Functional Aptamers In Vitro Evolution for Intranuclear Blockage of RNA-Protein Interaction.

Over the last 30 years, despite considerable research and endeavors aimed at harnessing aptamers as pharmaceutical molecules, the progress in developing aptamer-based drugs has been falling short of expectations. Sequential steps of affinity molecule acquisition and functional screening are typically required for discovering affinity-based macromolecule therapeutics, which can be time-consuming and limiting in candidate selection. Additionally, aptamers often necessitate tedious postselection modifications to overcome pharmacokinetic limitations, which usually impede the binding affinity. Herein, we propose a novel in vitro screening platform termed Functional Aptamers in vitro Evolution (FAIVE), which integrates affinity molecule acquisition with functional screening and introduces chemical diversity during the process. This platform aims to rapidly generate functional aptamers capable of binding to target proteins and regulating their functions. Illustrated by targeting intranuclear RNA-protein interactions involving HIV-1 Tat protein and TAR RNA, FAIVE demonstrates a selection of functional aptamers with significant intracellular blocking effects. The study also explores lipid nanoparticle delivery systems to enhance intracellular delivery efficiency, expanding aptamer targeting potential to broader intracellular and intranuclear domains. This study emphasizes the potential of FAIVE to expedite the development of aptamer-based drugs and facilitate the creation of more versatile and effective therapeutics.

The coexistence of papillary thyroid carcinoma, anaplastic thyroid carcinoma (squamous cell carcinoma subtype) and poorly differentiated thyroid carcinoma: a case report.

Background: Papillary thyroid carcinoma (PTC) accounts for about 60% of adult thyroid carcinoma and generally has an excellent prognosis. Primary squamous cell carcinoma of thyroid (PSCCT) is a rare thyroid tumor with high malignancy and poor prognosis. In 2022, the 5th edition of World Health Organization (WHO) has classified it as a subtype of anaplastic thyroid carcinoma (ATC), abbreviated as ATC-squamous cell carcinoma (SCC) subtype. Poorly differentiated thyroid carcinoma (PDTC) is a kind of follicular-derived malignancy, which is prone to recurrence and distant metastasis. Here, we report a rare case of the coexistence of PTC, ATC-SCC subtype and PDTC. Case Description: We herein report a case of 69-year-old female who initially presented with a history of left neck mass for one month. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of PTC combined with ATC-SCC subtype, and PDTC. Total thyroidectomy with radical left cervical lymph node dissection was performed, followed by thyroid-stimulating hormone (TSH) suppressive therapy, 131I, radiotherapy and chemotherapy. The patient showed no tumor recurrence or metastasis after a 5-month postoperative follow-up. Conclusions: The simultaneous occurrence of PTC, ATC-SCC subtype, and PDTC is extremely rare in clinical terms or literature reports. The treatment has not been standardized, and early radical surgery is the first choice. In addition, the combination of adjuvant therapies such as TSH suppressive therapy, radiotherapy, chemotherapy and 131I may further improve the prognosis of the patient.

Multiple pathological fractures and muscle atrophy caused by a parathyroid carcinoma with postoperative hungry bone syndrome: A case report.

BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia. CASE: A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient's PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range. CONCLUSION: The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.

[Influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation and acute graft-versus-host disease].

To investigate the influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation and acute graft-versus-host disease, peripheral blood samples of 20 healthy donors were collected before and after G-CSF mobilization. The whole blood was diluted with IMDM in ratio of 1:1 and then incubated with PMA + ionomycin + monensin at 37 degrees C, 5% CO2 for 4 hours. After being mobilized and stained, the IL-4, IFN-gamma and IL-2 positive cells were counted with three-color flow cytometry. The results showed that before G-CSF mobilization, the percentages of donor's CD3(+)IFN-gamma(+), CD4(+)IFN-gamma(+), CD8(+)IFN-gamma(+) T cells were 3.2% (0% - 45.9%), 1.3% (0% - 23.8%) and 1.5% (0% - 22.2%) respectively. The percentage of above mentioned cells in donor increased to 19.2% (0% - 53.9%), 9.5% (0% - 49.5%), 7.5% (0% - 38.1%) respectively after G-CSF mobilization. The IL-2 positive CD3(+), CD4(+) and CD8(+) T cell percentage in pre-G-CSF mobilized donors was 1.5% (0% - 31%), 0.8% (0% - 30.0%) and 0% (0% - 5.3%) respectively and subsequently increased to 25.7% (0% - 51%), 19.8% (0% - 39.7%), 4.6% (0% - 20.9%) respectively after G-CSF mobilization. The IL-4 positive T subpopulation did not increased significantly after G-CSF mobilization. In the early stage after peripheral blood stem cell transplantation, donor's Tc1 percentage in aGVHD group was significantly higher than that in non-aGVHD group. The morbidity of severe aGVHD in high Tc2 percentage group was significantly lower than that in low Tc2 percentage group. It is concluded that the donor's type I T cells increase after G-CSF mobilization, the Tc1 percentage of G-CSF mobilized donor is correlated with the occurrence of aGVHD in the early stage after HSCT, the percentage of Tc2 in donor is negatively correlated with aGVHD morbidity in recipients.