Objective:To investigate the therapeutic effect and safety of recombinant human thrombopoietin (rhTPO) combined with low-dose eltrombopag in the treatment of persistent thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective case series study was conducted. The retrospective analysis was conducted on the clinical data of 20 patients diagnosed with post-allo-HSCT thrombocytopenia at Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2018 to June 2021. All patients didn't meet the platelet implantation criteria [without the platelet count (Plt) ≥20×10 9/L for a consecutive period of 7 days and discontinuation of platelet transfusion] after transplantation, and they received subcutaneous injections of rhTPO (15 000 U) once daily and oral administration of eltrombopag (50 mg) once. Treatment efficacy was defined as maintaining Plt≥20×10 9/L for a consecutive period of 7 days after treatment and discontinuation of platelet transfusion; treatment inefficacy was defined as Plt<20×10 9/L after treatment or continuation of platelet transfusion. The therapeutic effect of rhTPO combined with low-dose eltrombopag was analyzed; the adverse reactions were evaluated; the clinical characteristics were compared between the effective treatment group and ineffective treatment group; the overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier method between the effective treatment group and ineffective treatment group. Results:Among the 20 patients, 9 were diagnosed with acute myeloid leukemia (AML), 5 with acute lymphoblastic leukemia (ALL), 4 with myelodysplastic syndromes (MDS), and 2 with severe aplastic anemia (SAA); 10 cases were primary failure of platelet recovery (PFPR), and 10 cases were secondary failure of platelet recovery (SFPR). The median time [ M ( Q1, Q3)] from transplantation to initiation of treatment was 79 days (50 days, 89 days), and the median duration of treatment was 19.5 days (15 days, 30 days). Of the total cohort, treatment was effective in 13 cases (65.0%, 8 cases of PFPR, 5 cases of SFPR), while 7 patients (35.0%) showed no response to treatment. The median time to achieve the therapeutic response among responders was 10 days (7 days, 19 days). During the combination treatment, 5 patients experienced elevated transaminase levels exceeding more than 2.5 times the upper limit of normal or bilirubin levels surpassing twice that limit. No instances of adverse reaction-related arterial thrombosis, myelofibrosis, or primary disease relapse occurred within this patient cohort. Megakaryocyte counts in the effective treatment group before combination treatment were higher than that in the ineffective treatment group, and the difference was statistically significant [14 (10, 20) vs. 2.5 (2, 4); Z = -2.33, P = 0.017]; Notably, no statistically significant differences were identified when comparing the compositions of gender, type of underlying diseases, human leukocyte antigen matching degree, blood type of donor and recipient, conditioning regimen use of antithymocyte globulin, quantity of CD34 + cells transfused, type of thrombocytopenia, acute graft-versus-host disease, fungal or bacterial infections, and viral infections between the two groups (all P > 0.05). The 1-year OS rates for the effective and ineffective treatment groups were 100.0% and 42.9%, respectively, and the difference in OS between the two groups was statistically significant ( P = 0.001). The 1-year DFS rates for the effective and ineffective treatment groups were 92.3% and 28.6%, respectively, and the difference in DFS between the two groups was statistically significant ( P = 0.003). Conclusions:The combination of rhTPO and low-dose eltrombopag has demonstrated certain therapeutic efficacy and good safety in the treatment of persistent thrombocytopenia after allo-HSCT.

