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Ailing Liu,1,2,* Jinxiang Wu,1,* Aijun Li,2 Wenxiang Bi,3 Tian Liu,1 Liuzhao Cao,1 Yahui Liu,1 Liang Dong1 1Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Pulmonary Diseases, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China; 3Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objectives: Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence) or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE) induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence.Methods: Human bronchial epithelial cells (16HBE cells) cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS), PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway.Results: Cellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence.Conclusion: CSE can induce cellular senescence in human bronchial epithelial cells, and ROS/PI3K/AKT/mTOR signaling pathway may play an important role in this process. C. sinensis can inhibit the CSE-induced senescence. Keywords: senescence, Cordyceps sinensis, ROS/PI3K/AKT/mTOR signaling pathway, COPD

Adolescent obesity can impair cardiopulmonary function, vascular elasticity, endothelial function, and vago-sympathetic balance. While moderate-intensity continuous training (MICT) benefits cardiovascular health in obese adolescents, the effects of high-intensity interval training (HIIT) are less understood. We hypothesize that HIIT may be more effective than MICT in improving VO 2 peak, vascular elasticity, endothelial function, and vago-sympathetic balance in obese adolescent boys. Forty four participants were randomly assigned to the HIIT (10 × 1-min at 85%-95% peak HR, intersperse with 2-min active recovery at 60%-70% peak HR) or MICT (35 min at 65%-75% peak HR) for an 8-week program. The primary outcome measured was the change in VO 2peak with secondary outcomes including brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation (FMD), and heart rate variability (HRV). Forty four adolescent boys with obesity (age, 14 ± 1 years old, body mass index, 31.6 ± 1.3 kg/m 2 ) were enrolled and 43 (97.73%) completed the 8-week exercise. No significant difference of VO 2peak was found between the HIIT and MICT group (p = 0.243). There was no significant difference of baPWV between the groups (p = 0.789). Change in FMD% was significantly higher in the HIIT group compared to the MICT group (p < 0.001). The Change in HRV-high frequency (HRV-HF; p = 0.009) and HRV-low frequency/high frequency (HRV-LF/HF; p = 0.035) was significantly higher in the HIIT group compared to the MICT group. Among adolescent boys with obesity, 8-week HIIT and MICT had similar effects on improving VO 2peak . HIIT may be superior to MICT to improve endothelial function and vago-sympathetic balance., (© 2024 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

We study a hybrid system of a plasmonic cavity coupled to a pair of different molecular vibration modes with the strong optomechanical-like interactions. Here, this plasmonic cavity is considered as a quantum data bus and then assist several applications. For instance, it can first establish a bimolecular interface to ensure the reciprocal or non-reciprocal information transmission, and then engineer both molecules into the steady-state quantum entanglement of the continuous variable through the dissipative method. In contrast to the traditional optomechanical system, this hybrid system can provide the stronger optomechanical-like interactions and more convenient controls to the molecular quantum units. This investigation is believed to be able to further expand the practical application range of quantum technology., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The chirality-controlled two-mode Lipkin-Meshkov-Glick (LMG) models are mimicked in a potential hybrid quantum system, involving two ensembles of solid-state spins coupled to a pair of interconnected surface-acoustic-wave cavities. With the assistance of dichromatic classical optical drives featuring chiral designs, it can simulate two-mode LMG-type long-range spin-spin interactions with left-right asymmetry. For applications, this unconventional LMG model can not only engineer both ensembles of collective spins into two-mode spin-squeezed states but also simulate novel quantum critical phenomena and time crystal behaviors, among others. Since this acoustic-based system can generate ion-trap-like interactions without requiring any additional trapping techniques, our work is considered a fresh attempt at realizing chiral quantum manipulation of spin-spin interactions using acoustic hybrid systems., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Exercise is an effective way to alleviate breast cancer-induced cardiac injury to a certain extent. However, whether voluntary exercise (VE) activates cardiac signal transducer and activator of transcription 3 (STAT3) and the underlying mechanisms remain unclear. This study investigated the role of STAT3-microRNA(miRNA)-targeted protein axis in VE against breast cancer-induced cardiac injury.VE for 4 weeks not only improved cardiac function of transgenic breast cancer female mice [mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT +)] compared with littermate mice with no cancer (MMTV-PyMT -), but also increased myocardial STAT3 tyrosine 705 phosphorylation. Significantly more obvious cardiac fibrosis, smaller cardiomyocyte size, lower cell viability, and higher serum tumor necrosis factor (TNF)-α were shown in MMTV-PyMT + mice compared with MMTV-PyMT - mice, which were ameliorated by VE. However, VE did not influence the tumor growth. MiRNA sequencing identified that miR-181a-5p was upregulated and miR-130b-3p was downregulated in VE induced-cardioprotection. Myocardial injection of Adeno-associated virus serotype 9 driving STAT3 tyrosine 705 mutations abolished cardioprotective effects above. Myocardial STAT3 was identified as the transcription factor binding the promoters of pri-miR-181a (the precursor of miR-181a-5p) and HOX transcript antisense RNA (HOTAIR, sponged miR-130b-3p) in isolated cardiomyocytes. Furthermore, miR-181a-5p targeting PTEN and miR-130b-3p targeting Zinc finger and BTB domain containing protein 20 (Zbtb20) were proved in AC-16 cells. These findings indicated that VE protects against breast cancer-induced cardiac injury via activating STAT3 to promote miR-181a-5p targeting PTEN and to promote HOTAIR to sponge miR-130b-3p targeting Zbtb20, helping to develop new targets in exercise therapy for breast cancer-induced cardiac injury., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress., Method: CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C-C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR)., Results: CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP., Conclusion: ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment., (© 2024. The Author(s).)

