A nomogram-based predictive model for tooth survival in Chinese patients with periodontitis: An 11-year retrospective cohort study.

AIM: To develop a nomogram-based predictive model of tooth survival by comprehensively analysing clinical and radiographic risk factors of tooth loss (TL). MATERIALS AND METHODS: In this study, 3447 teeth of 131 subjects who underwent non-surgical periodontal treatment were examined retrospectively within a mean follow-up period of 11.6 years. The association of risk factors including clinical and radiographic parameters with TL was assessed using univariate and multivariate Cox regression analyses. A nomogram-based predictive model was developed, and its validation and discriminatory ability were analysed. RESULTS: In all, 313 teeth were lost in 94 patients in this study (overall tooth loss [OTL] 9.08%; 0.21 teeth/patient/year). Male, heavy smoking, molar teeth, probing depth (PD), attachment loss (AL), tooth mobility and radiographic bone loss were significantly associated with TL (p < .05). A gradient effect of tooth mobility on TL increased from degree I to III versus none (p < .0001). The area under the curve (AUC) of the model was 0.865. Calibration curve and decision curve analysis demonstrated good performance and high net benefit, respectively. CONCLUSIONS: Adopting a specific nomogram could facilitate the prediction of tooth survival and the development of tailored treatment plans in Chinese patients with advanced periodontitis.

Development and international validation of logistic regression and machine-learning models for the prediction of 10-year molar loss.

AIM: To develop and validate models based on logistic regression and artificial intelligence for prognostic prediction of molar survival in periodontally affected patients. MATERIALS AND METHODS: Clinical and radiographic data from four different centres across four continents (two in Europe, one in the United States, and one in China) including 515 patients and 3157 molars were collected and used to train and test different types of machine-learning algorithms for their prognostic ability of molar loss over 10 years. The following models were trained: logistic regression, support vector machine, K-nearest neighbours, decision tree, random forest, artificial neural network, gradient boosting, and naive Bayes. In addition, different models were aggregated by means of the ensembled stacking method. The primary outcome of the study was related to the prediction of overall molar loss (MLO) in patients after active periodontal treatment. RESULTS: The general performance in the external validation settings (aggregating three cohorts) revealed that the ensembled model, which combined neural network and logistic regression, showed the best performance among the different models for the prediction of MLO with an area under the curve (AUC) = 0.726. The neural network model showed the best AUC of 0.724 for the prediction of periodontitis-related molar loss. In addition, the ensembled model showed the best calibration performance. CONCLUSIONS: Through a multi-centre collaboration, both prognostic models for the prediction of molar loss were developed and externally validated. The ensembled model showed the best performance in terms of both discrimination and validation, and it is made freely available to clinicians for widespread use in clinical practice.

Analysis of factors influencing the organizational capacity of Institutional Review Boards In China: a crisp-set Qualitative Comparative Analysis based on 107 cases.

BACKGROUND: Institutional Review Boards (IRBs) play a vital role in safeguarding the rights and interests of both research participants and researchers. However, China initiated the establishment of its own IRB system relatively late in comparison to international standards. Despite commendable progress, there is a pressing need to strengthen the organizational capacity building of Chinese IRBs. Hence, this study aims to analyze the key factors driving the enhancement of organizational capacity within these committees. METHOD: The cross-sectional survey for this research was conducted from July 2020 to January 2022. Following the statistical grouping based on the "2020 China Health Statistical Yearbook", a systematic investigation of IRBs in various provinces of China was carried out. In-depth interviews and questionnaire surveys were conducted with the chairpersons and administrative executives (or secretaries) of highly cooperative IRBs. Subsequently, data were collected from 107 IRBs. Qualitative Comparative Analysis (QCA) was employed as the method to analyze the factors influencing the organizational capacity of medical ethics committees and explore the diverse combinations of these factors. RESULTS: Through a singular necessary condition analysis, the variable "protection of rights and interests" emerges as a critical factor contributing to the robust construction of Institutional Review Boards Institutional Review Boards (IRBs). Conversely, the variables of "lack of member ability, absence of review process, and deficiency in the supervision mechanism" collectively constitute a sufficient condition leading to weaker IRB construction. The state analysis uncovers three interpretation modes: member ability-oriented (M1), system process-oriented mode (M2), and resource system-oriented mode (M3). CONCLUSIONS: The results of this study are effectively explicable using the "Triangular Force" model proposed for the hypothesis of IRBs' organizational capacity, which provides a solid foundation for the development of organizational capabilities in IRBs. To enhance the organizational capacity of IRBs in China, it is imperative to elevate the competence of committee members and strengthen team development. This can be achieved by establishing a comprehensive regulatory framework and refining procedural protocols. Moreover, clarifying the organizational structure and optimizing resource allocation are essential steps in bolstering the overall organizational capabilities of these committees.