AIM:To investigate the effect of ankyrin repeat domain 49(ANKRD49)on epithelial-mesenchy-mal transition(EMT)in NCI-H1299 cells,and to explore its mechanism.METHODS:The ANKRD49 was over-ex-pressed in NCI-H1299 cells.The morphological changes of ANKRD49-overpressing NCI-H1299 cells were observed under microscope.The mRNA and protein expression levels of EMT-related markers[E-cadherin,transforming growth factor-β1(TGF-β1),vimentin and α-smooth muscle actin(α-SMA)]and EMT-related transcription factors(Snail1,Slug,Twist and ZEB1)were detected by RT-qPCR Western blot.Immunofluorescence staining was performed to observe the localiza-tion and expression of E-cadherin and vimentin in ANKRD49-overexpressing cells or control cells.Immunohistochemical method was performed to examine the levels of E-cadherin,α-SMA,Snail,Slug and ZEB1 in lung tissues of nude mice in-oculated with ANKRD49-overexpressing H1299 cells or control cells.RESULTS:Compared with the control group,the ANKRD49 overexpressing cells showed mesenchymal cell morphology(fusiform and less tight connections).RT-qPCR and Western blot results showed that the mRNA and protein levels of mesenchymal markers vimentin and α-SMA in ANKRD49 overexpressing cells were significantly higher than those in cells of control group,while the mRNA and protein levels of epithelial marker E-cadherin were lower than those in cells of control group.Compared with control group,the im-munofluorescence intensity of E-cadherin of H1299 cells decreased in after ANKRD49 overexpression,while that of vimen-tin increased significantly.Snail,Slug and ZEB1 expression were significantly elevated in ANKRD49 overexpressing cells compared with control group.The levels of E-cadherin in lung tissues of nude mice inoculated with ANKRD49-overexpressing H1299 cells declined,while the levels of α-SMA,Snail,Slug and ZEB1 increased compared with those in control mice.CONCLUSION:ANKRD49 promoted EMT of NCI-H1299 cells by increasing the expression of Snail1,Slug and ZEB1 and consequent downreguation of E-cadherin and upregulation of vimentin and α-SMA.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

OBJECTIVE: To investigate the mid-term effectiveness of arthroscopic Bankart repair for recurrent anterior shoulder dislocation. METHODS: The clinical data of 107 patients with recurrent anterior shoulder dislocation who met the inclusion criteria between January 2017 and June 2021 was retrospectively analyzed, and all patients underwent arthroscopic Bankart repair. There were 88 males and 19 females. The age of the primary dislocation ranged from 13 to 48 years (mean, 23.3 years). The number of preoperative dislocations was 2-160 times (median, 7 times). The duration of preoperative instability was 0.2-240.0 months (median, 36.0 months). The mean age at operation was 28.2 years (range, 16-61 years). There were 43 cases of left shoulder and 64 cases of right shoulder. The proportion of glenoid defects in 63 patients was 1.7%-16.1% (mean, 8.1%). MRI showed that none of the patients had rotator cuff tears or shoulder stiffness. The CT three-dimensional reconstruction was performed at 1 day after operation to evaluate the distribution of implanted anchors and the occurrence of glenoid split fracture and whether there were nails pullout at the implant site. The postoperative complications were observed, and the pain and function of the shoulder were evaluated by visual analogue scale (VAS) score, Rowe score, Constant-Murley score, and American Shoulder and Elbow Surgeons (ASES) score. The recurrence of instability, the results of apprehension test, the number of patients who returned to preoperative sports level, and the satisfaction rate of patients were recorded. RESULTS: All patients were successfully operated and were followed up 20-73 months (mean, 41.5 months). All incisions healed by first intention. The CT three-dimensional reconstruction at 1 day after operation showed that the anchors were located at the 2 : 00-5 : 30 positions of the glenoid, and there was no glenoid split fracture or nails pullout at the implant site. At last follow-up, VAS score was significantly lower than that before operation, and Rowe score, Constant-Murley score, and ASES score were significantly higher than those before operation ( P<0.05). Seven patients (6.5%) had recurrence of anterior shoulder dislocation at 23-55 months (mean, 39.9 months) after operation, including 6 cases of dislocation and 1 case of subluxation. At last follow-up, 51 patients (47.7%) returned to preoperative sports level, and 11 patients (10.3%) had a positive apprehension test. The patients' satisfaction rate was 90.7% (97/107). Among the 10 patients who were not satisfied with the surgical effectiveness, 7 patients had postoperative recurrence of instability, and 3 patients felt that they did not return to preoperative sports level. CONCLUSION Arthroscopic Bankart repair has good mid-term effectiveness in patients with recurrent anterior shoulder dislocations, minimal or no glenohumeral bone defects and low sports need.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Shoulder Dislocation/surgery* ; Retrospective Studies ; Joint Instability/etiology* ; Arthroscopy/methods* ; Shoulder Joint/surgery* ; Recurrence

