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【Objective】 To study the protective effect of glycine solution on frozen red blood cell thawing process. 【Methods】 A total of 20 bags of 1 U of leukocytes reduced suspended red blood cells within 6 days were selected for the study. After mixing, each 2 bags of suspended red blood cells were divided into 2 bags and into two groups with 10 bags of 1 U in each group, and were frozen for storage. One group was deglycerolized with sodium chloride solution (control group), and one group was deglycerolized with glycine solution (experimental group). The hemoglobin, free hemoglobin, residual glycerol, total glycerol in red blood cells, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were detected in the two groups. 【Results】 Compared with the free hemoglobin content (0.90±0.05)g/L and residual glycerol content (1.17± 0.08)g/L in the control group, the final product red blood cell supernatant free hemoglobin content (0.77±0.15)g/L and residual glycerol content (0.79±0.33)g/L in the experimental group were decreased, and the difference was statistically significant (P<0.05). Compared with the ATP content (4.03±0.38)µmol/gHb and 2,3-DPG content (485.65±78.08)µg/L in the control group, the ATP content (4.41±0.35)µmol/gHb and 2,3-DPG content (656.28±116.68)µ g/L in the experimental group were significantly increased, with statistical significance (P<0.05). 【Conclusion】 Using glycine solution instead of sodium chloride solution to prepare frozen thawed deglycerolized erythrocytes achieved the effect of protecting erythrocytes, reduced the hemolysis rate of erythrocytes and glycerin residue, and increased the recovery rate of erythrocytes.
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【Objective】 To investigate the correlation between the titer of anti-A or anti-B antibodies before and after the absorption of IgG anti-AB antibodies in the serum of type O mothers with ABO hemolytic disease of fetus and newborn (ABO-HDFN) and the total bilirubin in the serum of the children. 【Methods】 Serum samples from 119 children diagnosed with ABO-HDFN and their mothers sent to the Beijing Red Cross Blood Center from January to December 2020 were selected, and clinical data of the children were collected. Three hemolysis tests and serum total bilirubin (TBIL) determination were conducted on the children. IgG anti-A or anti-B antibody titers were tested before and after the mother′s serum absorbed IgG anti-AB antibodies. Statistical analysis was conducted on the IgG antibody titers and the TBIL results of the children. The differences in TBIL results corresponding to different IgG antibody titers were compared. The Spearman test was used to analyze the correlation between the IgG anti-A or -B antibody titers and TBIL results before and after the absorption of IgG anti-AB antibodies. 【Results】 There were differences in the TBIL results corresponding to IgG anti-A or anti-B titers at different levels in the serum of type O mothers after absorption by IgG anti-AB antibodies (F=8.401, 19.622, P0.05). The IgG anti-A or anti-B titers of maternal serum absorbed by IgG anti-AB antibodies were positively correlated with neonatal TBIL results (r=0.487, 0.629, P<0.05). 【Conclusion】 There is a positive correlation between the titer of IgG anti-A or anti-B antibodies in the serum of type O mothers after absorbing IgG anti-AB antibodies and the TBIL results of ABO-HDFN children. The trend of increased total bilirubin in newborn serum ban be accurately predicted by detecting the titer level of IgG anti-A or anti-B antibodies in the serum of mothers after absorbing IgG anti-AB antibodies.
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【Objective】 To investigate the inactivation function of 25Gy X-ray irradiation on apheresis platelets’ lymphocytes and its effect on the quantity of apheresis platelets(AP). 【Methods】 Twenty healthy voluntary AP donors from January to May 2021 in our center were selected, and 2 bags of AP were donated by each of them. The APs were divided into two groups to undergo X-ray and γ-ray irradiation for 10 min. Lymphocytes were separated from AP samples, before and after irradiation, by lymphocyte separation solution to analyze and compare the effect of X-ray and γ-ray on lymphocyte proliferation. The CD41b, CD62p, blood routine and pH of APs before and 1-day/3-day after irradiation were detected. SPSS statistical software was used to analyze and compare the differences between groups by independent sample t-test. 【Results】 After 25Gy X-ray and γ-ray irradiation, the inhibition rates of lymphocytes were (98.034±1.778)% and (97.882±1.915)%, respectively.Compared with the γ irradiation group, the difference of Plt, PDW, MPV, P-LCR, PCT, pH, CD41b and CD62p between 1-day and 3-day group after 25Gy X-ray irradiation showed not statistically significance (P>0.05). 【Conclusion】 25Gy X-ray irradiation can effectively inactivate lymphocytes in APs, and the radiation effect was equivalent with γ-ray; at the same time, there was no significant influence on the quantity of APs.