A nomogram prediction for mandibular molar survival in Chinese patients with periodontitis: A 10-year retrospective cohort study.

AIMS: To develop a nomogram prediction model of mandibular molar survival by comprehensively analysing clinical and radiographic risk factors of mandibular molar loss. MATERIALS AND METHODS: Four hundred and seventy-eight mandibular molars of 139 subjects who underwent non-surgical periodontal treatment were examined retrospectively within a mean follow-up period of 11.1 years. The association of risk factors including clinical and radiographic parameters with mandibular molar loss was assessed using univariate and multivariate Cox regression analyses. A nomogram prediction model was developed, and the validation and discriminatory ability of it were analysed. RESULTS: Hundred and four molars were lost in this study. Probing depth (PD), attachment loss (AL), furcation involvement (FI), bleeding on probing (BOP), tooth mobility and radiographic bone loss were significantly associated with tooth loss (p < .01). A gradient effect of degree of FI on mandibular molar loss existed increasing from degree Ⅱ (HR = 2.37, 95% CI: 1.48, 3.79) to Ⅲ (HR = 5.61, 95% CI: 3.01, 10.45) versus none & degree Ⅰ. The area under the curve (AUC) of the model was 0.891. The calibration curve and decision curve analysis demonstrated good performance and high net benefit of nomogram, respectively. CONCLUSIONS: A specific nomogram could be adopted to predict the mandibular molar survival and formulate tailored treatment plans in Chinese.

Minimal Residual Disease-guided Risk Restratification and Therapy Improves the Survival of Childhood Acute Lymphoblastic Leukemia: Experience From a Tertiary Children's Hospital in China.

The minimal residual disease (MRD) has been shown to be very important to evaluate the prognostic significance in childhood acute lymphoblastic leukemia (ALL), but the impact under the current treatment protocol in China has not been fully elucidated. The aim of this study was to investigate the efficacy of MRD-guided risk restratification of ALL. A total of 676 children with ALL were enrolled. In the predictive study group, 476 patients were enrolled with 5-year cumulative incidence of relapse rates of the low-risk (LR), intermediate-risk (IR), and high-risk groups being 11.0%±2.3%, 12.6%±3.3%, and 32.7%±4.9%, respectively. In the intervention study group, 19/200 patients enrolled were reclassified into risk groups according to the MRD levels. The 3-year event-free survival and overall survival were 85.2%±2.9% and 90.6%±2.1%, respectively, which were higher than those of the predictive study group (79.1%±1.9% and 84.7%±1.7%, respectively; P<0.05). The 3-year cumulative incidence of relapse in the LR and IR groups of the intervention study group were 4.2%±3.1% and 6.4%±3.1%, respectively, which were significantly lower than those in the predictive study group (7.2%±1.8% and 11.8%±3.2%, respectively; P<0.05). We conclude that the risk of relapse in the LR and IR groups can be significantly reduced after MRD-guided risk restratification.

Corticosteroid administration is associated with improved outcome of patients presenting high inflammatory cytokine levels during septic shock.

