreased, and the levels of above index in the observation group were lower than those in the control group: (38.14 ± 7.28) U/L vs. (45.04 ± 8.12) U/L, (637.15 ± 75.25) U/L vs. (756.24 ± 85.24) U/L, (553.28 ± 53.14) U/L vs. (632.17 ± 62.81) U/L, (162.43 ± 15.41) U/L vs. (181.74 ± 19.25) U/L, (0.32 ± 0.15) μg/L vs. (0.39 ± 0.11) μg/L, the differences were statistically significant ( P<0.05). Conclusions:The application of Tongxinluo capsule in patients with coronary heart disease after PCI can effectively alleviate clinical symptoms, improve cardiac function, and regulate the enzyme activity of the body.
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Objective:To study the feasibility for transumbilical single-incision laparoscopic appendectomy (SILA) with conventional laparoscopic instruments, and compare SILA with the traditional three-port laparoscopic appendicectomy (LA).Methods:The clinical data of 113 patients with acute appendicitis from January 2018 to August 2020 in the Second Hospital of Jiaxing City were retrospectively analyzed. Among them, 61 patients received traditional three-port LA (three-port LA group), 52 patients received transumbilical SILA (SILA group). The operative time, intra-operative blood loss, surgical complications, length of hospital stay and hospitalization costs were recorded. Pain score 6 h after operation was assessed by visual analogue scale. C-reactive protein (CRP) on the first day after operation was detected. All patients were followed up for 1 month.Results:In 2 groups, all patients did not suffered from the conversion to open operation or multi-port method, massive bleeding and accessory injury during the operation. Moreover, severe pain, severe incision infection, residual abdominal abscess and incisional hernia did not occur. Patients in SILA group had more hidden abdominal scars. there were no statistical differences in operative time, intra-operative blood loss and CRP on the first day after operation between 2 groups ( P>0.05); the rate of moderate pain degree 6 h after operation, length of hospital stay and hospitalization costs in SILA group were significantly lower than those in three-port LA group: 15.38% (8/52) vs. 34.43% (21/61), (3.63 ± 1.22) d vs. (4.31 ± 1.38) d and (8 802 ± 1 466) yuan vs. (9 559 ± 1 617) yuan, and there were statistical differences ( P<0.05 or <0.01). Conclusions:The transumbilical SILA with conventional laparoscopic instruments is safe and feasible, the scar is more difficult to see, the cosmetic effect is much clearer, and the length of hospital stay is shorter.
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Objective:To investigate the level of serum Omentin-1 in subjects with abdominal obesity, and to analyze the influencing factors of Omentin-1 and its relationship with body fat distribution, insulin resistance and metabolic parameters.Methods:A retrospective case-control study was conducted to analyze the clinical data of one hundred and fifty adults with abdominal obesity (BMI≥28 kg/m 2) who were randomly selected from Obesity Multidisciplinary Diagnosis and Treatment Center, Subei People's Hospital from Januray 2018 to December 2021. Meanwhile, 150 healthy adults were enrolled as a normal control group. Fasting serum Omentin-1 and glucose metabolism were measured, and homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated. Body fat composition was measured by bioelectrical impedance analysis. The relationship between Omentin-1 and other variables were presented by the Pearson correlation coefficients. Stepwise regression model was used to analyze the influencing factors of Omentin-1. Results:The serum omentin-1 level of patients with abdominal obesity was (36.97±6.99) μg/L, that of normal control group was (72.35±6.09) μg/L. The difference between the two groups was statistically significant ( t=46.69, P<0.001). The body fat level of patients with abdominal obesity was (43.40±14.59) kg, that of normal control group was (13.78±4.13) kg. The difference between the two groups was statistically significant ( t=23.93, P<0.001). The fasting insulin of patients with abdominal obesity was 29.05 (22.01,34.60) pmol/L, that