National Approach to Premarital Diagnosis of Trait Thalassemia and Silent Carriers

Background: Major β-thalassemia occurs when impaired genes received by a neonate from the parents. In most of the parents, there are no apparent clinical manifestation and they just show some impairments in hematological indices. This study was designed to determine prevalence of minor and silent carries parents that have children suffering from major β-thalassemia, compare it with national protocol about prevention of thalassemia. Methods: A blood sample was taken from parents of all major thalassemic patients covered by TaleghaniHospitalin Gorgan (n = 195), CBC and Hemoglobin electrophoresis were done. Data were analyzed using SPSS software. Results: Amongst 196 parents one case have normal level of MCV, MCH, RBC, HbA, HbF and mentzer = 22.05 (0.51%) that diagnosed as alpha triplication/N by real time PCR, RFLP informative. The means of hematological indices were based on the national protocol. Conclusion: Present results showed that there are a few cases of thalassemia disorders with normal MCV, MCH, RBC, Mentzer index and Hb electrophoresis which could be missed in routine and pre-marital screening tests, resulted in a thalassemia child that it is possible in every screening test. Generally, indices were according to range of the national guideline.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Cracking the silent gallstone code:Wait or operate?

The widespread availability of abdominal ultrasound has revealed the common occurrence of asymptomatic gallstones.While the treatment for symptomatic gallstones is clear,the benefits of minimally invasive laparoscopic cholecystectomy have sparked debate about the best approach to managing silent gallstones.The potential for asymptomatic gallstones to become symptomatic or lead to complications complicates the decision-making process regarding surgical intervention,as it's uncertain when or which patients might develop complications.Consequently,risk stratification appears to play a critical role in guiding decisions about silent gallstones.However,there is no definitive evidence to direct management,and a consensus-based on high-quality evidence is yet to be established.

Liver disease in patients with transfusion-dependentβ-thalassemia:The emerging role of metabolism dysfunction-associated steatotic liver disease

In this Editorial,we highlight the possible role that metabolism dysfunction-associated steatotic liver disease(MASLD)may play in the future,regarding liver disease in patients with transfusion-dependent β-thalassemia(TDBT).MASLD is characterized by excessive accumulation of fat in the liver(hepatic steatosis),in the presence of cardiometabolic factors.There is a strong correlation between the occurrence of MASLD and insulin resistance,while its increased prevalence parallels the global epidemic of diabetes mellitus(DM)and obesity.Patients with TDBT need regular transfusions for life to ensure their survival.Through these transfusions,a large amount of iron is accumulated,which causes saturation of transferrin and leads to the circulation of free iron molecules,which cause damage to vital organs(primarily the liver and myocardium).Over the past,the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C,for which modern and effective treatments have been found,resulting in successful treatment.Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths,and an increase in their life expectancy.This increased survival makes them vulnerable to the onset of diseases,which until recently were mainly related to the non-thalassemic general population,such as obesity and DM.There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence.However,it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia(Padeniya et al,BJH),that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis.These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence,the risk factors,and the effect of MASLD on these patients.

Comparative Study of Neurosurgical Complications of Thalassemia and Sickle Cell Disease

Introduction: Sickle cell disease and thalassemia are the most frequent hemoglobinopathies. During their evolution, they present certain complications, among which are two neurosurgical emergencies, namely spontaneous cranial epidural hematoma and non traumatic radiculo-medullary compression, with some particularities for each. Method: In order to highlight these particularities, we compared the characteristics of these two complications, from a number of publications reported between 2000 and 2021. Results: Sickle cell disease was complicated by spontaneous cranial epidural hematoma. Forty-two cases were reported, the mean age was 14.7 years (2 - 21 years) and the sex ratio was 6.4. The clinical presentation combined, in a non-traumatic context, signs of intracranial hypertension with those of neurological focalization. Neuroimaging showed epidural-type collection, often frontal and parietal in location. The incriminating mechanisms were ischemia, hemorrhage and extra medullary hematopoiesis. The treatment was surgical. Non traumatic radiculo-medullary was the complication of thalassemia. Of the 77 cases reported, the mean age was 27.5 years (9 - 66 years) and the sex ratio was 4.1. The lesions were epidural with a clear thoracic predominance and resulted from extra marrow hematopoiesis. Treatment included: hypertransfusion, radiotherapy, hydroxyurea and surgery. Vital and functional prognosis were globally satisfactory when the management was rapid. Conclusion: Cranial and spinal epidural lesions, respective complications of sickle cell disease and thalassemia, result from similar mechanisms. Their prognosis depends on the rapidity of management. .