BACKGROUND: This study aimed to investigate the corticosteroid effects on pediatric hematology/oncology patients with septic shock. PROCEDURE: We performed a retrospective study by examining data from a prospective observational study in pediatric hematology/oncology patients with septic shock. We compared the clinical features and the outcomes of the patients treated with and without corticosteroid. RESULTS: One hundred episodes of septic shock were recorded in this study. The 28-day mortality of this cohort was 14.0%. Sixty-eight episodes of shock were treated with corticosteroids while 32 were not. The demographic features and disease severity were comparable between patients with and without corticosteroid treatment. Corticosteroid therapy was associated with improved shock reversal rate (92.6% vs. 78.1%, P = 0.049) and decreased 28-day mortality rate (8.8 ± 3.4% vs. 25.0 ± 7.7%, P = 0.032) in univariate analysis. For patients who received vasopressor support, corticosteroid therapy was associated with shortened duration of vasopressor infusion in univariate analysis as well (median: 44 hour vs. 92 hour, P = 0.035). In multivariate analysis, corticosteroid therapy did not show significant impact on the outcome for the whole cohort (HR = 0.36, P = 0.079), but it decreased the 28-day mortality of patients presenting high inflammatory cytokine levels (HR = 0.29, 95% CI, 0.09-0.95, P = 0.040). Corticosteroid administration did not increase the superinfection rate (24.2% vs. 8.3%, P = 0.134) and did not result in superinfection-related death in this cohort. CONCLUSIONS: Corticosteroid administration is associated with improved outcome in pediatric hematology/oncology patients presenting high inflammatory cytokine levels during septic shock. Pediatr Blood Cancer 2014;61:2243-2248. © 2014 Wiley Periodicals, Inc.

A multiplex cytokine score for the prediction of disease severity in pediatric hematology/oncology patients with septic shock.

Although many inflammatory cytokines are prognostic in sepsis, the utility of cytokines in evaluating disease severity in pediatric hematology/oncology patients with septic shock was rarely studied. On the other hand, a single particular cytokine is far from ideal in guiding therapeutic intervention, but combination of multiple biomarkers improves the accuracy. In this prospective observational study, 111 episodes of septic shock in pediatric hematology/oncology patients were enrolled from 2006 through 2012. Blood samples were taken for inflammatory cytokine measurement by cytometric bead array (CBA) technology at the initial onset of septic shock. Interleukin (IL)-6 and IL-10 were significantly elevated in majority of patients, while tumor necrosis factor (TNF)-α and interferon (IFN)-γ were markedly increased in patients with high pediatric index of mortality 2 (PIM2) score and non-survivors. All the four cytokines paralleled the PIM2 score and differentially correlated with hemodynamic disorder and fatal outcomes. The pediatric multiplex cytokine score (PMCS), which integrated the four cytokines into one score system, was related to hemodynamic disorder and mortality as well, but showed more powerful prediction ability than each of the four cytokines. PMCS was an independent predictive factor for fatal outcome, presenting similar discriminative power with PIM2, with accuracy of 0.83 (95% CI, 0.71-0.94). In conclusion, this study develops a cytokine scoring system based on CBA technique, which performs well in disease severity and fatality prediction in pediatric hematology/oncology patients with septic shock.

Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children.

OBJECTIVE: The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic lymphohistiocytosis (HLH) in febrile children. STUDY DESIGN: In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques. RESULTS: Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%. CONCLUSIONS: The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.

Th1/Th2 cytokine profiles in G+/G- bacteremia in pediatric hematology/oncology patients.

BACKGROUND: Early diagnosis of infection and appropriate choice of antibiotics are essential not only to improve the prognosis of the patients but also to prevent from the abuse of the antibiotics in hematology/oncology children at the time of neutropenia after intensive chemotherapy. PROCEDURE: We evaluated the quantification of Th1/Th2 cytokines with flow cytometry bead assay (CBA) in 145 hospitalized febrile hematology/oncology children with positive blood culture to seek for a rapid diagnostic method to determine the type of infection. RESULTS: IL-4, IL-6, IL-10, TNF-α, and IFN-γ levels from both G- and G+ bacteremia groups were significantly higher than those of controls (P < 0.001). The median levels of IL-6, IL-10, TNF-α of Group G- were 525.4, 96.0, and 6.9 pg/ml, respectively, significantly higher than those of Group G+ (150.0, 22.6, and 4.5 pg/ml, respectively, P < 0.001). According to the different degrees of increased IL-6 and IL-10 levels, we named the G- bacterial infection related cytokine profile G- BIRCP and the G+ BIRCP. The specificity and sensitivity of BIRCP prediction for G- and G+ bacteria cultures were 60.2% and 75.4%, 66.8% and 70.1%, respectively. Similar therapeutic efficacy was achieved between BIRCP-based and broad-spectrum antibiotics groups (86.1% vs. 89.3%, P > 0.05), which was significantly increased as compared with that (65.5%, P < 0.05) of empirical group. CONCLUSIONS: These results showed the promising use of the IL-6/IL-10/TNF-α determination with CBA technology for the early and rapid diagnosis, evaluation of G+/G- bacteremia in pediatric hematology/oncology patients.