of normal control group was 127.90 (84.08,201.45) pmol/L. The difference between the two groups was statistically significant( Z=14.75, P<0.001). The HOMA-IR of patients with abdominal obesity was 0.87 (0.68,1.05), that of normal control group was 4.19 (2.77,7.31). The difference between the two groups was statistically significant ( Z=14.75, P<0.001). Pearson linear correlation analysis showed that serum omentin-1 levels were negatively correlated with BMI, waist circumference, waist-hip ratio (WHR), body fat, visceral Fat area (VFA), HOMA-IR, triglyceride, total cholesterol and low density lipoprotein cholesterol ( r=-0.825, -0.843, -0.756, -0.777, -0.835, -0.583, -0.429, -0.353, -0.503, -0.938, all P<0.001). Whereas, a significantly positive correlation was found between serum Omentin-1 levels and high density lipoprotein cholesterol ( r=0.528, P<0.001). Omentin-1 concentrations were not related to age or gender ( r=-0.093, -0.040; P=0.669, 0.489). In multiple linear stepwise regression analysis, only VFA remained significantly associated with Omentin-1 ( β=-0.026, t=-2.250, P=0.026). Conclusion:The level of serum omentin-1 in patients with abdominal obesity was significantly lower than that in normal subjects, and it was closely related to body fat distribution and insulin resistance. VFA is an independent influencing factor of serum omentin-1, which can be used as a biomarker of abdominal obesity related metabolic disorders.
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β-thalassemia is a type of inherited hemolytic anemia caused by decreased globin production due to defect of the HBB gene. The pathogenesis of the disease is imbalance of α/β globin chains. The excess of α-globin chains will form hemichromes which can damage red blood cell membranes and lead to hemolysis, ineffective erythropoiesis, and secondary iron overload. Iron overload in turn can cause complications such as growth retardation, liver cirrhosis, cardiac insufficiency, and aggravate the disease phenotype. In recent decades, genes participating in iron metabolism have been discovered, and the mechanism of iron metabolism in the development of thalassemia has gradually been elucidated. Subsequently, by manipulating the expression of key genes in iron metabolism such as hepcidin and transferrin receptor, researchers have revealed that iron restriction can improve ineffective hematopoiesis and iron overload, which may provide a potential approach for the treatment of thalassemia. This article reviews the progress of research on iron metabolism-related genes and related pathways in β-thalassemia.
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Humans , Iron/metabolism , Iron Overload/genetics , Phenotype , Research/trends , beta-Thalassemia/physiopathologyABSTRACT
Objective:To investigate the association of muscle mass loss with atherosclerosis in elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 322 patients with T2DM aged≥60 years old were divided into muscle mass loss group( n=152) and non-muscle mass loss group( n=170) according to their appendicular skeletal muscle mass index(ASMI). All participants underwent physical examination, dual-energy X-ray absorptiometry check, carotid and lower extremity ultrasound, as well as laboratory tests. Results:Among 322 patients, 49(15.22%) patients were suffered from sarcopenia and 152(47.2%) patients with reduced muscle mass. The carotid and lower extremity atherosclerosis grades in the muscle mass loss group were significantly higher than those in the non-muscle mass loss group( P<0.05), with lower body mass index(BMI), T-score, ASMI, uric acid, and homeostasis model assessment of insulin resistance index( P<0.05). Multivariate logistic regression analysis showed that carotid atherosclerosis and lower extremity atherosclerosis were risk factors for muscle mass loss while BMI and 25-(OH)D 3 were protective factors for muscle mass loss. There existed a consistency in carotid atherosclerosis grade and lower extremity atherosclerosis grade of elderly patients with T2DM( P<0.01). Conclusion:Atherosclerosis has a predictive value for early sarcopenia in elderly patients with T2DM.