The Silent Curriculum:Classical Aesthetics as a Catalyst for Emotional and Social Skills in Higher Vocational Education

This study examines the integration of classical aesthetics into the silent curriculum of higher vocational education,emphasizing its potential to significantly enhance emotional and social skills.Incorporating aesthetic principles into education emphasizes the importance of nurturing emotional intelligence,creativity,and cultural awareness in students-skills that go beyond the classroom and are essential for their growth,adaptability,and future careers.It explores theoretical foundations and practical implementations and addresses challenges such as the need for specialized educator training,overcoming institutional resistance,and securing adequate resources.Advocating for empirical research and strategic cultural partnerships,the paper proposes a transformative approach to vocational education,aligning it with contemporary societal and labor market demands,and underscores the vital role of classical aesthetics in enriching vocational training and enhancing student outcomes.

α7烟碱型乙酰胆碱受体与阿尔茨海默病的关系

背景:α7烟碱型乙酰胆碱受体在大脑皮质和海马高度表达,并在阿尔茨海默病的病理发展过程中起重要调控作用,是阿尔茨海默病治疗的潜在靶点。目的:总结α7烟碱型乙酰胆碱受体和阿尔茨海默病的密切关系和相互作用机制。方法:检索中国知网、PubMed数据库中相关文献,中文检索词为“α7烟碱型乙酰胆碱受体,阿尔茨海默病,β-淀粉样蛋白,激动剂,正变构调节剂,拮抗剂”;英文检索词为“alpha 7 nicotinic acetylcholine receptor,Alzheimer’s disease,beta amyloid protein,agonist,positive allosteric modulator,antagonist”,文献检索时限为各数据库建库至2024年7月,依据入选标准对检索结果进行录用或排除,最终纳入符合标准的83篇文献进行综述。结果与结论:α7烟碱型乙酰胆碱受体通过与β-淀粉样蛋白的相互作用减轻β-淀粉样蛋白的神经毒性,如促进阿尔茨海默病的突触可塑性和胆碱能突触的快速传递、减轻β-淀粉样蛋白诱导的神经中枢炎症反应、抵抗神经细胞凋亡,从而对阿尔茨海默病患者的脑具有保护作用等。α7烟碱型乙酰胆碱受体作为阿尔茨海默病治疗靶标具有很大的潜能,但是又存在一系列问题有待解决,比如α7烟碱型乙酰胆碱受体的脱敏性、适度活性稳定性及基因多态性等问题。筛选高特异、安全性和以α7烟碱型乙酰胆碱受体为核心的多靶点结合作用的药物,将成为未来阿尔茨海默病治疗研究的一个方向。

基于DIgSILENT数据接口DGS的含风电电力系统随机潮流分析

同一风区的不同风电场由于地理位置相近,各风电场的风速和出力具有强相关性。针对该特点,提出了一种考虑风电场之间相关性的含风电电力系统随机潮流算法。首先建立了多个风电场出力的离散化联合概率分布模型,在此基础上采用线性化潮流方法分析随机潮流的各项指标。结合随机潮流算法和DIg SILENT软件的优势,研究了一种基于DIg SILENT数据接口DGS的数据转换方法,有效地提高了计算效率。最后利用IEEE-24节点系统以及我国新疆地区2015年规划电网进行方法验证。算例结果表明,建立的考虑风电场相关性的含风电电力系统随机潮流算法具有可行性和优越性,DGS数据接口技术可以使该潮流算法在实际大型电力系统中推广使用,工程实用性较强。