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BACKGROUND AND OBJECTIVE: Interstitial lung disease with lung cancer (ILD-LC) is rare and its management has not been fully described. This study aimed to investigate the management and prognosis of ILD-LC patients in China. METHODS: The present analysis is a retrospective real-world cohort study. Clinical data of ILD-LC patients were obtained from 3 hospitals in China. The overall survival (OS) of patients was analyzed. Univariate and multivariate regression analyses were performed. RESULTS: One hundred eighty-four ILD-LC patients included were biased toward male (85.3%), smokers (75.5%), idiopathic pulmonary fibrosis (IPF) (58.2%) patients with comorbidities (67.9%) and ECOG-PS score of 1 (65.2%). Most patients were advanced peripheral non-small cell lung cancer. The initial anti-cancer regimen for ILD-LC is mainly chemotherapy, and patients with early-stage LC prefer surgery. In the anti-cancer cohort, the number of ILD-LC patients who underwent the 2nd and 3rd or more anti-cancer regimens were 78 (55.7%) and 32 (22.8%), respectively. In the non-anticancer cohort, the median OS was 3.5 months. In the early-stage cohort, the median OS was 14.2 months in the systematic therapy group; however, the median OS was not reached in the surgery group. In the advanced-stage cohort with systematic therapy, the median OS was 7.2 months. Interstitial pneumonia (IIP) and anti-angiogenesis were associated with OS in the univariate analysis, whereas anti-angiogenesis was an independent protective factor for advanced LC with ILD. CONCLUSION: Patients with ILD-LC have very poor prognosis. Appropriate anti-tumor treatment can prolong the survival time of patients who can tolerate it. Targeted therapy and immunotherapy are alternative treatments for LC patients with mild ILD. For ILD patients with advanced LC, antiangiogenic regimens significantly improve the prognosis of the disease.
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Regulated necrosis is a newly discovered new cell death pathway, including necroptosis, pyroptosis and ferroptosis. It has been reported to play a key role in acute kidney injury (AKI) induced by ischemia/reperfusion, cisplatin and other drugs, and rhabdomyolysis. Studying the role of regulated necrosis-related pathways in AKI is expected to provide a new direction for clarifying the pathogenesis and treatment of AKI, with potential therapy and application prospects. In this review, we summarize the related signaling pathways of necroptosis, pyroptosis and ferroptosis, and the related research progress in AKI, in order to provide potential targets for the prevention and treatment of AKI.
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OBJECTIVE@#To establise the bank of platelet donors with the human platelet antigen (HPA) 1-6, 15 genes so as to provide the HPA-matched platelets for the patients.@*METHODS@#The HPA genotyping of platelets donors and patients with platelet antibody positive confirmed by sercening was performed by using the SSP-PCR; the efficacy of transfusing the HPA-matched platelets for 37 cases platelet antibody positive was analyzed.@*RESULTS@#The most common genotype in platelet donors were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b, followed by HPA-1a/1a-2a/2a-3a/3a-4a/4a-5a/5a-6a/6a-15a/15b; the most common genotype in 53 cases of platelet antibody positive confirened by screening were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b. Among 37 patients with platelet antibody positive confirened by screeming, 28 showed that the transfusion of HPA-matched platelets was effective with statistically significant difference in comparison with random transfusion group. The HPA-3, HPA-15 were the main factors leading to polymorphisms.@*CONCLUSION@#HPA-3 and HPA-15 are polymorphic, which should be focused on. HPA-matched platelets can improve the efficiency of platelet transfusion, and avoid the waste of blood resources. The genotypes of platelet donors can basically meet the requirements for common genotype transfusion.