A missense mutation in the VHYNP motif of a DELLA protein causes a semi-dwarf mutant phenotype in Brassica napus.

Although dwarf genes have been widely used to improve lodging resistance and enhance harvest index in cereal crops, lodging is still a serious problem in rapeseed (Brassica napus) production. A semi-dwarf B. napus mutant, ds-1, was identified through EMS mutagenesis of a microspore-cultured DH line. The mutant had a significant reduction in height due to a lower first branch position and shorter internodes when compared with wild-type cultivars. This dwarfism was inherited as a single semi-dominant gene, ds-1. DS-1 locus was mapped to chromosome A6, and co-segregated with a microsatellite marker BnEMS1125 derived from the gene BnRGA. BnRGA encodes a DELLA protein that functions as a GA signaling repressor. The expression of a mutant BnRGA allele from ds-1, Bnrga-ds, caused dwarf phenotypes in Arabidopsis. Comparative sequencing of RGA open-reading frames (ORFs) of ds-1 and wild-type cultivars revealed a single proline (P)-to-leucine (L) substitution that may lead to a gain-of-function mutation in GA signaling. The expression of the Arabidopsis homolog, Atrga-ds, bearing this site-directed mutation also rendered dwarf phenotypes in Arabidopsis, which demonstrated that the P-to-L mutation in the VHYNP motif of Bnrga-ds is responsible for the dwarfism. A yeast two-hybrid assay confirmed that this mutation inhibited the interaction between Bnrga-ds/Atrga-ds and the GA receptor, AtGID1A, in the presence of GA(3), suggesting that the conserved proline residue in the VHYNP motif of DELLA protein directly participates in DELLA-GID1 interaction. Identification and characterization of the dwarf gene ds-1 will facilitate its utilization in improving lodging resistance in Brassica breeding.

Influence of local anesthesia on the outcomes of non-surgical periodontal treatment.

BACKGROUND: There is limited evidence of the effects of local anesthesia (LA) on outcomes of non-surgical periodontal treatment (NSPT), in particular among the Chinese. This retrospective cohort study aimed to evaluate the effects of LA on short-term treatment outcomes of NSPT and to determine under what circumstances LA should be prescribed to improve these outcomes. METHODS: Data from periodontal examinations of 3980 patients were used. The data were from 3-month re-evaluation records of an electronic periodontal charting record system in the Department of Periodontology of Peking University School and Hospital of Stomatology from June 2008 to January 2015. Descriptive analyses included changes in probing depth (PD) and the Mazza bleeding index (BI). Two-level (patient and tooth) logistic regression models and three-level (patient, tooth, and site) linear regression models were constructed to analyze the influence of LA on PD for all teeth/sites and teeth/sites with an initial PD ≥ 5 mm. Decreases in PD and BI at sites under LA using the initial PD were also compared. RESULTS: A significantly higher mean decrease in PD after NSPT was found in the LA group than in the no local anesthesia (NLA) group (0.98 vs. 0.54 mm, t = 24.12, P < 0.001). A significantly higher probability of decreases was found in the LA group in BI (percentages of teeth with BI > 1 and BI > 2) for all teeth (16.7% vs. 13.8%, t = 3.75, P < 0.001; 34.7% vs. 28.1%, t = 6.73, P < 0.001) and PD for teeth with PD ≥ 5 mm (32.3% vs. 17.3%, t = 28.48, P < 0.001). The difference in PD between the LA and NLA groups increased as the initial PD increased. The difference between the two groups was 0.12 to 0.22 mm for sites with a baseline PD < 7 mm; however, it increased to 0.41 to 1.37 mm for sites with a baseline PD ≥ 7 mm. CONCLUSIONS: LA improved the decrease in PD after NSPT. Root debridement at sites with initial PD ≥ 7 mm should be performed under routine LA.

