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Polycystic ovary syndrome (PCOS) is a disease characterized by metabolic disorders. This study aimed to examine the effects of resveratrol treatment on ovulation in the PCOS rat model. Quantitative real-time PCR and immunohistochemistry were used to determine the mRNA and protein expression levels. TNUEL assay was used to evaluate cell apoptosis in ovary. The metabolites were evaluated by liquid chromatography with tandem mass spectrometry. Resveratrol alleviated disrupted estrous cycle and improved granular cell layers, and reversed the decreased proliferation and increased cell apoptosis of granulosa cells in the ovarian tissues of PCOS rats. Resveratrol restored the changes in the mRNA expression levels in the rate-limiting genes of glycolysis in the PCOS ovary. The expression of lactate dehydrogenase A (LDH-A), pyruvate kinase isozyme M2 (PKM2), and sirtuin 1 (SIRT1) was significantly downregulated in ovarian tissues of the PCOS rats; while the resveratrol treatment significantly increased the expression of LDH-A, PKM2, and SIRT1 in the ovarian tissues of PCOS rats. Collectively, the protective effects of resveratrol in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A, and SIRT1. Resveratrol may represent a good candidate in alleviating the development of PCOS. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is one of the most common monogenic hemolytic disorders in the world. Hong Kongαα (HKαα) thalassemia was initially found among the people of southern China. Because of the complexity of genetic changes in HKαα thalassemia, we lack a precise sequence analysis of the HKαα allele. Here we aim to detect the specific genotype and trace the law of inheritance of this rare genotype. Methods: We recruited an unprecedented huge pedigree containing 11 individuals carrying the HKαα thalassemia gene and 4 nongenetic‐related patients suffering from HKαα from south China. Regular hematological analysis and routine genetic screening were performed on the pedigree and two‐round nested PCR (polymerase chain reaction) for HKαα thalassemia were performed on each individual. The first‐generation gene sequencing was performed on six individuals, including four nongenetic‐related patients. Result: We found that five family members were positive for the HKαα allele. Patients Ⅱ‐2, Ⅲ‐1, and Ⅱ‐3 with only HKαα/‐‐SEA or HKαα/‐α4.2 presented with α‐thalassemia minor trait. Ⅰ‐1, the carrier of both HKαα/‐α3.7 and β41‐42/βN, showed a typical β‐thalassemia trait. Fetus with genotype HKαα/‐α4.2 alone was not likely to suffer from any deleterious effects after birth. The whole sequence of HKαα allele revealed that HKαα alleles in the six patients shared a high similarity, implying that all HKαα alleles are likely from the same ancestor. Moreover, pedigree and sequencing analyses demonstrated that the HKαα allele contained αααanti4.2 mutation, ‐α3.7 mutation, and a fragment from α‐hemoglobin gene; thus, the composition and formation of HKαα allele was revealed. Finally, the high similarity and composition of HKαα alleles implies that once HKαα formed, αααanti4.2 and ‐α3.7 mutations tended to be a fusion gene and quite impossible to be inherited separately. Conclusion: The two‐round nested PCR is an effective method to detect HKαα allele. Besides, our study for the first time revealed the sequence of the HKαα allele, the evidence of the same ancestor with HKαα thalassemia and enriched the composition as well as the formation mechanism of HKαα allele, and immediately opened up novel potential diagnosis and prenatal counseling for HKαα thalassemia. [ABSTRACT FROM AUTHOR]

Rationale: Compound heterozygotes for deletional β-thalassemia can be difficult to diagnose due to its diverse clinical presentations and no routine screenings. This can lead to disease progression and delay in treatment., Patient Concerns: We reported pedigree analysis and genetic research in a family with rare β-thalassemia., Diagnosis: Pedigree analysis and genetic research demonstrated that the patient was a compound heterozygote for β-thalassemia CD17/Southeast Asian hereditary persistence of fetal hemoglobin deletion, inherited from the parents. Magnetic resonance imaging T2* examination revealed severe iron deposition in the liver. Echocardiography revealed endocardial cushion defect., Interventions: The patient was treated with Deferasirox after receiving the final molecular genetic diagnosis. The initial once-daily dose of Deferasirox was 20 mg/kg/d., Outcomes: The patient discontinued the medication three months after the first visit. Two years