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

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

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.

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: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

Objective:To investigate the correlation between paraspinal muscle atrophy, morphological changes of facet joints and adjacent segment disease (ASDis) after lumbar fusion operation.Methods:A retrospective study was conducted among 195 patients who underwent posterior lumbar fusion again for ASDis at this institution from January 2014 to December 2020, including 29 patients with ASDis whose initial surgical fusion segment was L 4,5. According to Roussouly's staging, there were 5 cases of type I, 9 cases of type II, 10 cases of type III, and 5 cases of type IV. Another 29 cases were selected from patients without ASDis after lumbar fusion as a control group. The control group was paired 1∶1 with the ASDis group according to gender, fusion segment, and Roussouly typing of the lumbar spine. The cross-sectional area (CSA) and fat infiltration (FI) of paravertebral muscle, facet joint angle (F-J) and pedicle facet (P-F) angle before the first (second) operation were measured and compared between the two groups. Then logistic regression analysis was used to determine the predictors of ASDis after posterior lumbar fusion. Finally, the receiver operation characteristic (ROC) curve was described, and the area under the curve (AUC) and cut-off point were calculated. At the same time, the paraspinal muscle atrophy before the second operation in ASDis group was measured. Results:The average follow-up time of 98 patients was 59.25±6.38 months (range, 49-73 months). The average body mass index (BMI) of ASDis group was 24.76±3.64 kg/m 2, which was higher than that in control group (22.24±2.92 kg/m 2) ( t=2.481, P=0.041). The average CSA and relative cross-sectional area (rCSA) of paraspinal muscle in ASDis group were 3 214.32± 421.15 mm 2 and 1.69±0.36 respectively, which were less than 3 978.91±459.87 mm 2 and 2.26±0.29 in control group ( t=10.22, P=0.012; t=9.47, P=0.038). The FI degree of paraspinal muscle in ASDis group (21.95%±5.89%) was significantly higher than that in control group (14.64%±7.11%) ( t=7.32, P=0.002). The F-J angle in ASDis group was 35.06°±3.45°, which was less than 38.39°±4.67° in control group ( t=4.76, P=0.027). The P-F angle in ASDis group was 117.39°±8.13°, which was greater than 111.32°±4.78° in control group ( t=5.25, P=0.031). Multivariate logistic regression analysis showed that higher BMI ( OR=1.34, P=0.038), smaller rCSA of paraspinal muscle ( OR=0.02, P=0.017) and higher FI of paraspinal muscle ( OR=1.58, P=0.032) were the risk factors of postoperative ASDis. The ROC curve showed that the AUC of BMI was 0.680 and the cut-off point was 22.58 kg/m 2; The AUC of the FI of paraspinal muscle was 0.716 and the cut-off point was 15.69%; The AUC of rCSA of paraspinal muscle was 0.227 and the cut-off point was 1.92. For ASDis patients, the paraspinal muscle before the second operation had a higher degree of FI (25.47%±6.59% vs. 21.95%±5.89%, t=3.99, P=0.042) and a smaller rCSA (1.52±0.28 vs. 1.69±0.36, t=3.85, P=0.038) than that before the first operation. The difference between the FI degree of paraspinal muscle before the second operation and the first operation was negatively correlated with the occurrence time of ASDis ( r=-0.53, P=0.039) , and the difference of rCSA was positively correlated with the occurrence time of ASDis ( r=0.64, P=0.043) . Conclusion:When BMI >22.58 kg/m 2, FI of paraspinal muscle >15.69%, and rCSA of paraspinal muscle <1.92, it suggests that ASDis is more likely to occur after operation. And the more obvious paraspinal muscle atrophy after the first operation, the earlier ASDis may occur. Morphological changes of facet joints cannot be used as an index to predict the occurrence of ASDis.

ObjectiveTo analyze factors related to the suspected allergic reaction of elememe emulsion injection based on hospital information system. MethodData on cases that used elememe emulsion injection were collected from the information systems of 60 first-class hospitals nationwide. The nested case-control design method was adopted. Finally， 30 cases were included in the suspected allergy group and 120 cases in the control group. SAS 9.3 was employed for descriptive analysis of the gender， age， occupation， admission route， conditions of patients at the admission， and the diagnosis with frequency and percentage. The factors affecting the occurrence of suspected allergic reaction were analyzed by conventional logistic regression and propensity score weighted logistic regression. In the case that the number of independent variables was larger than the sample number， MCP （minimax concave penalty） was used to screen the key variables and the conditions of patients at admission， conditions of patients during hospitalization， hospital stay， diagnostic information， and medication information were compared between two groups. ResultThe male-to-female ratio was about 2∶1 in both groups and most of the patients were 46-65 years old. Patients in the control group were mainly "professional and technical personnel"， and the majority in the suspected allergy group were "business and service personnel" and "clerks and related personnel". They were mainly admitted at the outpatient and conditions of patients were average at the admission. Compared with the control group， suspected allergy group showed severe conditions during the hospitalization， short average hospital stay， large proportion with intravenous infusion， and low cure rate and effective rate. The results of logistic regression analysis showed no statistical difference in conditions of patients at admission， hospital stay， combined diseases， medicine dosage， and treatment course. ConclusionThe suspected allergic reaction of elememe emulsion injection mainly occurs in the first administration with rapid onset even with the dose lower than the commonly used one. The occurrence is related to the intravenous infusion and the severe conditions of patients during hospitalization and has nothing to do with the conditions of patients at admission， hospital stay， treatment course， use of other medicines， and diagnostic information. In summary， it is mainly related to the constitution and immune status of patients.