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

Accurate segmentation of pediatric echocardiograms is a challenging task, because significant heart-size changes with age and faster heart rate lead to more blurred boundaries on cardiac ultrasound images compared with adults. To address these problems, a dual decoder network model combining channel attention and scale attention is proposed in this paper. Firstly, an attention-guided decoder with deep supervision strategy is used to obtain attention maps for the ventricular regions. Then, the generated ventricular attention is fed back to multiple layers of the network through skip connections to adjust the feature weights generated by the encoder and highlight the left and right ventricular areas. Finally, a scale attention module and a channel attention module are utilized to enhance the edge features of the left and right ventricles. The experimental results demonstrate that the proposed method in this paper achieves an average Dice coefficient of 90.63% in acquired bilateral ventricular segmentation dataset, which is better than some conventional and state-of-the-art methods in the field of medical image segmentation. More importantly, the method has a more accurate effect in segmenting the edge of the ventricle. The results of this paper can provide a new solution for pediatric echocardiographic bilateral ventricular segmentation and subsequent auxiliary diagnosis of congenital heart disease.
Adult ; Humans ; Child ; Heart Ventricles/diagnostic imaging* ; Echocardiography ; Image Processing, Computer-Assisted

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the clinical, pathological and genetic characteristics of myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD).Methods:The detailed clinical data, muscle biopsy pathology and molecular results of 4 patients with genetically confirmed myopathy-type VLCADD admitted to Henan Provincial People′s Hospital and Xuanwu Hospital, Capital Medical University from June 2014 to November 2019 were retrospectively analyzed.Results:All of the 4 patients were late-onset myopathy-type VLCADD. The onset age ranged from 13 to 16 years, with a mean age of 14.5 years. The age at diagnosis ranged from 21 to 54 years, with a mean age of 42.5 years. The main clinical manifestation was repeated rhabdomyolysis, including myalgia, weakness and dark urine. Obvious somnolence was observerd in 1 patient. Muscle biopsy pathology revealed mild lipid accumulation, without vacuoles. Six ACADVL variations were detected in the 4 patients, including c.1283G>A (p.R428H), c.1532G>A (p.R511Q), c.833_835delAGA (p.K278del), c.1843C>T (p.R615 *), c.1748C>T (p.S583L) and c.1391C>T (p.T464I),among which c.1391C>T (p.T464I) was a novel variation, predicted to be likely pathogenic. Other 5 variations were reported pathogenic variations. Conclusions:Myopathy-type VLCADD is characterized by paroxysmal rhabdomyolysis and can be associated with somnolence. There is no specificity in muscle pathology. There are ACADVL variations, among which c.1391C>T is a novel variation.

Magnolol, a hydroquinone containing an allyl side chain, is one of the major active components of magnolia for antioxidation and anti-aging. To enhance the anti-aging activity and improve the intramolecular hydrogen bonding of magnolol, magnolol was reacted with cinnamic acid to obtain 2-O-cinnamic acid magnolol by esterification. The anti-aging activity of magnolol 2-O-cinnamate was investigated based on Caenorhabditis elegans model. The results showed that 2-O-cinnamic acid magnolol can reduce lipofuscin accumulation in the nematode body, and the effect is better than that of magnolol. 2-O-Cinnamic acid magnolol can extend nematode lifespan, reduce ROS levels in nematodes during normal aging and oxidative stress and improve nematode stress resistance under heat stress and oxidative stress. 2-O-Cinnamic acid magnolol could induce DAF-16 translocation from the cytoplasm to the nucleus and upregulate the expression of the sod-3 gene encoding superoxide dismutase in the nematode TJ356 expressing DAF-16 fused with GFP. 2-O-Cinnamic acid magnolol did not improve the survival rate of hsp-16.2 gene deficient nematodes under oxidative stress, indicating that 2-O-cinnamic acid magnolol improves stress resistance of nematodes under oxidative stress may be associated with sod-3 and hsp-16.2. Moreover, 2-O-cinnamic acid magnolol did not extend the lifespan of daf-16 and age-1 mutants, indicating that age-1 and daf-16 are required for 2-O-cinnamic acid magnolol to delay aging. It showed that magnolol 2-O-cinnamic acid has the potential to improve antioxidant capacity and delay aging, and the mechanism may be related to the insulin/insulin-like growth factor signaling pathway.