Risk of fall in patients with chronic kidney disease: results from the China health and retirement longitudinal study (CHARLS).

BACKGROUND: Chronic kidney disease (CKD), often coexisting with various systemic disorders, may increase the risk of falls. Our study aimed to assess the prevalence and risk of falls among patients with CKD in China. METHODS: We included patients with/without CKD from China Health and Retirement Longitudinal Study (CHARLS). Our primary outcome was the occurrence of fall accidents within the past 2 years. To enhance the robustness of our findings, we employed a multivariable logistic regression model, conducted propensity score analysis, and applied an inverse probability-weighting model. RESULTS: A total of 12,658 participants were included, the prevalence of fall accident rates were 17.1% (2,028/11,837) among participants without CKD and 24.7% (203/821) among those with CKD. In the inverse probability-weighting model, participants with CKD exhibited higher fall accident rates (OR = 1.28, 95% CI: 1.08-1.53, p = 0.005 ). Sensitivity and subgroup analysis showed the results still stable. CONCLUSIONS: The population in China afflicted with CKD has a significantly heightened risk of experiencing falls, underscoring the crucial importance of intensifying efforts in assessing and preventing fall risks.

Prognostic implications of CD9 in childhood acute lymphoblastic leukemia: insights from a nationwide multicenter study in China.

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1+ rather than KMT2A-rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL.

Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

The association between dietary inflammatory index and cognitive function in adults with/without chronic kidney disease.

Background and aims: Cognitive impairment (CI) is a prevalent condition in patients with chronic kidney disease (CKD), who face an elevated risk of developing cognitive decline. The fundamental mechanism underlying CI is linked to chronic inflammation, which can be gauged by the Dietary Inflammatory Index (DII). The DII is categorized into anti-inflammatory diets with lower scores and pro-inflammatory diets with higher scores. Specifically, pro-inflammatory diets may contribute to chronic inflammation. However, the correlation between the inflammatory potential of diet and cognitive function in patients with CKD has not been explored. This study aims to investigate the connection between the inflammatory potential of diet and cognitive function in individuals with or without chronic kidney disease. Methods: Data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey (NHANES) were utilized. Participants under the age of 60 or lacking DII, CI, CKD, and other essential data were excluded. DII was computed based on a 24-h dietary recall interview for each participant. Cognitive performance was evaluated using three cognitive tests: the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, the Animal Fluency Test (AFT), and the Digital Symbol Substitution Test (DSST). Logistic regression analysis and subgroup analysis were conducted to assess the independent relationship between DII score and CI in the CKD and non-CKD populations. Results: The study included a total of 2069 subjects, with CI prevalence ranging from 21.4 to 23.5%. Multiple regression models showed that after adjusting for all covariates of the three cognitive function tests, higher DII scores were significantly associated with increased risk of CI (CERAD OR = 1.18, 95% CI: 1.1 ~ 1.26, AFT OR = 1.15, 95% CI: 1.08 ~ 1.23, DSST OR = 1.19, 95% CI: 1.11 ~ 1.28). Subgroup analysis indicated that the effect of DII score on CI remained consistent in all subgroups (p > 0.05). Conclusion: Higher DII scores were associated with an increased risk of cognitive impairment in people with or without CKD, suggesting that consuming a pro-inflammatory diet may contribute to the impairment of the cognitive function.

Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

PURPOSE: Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS: This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS: We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION: HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Sulfur-decorated Fe/C composite synthesized from MIL-88A(Fe) for peroxymonosulfate activation towards tetracycline degradation: Multiple active sites and non-radical pathway dominated mechanism.

Peroxymonosulfate (PMS)-mediated advanced oxidation processes gain growing attention in degrading antibiotics (e.g., tetracycline (TC)) in wastewater for their high capacity and relatively low cost, while designing efficient catalysts for PMS activation remains a challenge. In this study, a sulfur-doped Fe/C catalyst (Fe@C-S) synthesized from iron metal-organic frameworks (Fe-MOFs) was developed for PMS activation towards TC removal. Under optimal conditions, the TC removal efficiency of Fe@C-S150/PMS system within 40 min was 91.2%. Meanwhile, the k value for Fe@C-S150/PMS system (0.2038 min-1) was 3.36-fold as high as the S-free Fe@C-based PMS system. Also, Fe@C-S150/PMS system showed high robustness in different water matrices. Further studies found that the TC degradation mechanism was mainly ascribed to the non-radical pathway (1O2 and electron transfer). Fe nanoparticles, S and CO groups on the catalyst all participated in the generation of reactive oxygen species (ROS). Besides, S species could enhance the Fe2+/Fe3+ redox cycle and accelerate the electron transfer process. This work highlights the critical role of S in enhancing the catalytic performance of Fe/C-based catalysts for PMS activation, which would provide meaningful insights into the design of high-performance PMS activators for the sustainable remediation of emerging contaminants-polluted water bodies.

