BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective:To prepare domestic 64Cu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors (NETs). Methods:DOTATATE was labeled with the domestic 64Cu to obtain 64Cu-DOTATATE. The lipophilicity, in vitro stability, and pharmacokinetics were studied. Biodistribution experiments and microPET imaging were performed on NCI-H727 (somatostatin receptor (SSTR)2 positive expression) tumor-bearing nude mice. The preliminary clinical applications were conducted on 10 NETs patients (5 males, 5 females; age (58.5±13.0) years) from Chinese PLA General Hospital between May 2023 and April 2024. Data were analyzed by using independent-sample t test. Results:64Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%, log P of -2.609±0.051 and good stability. Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug (elimination half-time of 22.78min). Biodistribution results in tumor-bearing mice showed that 64Cu-DOTATATE was mainly metabolized through the liver and kidneys, with significant tumor uptake at 1h ((2.519±0.273) percentage activity of injection dose per gram of tissue (%ID/g)) and sustained high uptake at 24h ((4.331±0.549)%ID/g). MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h, with a significant statistical difference compared to the blocked group ((2.197±0.250) vs (0.985±0.064) % ID/g; t=6.40, P=0.008). The tumor/liver ratios were 0.075±0.007, 0.083±0.011, 0.118±0.005, 0.263±0.031 at 1, 2, 6 and 24h, respectively. Preliminary clinical application indicated that 64Cu-DOTATATE exhibited good targeting in patients, and the liver radioactivity distribution was moderate (SUV max=10.62±3.46), providing good image quality. Conclusion:Domestic 64Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.

Objective:To prepare domestic 64Cu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors (NETs). Methods:DOTATATE was labeled with the domestic 64Cu to obtain 64Cu-DOTATATE. The lipophilicity, in vitro stability, and pharmacokinetics were studied. Biodistribution experiments and microPET imaging were performed on NCI-H727 (somatostatin receptor (SSTR)2 positive expression) tumor-bearing nude mice. The preliminary clinical applications were conducted on 10 NETs patients (5 males, 5 females; age (58.5±13.0) years) from Chinese PLA General Hospital between May 2023 and April 2024. Data were analyzed by using independent-sample t test. Results:64Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%, log P of -2.609±0.051 and good stability. Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug (elimination half-time of 22.78min). Biodistribution results in tumor-bearing mice showed that 64Cu-DOTATATE was mainly metabolized through the liver and kidneys, with significant tumor uptake at 1h ((2.519±0.273) percentage activity of injection dose per gram of tissue (%ID/g)) and sustained high uptake at 24h ((4.331±0.549)%ID/g). MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h, with a significant statistical difference compared to the blocked group ((2.197±0.250) vs (0.985±0.064) % ID/g; t=6.40, P=0.008). The tumor/liver ratios were 0.075±0.007, 0.083±0.011, 0.118±0.005, 0.263±0.031 at 1, 2, 6 and 24h, respectively. Preliminary clinical application indicated that 64Cu-DOTATATE exhibited good targeting in patients, and the liver radioactivity distribution was moderate (SUV max=10.62±3.46), providing good image quality. Conclusion:Domestic 64Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.

Objective:To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) .Methods:The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups.Results:The baseline parameters were balanced between the two groups ( P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant ( P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups ( P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% ( P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) ( P=0.198) . Conclusion:The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Bone tissue plays an important role in maintaining physical activity and health. The study of the biological functions of bone tissue cells and their application in tissue engineering is of great significance for clinical prevention and treatment of orthopedic-related diseases. Tea polyphenols are the main components of tea, with natural antioxidant, scavenging free radical activity and anti-inflammatory effects. Research results indicated that tea polyphenols can promote the bone remodeling process mainly by enhancing the formation of osteoblasts and reducing the occurrence of osteoclasts. In addition, tea polyphenols can also be used as surface modification molecules of artificial bone materials and are widely used in the field of bone tissue engineering. In this paper, the regulatory effects of tea polyphenols in bone tissue cells and its application in tissue engineering were reviewed, and related research contents were summarized and prospected, in order to provide reference and theoretical basis for subsequent research work.