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The overall prevalence of uniparental disomy (UPD) across all chromosomes was estimated to be around one birth in 2000. To date, more than 4170 UPD cases have been registered. UPD for chromosomes 6, 7, 11, 14, 15, and 20 can result in clinically recognizable imprinting disorders due to abnormal levels of imprinted gene expression. For other chromosomes, the clinical consequences associated with UPD are not apparent, unless when a recessive genetic disorder is unmasked by UPD or regions of homozygosity (ROH). A clinical practice guideline will assist in strengthening the precise analysis and interpretation of the clinical significance of ROH/UPD. This guideline summarizes the conception, mechanism and clinical consequences of ROH/UPD, as well as the principles for data analysis, with an aim to standardize the clinical application and data interpretation.
Subject(s)
Humans , Gene Expression , Genomic Imprinting , Homozygote , Uniparental Disomy/geneticsABSTRACT
The overall prevalence of uniparental disomy (UPD) across all chromosomes was estimated to be around one birth in 2000. To date, more than 4170 UPD cases have been registered. UPD for chromosomes 6, 7, 11, 14, 15, and 20 can result in clinically recognizable imprinting disorders due to abnormal levels of imprinted gene expression. For other chromosomes, the clinical consequences associated with UPD are not apparent, unless when a recessive genetic disorder is unmasked by UPD or regions of homozygosity (ROH). A clinical practice guideline will assist in strengthening the precise analysis and interpretation of the clinical significance of ROH/UPD. This guideline summarizes the conception, mechanism and clinical consequences of ROH/UPD, as well as the principles for data analysis, with an aim to standardize the clinical application and data interpretation.
Subject(s)
Humans , Gene Expression , Genomic Imprinting , Homozygote , Practice Guidelines as Topic , Uniparental Disomy/geneticsABSTRACT
Objective:To explore the related factors of muscle mass loss in patients with type 2 diabetes mellitus, and to provide evidence for prevention of sarcopenia in type 2 diabetic patients.Methods:A cross-sectional survey was used to select type 2 diabetic patients admitted to the Department of Endocrinology, Affiliated Hospital of Qingdao University from January 2019 to August 2019. All subjects underwent dual-energy X-ray absorptiometry check. According to the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), the subjects were divided into a muscle reduction group and a non-muscle reduction group. Data including age, gender, body mass index, course of disease, blood index, urinary albumin-creatinin ration (UACR), and appendicular skeletal muscle index (ASMI) were collected. The relevant clinical data of viscera fat/subcutaneous fat (VAT/SAT), percentage of abdominal fat/percentage of hip fat (A/G), grip strength, and pace were analyzed for the related factors of muscle mass loss in type 2 diabetic patients.Results:A total of 369 patients with type 2 diabetes were enrolled, including 42 patients with sarcopenia (an incidence rate of 11.38%), and 155 patients with reduced muscle mass (an incidence of 42.01%). Age, systolic blood pressure, high density lipoprotein-cholesterol, UACR, VAT/SAT, and A/G in the muscle reduction group were higher than those in the non-muscle reduction group ( P<0.05). The parameter of body mass index, homeostasis model assessment for insulin resistance, estimated glomerular filtration rate (eGFR), ASMI, and grip strength were lower in the muscle reduction group than in the non-muscle reduction group ( P<0.05). Multivariate logistic regression analysis showed age, UACR, A/G, and VAT/SAT were risk factors for muscle loss, body mass index, eGFR, and grip strength were protective factors for muscle mass reduction. Conclusion:It is of great practical significance for type 2 diabetic patients, especially those with advanced age, central obesity, low body mass index, low grip strength, low glomerular filtration rate, and high UACR to perform an early screening and to begin an early intervention.