Muramyl dipeptide CD10 monoclonal antibody immunoconjugates inhibited acute leukemia in nude mice.

Minimal residual disease (MRD) is one of the causes of leukemia recurrence. Previously, we developed anti-CD10 mAb conjugated to muramyl dipeptide immunoconjugate (MDP-Ab) for immune enhancement. The present study aimed to investigate anti-leukemia effect of MDP-Ab administered via different methods in leukemia ectopic graft nude mouse model. BALB/c nude mice were injected with Nalm-6 cells subcutaneously to establish leukemia xenografts in nude mice as a model. MDP-Ab or/and human lymphocytes (LYM) was injected into different sites of the nude mice. Immunohistochemistry staining of CDs in the bone marrow, liver and spleen was performed. IFN-γ was detected by ELISA. We detected the metastasis of leukemia cells to the liver, spleen and bone marrow in nude mouse leukemia model. MDP-Ab and LYM inhibited the growth of tumors, and simultaneous injection of MDP-Ab and LYM into the tumor inhibited the growth of tumors. IFN-γ levels in MDP-Ab (ca) + h-LYM (ca) group, MDP-Ab (ca) + h-LYM (ip) group, MDP-Ab (iv) + h-LYM (ip) group and PBS (ca) + h-LYM (ca) group were significantly higher than those in control group, while IFN-γ level in MDP-Ab (ca) + h-LYM (ca) group was the highest. Moreover, MDP-Ab and h-LYM promoted the expression of hCD4 and hCD8, with the highest expression in MDP-Ab (ca) + h-LYM (ca) group. In conclusion, MDP-Ab effectively promoted the production of IFN-γ, enhanced the antitumor immunity of T lymphocytes and inhibited leukemia.

Spontaneous FeIII/FeII redox cycling in single-atom catalysts: Conjugation effect and electron delocalization.

The mechanism of spontaneous FeIII/FeII redox cycling in iron-centered single-atom catalysts (I-SACs) is often overlooked. Consequently, pathways for continuous SO4 ·-/HO⋅ generation during peroxymonosulfate (PMS) activation by I-SACs remain unclear. Herein, the evolution of the iron center and ligand in I-SACs was comprehensively investigated. I-SACs could be considered as a coordination complex created by iron and a heteroatom N-doped carbonaceous ligand. The ligand-field theory could well explain the electronic behavior of the complex, whereby electrons delocalized by the conjugation effect of the ligand were confirmed to be responsible for the FeIII/FeII redox cycle. The possible pyridinic ligand in I-SACs was demonstrably weaker than the pyrrolic ligand in FeIII reduction due to its shielding effect on delocalized π orbitals by local lone-pair electrons. The results of this study significantly advance our understanding of the mechanism of spontaneous FeIII/FeII redox cycling and radical generation pathways in the I-SACs/PMS process.

A prospective multicenter study on varicella-zoster virus infection in children with acute lymphoblastic leukemia.

Background and methods: The study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL) using data from the multicenter Chinese Children's Cancer Group ALL-2015 trial. Results: In total, 7,640 patients were recruited, and 138 cases of VZV infection were identified. The incidence of VZV infection was higher in patients aged ≥ 10 years (22.5%) and in patients with the E2A/PBX1 fusion gene (11.6%) compared to those aged < 10 years (13.25%, P = 0.003) or with other fusion genes (4.9%, P = 0.001). Of the 10 deaths in children with ALL and VZV infection, 4 resulted from VZV complications. The differences between groups in the 5-year overall survival, event-free survival, cumulative recurrence, and death in remission were not statistically significant. The proportion of complex infection was higher in children with a history of exposure to someone with VZV infection (17.9% vs. 3.6%, P = 0.022). Conclusion: VZV exposure was associated with an increased incidence of complex VZV infection and contributed to VZV-associated death in children with ALL.

Ultraviolet Radiation Promoted Hypoxia-Induced Apoptosis in HL-60 Human Promyelocytic Leukemia Cell Line.