Supertough and Transparent Poly(lactic acid) Nanostructure Blends with Minimal Stiffness Loss.

This contribution is an attempt to explore the effectiveness of a series of newly obtained thermoplastic elastomers (TPEs) as a toughening agent for modifying poly(lactic acid) (PLA). The TPEs, including ionically modified isotactic polypropylene-graft-PLA (iPP-g-PLA) copolymers with explicit graft length, graft density, and ionic group content, and an iPP-g-PLA copolymer with a very high molecular weight and explicit graft density, were elaborately designed and synthesized. The semicrystal or rubbery copolymer backbone originated from iPP was designed to improve the toughness and maintain a relatively high strength, while the grafted PLA side chain was to ensure a high level of compatibility with the PLA matrix. To obtain further enhancement in interfacial reinforcement, the imidazolium-based ionic group was also added during graft onto reaction. All of these graft copolymers were identified with randomly distributed PLA branches, bearing a very high molecular weight ((33-398) × 104) and very high PLA content (57.3-89.3 wt %). Unprecedentedly, with a very small amount of newly designed TPE, the modified PLA blends exhibited a significantly increased elongation at break (up to about 190%) and simultaneously retained the very high stiffness and excellent transparency. The nanometer-scale phase-separated particles with good compatibility and refractive index matching to the PLA matrix were demonstrated to play a crucial role in the excellent performance. The findings suggested that the newly designed iPP-g-PLA copolymers are very economic, promising, and effective modifying agents for developing highly transparent and tough PLA-based sustainable materials.

A Ruthenium Nitrosyl-Functionalized Magnetic Nanoplatform with Near-Infrared Light-Controlled Nitric Oxide Delivery and Photothermal Effect for Enhanced Antitumor and Antibacterial Therapy.

Developing a spatiotemporal-controlled nitric oxide (NO) delivery nanoplatform is highly desirable for its biological applications as a tumor inhibitor and antibacterial agent. In this study, a novel multifunctional magnetic nanoplatform {Fe3O4@PDA@Ru-NO@FA} (1) was developed for the near-infrared (NIR) light-controlled release of NO in which a ruthenium nitrosyl (Ru-NO) donor and a folic acid (FA)-directing group were covalently functionalized onto Fe3O4@PDA. Nanoplatform 1 preferentially accumulated in folate receptor-overexpressing cancer cell lines and magnetic field-guided tumor tissue, instantly released NO, and simultaneously produced a prominent photothermal effect upon 808 nm NIR light irradiation, leading to remarkable in vitro and in vivo antitumor efficacy. When nanoplatform 1 was treated only once, the potential MRI contrast agent was sufficient to significantly inhibit or eliminate the tumor tissues in living mice, thus offering opportunities for future NO-involved multimodal cancer therapy. In addition, a NO delivery nanoplatform {Fe3O4@PDA@Ru-NO} was imbedded in the matrix of a chitosan (CS)-poly(vinyl alcohol) (PVA) material to develop a hybrid thermosensitive CS-PVA/NO hydrogel. The CS-PVA/NO hydrogels demonstrated mild (<150 mW cm-2) NIR light-controlled NO delivery and thus produced an efficient antibacterial effect for both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Therefore, these hydrogels have potential as antibacterial dressings for wound bacterial infection treatment.

[Efficacy of chemotherapy using 10-hydroxycamptothecin on recurrent or refractory neuroblastoma in children].