Global-minimum optimizations combined with relativistic quantum chemistry calculations have been performed to characterize the ground-state stable structures of four titled compounds and to analyze the bonding properties. Th 2 C 8 was identified as being a ThC 4 -Th(C 2 ) 2 structure, U 2 C 8 has been found to favor the U-U(C 8 ) structure, and both Th 3 C 8 and U 3 C 8 adopt the (AnC 3 ) 2 -(AnC 2 ) structure. Then, the wave function analyses reveal that the interactions between the Th 7 s -based orbital and the σ g molecular orbital of the C 2 unit compensate for the excitation energy of 7 s 1 6 d 1 → 6 d 2 and lead to the stabilization of two Th(IV)s in the ThC 4 -Th(C 2 ) 2 structure. It also reveals that the U species exhibit magnetic exchange coupling behavior in U x C 8 , for instance, as seen in the direct interaction of U 2 C 8 and the superexchange pathway of U 3 C 8 , which effectively stabilizes their low-spin states. This interpretation indicates that the geometric and electronic structures of An x C 8 species are largely influenced by the local magnetic moment and spin correlation.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank., (© 2023. Springer Nature Limited.)

The bonding situation and the oxidation state of plutonium in heterodinuclear plutonium boron group carbonyl compounds XPu(CO) n (X = B, Al, Ga; n = 2 to 4) were investigated by systematically searching their ground-state geometrical structures and by analyzing their electronic structures. We found that the series of XPu(CO) n compounds show various interesting structures with an increment in n as well as a changeover from X = B to Ga. The first ethylene dione (OCCO) compounds of plutonium are found in AlPu(CO) n ( n = 2, 3). A direct Ga-Pu single bond is first predicted in the series of GaPu(CO) n , where the bonding pattern represents a class of the Pu → CO π back-bonding system. There is a trend where the Pu-Ga bonding decreases and the Pu-C(O) covalency increases as the Ga oxidation state increases from Ga(0) to Ga(I). Our finding extends the metal → CO covalence back-bonding concept to plutonium systems and also enriches plutonium-containing bonding chemistry.