Minimal residual disease (MRD) is an important reason for the failure of autologous hematopoietic stem cell transplantation (auto-HSCT). Reducing MRD in grafts is particularly important to improve the efficacy of auto-HSCT. Previously, we reported that ultraviolet light-emitting diode (UV LED) suppressed the expression of Bcl-2 to induce apoptosis in HL-60 cells. Leukemia can lead to severe hypoxia of the bone marrow. Therefore, this study aimed to investigate the effect of UV LED on leukemia cells under hypoxia. HL-60 cells were irradiated with a UV LED (30 J/m2) and simulated under hypoxia with cobalt chloride. We found that UV LED irradiation or CoCl2 inhibited proliferation, induced apoptosis, decreased the Bcl-2/Bax ratio, and increased the levels of caspase 3, cleaved-caspase 3, and caspase 9 in HL-60 cells. In particular, the combined application of UV and CoCl2 significantly enhanced the apoptosis of HL-60 cells. In conclusion, UV LED in hypoxia exacerbated the inhibition of proliferation and induction of apoptosis and necrosis in HL-60 cells via the regulation of caspase 3/9 and the Bcl-2/Bax ratio-dependent pathway. The application of UV LEDs in hypoxia conditions may be a promising approach to kill residual drug-resistant leukemia cells in autologous grafts.

Tyrosine Kinase Inhibitors for Pediatric Leukemia: History and Current Status.

Tyrosine kinase inhibitors (TKIs) block the activity of tyrosine kinases by competitive inhibition of ATP at the catalytic tyrosine kinase binding site and inhibit oncogenic signaling. One important target of TKIs is BCR-ABL1, which is constitutively activated in leukemia cells. In this review, we briefly describe the development of TKIs from the first generation to the third generation, and summarize their use in the treatment of chronic myeloid leukemia and acute lymphoblastic leukemia in children. We highlight several future directions in the development of TKIs for pediatric leukemia therapy. In conclusion, we focus on chronic myeloid leukemia and acute lymphoblastic leukemia as the examples of pediatric blood cancer that significantly benefit from TKIs-based target therapy. Further development of TKIs will allow us to better manage pediatric leukemia.

2D/1D BiOI/g-C3N4 nanotubes heterostructure for photoelectrochemical overall water splitting.

To boost the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performances, the BiOI/graphitic carbon nitride nanotubes (g-C3N4 nanotubes) heterojunction was synthesized herein through the hydrothermal method. BiOI in-situ grew on the surface of g-C3N4 nanotubes derived from melamine. The rapid recombination between photoexcited electrons and holes of pristine semiconductors was prevented via building the stable heterojunction. The SEM results indicated that the BiOI was wrapped around the surface of g-C3N4 nanotubes, resulting in an optimized electronic transmission pathway. Much lower charge transfer resistance at the p-n heterojunction was demonstrated compared with pristine BiOI according to the EIS results, thus leading to the faster surface reaction rates. Moreover, the composite exhibited both outstanding OER and HER activities under illuminated conditions. This study may shed light upon establishing a bifunctional photoelectrocatalysis for photoelectrochemical water splitting based on stable 2D metal and 1D metal-free nanocomposite.

[Establishment of An Animal Model of Acute B Lymphoblastic Leukemia with Minimal Residual Disease].

OBJECTIVE: To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease. METHODS: The transplanted tumor was formed by subcutaneous injection of 2×107 Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis. RESULTS: There were 2×107 Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections. CONCLUSION: The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.

Chain Mediation Model of Perceived Stress, Resilience, and Social Support on Coping Styles of Chinese Patients on Hemodialysis During COVID-19 Pandemic Lockdown.

BACKGROUND The recurrence of COVID-19 and the continuous escalation of prevention and control policies can lead to an increase in mental health problems. This study aimed to investigate the perceived stress, coping style, resilience, and social support among patients on maintenance hemodialysis (MHD) during the COVID-19 epidemic lockdown in China. MATERIAL AND METHODS This cross-sectional observational study enrolled 197 patients on MHD from the Guangdong Province Traditional Chinese Medical Hospital and the Hedong Hospital of Guangzhou Liwan District People's Hospital during July 2021. AMOS 24.0 and PROCESS Macro 3.1 model 6 were used for analyses of moderating mediating effects. RESULTS Perceived stress was negatively correlated with positive coping style (r=-0.305, P<0.001) and resilience (r=-0.258, P<0.001), whereas resilience (r=0.631, P<0.001) and social support (r=0.300, P<0.001) were positively correlated with positive coping style among patients on MHD. In the moderated mediating model, perceived stress had significant direct predictive effects on positive coping style (95% CI -0.33, -0.07), and perceived stress had significant indirect predictive effects on positive coping styles through resilience (95% CI -0.26, -0.06) or social support (95% CI 0.01, 0.06). Perceived stress had significant indirect predictive effects on positive coping style through both resilience and social support (95% CI -0.04, -0.01). CONCLUSIONS Perceived stress not only predicted coping style directly, but also indirectly predicted coping style through resilience and social support. Coping style was affected by internal and external factors during the COVID-19 pandemic lockdown period.

Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study.

Introduction: Whether steroid response is an independent risk factor for acute lymphoblastic leukemia (ALL) is controversial. This study aimed to investigate the relationship between response to dexamethasone and prognosis in children with ALL. Methods: We analyzed the data of 5,161 children with ALL who received treatment in accordance with the Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015, and December 31, 2018, in China. All patients received dexamethasone for 4 days as upfront window therapy. Based on the peripheral lymphoblast count on day 5, these patients were classified into the dexamethasone good response (DGR) and dexamethasone poor response (DPR) groups. A peripheral lymphoblast count ≥1× 109/L indicated poor response to dexamethasone. Results: The age, white blood cell counts, prevalence of the BCR/ABL1 and TCF3/PBX1 fusion genes, and rates of recurrence in the central nervous system were higher in the DPR than in the DGR group (P<0.001). Compared to the DPR group, the DGR group had a lower recurrence rate (18.6% vs. 11%) and higher 6-year event-free survival (73% vs. 83%) and overall survival (86% vs. 92%) rates; nevertheless, subgroup analysis only showed significant difference in the intermediate-risk group (P<0.001). Discussion: Response to dexamethasone was associated with an early treatment response in our study. In the intermediate-risk group, dexamethasone response added a prognostic value in addition to minimal residual disease, which may direct early intervention to reduce the relapse rate.

[Effect of ultraviolet irradiation on the proliferation of acute promyelocytic leukemia cells under hypoxic conditions and related mechanisms].

OBJECTIVE: To study the effect of 280 nm-LED ultraviolet irradiation on the proliferation of acute promyelocytic leukemia (APL) HL-60 cells under hypoxic conditions and related mechanism. METHODS: HL-60 cells in the logarithmic growth phase were selected and divided into control, hypoxia, ultraviolet and hypoxia+ultraviolet groups. The cells in the hypoxia group were treated with cobalt chloride (with a final concentration of 150 µmol/L), those in the ultraviolet group were irradiated by 280 nm-LED ultraviolet with an energy intensity of 30 J/m2, and those in the hypoxia+ultraviolet group were treated with cobalt chloride and then irradiated by 280 nm-LED ultraviolet. After 48 hours of treatment, the cells were placed under an invert microscope to observe cell morphology. CCK-8 assay was used to measure the inhibition rate of cell proliferation. Annexin V-FITC/PI double staining flow cytometry was used to evaluate cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression of Bcl-2. Each experiment above was repeated three times independently. RESULTS: Compared with the control group, the experimental groups showed shrinkage, decreased brightness, and disordered arrangement of cells, and the number of cells decreased over the time of culture. There were significant differences in the inhibition rate of cell proliferation and cell apoptosis rate among the groups (P<0.01), and the hypoxia+ultraviolet group showed the strongest inhibition of cell proliferation and induction of cell apoptosis, followed by the ultraviolet group and the hypoxia group. Compared with the control group, the other three groups had a gradual reduction in the mRNA expression of Bcl-2, and the hypoxia+ultraviolet group had a significantly greater reduction than the hypoxia and ultraviolet groups (P<0.01). CONCLUSIONS: Both hypoxia and ultraviolet irradiation can inhibit the proliferation of HL-60 cells and induce cell apoptosis, and ultraviolet irradiation has a better effect on proliferation inhibition and cell apoptosis under hypoxic conditions than under normoxic conditions, possibly by downregulating the mRNA expression of Bcl-2.

Angelica sinensis polysaccharide inhibits proliferation, migration, and invasion by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y.

Neuroblastoma is the most common tumor diagnosed in children and infants, with high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose average molecular weight is 72,900 Da possesses various bioactivities. We aimed to explore the effects of AP on neuroblastoma SH-SY5Y cells as well as the underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis, migration, invasion, and expressions of long noncoding RNA H19 (lncRNA-H19), microRNA (miR)-675, and CD44 were assessed. Then, effects of miR-675 overexpression on AP-treated cells were analyzed. Next, expression of key kinases in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of miR-675 was finally explored. Cell viability was reduced by 200-500 µg/mL AP. Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced apoptosis. Expressions of lncRNA-H19 and miR-675 were upregulated in neuroblastoma cells, and were downregulated by AP. AP was also identified to upregulate CD44. We next found AP affected SH-SY5Y cells through downregulating miR-675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by AP stimulation, while these downregulations were abrogated by miR-675 overexpression. KIF1B isoform ß (KIF1Bß) is proved to be a target of miR-675. In conclusion, AP was first identified to inhibit proliferation, migration, and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of SH-SY5Y cells through miR-675-mediated inactivation of the PI3K/AKT and JAK/STAT pathways. Besides, KIF1Bß might be a target of miR-675.