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Objective:To explore the application of contrast-enhanced ultrasound (CEUS) combined with mathematical model in differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and prophase of bacterial hepatic abscess (PBHA).Methods:Fifty-one ICC patients (ICC group)and 46 PBHA patients(PBHA group) from January 2010 to April 2019 in Henan Provincial People′s Hospital were analyzed retrospectively. All ICC patients and 41 PBHA patients were confirmed by surgery or puncture pathology, and 5 PBHA patients were confirmed by clinical follow-up. The characteristic information of ultrasound images of the lesions were analyzed.Partial least squares-discriminant analysis (PLS-DA) was used to establish ICC and PBHA mathematical models, and Monte Carlo simulation was used to verify their accuracy. Based on PLS-DA modeling method, variable importance in the projection (VIP) was used to obtain the variables that had a strong influence on identifying the two from all variables.Results:There were significant differences between ICC group and PBHA group in lesion sites, complications, internal characteristics and clearance characteristics of contrast-enhanced arterial phase (all P<0.05). The average positive and negative predictive values of PLS-DA were 92.30% and 91.17%, and the average positive and negative predictive values in the prediction set were 100% and 94.11%, respectively.Variables with VIP value >1 included X2 (complication), X4, X5, X7, X8, X9 (CEUS enhanced features), X10, X11 (clearing features), and these variables could be used as important indicators for differential diagnosis between ICC and PBHA. Conclusions:PLS-DA method based on CEUS parameters can construct a differential diagnosis model for ICC and PHBA, which is expected to provide a valuable and robust diagnostic method for these two diseases which are easily confused and lack of specific imaging manifestations.
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Objective To investigate the effect of liraglutide on glucagon release in obese type 2 diabetes (T2DM). Methods A multi-center, prospective, and self-comparison study was conducted in four hospitals in Qingdao. Twenty-four patients with T2DM were selected and treated with liraglutide for 12 weeks. Glucagon levels before and after treatment were detected before and 30 min, 60 min and 120 min after meals. Results After 12 weeks of treatment, the overall level of glucagon decreased, in which the differences in glucagon levels at 30 min [(220±79) ng/L vs. (203±77) ng/L, P<0.05] and 60 min [(248±119) ng/L vs. (203±82)ng/L, P<0.05] reached significance, respectively, comparing to those before treatment. The area under the curve of glucagon after treatment was significantly lower than that before treatment (438±190 vs. 389 ± 153, P<0.05). In contrast, after treatment, the overall level of C-peptide increased, especially the levels at 30 min [(1.53±1.02) nmol/L vs.(2.03±1.29) nmol/L ], 60 min [(1.93±1.19) nmol/L vs. (2.48±1.75) nmol/L] and 120 min [(2.36±1.47) nmol/L vs. (2.96±1.84) nmol/L], all P<0.05. The area under C-peptide curve increased significantly (3.6±2.2 vs. 4.6±2.9, P<0.05). Fasting plasma glucose, postprandial 2 h plasma glucose and glycosylated hemoglobin A1c were all lower than before, and the differences were statistically significant (P<0.05). Waist circumference and body mass index were significantly lower than before (P<0.05). The amount of insulin used for the treatment decreased by approximately 55.1% compared with that before liraglutide, and the difference was statistically significant (P<0.05). Conclusions Liraglutide inhibits glucagon secretion and lowers blood glucose. It can also reduce body weight, improve islet cell function and reduce insulin use in T2DM.
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Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
Subject(s)
Animals , Humans , Male , Mice , DNA, Mitochondrial , Genetics , Induced Pluripotent Stem Cells , Cell Biology , Metabolism , MELAS Syndrome , Genetics , Microsatellite Repeats , Genetics , Mitochondria , Genetics , Metabolism , Mutation , GeneticsABSTRACT
Obesity is becoming an increasingly common health problem in the world.People pay more attention to obesity and the way to lose weight is gradually evolving with the development of science and technology.The widely application of the sleeve gastrectomy in recent years makes the operation has become the world's second-ranked use of weight loss surgery.In this paper,indications and contraindications,surgical methods,surgical results and complications were summarized.
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Obesity is becoming an increasingly common health problem in the world.People pay more attention to obesity and the way to lose weight is gradually evolving with the development of science and technology.The widely application of the sleeve gastrectomy in recent years makes the operation has become the world's second-ranked use of weight loss surgery.In this paper,indications and contraindications,surgical methods,surgical results and complications were summarized.