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Volume management is recognized as an important determinant of dialysis adequacy. The optimal ultrafiltration and sodium removal will improve the volume management and reduce the cardiovascular mortality. Automated peritoneal dialysis (APD), as one of renal replacement therapies, has become a choice for more and more patients with end-stage renal disease. APD allows an individualized dialysis prescription by providing more dialysis doses and more exchange times to improve ultrafiltration and sodium removal, achieving or even exceeding the efficacy of continuous ambulatory peritoneal dialysis. New strategies for volume control have emerged, including adapted APD, using icodextrin and low-sodium dialysate, to provide new ideas for APD prescription adjustment.
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Objectives:To investigate the risk factors of sarcopenia in patients receiving maintenance peritoneal dialysis (MPD).Methods:One hundred and thirteen patients receiving maintenance MPD for ≥3 months during January and December 2017 were enrolled in this study. According to the Asian Working Group for Sarcopenia(AWGS)algorithm, there were 26 patients with sarcopenia accounting for 23.0% of all MPD patients. Demographic and anthropometric data were collected; laboratory tests were conducted, Kt/V urea and normalized protein equivalent of total nitrogen appearance were calculated; the bioelectrical impedance analysis (BIA) was performed and grip strength was tested. The nutritional status was evaluated with Subjective Global Assessment (SGA). Logistic regression was used to analyze the risk factors of sarcopenia in MPD patients. Results:BMI and dialysis dose of patients with sarcopenia were significantly lower than those without sarcopenia [(20.35±2.35) kg/m 2vs. (23.81±3.14) kg/m 2, t=-5.181, P<0.01; (5.57±1.83) L/d vs. (6.66±1.71) L/d, t=-2.795, P<0.01]. The bioelectrical impedance analysis showed that the total water content of patients with sarcopenia was higher than that of patients without sarcopenia [(35.44±6.40) kg vs. (28.52±4.89) kg, t=5.077, P<0.01]; while the protein content[(7.46±1.31) kg vs. (9.24±1.63) kg, t=-5.080, P<0.01] and skeletal muscle content [(20.54±4.18) kg vs. (25.88±4.95) kg, t=-4.980, P<0.01] of patients with sarcopenia were lower than those without sarcopenia. Multivariate analysis showed that decreased BMI( OR=0.934, 95 %CI: 0.723-0.998, P<0.01) and body protein ( OR=0.927, 95 %CI: 0.698-0.996, P<0.01), increased total body water( OR=1.382, 95 %CI: 1.053-1.813, P=0.02) were independent risk factors for sarcopenia in MPD patients. Conclusion:The incidence of sarcopenia in MPD patients is high, which is associated with the excessive volume load and malnutrition of patients.
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Volume management is recognized as an important determinant of dialysis adequacy. The optimal ultrafiltration and sodium removal will improve the volume management and reduce the cardiovascular mortality. Automated peritoneal dialysis (APD), as one of renal replacement therapies, has become a choice for more and more patients with end-stage renal disease. APD allows an individualized dialysis prescription by providing more dialysis doses and more exchange times to improve ultrafiltration and sodium removal, achieving or even exceeding the efficacy of continuous ambulatory peritoneal dialysis. New strategies for volume control have emerged, including adapted APD, using icodextrin and low-sodium dialysate, to provide new ideas for APD prescription adjustment.
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Objective To explore the treatment strategies of pleuroparenchymal fibroelastosis (PPFE). Methods A 22-year-old male patient was complicated with PPFE after receiving chemotherapy in combination with stem cell transplantation for lymphoma. He underwent thoracoscopic left lung tongue wedge resection, bilateral pleurodesis followed by allogeneic left lung transplantation. Literature review was performed to analyze the etiology, pathogenesis, imaging features, pathological features and treatment of PPFE. Results The PPFE patient required the non-invasive ventilator for 24 h before lung transplantation. After lung transplantation, the shortness of breath and respiratory failure were cured and the quality of life was significantly improved. No eligible studies was found in the domestic database, and 26 literatures published in English were found in the international databases. Among them, 9 literatures (case reports) were finally included after screening. PPFE could be divided into the primary and secondary categories according to the etiology. The clinical manifestations of PPFE mainly included dry cough, dyspnea on exertion, chest pain, repeated pneumothorax and body weight loss. Chest CT scan demonstrated irregular thickening of the pleura in bilateral upper lungs. Pathological manifestations consisted of evident thickening of the visceral pleura, fibroelastosis and arrangement disorder in the pleura and the underlying pulmonary interstitium. PPFE could progress rapidly. Adrenocortical hormone and other immunosuppressive agents yielded low clinical efficacy and poor clinical prognosis. Lung transplantation was a necessary treatment for PPFE. Conclusions PPFE cannot be effectively treated by conservative therapy. It is recommended to deliver lung transplantation as early as possible.