OBJECTIVE: The patients with recurrent or refractory neuroblastoma have a very poor prognosis and high mortality. 10-hydroxycamptothecin (HCPT) is a new agent extracted from comptotheca acuminate, a native plant. It has been shown to be very effective in some solid tumors such as gastric and colon cancers, lung cancers and ovary cancers. However, its efficacy in neuroblastoma has not been determined. This study aimed to investigate the therapeutic effects of HCPT in the treatment of recurrent or refractory neuroblastoma in children. METHODS: Ten children with recurrent neuroblastoma and two children with refractory neuroblastoma were treated with HCPT. Of them, 5 children with recurrent neuroblastoma were treated with HCPT alone, and the other 7 patients received combination chemotherapy of HCPT plus other agents. The HCPT alone treatment group was injected with HCPT (7.5 mg/m2 daily) for 14 consecutive days. The combination chemotherapy group was alternately treated with the modified new protocol A1 (cyclophosomide 1 200 mg/m2 on day 1, etoposide 100 mg/m2 on days 1-5, HCPT 5 mg/m2 on days 1-3, cisplatin 90 mg/m2 on day 4) and the modified protocol B (ifosfomide 1.5 g/m2 on days 1-5, HCPT 5 mg/m2 on days 1-3, carboplatin 450 mg/m2 on day 2). RESULTS: Four patients (33.3%) achieved partial remission and 8 patients (66.7%) had stable disease. The median remission duration was 3.5 months (2-5 months). HCPT treatment as a single agent resulted in mild side effects. Myelosuppression and digestive disorders were found as the main adverse events in the combined chemotherapy group. No chemotherapy related deaths were found. CONCLUSIONS: HCPT is safe and effective in the treatment of recurrent or refractory neuroblastoma. The toxicities of HCPT are tolerable. The long-term efficacy of HCPT warrants further research.

Targeted and NIR light-controlled delivery of nitric oxide combined with a platinum(iv) prodrug for enhanced anticancer therapy.

This study reports a strategy of combining a Pt(iv) prodrug and a ruthenium nitrosyl (Ru-NO) donor into a single nanoplatform {N-GQDs@Ru-NO-Pt@FA} in which the platinum(iv) prodrug is conjugated onto a photoactivatable NO donor (Ru-NO) through a covalent bond and the nitric oxide-releasing platinum prodrug and folate groups are decorated on N-doped graphene quantum dots (N-GQDs). After cellular uptake of the nanoplatform, the platinum(iv) prodrug was reduced to an active anti-cancer Pt(ii) species inside the cancerous cells, and simultaneously, near-infrared (NIR) light illumination induced the release of NO, accompanied by a prominent photothermal effect. This nanoplatform is capable of targeting intracellular co-delivery of Pt(ii) and NO under 808 nm NIR light irradiation, accompanied by photothermal therapy, thereby leading to a significant synergistic therapeutic effect.

Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome.

The haemophagocytic syndrome (HPS) is a rare but frequently fatal disorder of immune regulation caused by hypercytokinemia. Using cytometric bead array technique, the serum T-helper cell type 1 (Th1) and 2 (Th2) cytokines including interferon-gamma (IFN-gamma), tumour necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 were determined in 24 children with de novo HPS and 87 children as control. The median levels of serum IFN-gamma, IL-10 and IL-6 in the acute phase of HPS were 901.7, 879.0 and 63.8 pg/ml, respectively, significantly higher than those after remission, and in the healthy volunteers and patients with viral infection. IL-4 was slightly elevated while IL-2 and TNF were within normal range in acute phase. Patients with bacterial sepsis showed an extremely high level of IL-6 and moderate level of IL-10, whereas IFN-gamma was only slightly elevated. Five patients were diagnosed with HPS according to the Th1/Th2 cytokine pattern 3-13 d earlier than they fulfilled the relevant diagnostic criteria. IL-10 level >2000 pg/ml was an unfavorable prognostic factor for HPS treatment response (P = 0.033) and outcome (P = 0.009). We conclude that the significant increase of IFN-gamma and IL-10 and a slightly increased level of IL-6 is an early, specific and prognostic cytokine pattern for childhood HPS.

Long-term outcome of childhood acute lymphoblastic leukemia treated in China.

BACKGROUND: To retrospectively determine the treatment outcome and causes of treatment failure of ALL children treated in a single institution at East China. PROCEDURE: Between January 1998 and October 2004, 346 newly diagnosed ALL patients

[Long-term follow-up of treatment outcome and prognosis on 46 children with acute promyelocytic leukemia].