later, the patient visited the Department of Hepatobiliary and Pancreatic Diseases. He was recommended to undergo splenectomy after surgical repair of the congenital heart disease. However, the patient refused surgical treatment because of the economic burden., Lessons: We report that fetal hemoglobin is a sensitive indicator for screening large deletions of the β-globin gene, which can be effectively confirmed by the multiplex ligation-dependent probe amplification assay. In non-transfusion-dependent thalassemia patients, iron status assessment should be regularly performed, and iron chelation treatment should be initiated early. This case will provide insights for the diagnosis of rare genotypes of β-thalassemia and has important implications for genetic counseling., Competing Interests: The authors have no other conflicts of interest to declare., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The Hong Kongαα (HKαα) allele is a complex structural rearrangement of the α-globin gene containing -α 3.7 and ααα anti 4.2 crossover junctions. Clinically, individuals carrying the HKαα allele are often misdiagnosed or missed using conventional thalassemia gene detection technology. This study aims to identify and validate different HKαα thalassemia subtypes using third-generation sequencing (TGS) technology., Methods: Between January 2015 and June 2021, 32 patients suspected of having HKαα thalassemia were included in this study. Genomic DNA was extracted, and gap-polymerase chain reaction (PCR), two-round nested PCR, multiplex ligation-dependent probe amplification (MLPA), and TGS were used for thalassemia gene detection., Results: The results of HKαα/αα and HKαα/-α 3.7 were similar to -α 3.7 /αα using the gap-PCR method. Two-round nested PCR could be used to verify the HKαα gene, but could not distinguish the subtypes of HKαα thalassemia. The MLPA assay was used to detect the change in the copy number of the α-globin gene, but it could not determine whether -α 3.7 and ααα anti 4.2 were in cis or in trans. Long-read TGS technology could accurately detect the HKαα allele and distinguish the genotypes of HKαα/αα, HKαα/-α 3.7 , HKαα/-α 4.2 , and HKαα/-- SEA without pedigree analysis. The contiguous sequence of the HKαα allele was detected using the TGS approach. This study also demonstrated that individuals with HKαα/αα and β N /β N genotypes tended to have normal hematological phenotypes., Conclusions: Long-read TGS is a reliable and efficient approach for accurate detection of HKαα thalassemia, which can be widely used in clinical practice. Accurate molecular diagnosis of HKαα thalassemia will benefit clinical genetic counseling and prenatal diagnosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4309/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: To report on a case of Smith-Magenis syndrome (SMS) due to a rare small-scale deletion., Methods: Muscle samples from the the third fetus was collected after the in Medical history and clinical data of the patient were collected. The child and his parents were subjected to chromosome karyotyping analysis, multiplex ligation-dependent probe amplification (MLPA) and copy number variation sequencing (CNV-seq)., Results: The child was found to have a normal karyotype. MLPA and CNV-seq detection showed that he has harbored a 1.22 Mb deletion and a 0.3 Mb duplication in the 17p11.2 region. Neither of his parents was found to have similar deletion or duplication., Conclusion: The child was diagnosed with SMS due to a rare 1.22 Mb deletion in the 17p11.2 region, which is among the smallest deletions associated with this syndrome.

In stochastic contextual bandit (SCB) problems, an agent selects an action based on certain observed context to maximize the cumulative reward over iterations. Recently there have been a few studies using a deep neural network (DNN) to predict the expected reward for an action, and the DNN is trained by a stochastic gradient based method. However, convergence analysis has been greatly ignored to examine whether and where these methods converge. In this work, we formulate the SCB that uses a DNN reward function as a non-convex stochastic optimization problem, and design a stage-wise stochastic gradient descent algorithm to optimize the problem and determine the action policy. We prove that with high probability, the action sequence chosen by this algorithm converges to a greedy action policy respecting a local optimal reward function. Extensive experiments have been performed to demonstrate the effectiveness and efficiency of the proposed algorithm on multiple real-world datasets.