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Objective To investigate mental health literacy (MHL) of community medical staffs in district and town of Zhongshan city,and to provide data to improve MHL of community medical staffs.Methods Totally 352 medical staffs who were not psychiatric physician and 81 psychiatric physician were selected.The Chinese Mental Health Knowledge Awareness Questionnaire (published by Ministry of Health) was used to investigate the awareness rate of mental health knowledge.Five vignettes of two schizophrenia,one bipolar disorder,one depression and one obsessive compulsive disorder,each with 8 related questions,were used to investigate the recognition and response ability.Results The average awareness rate of the two groups was more than 80.0% (87.6%,91.6%).For the item 2(75.6%,88.6%),6(74.1%,62.6%),19(36.5%,65.6%),and 20(74.1%,86.2%),the awareness rates were lower than 80.0%,and there were significant differences between the two groups (x2=8.45,4.92,27.48,6.99,all P<0.05).In vignettes survey,the correct rate was lower in the staffs who did not engaged in the mental health work than those in the other group,the difference was statistically significant(64.6% vs.75.9%,P<0.001).For both of the two groups the correct rate of depression was the lowest(x2=44.46,P<0.001).There was statistically significant difference between the total (x2=141.17,P<0.001).Conclusion The awareness rate of mental health knowledge has reached the national standards for community medical staffs,but they have to improve for some knowledge point.Their recognition and response ability for mental illness should be improved.
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Objective The purpose of this study is to investigate the molecular mechanisms of p.C310R(c.T928C) and p.E396V(c.A1187T) lipoprotein lipase(LPL) gene mutations in vitro, which may help to construct the spectrum of LPL gene mutations and phenotype. It also can provide accurate early diagnosis for high-risk population of familial hypertriglyceridemia and provide the basis for the development of gene targeted therapy. Methods Genomic DNA was extracted from proband′s family members′ peripheral blood cells and screened by whole-exome sequencing to verify candidate gene variations. PCR products were afterwards directly sequenced again to confirm corresponding LPL variants. At the cellular level, lentiviruses containing LPL mutations were constructed and then transfected into COS-1 cells. Functional significance of the mutants was corroborated by analyzing LPL activity and mass in the cell medium and lysates via ELISA and enzyme-fluorescent method. mRNA was assayed by RT-PCR to confirm the effect on gene transcription. Results DNA sequence analysis revealed that the proband was a heterozygote for a novel c.T928C mutation in exon 6 of LPL gene, while his nephew was a compound heterozygote for the c.T928C mutation in exon 6 and a novel c.A1187T mutation in exon 8. In vitro studies, these two mutations can cause decreased activity and mass of extracellular LPL(P<0.05). Moreover, further investigation indicated that LPL C310R mutation tremendously affected post-transcriptional modification of LPL gene, whereas LPL E396V mutation dampened intracellular LPL trafficking. Conclusion Both the mutations are pathogenic by reducing the activity and mass of LPL in the plasma, which affected normal metabolism of triglycerides.
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The CRISPR-Cas9 system is a new targeted nuclease for genome editing, which can directly introduce modifications at the targeted genomic locus. The system utilizes a short single guide RNA (sgRNA) to direct the endonuclease Cas9 in the genome. Upon targeting, Cas9 can generate DNA double-strand breaks (DSBs). As such DSBs are repaired by non-homologous end joining (NHEJ) or homology directed repair (HDR), therefore facilitates introduction of random or specific mutations, repair of endogenous mutations, or insertion of DNA elements. The system has been successfully used to generate gene targeted cell lines including those of human, animals and plants. This article reviews recent advances made in this rapidly evolving technique for the generation of animal models for human diseases.