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OBJECTIVE： To study the effects of cimetidine on low dose rate irradiation-induced liver cell apoptosis in Beagle dogs. METHODS： Healthy male Beagle dogs were randomly divided into normal control group， model control group， positive drug group （lentinan， 21.33 mg/kg） and cimetidine low-dose， medium-dose and high-dose groups （5.33， 10.67， 21.33 mg/kg）， with 4 Beagle dogs each. Except for normal control group， other groups were given 60Co-γ accumulative irradiation （dosage rate： 0.040 8 mGy/min） for 23 d； the medication groups were given relevant medicine orally before irradiation， once a day. Twenty-four hours after stopping irradiation， TUNEL method was used to detect the apoptosis of liver cells in Beagle dogs. The percentage of apoptotic cells was calculated. The expression level of apoptosis-related proteins （Bax， Bcl-2， Caspase-3， p53） in liver tissue was detected by immunohistochemistry. RESULTS： Compared with normal control group， apoptotic cells and Bax， Caspase-3， p53 positive cells were increased significantly in liver tissue of Beagle dogs in model control group； the percentage of apoptotic cells， protein expression levels of Bax， Caspase-3 and p53 were increased significantly； Bcl-2 positive cells were decreased significantly， and its protein expression level was decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， above positive cells of liver tissue in Beagle dogs were changed to different extents in medication groups； the percentage of apoptotic cells and protein expression levels of p53 in medication groups， protein expression levels of Bax in positive drug group， cimetidine low-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were decreased significantly； protein expression levels of Bcl-2 were increased significantly in cimetidine groups. The percentage of apoptotic cells in cimetidine medium-dose and high-dose groups as well as protein expression levels of Caspase-3 in cimetidine groups were all lower than positive control group. Protein expression level of p53 in cimetidine low-dose group was significantly higher than positive drug group （P＜0.05 or P＜0.01）. CONCLUSIONS： Cimetidine can inhibit the low dose rate irradiation-induced apoptosis of liver cells in Beagle dogs， and certainly protect liver cells against irradiation. The mechanism of it may be associated with up-regulating the protein expression of Bcl-2 and down-regulating the protein expression of Bax， Caspase-3 and p53 in liver cells.
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Objective To develop a detergent for decontamination of Co2+ and Mn2+ on skin.Methods Single-factor experimental and orthogonal experimental designs were performed to study the formula composition of the decontaminant.The skin irritation experiment was performed and assessed according to the standard method.The detergent was prepared according the conventional process of showering gel.The pH,ethylenediaminetetraacetic acid (EDTA) level,total active substances of the detergent,and its stability were evaluated according to the chemical method recommended in the national standard GB/T 13173-2008.The decontamination efficiency on stable isotopes of Co2+ and Mn2+ contamination was measured on the back of hand skin of volunteers.Results The formula composition of the decontaminant was obtained through the orthogonal experiment.The pH value of the detergent was 6.99,total active substance was 20.49％ and the content of EDTA was 5.99％.After being kept at-5 ℃ and 40℃℃ for 24h,the decontaminant showed no strange smell,no precipitation,no discoloration and still kept transparent.The decontamination effects on Co2+ and Mn2+ contaminated on hand skin were 103.13％ ± 0.05％ and 100.62％ ± 0.09％,respectively,which was significantly higher than that of distilled water (81.77％ ± 0.23％ and 79.63％ ± 0.23％,P＜0.01,respectively).Conclusion The decontaminant has a high effect on decontamination of Co2+ and Mn2+ polluted on skin,and is hopeful to be developed as an effective detergent on radioactive isotopes contamination.