Crocin improves the proliferation and cytotoxic function of T cells in children with acute lymphoblastic leukemia.

OBJECTIVE: Immunotherapy is important to improve the survival of children with acute lymphoblastic leukemia (ALL). This study aimed to assess the effects of crocin on the proliferation and function of T cells isolated from children with ALL. METHODS: The mononuclear cells were isolated from peripheral blood of children with ALL and then treated with different final concentrations of crocin. The levels of different cytokines secreted by T cells and the ratio of CD4 and CD8 were measured. Tail DNA% (TDNA), Tail moment (TM), Tail length (TL) and sister chromatid exchange (SCE) were detected to assess DNA damage of T cells. RESULTS: Crocin significantly promoted T cell proliferation and the secretion of IL-2 and IL-4 in a concentration dependent manner. In addition, crocin increased CD4/CD8 ratio of T subset. Crocin itself caused no significant damage to T cells but reduced DNA damage in T cells treated with Ara-C. CONCLUSIONS: Crocin could improve the proliferation and cytotoxic function of T cells, and reduce DNA damage caused by Ara-C.

Expression of keratinocyte growth factor and its receptor in oral lichen planus.

This study aimed to investigate the expression of keratinocyte growth factor (KGF) and its receptor KGFR in oral lichen planus (OLP). Oral mucosa specimens from 30 OLP patients and ten healthy controls were collected. The expression of KGF and KGFR proteins was detected by immunohistochemistry and the expression of KGF mRNA was detected by in situ hybridization. We observed KGF protein expression but not KGF mRNA expression in the epithelium of both OLP and normal oral mucosa. The expression intensity of KGF protein was much lower in the epithelium of OLP than in that of normal oral mucosa. KGF protein was also expressed in the cytoplasm of some fibroblasts and vascular endothelial cells in the connective tissues underlying the epithelium for both OLP and normal oral mucosa, but the expression intensity of KGF was lower in the connective tissues for OLP. KGF mRNA was expressed in the cytoplasm of some fibroblasts and vascular endothelial cells in the connective tissues underlying the epithelium for both OLP and normal oral tissues. Although KGFR was expressed in vascular endothelial cells of connective tissue and in all epithelium of normal oral mucosa, it was only expressed in the basal layer and prickle layer of the epithelium and in vascular endothelial cells of the connective tissue of OLP. Compared to normal oral mucosa, OLP had lower expression of KGFR in the epithelium but higher expression of KGFR in the connective tissue underlying the epithelium. In conclusion, this study revealed significant differences in the expression intensity and distribution of both KGF and KGFR between OLP and normal oral mucosa tissues. KGF and its receptor KGRF may play an important role in the development and progression of OLP.

Muramyl dipeptide and anti-CD10 monoclonal antibody immunoconjugate enhances anti-leukemia immunity of T lymphocytes.

It is necessary to completely eliminate minimal residual disease (MRD) to cure acute leukemia. Monoclonal antibodies (MAb) have been shown to be effective to eliminate MRD. In this study we aimed to investigate the effect of anti-CD10 MAb conjugated to muramyl dipeptide immunoconjugate (MDP-Ab) on the function of lymphocytes and activated lymphocytes using leukemia xenografts in nude mice as a model. Peripheral blood mononuclear cells were isolated from children with acute lymphoblastic leukemia and induced into dendritic cells (DCs) and lymphocytes. Cytotoxic activity of lymphocytes was detected by LDH release assay. Leukemia xenografts in nude mice were established to assess tumor growth. We found that the killing rate was significantly higher in MDP-Ab group, LPS group and MDP-Ab+LPS group than in control group, and was the highest in MDP-Ab+LPS group. Tumor-bearing mice in MDP-Ab group showed obvious coagulation necrosis. In conclusion, our data suggest that MDP-Ab could effectively prime DCs to improve the anti-tumor immunity of T lymphocytes and inhibit the tumor growth. MDP-Ab may be used as suitable candidate for eliminating residual leukemia cells to prevent relapse.