少年儿童翻译文学的译本风格计量研究——以Silent Spring三译本为例

本研究基于自建Silent Spring(《寂静的春天》)英汉平行语料库,以教育部编义务教育语文教材中的科普文章为标准参照,从可读性、趣味性和具象性三个维度,探讨少年儿童文学翻译文本风格特征及其与目标读者认知水平和接受能力的契合度,希冀能拓宽少年儿童翻译文学风格计量研究视野,为少年儿童文学的翻译传播研究提供参考。

PROPER CONDITIONS OF MESHING FOR Hy-Vo SILENT CHAIN AND SPROCKET

Proper meshing of Hy-Vo silent chain and sprocket is important for realizing the transmission of the silent chain with more efficiency and less noise. Based on the study of the meshing theory of the Hy-Vo silent chain with the sprocket and the roll cutting machining principle of the sprocket with the hob, the proper conditions of the meshing for the Hy-Vo silent chain and the sprocket are put forward with the variable pitch characteristic of the Hy-Vo silent chain taken into consideration, and the proper meshing design method on the condition that the value of the link tooth pressure angle is unequal to the value of the sprocket tooth pressure angle is studied. Experiments show that this new design method is feasible. In addition, the design of the pitch, the sprocket tooth pressure angle and the fillet radius of the sprocket addendum circle are studied. It is crucial for guiding the design of the hob which cuts the Hy-Vo silent chain sprocket.

Genetic diversity of HCV among various high risk populations(IDAs,thalassemia,hemophilia,HD patients) in Iran

Objective:To determine the patterns of distribution of HCV genotypes among high risk population in north of Iran.Methods:A cross-sectional study was conducted on 135 HCV RNA-positive high risk individuals including thalassemia,hemophilia,patients under hemodialysis and intravenous drug addicts.HCV genotypes were determined based on amplification with type-specific primers methods.Results:Among the 187 anti-HCV positive samples,only 135 (72.2%)gave HCV-RNA positvity.Over all,the most identified HCV type was genotype 3a(51.1%) followed by 1a(27.4%),1b(8.2%).Sixteen(11.9%)out of 135 HCV RNA-positive participants have infected with more than one genotype or subtypes as follow:1a/1b in 11(8.2%),2/3a in 3 (2.2%),and 1a/1b/3a in 2(1.5%).Stratification of participants revealed that HCV subtype 3a was more prominent in thalassemia,hemophilia and HD patients but 1a and 1b were frequent in intravenous drug addicts.Conclusions:This study is the first report on HCV genotypes among Iranian subjects with different exposure categories resided in Mazandaran.where genotype 3a was found to be the most frequent genotype in thalassemia,hemophilia,and hemodialysis patients but not in IDAs.Since the addiction age is decreasing in Iran and a lot of addicts are IDAs.it might change the subtype pattern of HCV in general population.

MESHING THEORY AND DESIGN METHOD OF NEW SILENT CHAIN AND SPROCKET

Based on the study of the meshing theory of a new silent chain and sprockets, and the rolling cutting theory of sprocket and hob, the harmonious relations of dominating dimensions among the new silent chain, sprocket and hob is build, the meshing conditions are expatiated, and the resolved expression, which can instruct design and calculation, is educed. The tests show that the meshing design method is feasible.

Effectiveness of Using Mean Corpuscular Volume and Mean Corpuscular Hemoglobin for Beta-thalassemia Carrier Screening in the Guangdong Population of China

Beta(β)-thalassemia is one of the most common hemoglobinopathies worldwide,creating major public health problems and social burdens in many regions.Screening forβ-thalassemia carriers is crucial for controlling this condition.To investigate the?effectiveness?of?mean?corpuscular?volume?(MCV)and mean corpuscular hemoglobin(MCH)for screeningβ-thalassemia,retrospective data were analyzed for 6,779β-thalassemia carriers subjected to genetic testing following thalassemia screening in Guangdong province between January 2018 and December 2019.

Can a polymorphism in the thalassemia gene and a heterozygote CFTR mutation cause acute pancreatitis?

