Study on the value of second-generation sequencing technology in the clinical diagnosis of osteoarticular brucellosis.

To assess the value of next-generation sequencing (NGS) technology in the diagnosis of osteoarticular brucellosis pathogenesis. Fifty eight patients admitted to the Department of Orthopaedics, Hebei Provincial Chest Hospital from January 2021 to January 2023 were retrospectively analyzed, and the patients were classified into 48 cases in the osteoarticular brucellosis group and 10 cases in the nonosteoarticular brucellosis group according to the final clinical diagnosis. All patients underwent serum agglutination test (SAT), CT-guided puncture or surgical sampling of lesions for bacteriological culture and NGS after admission. The diagnostic efficacy of these three methods for osteoarticular brucellosis was compared using the final clinical diagnosis as the reference standard. Among the 58 patients with suspected osteoarticular brucellosis, 40 cases (68.97%) were positive by NGS, 33 cases (56.89%) by SAT and 10 cases (17.24%) by culture, and the differences were statistically significant (p < 0.05). Using the final clinical diagnosis as a criterion, the sensitivity of NGS, SAT, and culture for the detection of osteoarticular brucellosis was 83.33%, 62.50%, and 20.83%, respectively, the specificity was 100.00%, 70.00%, and 100.00%, the diagnostic accuracy was 86.20%, 63.79%, and 34.49%, and the κ values were 0.799, 0.590, and 0.504, respectively. NGS has a high pathogen detection rate and sensitivity in the pathogenetic diagnosis of patients with osteoarticular brucellosis and can provide clinical guidance for the diagnosis and management of patients with osteoarticular brucellosis.

Predictive Value of Vertebral Bone Destruction Classification Based on Computed Tomography in Diagnosing on Adult Spinal Tuberculosis.

OBJECTIVE: Although magnetic resonance imaging (MRI) is well-established for evaluation of spinal tuberculosis (TB), the importance of computed tomography (CT) should not be overlooked. The purpose of this study was to determine the characteristics of spinal TB and the relationship between spinal TB and the bone lesion pattern seen on three-dimensional CT images. METHODS: One hundred and sixty-one subjects were divided into a TB-positive group and a TB-negative group based on laboratory (X-pert mycobacterium tuberculosis/ rifampin) results and then subdivided further according to whether the bone lesion pattern seen on three-dimensional CT images was fragmentary, osteolytic, sclerotic, or had no evidence of bone destruction. The diagnostic value of the bone lesion pattern was compared between the TB-positive and TB-negative groups. RESULTS: Ninety-nine of the 161 patients were TB-positive and 62 were TB-negative. Fifty-six (34.8%) of the 161 patients had fragmentary/osteolytic lesions, seventy-four (45.9%) had absolute osteolytic lesions, 13 (8.1%) had osteosclerotic lesions, and 18 (11.2%) had no evidence of bone destruction. The fragmentary/osteolytic lesion pattern was strongly predictive of spinal TB (odds ratio 3.33), and when combined with 3 MRI findings (thin abscess wall, more than one half of the vertebral body destroyed, and subligamentous spread) had an even stronger diagnostic value (odds ratio 15.58). CONCLUSIONS: The absolute osteolytic pattern was the most common of the bone lesion patterns. The fragmentary/osteolytic pattern is highly suggestive of spinal TB, especially when combined with MRI findings of a thin abscess wall, destruction of more than one half of the vertebral body, and subligamentous spread.

Integrated insight into the molecular mechanisms of selenium-modulated, MPP+-induced cytotoxicity in a Parkinson's disease model.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disease that is associated with oxidative stress. Due to the anti-inflammatory and antioxidant functions of Selenium (Se), this molecule may have neuroprotective functions in PD; however, the involvement of Se in such a protective function is unclear. METHODS: 1-methyl-4-phenylpyridinium (MPP+), which inhibits mitochondrial respiration, is generally used to produce a reliable cellular model of PD. In this study, a MPP+-induced PD model was used to test if Se could modulate cytotoxicity, and we further capture gene expression profiles following PC12 cell treatment with MPP+ with or without Se by genome wide high-throughput sequencing. RESULTS: We identified 351 differentially expressed genes (DEGs) and 14 differentially expressed long non-coding RNAs (DELs) in MPP+-treated cells when compared to controls. We further document 244 DEGs and 27 DELs in cells treated with MPP+ and Se vs. cells treated with MPP+ only. Functional annotation analysis of DEGs and DELs revealed that these groups were enriched in genes that respond to reactive oxygen species (ROS), metabolic processes, and mitochondrial control of apoptosis. Thioredoxin reductase 1 (Txnrd1) was also identified as a biomarker of Se treatment. CONCLUSIONS: Our data suggests that the DEGs Txnrd1, Siglec1 and Klf2, and the DEL AABR07044454.1 which we hypothesize to function in cis on the target gene Cdkn1a, may modulate the underlying neurodegenerative process, and act a protective function in the PC12 cell PD model. This study further systematically demonstrated that mRNAs and lncRNAs induced by Se are involved in neuroprotection in PD, and provides novel insight into how Se modulates cytotoxicity in the MPP+-induced PD model.

Development and Validation of a Deep Learning Predictive Model Combining Clinical and Radiomic Features for Short-Term Postoperative Facial Nerve Function in Acoustic Neuroma Patients.

OBJECTIVE: This study aims to construct and validate a predictable deep learning model associated with clinical data and multi-sequence magnetic resonance imaging (MRI) for short-term postoperative facial nerve function in patients with acoustic neuroma. METHODS: A total of 110 patients with acoustic neuroma who underwent surgery through the retrosigmoid sinus approach were included. Clinical data and raw features from four MRI sequences (T1-weighted, T2-weighted, T1-weighted contrast enhancement, and T2-weighted-Flair images) were analyzed. Spearman correlation analysis along with least absolute shrinkage and selection operator regression were used to screen combined clinical and radiomic features. Nomogram, machine learning, and convolutional neural network (CNN) models were constructed to predict the prognosis of facial nerve function on the seventh day after surgery. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate model performance. A total of 1050 radiomic parameters were extracted, from which 13 radiomic and 3 clinical features were selected. RESULTS: The CNN model performed best among all prediction models in the test set with an area under the curve (AUC) of 0.89 (95% CI, 0.84-0.91). CONCLUSION: CNN modeling that combines clinical and multi-sequence MRI radiomic features provides excellent performance for predicting short-term facial nerve function after surgery in patients with acoustic neuroma. As such, CNN modeling may serve as a potential decision-making tool for neurosurgery.

CircLPAR1 Promotes Neuroinflammation and Oxidative Stress in APP/PS1 Mice by Inhibiting SIRT1/Nrf-2/HO-1 Axis Through Destabilizing GDF-15 mRNA.

Circular RNA LPAR1 (circLPAR1) was revealed to be elevated in Alzheimer's disease (AD); nevertheless, its role and mechanisms in AD remain unknown. Memory performance of APP/PS1 mice was assessed by Morris water maze test. Expression of circLPAR1 and indicated messenger RNA (mRNA) in mouse brain tissues or/and SH-SY5Y cells were tested by quantitative real-time PCR (qRT-PCR). Protein expression of indicated gene was examined by western blot. Production of proinflammatory cytokines (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; interleukin-1ß, IL-1ß; and interleukin-8, IL-8) and oxidative stress-related factors (reactive oxygen species, ROS; malondialdehyde, MDA; superoxide dismutase, SOD; and glutathione, GSH) were assessed by commercial kits. RNA pull down and RNA immunoprecipitation were performed to verify the interplay between up-frameshift protein 1 (UPF1) and circLPAR1 or growth differentiation factor 15 (GDF-15). CircLPAR1 was elevated, while GDF-15 was decreased in both APP/PS1 mice and Aß-treated SH-SY5Y cells. Knockdown of circLPAR1 and overexpression of GDF-15 protected cells against Aß-caused inflammation, oxidative stress, and neuronal apoptosis. CircLPAR1 knockdown was also proved to improve AD-related pathological traits and ameliorate cognitive dysfunctions in vivo. In mechanism, we found that circLPAR1 repressed GDF-15 expression by decreasing GDF-15 mRNA stability through UPF1 recruitment. Rescue assays suggested that sirtuin 1 (SIRT1) knockdown reversed GDF-15 overexpression-induced inhibition on Aß-induced neuronal damage and nuclear factor E2-related factor (Nrf-2)/heme oxygenase-1 (HO-1) pathway inhibition. Moreover, the protective effect of circLPAR1 knockdown against Aß-induced apoptosis was abolished by GDF-15 knockdown, and SIRT1 overexpression could counteract this effect of GDF-15 knockdown. CircLPAR1 knockdown improved AD-related pathological traits in vitro and in vivo by inhibiting SIRT1/Nrf-2/HO-1 axis through GDF-15.

Multi-omics analysis reveals cuproptosis and mitochondria-based signature for assessing prognosis and immune landscape in osteosarcoma.

Background: Osteosarcoma (OSA), the most common primary mesenchymal bone tumor, is a health threat to children and adolescents with a dismal prognosis. While cuproptosis and mitochondria dysfunction have been demonstrated to exert a crucial role in tumor progression and development, the mechanisms by which they are regulated in OSA still await clarification. Methods: Two independent OSA cohorts containing transcriptome data and clinical information were collected from public databases. The heterogeneity of OSA were evaluated by single cell RNA (scRNA) analysis. To identify a newly molecular subtype, unsupervised consensus clustering was conducted. Cox relevant regression methods were utilized to establish a prognostic gene signature. Wet lab experiments were performed to confirm the effect of model gene in OSA cells. Results: We determined 30 distinct cell clusters and assessed OSA heterogeneity and stemness scRNA analysis. Then, univariate Cox analysis identified 24 candidate genes which were greatly associated with the prognosis of OSA. Based on these prognostic genes, we obtained two molecular subgroups. After conducting step Cox regression, three model genes were selected to construct a signature showing a favorable performance to forecast clinical outcome. Our proposed signature could also evaluate the response to chemotherapy and immunotherapy of OSA cases. Conclusion: We generated a novel risk model based on cuproptosis and mitochondria-related genes in OSA with powerful predictive ability in prognosis and immune landscape.

Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein-Barr virus infection.

Importance: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the only effective treatment for chronic active Epstein-Barr virus infection (CAEBV). The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear. Objective: To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning (MAC) regimen for children with CAEBV and also the factors affecting the outcomes. Methods: We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children's Hospital, Capital Medical University from October 2016 to June 2021. Data related to the clinical manifestations, engraftment, and outcome were extracted from the medical records. Results: The cohort comprised 41 patients (24 males, 17 females) with a median transplantation age of 92.6 (60.4, 120.7) months and a median follow-up time of 28.2 (15.3, 40.2) months. Four patients (9.8%) died, among which three died from primary disease relapse, and one died from grade IV acute graft-versus-host diseases (aGVHD) after stopping treatment. The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates were 88.8% ± 5.4% and 85.0% ± 5.7%, respectively. The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis (HLH) and the patient without HLH (87.7% ± 6.8% vs. 91.7% ± 8.0%, P = 0.790; 85.0% ± 6.9% vs. 84.6% ± 10.0%, P = 0.921), or among the patients with complete remission, partial remission, and activity disease before HSCT (all P > 0.05). Multivariate analysis showed that grade III-IV aGVHD was a risk factor for mortality (Hazards ratio: 11.65, 95% confidence interval: 1.00, 136.06; P = 0.050). Interpretation: Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV. This treatment benefits patients with HLH or active disease. Patients with Grade III-IV aGVHD may be associated with worse outcomes.

Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study.

BACKGROUND: Despite the substantial burden caused by childhood cancer globally, childhood cancer incidence obtained in a nationwide childhood cancer registry and the accessibility of relevant health services are still unknown in China. We comprehensively assessed the most up-to-date cancer incidence in Chinese children and adolescents, nationally, regionally, and in specific population subgroups, and also examined the association between cancer incidence and socioeconomic inequality in access to health services. METHODS: In this national cross-sectional study, we used data from the National Center for Pediatric Cancer Surveillance, the nationwide Hospital Quality Monitoring System, and public databases to cover 31 provinces, autonomous regions, and municipalities in mainland China. We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China through stratified proportional estimation. We classified regions by socioeconomic status using the human development index (HDI). Incidence rates of 12 main groups, 47 subgroups, and 81 subtypes of cancer were reported and compared by sex, age, and socioeconomic status, according to the third edition of the International Classification of Childhood Cancer. We also quantified the geographical and population density of paediatric oncologists, pathology workforce, diagnoses and treatment institutions of paediatric cancer, and paediatric beds. We used the Gini coefficient to assess equality in access to these four health service indicators. We also calculated the proportions of cross-regional patients among new cases in our surveillance system. FINDINGS: We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China from Jan 1, 2018, to Dec 31, 2020. An estimated 121 145 cancer cases were diagnosed among children and adolescents in China between 2018 and 2020, with world standard age-standardised incidence rates of 122·86 (95% CI 121·70-124·02) per million for children and 137·64 (136·08-139·20) per million for adolescents. Boys had a higher incidence rate of childhood cancer (133·18 for boys vs 111·21 for girls per million) but a lower incidence of adolescent cancer (133·92 for boys vs 141·79 for girls per million) than girls. Leukaemias (42·33 per million) were the most common cancer group in children, whereas malignant epithelial tumours and melanomas (30·39 per million) surpassed leukaemias (30·08 per million) in adolescents as the cancer with the highest incidence. The overall incidence rates ranged from 101·60 (100·67-102·51) per million in very low HDI regions to 138·21 (137·14-139·29) per million in high HDI regions, indicating a significant positive association between the incidence of childhood and adolescent cancer and regional socioeconomic status (p<0·0001). The incidence in girls showed larger variation (48·45% from the lowest to the highest) than boys (36·71% from lowest to highest) in different socioeconomic regions. The population and geographical densities of most health services also showed a significant positive correlation with HDI levels. In particular, the geographical density distribution (Gini coefficients of 0·32-0·47) had higher inequalities than population density distribution (Gini coefficients of 0·05-0·19). The overall proportion of cross-regional patients of childhood and adolescent cancer was 22·16%, and the highest proportion occurred in retinoblastoma (56·54%) and in low HDI regions (35·14%). INTERPRETATION: Our study showed that the burden of cancer in children and adolescents in China is much higher than previously nationally reported from 2000 to 2015. The distribution of the accessibility of health services, as a social determinant of health, might have a notable role in the socioeconomic inequalities in cancer incidence among Chinese children and adolescents. With regards to achieving the Sustainable Development Goals, policy approaches should prioritise increasing the accessibility of health services for early diagnosis to improve outcomes and subsequently reduce disease burdens, as well as narrowing the socioeconomic inequalities of childhood and adolescent cancer. FUNDING: National Major Science and Technology Projects of China, National Natural Science Foundation of China, Chinese Academy of Engineering Consulting Research Project, Wu Jieping Medical Foundation, Beijing Municipal Administration of Hospitals Incubating Program.

How to Precisely Open the Internal Auditory Canal for Resection of Vestibular Schwannoma via the Retrosigmoid Approach.

Objective: The aim of this study was to investigate how to precisely expose the intrameatal portion of vestibular schwannomas (VSs) without damaging the labyrinth. Methods: This was a retrospective study of patients who had undergone retrosigmoid resection of a VS in our institution from April 2018 to December 2021. The patients were divided into microsurgery (MS) and navigation endoscopic-assisted (combined surgery, CS) groups and the effects of image guidance and endoscopy evaluated. The tumors in the CS group were then divided into medial and lateral types by fusion imaging and the differences between the two types analyzed. Results: Data of 84 patients were analyzed. Residual tumor was detected by postoperative MRI at the fundus of the internal auditory canal in 5 of the 31 patients in the MS group and 1 of the 53 in the CS group. The labyrinth was damaged in four patients in the MS group but was not damaged in any of the CS group patients. The CS group included 29 lateral type and 24 medial type schwannomas. Endoscopic-assisted resection of residual tumor in the IAC was performed significantly more often on medial than on lateral tumors. Conclusion: Navigation and endoscopy are useful in assisting the exposure of the intrameatal portion of VSs. Preoperative MRI/CT fusion imaging is helpful in preoperative evaluation and surgical planning in patients undergoing VS surgery. Tumors of the medial type require endoscopic assistance for resection.

Efficacy of hematopoietic stem cell transplantation in the treatment of children with non-severe aplastic anemia.

BACKGROUND: Non-severe aplastic anemia is more likely to develop into severe aplastic anemia, and there is no widely accepted treatment plan at present. Hematopoietic stem cell transplantation might be a new therapeutic strategy. METHODS: Retrospectively analyzed 32 patients with non-severe aplastic anemia who underwent hematopoietic stem cell transplantation from September 2007 to September 2020, and the 5-year estimated overall survival rate and the incidence of graft-versus-host disease were analyzed to evaluate the efficacy and safety of hematopoietic stem cell transplantation in the treatment of pediatric non-severe aplastic anemia. RESULTS: Thirty-two patients who underwent transplantation, 29 patients (90.6%) survived, 3 patients (9.4%) died. The incidence of acute graft-versus-host disease was 51.6% (16/31), including 15 cases (48.4%) of grade I-II and 1 case (3.2%) of grade III-IV. The incidence of chronic graft-versus-host disease was 38.7% (12/31). The 5-year overall survival rate was 91.8%. CONCLUSIONS: Hematopoietic stem cell transplantation is a practicable, safe, and effective treatment option for non-severe aplastic anemia pediatric patients who are suitable for transplant.

Immune Reconstitution in Pediatric Aplastic Anemia after Allogeneic Hematopoietic Stem-cell Transplantation.

Background: Previous studies had revealed that immune reconstitution (IR) after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) affected the clinical prognosis of patients. However, few studies were based on pediatric patients and patients with aplastic anemia (AA). The purpose of this research was to analyze IR of pediatric AA after HSCT and further explore its clinical prognostic value. Methods: The whole of 61 pediatric patients with AA who underwent HSCT were enrolled. Lymphocyte subsets count in peripheral blood, CD4+/CD8+ T cell ratio, and serum concentration of immunoglobulins were detected using flow cytometry at regular intervals after HSCT. Results: Innate immunity recovered faster than adaptive immunity, T lymphocytes recovered faster than B lymphocytes. The number of transfused CD34+ cells and the implantation time of ANC significantly affected the early rapid IR of CD3+ T cells. The degree of HLA site coincidence significantly affected the early rapid IR of CD19+ B cells. The number of transfused MNC and CD34+ cells significantly affected the early rapid IR of CD56+ NK cells. The overall survival (OS) and failure-free survival (FFS) of CD56+ NK cells in early rapid IR group were higher than those in non-IR group. The CD3+ T cell early rapid IR group and CD8+ T cell early rapid IR group had higher OS than the non-IR group. Conclusion: Early rapid IR after HSCT is a good predictor of clinical prognosis in children with AA. This study provides a reasonable prediction for early rapid IR, which may improve clinical outcomes of children.

Comparison of Sex Differences in Outcomes of Patients With Aneurysmal Subarachnoid Hemorrhage: A Single-Center Retrospective Study.

Background: Sex differences in the outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. The aim of this study was to evaluate sex differences in the outcomes of patients with aSAH. Method: This study retrospectively analyzed the clinical data of consecutive patients with aSAH, admitted to the Department of Neurosurgery, Wuhan University Zhongnan Hospital, from May 1, 2020 to December 31, 2020. The modified Rankin Scale (mRS) score was used to evaluate the prognosis of patients at discharge. Outcome indicators included cerebral ischemia, hydrocephalus, and mRS ≥ 2 at discharge. Results: The majority (65%) of the 287 patients with aSAH included in the study were females. Patients were divided into female (n = 184) and male (n = 99) groups; the female patients were significantly older than the male patients (61.3 ± 8.5 years vs. 60.0 ± 8.5 years, p = 0.032). The incidence of comorbidities (hypertension, diabetes, and heart disease) was higher in the female group than in the male group, but the difference was not statistically significant. Although more female patients than male patients underwent endovascular treatment, there was no statistical difference in the treatment approach between the two groups. Comparison of post-operative complications and mRS scores at discharge revealed that the rate of cerebral ischemia and mRS ≥ 2 at discharge were significantly higher among female patients than among male patients. Moreover, this difference persisted after propensity adjustment for age and treatment approach. Analysis of risk factors for poor prognosis at discharge in both pre- and post-adjustment patients revealed cerebral ischemia and high mFisher score (mFisher = 3/4) to be independent risk factors. Conclusion: Female patients with aSAH have a worse prognosis than male patients, and this difference may be because women are more susceptible to cerebral ischemia.

Evidence of Omics, Immune Infiltration, and Pharmacogenomics for BATF in a Pan-Cancer Cohort.

Background: Cytotoxic CD8+ T-cell exhaustion is the major barrier for immunotherapy in tumors. Recent studies have reported that the basic leucine zipper activating transcription factor-like transcription factor (BATF) is responsible for countering cytotoxic CD8+ T-cell exhaustion. Nevertheless, the expression and roles of BATF in tumors have been poorly explored. Methods: In the present study, we conducted a multi-omics analysis, including gene expression, methylation status, DNA alterations, pharmacogenomics, and survival status based on data from the Cancer Genome Atlas (TCGA) database to discern expression patterns and prognostic roles of BATF in tumors. We also explored potential roles of BATF in a pan-cancer cohort by performing immune infiltration, Gene Ontology (GO) enrichment, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In vitro assay was also performed to explore roles of BATF in tumor cells. Results: We found that BATF was aberrantly upregulated in 27 types of tumors with respect to the corresponding normal tissues. Abnormal BATF expression in tumors predicted survival times of patients in a tissue-dependent manner. The results of GO, immune infiltration, and KEGG analysis revealed that increased BATF expression in tumors participated in modulating immune cell infiltration via immune-related pathways. BATF expression could also predict immunotherapeutic and chemotherapy responses in cancers. Moreover, knockdown of BATF suppresses tumor cell viability. Conclusion: Our present study reports the vital roles of BATF in tumors and provides a theoretical basis for targeting BATF therapy.

Pediatric acute myeloid leukemia patients with KMT2A rearrangements: a single-center retrospective study.

PURPOSE: Pediatric acute myeloid leukemia (AML) with KMT2A rearrangements has a very different prognosis. Poor outcomes cannot be avoided even after hematopoietic stem cell transplantation. In order to investigate the prognosis and efficacy, we conducted a retrospective analysis. PATIENTS AND METHODS: We retrospectively analyzed a total of 32 children with KMT2A rearrangements AML treated in our hospital between January 2015 and February 2021. RESULTS: The proportion of patients with KMT2A-rearranged in the medium-risk group of overall survival (OS) and event-free survival (EFS) was 100%. No differences in OS, EFS and cumulative incidence of relapse (CIR) were detected between the haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and full matched HSCT (P = 0.289, P = 0.303, P = 0.303). Acute graft-versus-host disease (aGVHD) was often detected in the haplo-HSCT cohort, while full matched HSCT had no obvious aGVHD, assessed as≤1 grade (P < 0.05). Patients in the medium-risk pediatric group could acquire 100% OS and EFS only after chemotherapy. There was no significant difference in OS, EFS and CIR between full matched HSCT and haploidentical transplantation in pediatric AML with KMT2A rearrangements, but full matched HSCT seemed to have a lower death rate. The severity of aGVHD in the full matched HSCT was less than that in the haploidentical transplantation group. CONCLUSION: The primary choice of donor can be HLA-matched sibling donors or matched unrelated donors for children with AML with KMT2A rearrangements, and the secondary choice can be haploid donors.

Safety and efficacy of intravenous tirofiban for stent-assisted coiling in acutely ruptured intracranial aneurysms: A single center experience.

BACKGROUND: There have been few reports on the use of tirofiban in ruptured intracranial aneurysms and the results were conflicting. However, the safety and efficacy of optimal dosage and the reasonable treatment course of tirofiban have not been determined. OBJECTIVE: To determine the safety and efficacy of a new protocol for its prophylactic tirofiban application during the endovascular treatment of ruptured intracranial aneurysms with no oral antiplatelet medications. METHODS: This retrospective study was based on 105 patients with ruptured aneurysms who underwent stent-assisted coiling at our institution between August 2017 and July 2020. Intravenous tirofiban was administered to patients after stent deployment. Tirofiban was administered as an intravenous bolus (5 µg/kg) over a 3 min period immediately after stent deployment, followed by a 0.06-0.08 µg/kg/min maintenance infusion for 12-24 h. Dual oral antiplatelet therapy was overlapped with half the tirofiban dose 2 h before the cessation of the tirofiban infusion. Cases of intracranial hemorrhage or thromboembolism were recorded. RESULTS: This study included a total of 105 patients with ruptured intracranial aneurysms, who underwent stent-assisted coiling. In terms of clinical severity, a presenting Hunt-Hess clinical-grade I was observed in 47 (44.8%) cases, grade II in 19 (18.1%) cases, grade III in 30 (28.6%) cases, grade IV in 6 (5.6%) cases, and grade V in 3 (2.9%) cases. None of the patients showed a newly developed tirofiban-related intracerebral hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, or ventriculostomy-related hemorrhage. There were 3 (2.8%) patients who had thromboembolic complications. CONCLUSIONS: We have determined a new protocol for prophylactic intraoperative tirofiban during the endovascular treatment of ruptured intracranial aneurysms with no oral antiplatelet medications. In our study, tirofiban showed a low risk of hemorrhagic or thromboembolic complications. Tirofiban appears to be a safe and alternative during the stent-assisted coiling of ruptured intracranial aneurysms.

Haploidentical hematopoietic stem cell transplantation for pediatric patients with chronic active Epstein-Barr virus infection: a retrospective analysis of a single center.

BACKGROUND: This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for the treatment of pediatric patients with chronic active Epstein-Barr virus infection (CAEBV). METHODS: Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital, Capital Medical University, from October 2016 to June 2020 were analyzed retrospectively. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. RESULTS: Twenty-five patients, including 16 males and 9 females, with an onset age of 5.0 ± 2.6 years and a transplantation age of 6.9 ± 2.9 years, were enrolled in this study. The mean time from diagnosis to transplantation was 3.8 (2.0-40.2) months. The mean observation time was 19.0 ± 12.0 months. Three patients received the reduced intensity conditioning regimen, and the remaining patients all received the modified myeloablative conditioning regimen. By the end of the follow-up, 23 patients were characterized by disease-free survival (DFS), 22 were characterized by event-free survival (EFS), and two died. One of the patients died of thrombotic microangiopathy (TMA), and another died of graft versus host disease (GVHD); this patient discontinued the treatment for economic reasons. The 3-year overall survival (OS) rate was estimated to be 92.0% ± 5.4%, and the 3-year EFS rate was estimated to be 87.4% ± 6.8%. All active patients survived after HSCT event-free. Acute GVHD degrees 1-3 were observed in ten patients (40.0%), and degree IV was observed in six (24.0%), who were all cured except for one patient. Chronic GVHD was observed in nine (36.0%), and most of these cases were mild. The incidence of TMA and veno-occlusive disease (VOD) was 28.0% and 4.0%. CONCLUSIONS: Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency transplantation. Patients with active disease before HSCT also benefited from haplo-HSCT. Haplo-HSCT requires careful monitoring for complications, such as GVHD and TMA. Early detection of TMA and timely treatment can reduce mortality and can improve the survival rate.

Haploidentical haematopoietic stem cell transplantation for malignant infantile osteopetrosis and intermediate osteopetrosis: a retrospective analysis of a single centre.

OBJECTIVE: To evaluate the clinical efficacy of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for the treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis. METHODS: Children with MIOP and IOP who underwent haplo-HSCT in Beijing Children's Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analysed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. RESULTS: Twenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04-72) months were enrolled in this study. The median time from diagnosis to transplantation was 4 (1-23) months. All patients received haplo-HSCT with a myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). Graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin/anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3-126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The 5 year overall survival rate was 73.9%. Stage I-II acute GVHD was observed in 20 patients, stage III GVHD in 1 patient and no patients had stage IV disease. Chronic GVHD was observed in 11 patients (40.7%) and was controlled by anti-GVHD therapy. CONCLUSIONS: Haplo-HSCT was an effective treatment for MIOP and IOP, with a high survival rate and significantly improved clinical symptoms. For patients with a vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild and was effectively controlled by appropriate treatment. These data indicated that haplo-HSCT was a feasible treatment for MIOP and IOP.

miR-877 inhibits the proliferation, migration, and invasion of osteosarcoma cells by targeting gamma-glutamylcyclotransferase.

Gamma-glutamylcyclotransferase (GGCT) can promote the progression of osteosarcoma (OS). MicroRNAs also play significant roles in regulating the progression of OS. This study was designed to investigate whether miR-877 exerts its function in OS by targeting GGCT. The proliferation of OS cells (Saos-2 and U2OS) was detected by MTT and colony formation assays. The migration and invasion of OS cells were detected by transwell assays. The expressions of miRNAs and GGCT were detected by quantitative real-time PCR and Western blot. The luciferase reporter assay was performed to assess whether miR-877 could target GGCT. miR-877 was down-regulated both in OS tissues and OS cell lines (Saos-2 and U2OS). The overexpression of miR-877 inhibited the proliferation, migration, and invasion of OS cell lines, while the knockdown of miR-877 could negate effects. The expression of GGCT was increased in Saos-2 and U2OS cells. miR-877 could target GGCT, and the mRNA level of GGCT in Saos-2 and U2OS cells was decreased by the overexpression of miR-877. miR-877 overexpression inhibited the migration and invasion and suppressed the proliferation of Saos-2 and U2OS cells, and the overexpression of GGCT reversed this effects. The knockdown of miR-877 promoted the migration and invasion and facilitated the proliferation of Saos-2 and U2OS cells, and the silence of GGCT abolished this effects. Our findings suggested that miR-877 could inhibit the proliferation, migration, and invasion of OS cells by targeting GGCT.

Evaluation of Bone Wax Coated Bipolar Coagulation Forceps: Performance and Safety Assessment.

BACKGROUND: Improving the performance of bipolar coagulation forceps is crucial for safer and more accurate neurosurgery. In our department, we found that bone wax (BW) melted by thermal effect of bipolar electrocoagulation can achieve more efficient hemostasis and reduce the amount of BW in neurosurgical procedures associated with bleeding from emissary and diploic veins. Nevertheless, relevant studies are still lacking to verify our finding. OBJECTIVE: The study objectives were to evaluate the performance and safety in electrocoagulation: (1) compare the performance of BW coated bipolar coagulation forceps and the conventional anti-stick forceps in vivo, and (2) assess the safety of electrocoagulation with BW coated bipolar coagulation forceps in rat primary motor cortex. METHODS: Tissue adhesion was evaluated by comparing the wetting tension and the amount of protein adhered to the forceps tips after electrocoagulation. Thermal damage was assessed by analyzing the thermography and H&E staining of coagulated rat brain tissues. The hemostatic efficiency was reflected by the number of electrocoagulation until complete hemostasis and the condition of damaged common carotid arteries. The safety of BW coated forceps in electrocoagulation was assessed by evaluating the inflammation of coagulated rat primary motor cortex and the motor functions at the 7th day postoperatively. RESULTS: Bone wax coated forceps had a significantly higher contact angle and adhered less coagulum. Thermography was acquired at 3 s, 6 W units in rat primary motor cortex in vivo. The highest temperature recorded during BW coated tips application was significantly lower than the uncoated. In addition, there was a relatively smaller tissue injury area produced by the BW coated forceps. Additionally, BW coated forceps improved the hemostatic efficiency and caused fewer injuries on the damaged arteries (3 s, 10 W units). More importantly, electrocoagulation with BW coated forceps led to no significant motor function impairments and less glial and microglia responses. CONCLUSION: This study reveals that BW coated bipolar coagulation forceps can provide a convenient, cost-efficient, safer, and more efficient way for hemostasis. More research is needed to evaluate the electrocoagulation with BW in the long term and verify our finding in human beings.