Objective To evaluate the effect of pretransplant iron overload on the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). Methods Clinical data of 80 SAA recipients who underwent allo-HSCT for the first time were retrospectively analyzed. According to the incidence of iron overload, all recipients were divided into the iron overload group (n=20) and non-iron overload group (n=60). The engraftment rate, incidence of postoperative complications and clinical prognosis of the recipients afterallo-HSCT were statistically compared between two groups. The influencing factors of 2-year overall survival (OS) and 180 d transplantation related mortality (TRM) were analyzed by Cox proportional hazards regression model. Results The engraftment rate of neutrophils in the non-iron overload group was 98% (59/60), significantly higher than 75% (15/20) in the iron overload group (P < 0.05). The engraftment rate of platelet in the non-iron overload group was 90% (54/60), significantly higher than 65% (13/20) in the iron overload group (P < 0.05). The incidence rate of bloodstream infection in the non-iron overload group was 23% (14/60), remarkably lower than 40% (8/20) in the iron overload group (P < 0.05). The 180 d TRM of the recipients in the non-iron overload group was 17%, significantly lower than 45% in the iron overload group (P < 0.05). The 1- and 2-year OS of the recipients in the non-iron overload group were 82% and 80%, significantly higher than 50% and 44% in the iron overload group (both P < 0.05). Iron overload or not was an independent risk factor of the OS and TRM of the recipients (both P < 0.05). Conclusions Iron overload can affect the OS and TRM of SAA patients after allo-HSCT.

Objective: To evaluate the short-term efficacy of one-stage reverse shoulder arthroplasty in the treatment of complex proximal humeral fractures in the elderly. Methods: Data of 43 elderly patients with complex proximal humeral fractures who were treated by reverse shoulder arthroplasty from July 2017 to January 2019 were retrospectively analyzed. There were 12 males and 31 females with an average age of 72 years (range, 66-78 years). All fractures were fresh and close which caused by trauma. The average time from injury to operation was 8.0 days (range, 6-11 days). According to Neer classification, 21 cases (48.8%, 21/43) were three-part fractures, 22 cases (51.2%, 22/43) four-part fractures. Visual analogue scale (VAS), Neer shoulder replacement evaluation system and Constant-Murley score were used to evaluate the postoperative results. Results: All operations were successfully completed. The average operation time was 141.3 minutes (range, 120-170 minutes. The mean blood loss was 407 ml (range, 250-700 ml) and intraoperative blood transfusion was 446.5 ml (range, 400-800 ml). All patients were followed up for 10.9 months (range, 6 to 16 months). All patients were discharged within 7 days after operation, and no wounds related complications occurred. The bigger and lesser tuberosities of all patients healed completely within 8 weeks. At the latest follow-up, no loosening or dislocation of prosthesis occurred, and the forward elevation was 133.0° (range, 100°-165°); external rotation was 29.5° (range, 20°-35°); internal rotation was 46.7° (range, 30°-60°). VAS score was 0.8 (range, 0-3). The Neer score was 87 (range, 73-98), with 20 cases (46.5%, 20/43) excellent, 16 cases (37.2%, 16/43) good, and 7 cases (16.3%, 7/43) fair. Constant-Murley score was 88.7 (range, 70-98). A 71-year-old patient had symptoms of axillary nerve injury after operation and recovered completely 6 weeks after the operation, which did not affect the functional rehabilitation exercise or the stability of the prosthesis. During the follow-up, no other complications such as infection, acromial stress fracture and scapular notching were found in all patients. Conclusion The short-term effect of one-stage reverse shoulder arthroplasty for the treatment of complex proximal humeral fractures in the elderly is satisfactory.

Objective To analyze the epidemiologic and clinical features of post-engraftment blood stream infection (pePSI) after unrelated cord blood transplant (UCBT) in our hospital,and provide the basis for empiric antibacterial treatment.Methods 484 patients with hematological malignancies who received single-unit high intensity myeloablative UCBT in our hospital between April 2011 and November 2017 were enrolled.The incidence,etiology of BSI and associated mortality,drug resistance rate in the post-engraftment phase were investigated.Results Totally 25 episodes of BSI among 22 patients in the post-engraftment phase were documented,and the incidence of peBSI was 5 ％.Gram-negative organisms predominated over Gram positive,with Escherichia coli being the most frequent Gram-negative organism isolated (31.5％).Among Gram positive organisms,methicillin resistant Staphylococcus (MRS) was the most frequent species isolated (66％).Nearly 33％ of Escherichia coli isolates and 60％ Klebsiella pneumonia isolates were carbapenem-resistant.All Grampositive bacteria were sensitive to vaneomyein and linezolid.Among the 22 patients,14 patients were cured and survived (63％) eventually.Conclusion The most frequent causative agents of the peBSI after UCBT were Escherichia coli,Klebsiella pneumonia and MRS,etc.Combined antibacterial treatment including a carbapenem or beta lactamase inhibitor can be used for patients suffering fever in the post-engraftment phase as empiric antibacterial therapy.Vaneomyein and linezolid can be used as the first-line therapy for Gram-positive bacteria.

Objective: To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD. Methods: The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results: A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05). Conclusion There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.