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Secondary ion mass spectrometry ( SIMS) as a powerful surface analysis technique has been widely applied in semiconductor industry and geology research. Recently, with the development of instrumental technology, SIMS is attracting more and more attention in life sciences. SIMS can provide surface MS spectra, 2D/3D chemical images and depth profiling of substances simultaneously. The minimal lateral resolution of 2D SIMS imaging is 80 to 100 nm, and the longitudinal resolution of 3D SIMS imaging is about 1-5 nm. However, due to lack of specific ions to render the structures of organelles, SIMS imaging for single cells still has great challenges. Optical microscopy, in particular laser scanning confocal microscopy ( LSCM) , has been emerged to be an indispensable technique for single cell imaging and can obtain high spatial 2D/3D imaging to visualize the structures of organelles. Thus, the combinational use of SIMS and LSCM, which takes advantages of SIMS for molecular imaging and LSCM for morphological imaging, has greatly extended the application of SIMS imaging and ensured its accuracy at single cells level, providing novel insights into better understanding of the biological events inside cells. In this review, we focus on the development and application of SIMS imaging and the correlated SIMS and LSCM imaging in the research of cell biology and drug discovery. We anticipate that the combinational use of SIMS and LSCM imaging has promising future in biomedicine and life sciences.
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Bromodomain-containing 4 (BRD4) has been considered as an important requirement for disease maintenance and an attractive therapeutic target for cancer therapy. This protein can be targeted by JQ1, a selective small-molecule inhibitor. However, few studies have investigated whether BRD4 influenced acute promyelocytic leukemia (APL), and whether BRD4 had interaction with promyelocytic leukemia-retinoic acid receptor α (PML/RARα) fusion protein to some extent. Results from cell viability assay, cell cycle analysis, and Annexin-V/PI analysis indicated that JQ1 inhibited the growth of NB4 cells, an APL-derived cell line, and induced NB4 cell cycle arrest at G1 and apoptosis. Then, we used co-immunoprecipitation (co-IP) assay and immunoblot to demonstrate the endogenous interaction of BRD4 and PML/RARα in NB4 cells. Moreover, downregulation of PML/RARα at the mRNA and protein levels was observed upon JQ1 treatment. Furthermore, results from the RT-qPCR, ChIP-qPCR, and re-ChIP-qPCR assays showed that BRD4 and PML/RARα co-existed on the same regulatory regions of their target genes. Hence, we showed a new discovery of the interaction of BRD4 and PML/RARα, as well as the decline of PML/RARα expression, under JQ1 treatment.
Subject(s)
Humans , Apoptosis , Azepines , Pharmacology , Cell Differentiation , Down-Regulation , Gene Expression Regulation, Neoplastic , Leukemia, Promyelocytic, Acute , Drug Therapy , Genetics , Nuclear Proteins , Genetics , Promyelocytic Leukemia Protein , Genetics , RNA, Messenger , Genetics , Retinoic Acid Receptor alpha , Genetics , Transcription Factors , Genetics , Triazoles , Pharmacology , Tumor Cells, CulturedABSTRACT
In aged patients, acute kidney injury (AKI) is a common clinical complication after percutaneous coronary intervention (PCI), highlighting the need for timely and certain diagnosis of this disease. A single centre, nested case-control study was conducted, which assessed the usefulness of urinary liver-type fatty acid-binding protein (uL-FABP), neutrophil gelatinase-associated lipocalin (uNGAL), and kidney injury molecule-1 (uKIM-1) for early detection of AKI. One hundred and thirty-two patients at or over 60 years old undergoing PCI were included. Serum creatinine (SCr) was measured before PCI, 24 and 48 h after PCI; uL-FABP, uNGAL, and uKIM-1 were measured before PCI, 6, 24, and 48 h after PCI. We identified 16 AKI patients and selected 32 control patients matched by admission time (<1 week), age (±5 years), and gender. In the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUCs) for the relative measurements of uL-FABP, uNGAL, and uKIM-1 were 0.809, 0.867, and 0.512 at 6 h after PCI, and 0.888, 0.840, and 0.676 at 24 h after PCI, respectively. AUC for the combination of uL-FABP and uNGAL was 0.899 at 6 h after PCI, and 0.917 at 24 h after PCI. Thus, measurement of uL-FABP and uNGAL levels at 6 and 24 h after PCI may be useful in detecting AKI in aged patients. Measurement of uKIM-1 levels provides inferior predictive power for early diagnosis of AKI.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Acute Kidney Injury , Diagnosis , Urine , Early Diagnosis , Fatty Acid-Binding Proteins , Urine , Hepatitis A Virus Cellular Receptor 1 , Lipocalin-2 , Urine , Percutaneous Coronary InterventionABSTRACT
Sarcopenia is a degenerative syndrome mainly characterized by the atrophy of skeletal muscle,along with the decrease of muscle strength and function.Chronic kidney disease,especially in patients undergoing maintenance hemodialysis,can accelerate muscle consumption and increase the incidence rate of sarcopenia.Several factors were correlated with sarcopenia occurrence in chronic kidney disease,including inflammation,malnutrition,increased angiotensin Ⅱ,abnormal insulinsignaling pathway,abnormalities in myogenic regulatory factors,decreased hypogonadism,increased myostatins,mitochondrial disorders,decreased physical activity,etc.This paper has reviewed the research progress on the pathogenesis of sarcopenia in chronic kidney disease.