The case of a 32-year-old black woman of African descent who suffered from repeated episodes of acute pancreatitis, initially triggered when flying on airplanes, is reported. She did not drink alcohol or smoke. Genetic analysis was negative for cationic trypsinogen, serine protease inhibitor Kazal type 1 and chymotrypsin C. However, hemoglobin F was elevated. Sequencing of the thalassemia gene revealed a novel alteration in the 5' region indicative of a functional abnormality of the molecule. Sequencing the cystic fibrosis transmembrane conductance regulator(CFTR) gene revealed a heterozygote sequence variant. The combination of a hemoglobin gene mutation known for thalassemia in conjunction with the hitherto undescribed CFTR mutation is suggested to pave the road for initial and repetitive pancreatitis attacks. This will be discussed.

Study of concentration of amniotic fluid Alpha-fetal protein in thalassemia fetus

Objective:To test the hypothesis that concentration of amniotic fluid alpha-fetal protein(AFAFP) is increased in thalassemia fetus.Methods:A total of 135 cases of amniocentesis admitted from July 2013 to December 2014 were included in this study.Among them 98 cases of normal fetuses were assigned into control group and 37 cases of thalassemia fetus were included as thalassemia fetus group.Alpha-fetoprotein levels detected by enzyme linked immunosorbent assay and the alpha-fetoprotein concentration were compared between the two groups.There is no significant difference in gestrational age between the two groups.Results:1.AFP concentration in thalassemia fetus group was significantly higher than that of normal control group [(1541.65±734.78) μg/mL vs.(2728.84± 1539.97) μg/mL ],and amniotic fluid AFP concentration was related to fetal thalassemia.2.AFAFP concentration in pureα-thalassemia fetus was higher than that of β thalassemia fetus or mixed αand was not significant.Conclusions:Concentration of a β thalassemia fetus,but the difference mniotic fluid alpha-fetal protein is increased in thalassemia fetus.AFP concentration inα-thalassemia fetus was higher than that of β thalassemia or mixed αand lore β thalassemia fetus but difference was not significance.Further studies are needed to exp the possible correlation between Down syndrome and biochemical markers of Thalassemia.

Spectrum of thalassemia mutations in fetuses of Han and Li ethinicities in Hainan province, China

Objective: To analyze the frequency and spectrum of thalassemia mutations in amniotic fluid samples collected from Han and Li people in Hainan province of China.Methods: We carried out a retrospective analysis on prenatal diagnosis of amniotic fluid samples collected from pregnant women who may have next generation with high risks of medium or severe thalassemia between 2005 and 2016. Diverse fetal thalassemia genotypes and mutated alleles in Han and Li people were analyzed and cmpared. Results: We examined 536 amniotic fluid samples from Han people and 588 from Li people, among which 406 Han and 500 Li samples were found to carry at least one thalassemia gene mutation, with a detection rate of 75.75% and 85.03%, respectively. Among all α-and β-thalassemia mutant alleles detected, the most frequently found mutations in Han and Li samples were SEA-type of α-thalassemia and 41/42(–CTTT) of β-thalassemia, respectively. A total of 75 severe thalassemia cases were identified in Han samples and 53 in Li samples. In most of these severe cases, parents chose to terminate pregnancy after being informed of thalassemia-related risks. Conclusions: The thalassemia mutations shows ethnic and area specificity, and that prenatal diagnosis for high-risk thalassemia carrier pregnant women is an efficient approach to prevent and control the occurrence of severe thalassemia in the high-prevalence areas.

miR-211 promotes lens epithelial cells apoptosis by targeting silent mating-type information regulation 2 homolog 1 in age-related cataracts