OBJECTIVE: Acute promyelocytic leukemia (APL) is a specific type of hematopoietic malignancy, accounting for 10% of the de novo acute myeloid leukemia (AML). The data on long-term outcome of APL in children are limited. The aim of this study was to investigate the clinical biological features, diagnosis, prognosis and long-term survival of childhood APL. METHODS: A total of 46 children with newly diagnosed APL from April 1998 to October 2005 were enrolled into this study. Induction treatment containing all-trans retinoic acid (ATRA) plus daunorubicin (DNR) or pirarubicin (THP) was performed on these patients, followed by 6 courses of chemotherapy consolidation: DNR, homoharringtonine or etoposide plus Ara-C. A maintenance therapy was then administered once 3-6 months. The total period of treatment was 2.5 years. RESULTS: Of the 39 patients who had completed the regular treatment, 36 (92.3%) achieved a complete remission. The 5-year cumulative incidence of relapse (CIR) was 28.6%. The estimated overall survival (OS) rates at 1, 3 and 5 years were (86.1 +/- 5.8)%, (76.1 +/- 7.5)% and (70.2 +/- 8.9)% respectively, while the event free survival (EFS) rates were (78.4 +/- 6.8)%, (63.6 +/- 8.7)% and (53.1 +/- 10.0)% respectively. The 5-year OS rate of patients with WBC less than or equal to 10.0 X 10(9)/L was (81.4 +/- 10.3)%, which was significantly higher than that with WBC greater than 10.0 X 10(9)/L[(51.6 +/- 14.7)%, P < 0.05]. Five patients with RT-PCR positive for PML/RARalpha S (short) subtype died eventually although all of them achieved CR, but none of the 13 patients with PML/RARalpha L (long) subtype died. CONCLUSIONS: Remission induction therapy with ATRA + DNR or THP is effective and safe for newly diagnosed childhood APL. The remission induction therapy combined with chemotherapy containing high/intermediate dose Ara-C can improve the long-term survival rates of APL patients. High WBC count and S subtype of PML-RARa are two poor prognostic factors for children with APL.

A ruthenium-nitrosyl-functionalized nanoplatform for the targeting of liver cancer cells and NIR-light-controlled delivery of nitric oxide combined with photothermal therapy.

The development of light-controlled nitric oxide (NO)-releasing nanoplatforms that are capable of specifically targeting liver cancer cell lines and delivering an optimal amount of NO can significantly affect liver cancer therapy. In this study, a multifunctional nanoplatform {N-GQDs@Ru-NO@Gal} (1) for the near-infrared (NIR) light-responsive release of NO, consisting of a NO donor (Ru-NO) and a liver-targeting galactose derivative (Gal) covalently attached to N-doped graphene quantum dots (N-GQDs), was reported. Nanoplatform 1 preferentially targeted liver cancer cells over normal cells and instantly released NO as well as exhibited a prominent photothermal effect upon NIR irradiation at 808 nm, thereby leading to efficient anti-tumor efficacy. {N-GQDs@Ru-NO@Gal} with a small size (<10 nm), good biocompatibility, and fluorescent-tracing properties represents a unique example of a multifunctional NO-releasing nanoplatform that combines photodynamic and photothermal therapies for the targeted treatment of liver cancer. Hence, the developed nanoplatform demonstrates potential for applications in NO-mediated multimodal phototherapy in the near future.

[Preparation and characterization of a directly labeled mouse anti-human CD14 monoclonal antibody ZCH-2F9-FITC].

OBJECTIVE: To prepare fluorescein isothiocyanate (FITC) directly conjugated to monoclonal antibody (McAb) anti-human CD14, ZCH-7-2F9 (2F9-FITC). METHODS: After generation and purification, the purity and the murine immunoglobulin subtype of the antibody were evaluated with SDS-PAGE and multicolor flow cytometry (FCM). 2F9 McAb was directly labeled with FITC through modified Marsshall's method and the positive rate of the 2F9-FITC on different types of leukemic cells were compared with the standard CD14-FITC by FCM. RESULT: A large quantity of purified 2F9 McAb was prepared. The subtype of 2F9 was murine IgG1kappa. 2F9-FITC was successfully manufactured with A295/A280 ratio of 0.44. The positive cell percentages of 2F9-FITC and CD14-FITC on the monocytes were 84.50% and 90.08%, respectively, while those on lymphocytes were only 0.52% and 1.01%. There was no significant difference between the CD14 expressions with 2F9-FITC and CD14-FITC on each type of leukemia (n=23, t=0.922, P=0.367). CONCLUSION: 2F9-FITC has been successfully prepared and it can be applied in diagnosis and differentiation of monoblastic leukemias.