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Chronic heart failure,especially the end-stage heart failure,is often accompanied by the loss of muscle mass,strength and functions of muscle.A large amount of trust evidences supported that sarcopenia was linked to poor prognosis of heart failure.This paper has reviewed the epidensiological features,medchanisms,prognosis,and treatment of heart failure-related sarcopenia.
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OBJECTIVE: To explore the biological functions of E77.43, a gene segment of Microtus fortis, in treating Schistosoma japonicum infection. METHODS: Recombinant retroviral vectors of pRevTRE-E77.43 was constructed, and recombinant retroviral vectors were transfected into PA317 cells, and the stable cell lines were obtained by hygromycin screening, followed by the packaging, concentration and purification of recombinant retrovirus. The virus was transferred to the mice infected by S. japonicum via intravenous or intraperitoneal injection, through which the express of target gene and the treatment function in vivo were observed. RESULTS: The experiment showed the recombinant virus injected mice could efficiently express E77.43 on the 7th day after the injection which lasted for forty-five days thereafter. A significant reduction in adult worms (31.0%) and a high reduction (35.0%) in liver eggs were induced by pRevTRE-E77.43, while the reduction in adult worms and that in liver eggs was 1.2% and 0.9% induced by pRevTRE respectively (t = 3.524, 9.485, both Pï¼0.01). CONCLUSIONS: pRevTRE-E77.43 could be used for the treatment of S. japonicum infection, indicating that E77.43 may involve in the natural resistance of M. fortis to S. japonicum infection.
Subject(s)
Gene Transfer Techniques , Retroviridae , Schistosomiasis japonica/therapy , Animals , Arvicolinae/genetics , Cell Line , Mice , Schistosoma japonicumABSTRACT
Acute kidney injury (AKI) is a frequent syndrome in hospitalized patients .Recently, a number of studies have been reported that the close relationship exists between genetic polymorphism and AKI .The current research on genetic polymorphism related with AKI is reviewed in this article .
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High-throughput sequencing was performed for the peripheral blood DNA from two probands in the family with tuberous sclerosis complex (TSC) to determine the sequences of TSC-related genes TSC1 and TSC2 and their splicing regions and identify mutation sites. Amplification primers were designed for the mutation sites and polymerase chain reaction and Sanger sequencing were used to verify the sequences of peripheral blood DNA from the probands and their parents. The two probands had c.3981-3982 insA (p.Asp1327AspfsX87) and c.4013-4014 delCA (p.Ser1338Cysfs) heterozygous mutations, respectively, in the TSC2 gene. The parents of proband 1 had no abnormalities at these two loci; the mother of proband 2 had c.4013-4014 delCA heterozygous mutation in the TSC2 gene, while the father and the grandparents of proband 2 had no abnormalities. c.3981-3982 insA mutation may cause early coding termination of amino acid sequence at the 1413th site, and c.4013-4014 delCA mutation may cause early coding termination of amino acid sequence at the 1412th site. These two mutations are the pathogenic mutations for families 1 and 2, respectively, and both of them are novel frameshift mutations, but their association with the disease needs to be further verified by mutant protein function cell model and animal model.