AIM： To detect the expression of miR-211 in age-related cataract tissue, explore the effects of miR-211 on lens epithelial cell proliferation and apoptosis, and identify its target gene.METHODS： This study used real-time quantitative polymerase chain reaction（RT-q PCR） to measure the expression of miR-211 and its predicted target gene [silent matingtype information regulation 2 homolog 1（SIRT1）] in 46 anterior lens capsules collected from age-related cataract patients. Human lens epithelial cell line（SRA01/04） cells were transfected with either miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls, 72 h after transfection, miR NA and protein expression of SIRT1 were measured using RT-qP CR and Western blotting; then cells were exposed to 200 μmol/L H2O2 for 1h, whereupon cell viability was measured by MTS assay, caspase-3 assay was performed. Dual luciferase reporter assay was performed to verify the relationship between miR-211 of SIRT1.RESULTS： Compared to the control group, expression of miR-211 was significantly increased（P〈0.001）, the miR NA and protein expression of SIRT1 were significantly decreased（P〈0.001） in the anterior lens capsules of patients with age-related cataracts. Relative to the control group, SIRT1 miR NA and protein levels in the miR-211 mimic group were significantly reduced, cell proliferation activity significantly decreased, and caspase-3 activity was significantly increased（P〈0.001）. In the miR-211 inhibitor group, SIRT1 miRNA and protein expression were significantly increased, cell proliferation activity significantly increased, and caspase-3 activity was significantly decreased（P〈0.001）. A dual luciferase reporter assay confirmed that SIRT1 is a direct target of miR-211.CONCLUSION： miR-211 is highly expressed in the anterior lens capsules of patients with age-related cataracts. By negatively regulating the expression of SIRT1, miR-211 promotes lens epithelial cell apoptosis and inhibits lens epithelial cell proliferation.

Hepatocellular carcinoma in thalassemia:A critical review

Due to blood transfusions,thalassemics are often infected with either hepatitis C virus(HCV)or hepatitis B virus and often have hemochromatosis.Hepatocellular carcinoma(HCC)has emerged in thalassemics only recently as a result of the improvement in thalassemia outcomes.In fact,a prospective study estimated an HCC incidence inβ-thalassemia of about 2%.Although data are scanty,HCC screening in thalassemics with risk factors for HCC should be carried out.HCV treatments have some efficacy in HCV infected thalassemics despite partial contraindication to ribavirin and iron overload.However,there are no data on how HCV treatment translates into HCC prevention.Preliminary data suggest that HCC treatment in thalassemics should generally have the same outcomes as in nonthalassemics.Although coexistence of severe comorbidities makes liver transplantation challenging,this therapeutic possibility should not be precluded for well selected HCCβ-thalassemia patients.In fact,2 transfusion dependent adult HCCβ-thalassemia patients have recently undergone successful liver transplantation with a good outcome.In conclusion,HCC seems to be a developing issue in thalassemia and HCC screening should be carried out.HCC treatment,including liver transplantation,can be performed in selected patients. A multidisciplinary effort is needed for management.

Ocular findings in children with thalassemia major in Eastern Mediterranean

AIM: To investigate ophthalmologic findings in children with thalassemia major(TM) and compare the findings with healthy controls. ·METHODS: In a cross-sectional study,43 children with thalassemia major from pediatric hematology outpatient clinics from two university hospitals and age/sex matched 47 healthy children were included in the study. After a complete ophthalmic examination,tear function tests including the Schirmer test,fluorescein tear breakup time(BUT),ultrasound pachymetry,and axial length measurement were performed. Obtained data was recorded for statistical analysis and the values of right eyes were compared between groups. ·RESULTS: The mean best corrected visual acuity was 1.34 ±0.75 in TM and 1.08 ±0.28 in controls. It was found lower than 0.1 logMAR unit in 10(23.2%) children with TM and 2(4.2%) in controls,and the difference was statistically significant(P 【0.05). The mean central corneal thickness was 540±26.95 in children with TM and 536.98± 20.45μm in controls(P 】0.05). The mean axial length was 22.53±0.50 in TM and 22.57±0.43mm in the control group. The mean Schirmer test score was 19.94±6.91 in TM and 24.22±3.95mm in the control group(P 【0.01). The mean BUT score was 9.62 ±1.28 in TM and 9.73 ±0.6s in the control group(P 】0.05). ·CONCLUSION: In TM,while corneal thickness,axial length,and BUT are close to controls,the Schirmer scores are less than normal. The study revealed that TM may be affected by the tear function and visual acuity.

Early detection of cardiac involvement in thalassemia: From bench to bedside perspective

Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chelation is given to patients,the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition.Various direct and indirect methods of iron assessment,including serum ferritin level,echocardiogram,non-transferrin-bound iron,cardiac magnetic resonance T2*,heart rate variability,and liver biopsy and myocardial biopsy,have been proposed for early detection of cardiac iron overload in TM patients.However,controversial evidence and limitations of their use in clinical practice exist.In this review article,all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented.Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients,these two methods are also presented and discussed.The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed.