Genuine Active Species Generated from Fe3 N Nanotube by Synergistic CoNi Doping for Boosted Oxygen Evolution Catalysis.

The surface reconstruction of oxygen evolution reaction (OER) catalysts has been proven favorable for enhancing its catalytic activity. However, what is the active site and how to promote the active species generation remain unclear and are still under debate. Here, the in situ synthesis of CoNi incorporated Fe3 N nanotubes (CoNi-Fe3 N) on the iron foil through the anodization/electrodeposition/nitridation process for use of boosted OER catalysis is reported. The synergistic CoNi doping induces the lattice expansion and up shifts the d-band center of Fe3 N, which enhances the adsorption of hydroxyl groups from electrolyte during the OER catalysis, facilitating the generation of active CoNi-FeOOH on the Fe3 N nanotube surface. As a result of this OER-conditioned surface reconstruction, the optimized catalyst requires an overpotential of only 285 mV at a current density of 10 mA cm-2 with a Tafel slope of 34 mV dec-1 , outperforming commercial RuO2 catalysts. Density functional theory (DFT) calculations further reveal that the Ni site in CoNi-FeOOH modulates the adsorption of OER intermediates and delivers a lower overpotential than those from Fe and Co sites, serving as the optimal active site for excellent OER performance.

The expression of cytokines in aqueous humor of high myopic patients with cataracts.

Purpose: To analyze the expression of 440 human cytokines in aqueous humor of high myopic patients with cataracts. Methods: Eighty-five patients with cataracts were recruited in this study. In the screening stage, the RayBio G-Series Human Cytokine Antibody Array 440 was used to assay the aqueous humor samples collected from nine high myopic patients with cataracts and eight non-myopic patients with cataracts right before the surgery. The array was further used for verification of the screened cytokines, with aqueous humor samples obtained from 34 eyes of high myopic patients with cataracts and 34 eyes of non-myopic patients with cataracts. Results: Compared with the non-myopic patients with cataracts, the expression levels of decorin, receptor activator of NF-kB (RANK), angiopoietin-1 (ANG-1), C-X-C motif ligand 16 (CXCL16), ß-inducible gene-h3 (bIG-H3), insulin-like growth factor-binding protein 2 (IGFBP-2), and interleukin-17B (IL-17B) were statistically significantly higher in high myopic patients with cataracts (all p<0.000114). The matrix metalloproteinase-2 (MMP-2) level also increased in the aqueous humor of high myopic patients with cataracts (p = 0.0034). The concentrations of ANG-1 and MMP-2 were also increased in the aqueous humor of the confirmatory stage (all p<0.05). Conclusions: In this study, numerous cytokines in aqueous humor were detected in high myopic patients with cataracts and non-myopic patients with cataracts, and it was confirmed that the MMP-2 level in the aqueous humor of patients with high myopia was statistically significantly increased. Further verification also revealed the elevation of ANG-1 in the aqueous humor of high myopic patients with cataracts, which suggests that ANG-1 may be related to the pathogenesis of high myopia.

The high expression of the pain-related inflammatory factors in the eyes of cataract patients infected with hepatitis B virus.

In cataract surgery, it is often found that patients infected hepatitis B virus (HBV) are likely to suffer from more pain than other patients. In order to assess the inflammation status of the aqueous humor in the eyes of cataract patients infected with HBV. RayBio Human Inflammation Array was used to assay aqueous humor samples collected from 14 eyes of patients infected with HBV and 14 eyes of cataract patients without HBV infection (the controls) during the cataract surgery. RayBio Human Quantibody Cutom Array was adopted for the validation of the screened cytokines, with aqueous humor samples collected from 40 eyes of patients infected with HBV and 40 eyes of the controls. A pain questionnaire survey about the surgery was conducted in all patients after operation. The results of questionnaire showed that patients infected with HBV were more likely to have pain during operation. The Human Inflammation Array revealed that the expression levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α) and tumor necrosis factor ß (TNF-ß) were very high in HBV infected patients and IL-1ra was much lower in patients infected with HBV (all, P < 0.05). In validation, the Human Quantibody Cutom Array revealed that the expression levels of MCP-1 and TNF-α were high in HBV infected patients with significant difference (all P < 0.05). These results revealed that pain-related inflammatory factors MCP-1 and TNF-α were increased in aqueous humor of cataract patients infected with HBV, which indicates that patients infected with HBV may be more prone to intraoperative pain.

Current Treatment Patterns of Aplastic Anemia in China: A Prospective Cohort Registry Study.

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: The first nation-wide prospective multicenter study in China.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)-ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation-wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical-biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%-50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event-free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non-MRD group (5y-EFS: 82.4% vs 78.3%, P = .038; 5y-CIR: 10.7% vs 18.0%, P < .001). Our results demonstrated that the large-scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD-based risk stratification might improve the treatment outcome for childhood ALL.

A Novel Grading System for Diffuse Chorioretinal Atrophy in Pathologic Myopia.

INTRODUCTION: This study aims to quantitatively assess diffuse chorioretinal atrophy (DCA) in pathologic myopia and establish a standardized classification system utilizing artificial intelligence. METHODS: A total of 202 patients underwent comprehensive examinations, and 338 eyes were included in the study. The methodology involved image preprocessing, sample labeling, employing deep learning segmentation models, measuring and calculating the area and density of DCA lesions. Lesion severity of DCA was graded using statistical methods, and grades were assigned to describe the morphology of corresponding fundus photographs. Hierarchical clustering was employed to categorize diffuse atrophy fundus into three groups based on the area and density of diffuse atrophy (G1, G2, G3), while high myopic fundus without diffuse atrophy was designated as G0. One-way analysis of variance (ANOVA) and nonparametric tests were conducted to assess the statistical association with different grades of DCA. RESULTS: On the basis of the area and density of DCA, the condition was classified into four grades: G0, G1 (0 < density ≤ 0.093), G2 (0.093 < density ≤ 0.245), and G3 (0.245 < density ≤ 0.712). Fundus photographs depicted a progressive enlargement of atrophic lesions, evolving from punctate-shaped to patchy with indistinct boundaries. DCA atrophy lesions exhibited a gradual shift in color from brown-yellow to yellow-white, originating from the temporal side of the optic disc and extending towards the macula, with severe cases exhibiting widespread distribution throughout the posterior pole. Patients with DCA were significantly older [34.00 (27.00, 48.00) vs 29.00 (26.00, 34.00) years], possessed a longer axial length (28.85 ± 1.57 vs 27.11 ± 1.01 mm), and exhibited a more myopic spherical equivalent [- 13.00 (- 16.00, - 10.50) vs - 9.09 ± 2.41 D] compared to those without DCA (G0) (all P < 0.001). In eyes with DCA, a trend emerged as grades increased from G1 to G3, showing associations with older age, longer axial length, deeper myopic spherical equivalent, larger area of parapapillary atrophy, and increased fundus tessellated density (all P < 0.001). CONCLUSIONS: The novel grading system for DCA, based on assessments of area and density, serves as a reliable measure for evaluating the severity of this condition, making it suitable for widespread application in the screening of pathologic myopia.

[Clinical Analysis of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Children].

OBJECTIVE: To explore the clinical characteristics, molecular characteristics, treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) with a therapeutic target. METHODS: A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021. The data of age, gender, white blood cell (WBC) count at initial diagnosis, genetic characteristics, molecular biological changes, chemotherapy regimen, different targeted drugs were given, and minimal residual disease (MRD) on day 19, MRD on day 46, whether hematopoietic stem cell transplantation (HSCT) were retrospective analyed, and the clinical characteristics and treatment effect were summarized. Survival analysis was performed by Kaplan-Meier method. RESULTS: The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients, 10 patients were treated with targeted drugs during treatment, and 3 patients were bridged with HSCT, 1 patient died and 2 patients survived. Among the 24 patients who did not receive HSCT, 1 patient developed relapse, and achieved complete remission (CR) after treatment with chimeric antigen receptors T cells (CAR-T). The 3-year overall survival, 3-year relapse-free survival and 3-year event-free survival rate of 27 patients were (95.5±4.4)%, (95.0±4.9)% and (90.7±6.3)% respectively. CONCLUSION: Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children, combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor, and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

[Osteogenetic capacity of cross-linked adjustable anti-tuberculosis drug sustained-release artificial composite].

OBJECTIVE: To explore the osteogenetic capacity of cross-linked adjustable anti-tuberculosis drug sustained-release artificial composite (TPB/SA-RFP/PLA). METHODS: The model of femur bone defect was established in rabbits.TPB/SA-RFP/PLA complex was implanted into defect parts in the experimental group while TPB/SA/PLA in the blank control group. At Weeks 4, 8 and 12, gross specimens received radiographic, histological and immunohistochemical examinations to determine the osteogenetic performance of TPB/SA-RFP/PLA. RESULTS: As compared with the control group, TPB/SA-RFP/PLA complex had excellent osteogenic capacities while the TPB/SA/PLA group had no obvious osteogenic difference. Lane-sandhu histological and radiographic ratings demonstrated significant difference between TPB/SA-RFP/PLA (8.3 ± 0.3) and blank groups (2.2 ± 0.4) (P < 0.05). And TPB/SA/PLA showed no significant intragroup significance (P > 0.05). Two groups immunohistochemical Alkaline phosphatase was strongly positive in two test groups and weakly positive in the control group. CONCLUSION: TPB/ SA-RFP/PLA has excellent profiles of bone conductivity and regeneration.And the incorporation of rifampin does not affect its osteogenetic capacity.

Clinical Features of Fundus Tessellation and Its Relationship with Myopia: A Systematic Review and Meta-analysis.

INTRODUCTION: This study aims to assess the existing literature on fundus tessellation (FT), focusing on its prevalence, associated factors, distribution, and progression. METHODS: Systemic methods were employed to search and gather published literature on FT from databases such as the National Library of Medicine (PubMed), Web of Science (WOS), and Elsevier on July 1, 2023. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) and the Healthcare Research and Quality (AHRQ) criteria. A meta-analysis was conducted to compare tessellated and normal fundus with respect to age, gender, axial length, and spherical equivalent. RESULTS: The systematic review included 23 articles, encompassing a total of 3053 eyes in the meta-analysis. The prevalence of FT varied from 43.00 to 94.35%. The severity of FT was significantly associated with older age, male sex, lower body weight index, longer axial length, larger peripapillary atrophy, thinner choroid, thinner sclera, and larger corneal radius of curvature, suggesting a potential progression pattern. Notably, FT was observed predominantly in the macular and peripapillary regions. The meta-analysis revealed that tessellated fundus tended to be associated with older age (mean difference [MD] 4.76, 95% confidence interval [CI] 1.71-7.80, P < 0.01), longer axial length (MD 0.86, 95% CI 0.70-1.02, P < 0.01), and a lower spherical equivalent (MD - 1.16, 95% CI - 1.68 to 0.65, P < 0.01) compared to normal fundus. However, there was no significant difference in the proportion of males between individuals with tessellated and normal fundus (odds ratio [OR] 1.12, 95% CI 0.89-1.42, P = 0.32). CONCLUSIONS: Overall, this systematic review and meta-analysis shed light on the prevalence, characteristics, and factors associated with FT, offering valuable insights for clinicians and researchers in the field of ophthalmology. STUDY REGISTRATION: The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023442486).

Fundus Tessellated Density of Pathologic Myopia.

PURPOSE: The study aimed to quantitatively evaluate the fundus tessellated density (FTD) in different categories of pathologic myopia (PM) using fundus photographs with the application of artificial intelligence. METHODS: A retrospective review of 407 PM (META-PM, Category 2-Category 4) eyes was conducted, employing a biomimetic mechanism of human vision and integrated image processing technologies for FTD extraction and calculation. Different regions of interest were analyzed, including circle O4.5 (optic disc centered, diameter of 4.5 mm) and circle M1.0, M3.0, M6.0 (macular centered, diameter of 1.0, 3.0, and 6.0 mm), using 2 partitioning methods ("X" and "+"). The density of patchy (Category 3) or macular atrophy (Category 4) areas was quantified. Univariate and multivariate linear regression analyses were performed to assess the association with FTD. RESULTS: The mean FTD of total PM eyes was 0.283, ranging from 0.002 to 0.500, and demonstrating a negative correlation with the PM category. In multivariate analysis, age was found to be significantly associated with FTD ( P <0.05), while axial length did not show a significant association. Fundus tessellation of circle O4.5 and circle M6.0 displayed associations with the FTD across different PM categories. The "X" partitioning method better fit the circle M6.0 region, while both methods were suitable for the circle O4.5 region. After excluding the patchy and macular atrophic areas, the mean FTD values were 0.346 in Category 2, 0.261 in Category 3, and 0.186 in Category 4. CONCLUSIONS: The study revealed a decreasing trend in FTD values across different categories of PM, regardless of the presence or absence of patchy or macular atrophic areas. Quantifying FTD in PM could be a valuable tool for improving the existing PM classification system and gaining insights into the origin of posterior staphyloma and visual field defects in high myopia.

[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). METHODS: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed. RESULTS: Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred. CONCLUSION: Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.

Initiation of China Alliance of Research in High Myopia (CHARM): protocol for an AI-based multimodal high myopia research biobank.

INTRODUCTION: High myopia is a pressing public health concern due to its increasing prevalence, younger trend and the high risk of blindness, particularly in East Asian countries, including China. The China Alliance of Research in High Myopia (CHARM) is a newly established consortium that includes more than 100 hospitals and institutions participating across the nation, aiming to promote collaboration and data sharing in the field of high myopia screening, classification, diagnosis and therapeutic development. METHODS AND ANALYSIS: The CHARM project is an ongoing study, and its initiation is distinguished by its unprecedented scale, encompassing plans to involve over 100 000 Chinese patients. This initiative stands out not only for its extensive scope but also for its innovative application of artificial intelligence (AI) to assist in diagnosis and treatment decisions. The CHARM project has been carried out using a 'three-step' strategy. The first step involves the collection of basic information, refraction, axial length and fundus photographs from participants with high myopia. In the second step, we will collect multimodal imaging data to expand the scope of clinical information, for example, optical coherence tomography and ultra-widefield fundus images. In the final step, genetic testing will be conducted by incorporating patient family histories and blood samples. The majority of data collected by CHARM is in the form of images that will be used to detect and predict the progression of high myopia through the identification and quantification of biomarkers such as fundus tessellation, optic nerve head and vascular parameters. ETHICS AND DISSEMINATION: The study has received approval from the Ethics Committee of Beijing Tongren Hospital (TREC2022-KY045). The establishment of CHARM represents an opportunity to create a collaborative platform for myopia experts and facilitate the dissemination of research findings to the global community through peer-reviewed publications and conference presentations. These insights can inform clinical decision-making and contribute to the development of new treatment modalities that may benefit patients worldwide. TRIAL REGISTRATION NUMBER: ChiCTR2300071219.

The effect of multilevel anterior cervical fusion on neck motion.

BACKGROUND: Anterior cervical decompression and fusion (ACDF) procedures are successful in treating multilevel cervical radiculopathy and cervical myelopathy. It was reported that this procedure would result in a loss of cervical range of motion. However, few studies have focused on the exact impact of multilevel (more than 3 levels) ACDF on cervical range of motion. METHODS: 29 patients underwent a 3-level or 4-level ACDF. In all the patients, preoperative active cervical ROM measurement was performed, and postoperative measurement was performed at 1-year follow-up by a CROM device. The pre- and postoperative data were compared to each other using paired t tests (α = 0.05). RESULTS: The patients had significantly less ROM after the surgery in all planes of motion. Major reduction was observed in flexion (39.5%), left and right lateral flexion (25.7 and 25.9%), with relatively minor impact on extension (18.3%), left and right rotation (14.0 and 14.4%) observed. In the three cardinal planes, major reduction was observed in the sagittal plane (28.2%) and coronal plane (25.8%), while minor impact observed in the horizontal plane (14.1%). CONCLUSIONS: The patients of cervical spondylotic myelopathy had an obvious reduction in active cervical ROM following multilevel ACDF. However, patients might not experience great difficulties in performing daily activities with regard to the loss of neck motion after fusion.

[Efficacy of Chimeric Antigen Receptor T Cell in the Treatment of Refractory/Recurrent B Acute Lymphocytic Leukemia in Children].

OBJECTIVE: To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL). METHODS: Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T. RESULTS: The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis. CONCLUSION: CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.

[The Factors Affecting Relapse in Pediatric B-cell Acute Lymphoblastic Leukemia Patients without Prognostic Fusion Genes Following Up for 10 years].

OBJECTIVE: To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients. METHODS: B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients. RESULTS: There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients. CONCLUSION: Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.

[Effect of Chemotherapy Course Delay on the Relapse of Paediatric B-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the effect of course delay of CCLG-ALL-2008 regimen on the relapse of paediatric B-cell acute lymphoblastic leukemia (B-ALL) patients. METHODS: Paediatric B-ALL patients newly diagnosed and treated with CCLG-ALL-2008 regimen in the Children's Hospital of Soochow University from January 2011 to December 2014 were retrospectively analyzed to clarify the relationship between chemotherapy course delay and relapse, and explore the causes of course delay which led to relapse. Patients were followed up until July 2019. RESULTS: The correlation between treatment delay (number of weeks) and relapse rate was statistically significant (P=0.034), and hazard ratio indicated that longer than 4 weeks had a significant effect. The effect of positive minimal residual disease (MRD) (1×10-4≤MRD≤1×10-2) at the 12th week on the relapse rate was also statistically significant (P=0.041). Among the causes of treatment delay, the effect of myelosuppression on the relapse rate was statistically significant (P=0.01). CONCLUSION: Treatment delay exceeding 4 weeks, positive MRD at the 12th week, and myelosuppression are independent prognostic factors for relapse.

Mechanical strain induces Cx43 expression in spinal ligament fibroblasts derived from patients presenting ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic bone formation in spinal ligaments. Some evidence indicates that mechanical strain can lead to the development of OPLL, although the signaling mechanism is not fully understood. Connexin43 (Cx43), a gap-junction protein, has been shown to be of particular importance in bone formation. We hypothesized that Cx43 may play an important role in the signal transmission induced by mechanical strain during the development of OPLL. To explore this possibility, we cultured fibroblasts from spinal ligaments of OPLL and non-OPLL patients and preloaded mechanical stretch onto the cells via a Flexercell 4000 Tension Plus system. We evaluated expression changes in osteocalcin (OCN), alkaline phosphatase (ALP), type I collagen (COL I) and Cx43 via semi-quantitative RT-PCR and western blotting at 12 and 24 h after mechanical strain application in contrast to static conditions. We observed a significant gene up-regulation of OCN, ALP and COL I and Cx43 protein in OPLL cells after mechanical strain application, but no changes in non-OPLL cells. Notably, after RNA interference targeting Cx43 was performed in OPLL cells, we found that there were no significant changes in the expressions of OCN, ALP, COL I and Cx43 after the mechanical strain was applied for 24 h. Thus, we propose that the increase in Cx43 expression induced by mechanical strain in OPLL cells plays an important role in the progression of OPLL.

[Morphologic and apoptotic changes of cervical posterior longitudinal ligament fibroblasts in response to in vitro mechanical stretch].

OBJECTIVE: To investigate the effect of mechanical stretch force on the morphologic and apoptotic changes of fibroblasts derived from the OPLL (ossification of posterior longitudinal ligaments) patients. METHODS: The third passage cells were collected and subjected to 10% elongations cyclic mechanical stretching for 6 h and 24 h with Flexercell 4000(TM) strain unit. Their morphologic changes were observed and the post-stretching apoptotic rates quantified by flow cytometer. The gene expressions of alkaline phosphatase (ALP), collagen types I (COL I) and osteocalcin (OC) were examined. RESULTS: The treated cells were arranged along the vertical direction of force. Stretch force led to a slight increase of apoptosis rate at 6 h and a significant increase of apoptosis rate at 24 h. No significant difference in cellular senescence was observed between control group and treated group. The mRNA expressions of ALP, COL I and OC were positively up-regulated by cyclic stretch at 24 h. CONCLUSION: Stretching force can affect the cellular morphology, promote the osteogenic differentiation and enhance the cellular apoptosis.

[The Factors Related to Treatment Failure in Children with Acute Lymphoblastic Leukemia].

OBJECTIVE: To analyze the efficacy of CCLG-ALL-2008 protocol and the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 400 children newly-diagnosed ALL in Children's Hospital of Soochow University from March 1, 2008 to December 31, 2012 was retrospectively analyzed. All the children accepted CCLG-ALL-2008 protocol, and were followed-up until October 2019. The dates of relapse, death and causes of death were recorded. Treatment failure was defined as relapse, non-relapse death, and secondary tumor. RESULTS: Following-up for 10 years, there were 152 cases relapse or non-relapse death, the treatment failure rate was 38%, including 122 relapse (80.3%), 30 non-relapse deaths (19.7%) which included 7 cases (4 cases died of infection and 3 cases died of bleeding) died of treatment (23.3% of non-relapse deaths), 8 cases died of minimal residual disease (MRD) continuous positive (26.7% of non-relapse deaths) and 15 cases died of financial burden (50% of non-relapse deaths). According to the relapse stage, 37 cases (30%) in very early stage, 38 cases (31%) in early stage, and 47 cases (39%) in late stage, while according to the relapse site, 107 cases relapsed in bone marrow, 3 cases in testis, 3 cases in central nervous system (CNS), 5 cases in bone marrow plus testis and 4 cases in bone marrow plus CNS. Bone marrow relapse was the main cause of death in 89 cases, followed by nervous system. Initially diagnosed WBC count (≥50×109/L), T-cell immunophenotype, and MRD-positive at week 12 were the independent risk prognostic factors for relapse in children with ALL, while age (≥10 years), initially diagnosed WBC count (≥50×109/L), M3 bone marrow on day 15, and MRD-positive at week 12 were the independent risk factors due to treatment failure. No secondary tumors were found during the follow-up for 10 years. CONCLUSION: Relapse is the main cause of treatment failure in children with ALL. The initially diagnosed WBC count, immunophenotype and MRD at week 12 were the independent prognostic factors for relapse of the patients. Financial burden accounts for a large proportion of non-relapse death.

The significance of detecting WT1 expression in childhood acute leukemias.

WT1 (Wilms' tumor gene 1) overexpression is implicated in the prognosis of acute leukemia. The purpose of this study was to investigate WT1 expression and its clinical implication in childhood acute leukemia (AL) in Chinese population. Bone marrow specimen from 200 children at different stages of acute leukemia and from 21 children without leukemia were studied. The WT1 expression at diagnostic marrow specimen in both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) was higher than control group, whereas WT1 expression in AML was higher than in ALL, and WT1 expression level in relapse in ALL increased more significantly than in AML. The WT1 expression level showed positive correlation with the hypodiploidy and BCR-ABL fusion gene in acute leukemia. A rapidly decrease of WT1 expression level predicted a good response to the induction therapy and low expression of WT1 correlates with remission status. This study suggested that WT1 expression levels in acute leukemia can potentially be a marker for evaluating therapeutic efficacy, correlating with monitoring minimal residue disease, and predicting hematological relapse in children acute leukemia.