Subject(s)
Animals , Humans , Clustered Regularly Interspaced Short Palindromic Repeats , Genetics , Disease Models, Animal , RNA Editing , GeneticsABSTRACT
Objective To investigate the correlation of gestational diabetes mellitus and preeclampsia and its influence on delivery outcome.Methods A retrospective analysis of 4 636 pregnant women were made,who were sin-gleton pregnancy and gestational age≥32 weeks,and the data of GDM,PE,delivery outcome were collected.Then,the incidence of PE in GDM or non-GDM were compared,the delivery outcome in pregnant women without interval med-icine comorbidity ( A group) ,GDM pregnant women( B group) ,PE pregnant women( C group) ,pregnant women com-bined GDM and PE(D group) were analyzed.Results The incidence rate of GDM was 3.71%(172/4 636) in the whole,the incidence rate of PE was 5.65% (262/4 636).The incidence rates of PE among GDM and non-GDM pregnant women were 11.63%(20/172) and 5.42%(242/4 464),the difference was statistically significant(χ2 =5.983,P<0.05).The average pre-pregnant body mass index(BMI),Apgal scores at 1 minute and 5 minutes were compared,and the differences among the four groups were statistically significant( F=29.142,16.074,35.415,all P<0.01),and those in C group,D group were significantly lower than in group A and group B [t(C-A) =5.386, 4.821,5.224,t(C-B) =5.023,4.456,6.278,t(D-A) =6.753,5.012,6.443,t(D-B) =6.475,4.727,7.622,all P<0.01].The rates of neonate intensive care,giant baby natality,small-for-gestational-age children,premature labor were compared,and the differences among the four groups were statistically significant (χ2 =157.290, 96.129, 46.969,27.005,all P<0.1),the rates of neonate intensive care in C group and D group were higher than in A group and B group[χ2(C-A) =47.294,χ2(C-B) =15.547,χ2(D-A) =17.280,χ2(D-B) =7.088,all P<0.01],the rates of giant baby natality in B group were higher than A group,C group [χ2(B-A) =29.445,χ2(B-C) =6.597,all P<0.05],the rates of small-for-gestational-age children and premature labor in D group were higher than A group,B group and C group[χ2(D-A) =42.676,26.261,χ2(D-B) =9.070,10.879,χ2(D-C) =25.117,8.653,all P<0.01].Conclusion Pregnant women with GDM might have higher risk of suffering PE than those non-GDM gravidas,the PE,GDM com-bined with PE seriously influence perinatal outcome,pregnancy care should be strengthened to prevent and treat.
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<p><b>OBJECTIVE</b>To reprogram the 1q21.1 microdeletion pluripotent stem cells in order to establish an ideal model for further studying its pathogenesis.</p><p><b>METHODS</b>Human amniotic fluid-derived cells induced pluripotent stem cells (hAF-iPSCs) were induced from amniotic fluid cells harboring the 1q21.1 microdeletion by retroviral vectors encoding Oct4, Sox2, c-Myc and Klf4. Characteristics of the 1q21.1 microdeletion hAF-iPSCs were determined, which included in vitro pluripotency, karyotype, microarray analysis, the capacity of differentiation in vivo and in vitro, etc.</p><p><b>RESULTS</b>hAF-iPSCs derived from amniotic fluid cells harboring the 1q21.1 microdeletion have maintained self renewal, with expression of pluripotency marker genes detectable at mRNA level. Stem cell surface antigens were tested by immunocytochemistry. The 1q21.1 microdeletion hAF-iPSCs showed a normal karyotype after long-term culturing in vitro, and harbored the same microdeletion as confirmed by microarray analysis. The cells have maintained their differentiation capacity both in vivo and in vitro.</p><p><b>CONCLUSION</b>The hAF-iPSCs harboring the 1q21.1 microdeletion have all the characteristics of normal pluripotent stem cells, and can be used for directed differentiation into specific cells, which may provide an ideal model for studying the pathogenesis of 1q21.1 microdeletion in vitro.</p>