The incidence and mortality of lung cancer ranked the first in China. China had 787, 000 new cases of lung cancer in 2015, and a majority of these patients with advanced lung cancer. With the development and popularization of high-resolution computed tomography, more and more early-stage lung adenocarcinomas are found in screening. The imaging finding of early-stage lung adenocarcinomas often manifests as part solid nodule (PSN) containing ground glass opacity (GGO). Although the imaging manifestation of the nodules can′t accurately predict the pathologic type of nodules, the parts of solid nodule and GGO still have some pathologic indications, and the prognostic evaluation effect of the maximum diameter of PSN is superior to that of the whole nodule. With the development of the molecular radiography and molecular pathology, the relationship of imaging manifestation of the PSN and metastasis were focused on. Some PSNs with special nature are more active and rapidly progressed than the pure GGOs. While compared to the pure solid nodules, the aggressiveness of PSNs are insufficient, with lower metastatic rates of lymph node and better prognoses. Currently, international acknowledge recommends to take active intervention measure for PSNs which are highly suspected to be malignant. We focus on the diagnosis and treatment of PSNs, systemically depict their staging, follow-up, surgical treatment, gene detection and immunotherapy.

The incidence and mortality of lung cancer ranked the first in China. China had 787, 000 new cases of lung cancer in 2015, and a majority of these patients with advanced lung cancer. With the development and popularization of high-resolution computed tomography, more and more early-stage lung adenocarcinomas are found in screening. The imaging finding of early-stage lung adenocarcinomas often manifests as part solid nodule (PSN) containing ground glass opacity (GGO). Although the imaging manifestation of the nodules can′t accurately predict the pathologic type of nodules, the parts of solid nodule and GGO still have some pathologic indications, and the prognostic evaluation effect of the maximum diameter of PSN is superior to that of the whole nodule. With the development of the molecular radiography and molecular pathology, the relationship of imaging manifestation of the PSN and metastasis were focused on. Some PSNs with special nature are more active and rapidly progressed than the pure GGOs. While compared to the pure solid nodules, the aggressiveness of PSNs are insufficient, with lower metastatic rates of lymph node and better prognoses. Currently, international acknowledge recommends to take active intervention measure for PSNs which are highly suspected to be malignant. We focus on the diagnosis and treatment of PSNs, systemically depict their staging, follow-up, surgical treatment, gene detection and immunotherapy.

Objective:To explore the feasibility and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).Methods:From May 2014 to December 2019, clinical data were retrospectively reviewed for 7 PNH patients undergoing UCBT. The grades were severe ( n=6) and extremely severe ( n=1). The causes were primary PNH ( n=4) and PNH-aplastic anemia (AA) syndrome ( n=3). There were 5 males and 2 females with a median age of 29 (20-47) years, a median weight of 60(50-71) kg and a median time from diagnosis to transplantation of 62.5(7.7-171) months. All of them were accompanied by transfusion dependence. Myeloablative ( n=6) and reduced-intensity ( n=1) pretreatment was offered. The regimen of preventing GVHD was cyclosporine A plus short-term mycophenolate mofetil without ATG. The median number of input nucleated cells was 2.4(1.71-4.28)×10 7/kg and the median number of CD34+ cells 1.58(0.88-3.02)×10 5/kg. Results:Neutrophil and erythroid engraftment was obtained with a median neutrophil engraftment time of 17(15-21) days and a median erythroid engraftment time of 27. Engraftment time of 37(25-101) days for platelets >20×10 9/L and 62(27-157) days for platelets >50×10 9/L. The incidence of 100-day acute GVHD was 28.6%(95%CI 0-55.3%). The severity of GVHD was grade Ⅱ° acute ( n=2) and mild ( n=1). The median follow-up period was 13.5(3-71.4) months. Six patients survived while another with PNH-AA syndrome with iron overload died of gastrointestinal hemorrhage. The 2-year overall survival rate was 83.3%(95%CI 27.3-97.5%). Conclusions:With excellent engraftment and survival in the treatment of PNH, UCBT is indicated for patients without HLA full-match donor. PNH-AA syndrome with iron overload may be one of the important prognostic factors.