Background: Self-gravitation traction is 1 of the most popular treatments for lumbar disc herniation (LDH). This study aims to evaluate the effectiveness and safety of the self-gravitation traction device in the treatment of LDH and to confirm its positive treatment effect., Methodology: This trial is designed as a pragmatic double-center, single-blind, and 3-arm (1:1:1 ratio) randomized controlled trial. The recruited patients with LDH will be randomly allocated to the intervention (traction weight is 40% or 60% of its body weight) or control (traction weight is 20% of its body weight) group. Traction will be completed within 6 consecutive weeks (3 times a week), with 10 minutes of traction for the first 3 weeks, 20 minutes of traction for the next 3 weeks. After the experiment is completed, we will establish an experiment-related database. The software of SPSS, version 21 (SPSS Inc. Chicago, IL) will be used for statistical analysis, and measurement data will be expressed via mean and standard deviation (mean ± SD)., Discussion: Once the trial is completed, we will publish the study in journals in both Chinese and English to promote the dissemination and use of the results. In addition, we also plan to promote the research results at various academic conferences both domestically and internationally., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The ongoing Chinese Color Nest Project (CCNP) was established to create normative charts for brain structure and function across the human lifespan, and link age-related changes in brain imaging measures to psychological assessments of behavior, cognition, and emotion using an accelerated longitudinal design. In the initial stage, CCNP aims to recruit 1520 healthy individuals (6-90 years), which comprises three phases: developing (devCCNP: 6-18 years, N = 480), maturing (matCCNP: 20-60 years, N = 560) and aging (ageCCNP: 60-84 years, N = 480). In this paper, we present an overview of the devCCNP, including study design, participants, data collection and preliminary findings. The devCCNP has acquired data with three repeated measurements from 2013 to 2017 in Southwest University, Chongqing, China (CCNP-SWU, N = 201). It has been accumulating baseline data since July 2018 and the second wave data since September 2020 in Chinese Academy of Sciences, Beijing, China (CCNP-CAS, N = 168). Each participant in devCCNP was followed up for 2.5 years at 1.25-year intervals. The devCCNP obtained longitudinal neuroimaging, biophysical, social, behavioral and cognitive data via MRI, parent- and self-reported questionnaires, behavioral assessments, and computer tasks. Additionally, data were collected on children's learning, daily life and emotional states during the COVID-19 pandemic in 2020. We address data harmonization across the two sites and demonstrated its promise of characterizing the growth curves for the overall brain morphometry using multi-center longitudinal data. CCNP data will be shared via the National Science Data Bank and requests for further information on collaboration and data sharing are encouraged., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To analyze genetic characters of migratory dragonflies, we used 10 microsatellite markers and a partial sequence of the mitochondrial gene Cytb to investigate genetic diversity and demographic history among 19 populations of P. flavescens in eastern the monsoon region of China. In a Bayesian clustering analysis of the microsatellite data, three distinct clades were present, and each population consisted of a mixture of individuals from the three clusters. An AMOVA of the data from both the microsatellite loci and Cytb revealed that genetic variation was mainly within each population. For the 543 individuals from the 19 regions, 77 unique haplotypes were obtained by DnaSP 4.0, and a median-joining network showed no obvious geographical pattern and displayed high gene flow and minimal population genetic structure among the 19 populations. According to a Mantel test, there was no significant association between genetic distance and geographic distribution and no isolation by distance. Mismatch distribution and neutrality tests showed no demographic expansion for the 19 populations. Microsatellite and mitochondrial DNA data suggested there was high gene flow and low differentiation among the populations. These results will help provide valuable information to study the migratory route of insects, especially important agricultural pests.

Pantala flavescens (Fabricius 1798) (Odonata: Libellulidae) is one of the most common species of migratory dragonflies. P. flavescens adults were captured by a searchlight trap on Beihuang Island (BH Island; 38°24'N, 120°55'E) from 2003 to 2016, where there is no freshwater. This inspired our research to analyze the pattern of seasonal migration and population dynamics. Stable hydrogen isotope measurement and the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) were used to simulate the migration pathway of P. flavescens between different breeding habitats. The results showed that there was no significant difference among population numbers of this overseas migration across years (F13, 2161 = 0.85, P = 0.604); however, the numbers were significantly different across months (F5, 2161 = 3.91, P = 0.003). Our geospatial natal assignment model suggested that P. flavescens trapped on BH were originated in different geographical regions and might have three movement strategies: wandering around northern China and north-bound (positive) and south-bound (negative) movements. Among them, the majority were engaged in wandering around northern China. Model simulations suggested that P. flavescens toured around BH. The results contribute to the knowledge of P. flavescens population ecology in a large-scale geographic region and will aid in the prediction and interpretation of insect migration patterns in response to climate change.

Objective: In 2011, the International League Against Epilepsy (ILAE) proposed a consensus classification system of focal cortical dysplasia (FCD) to distinguish clinicopathological subtypes, for example, "isolated" FCD type Ia-c and IIa-b, versus "associated" FCD type IIIa-d. The histopathological differentiation of FCD type I and III variants remains, however, a challenging issue in everyday practice. We present a unique histopathological pattern in patients with difficult-to-diagnose FCD, which highlights this dilemma, but also helps to refine the current ILAE classification scheme of FCD., Methods: We present a retrospective series of 11 male and one female patient with early onset pharmacoresistant epilepsy of the posterior quadrant (mean age at seizure onset = 4.6 years). All surgical specimens were reviewed. Clinical histories were retrieved and extracted from archival patient files., Results: Microscopic inspection revealed abnormalities in cortical architecture with complete loss of layer 4 in all surgical samples of the occipital lobe, as confirmed by semiquantitative measurements (p < 0.01). Clinical history reported early transient hypoxic condition in nine patients (75%). Magnetic resonance imaging (MRI) revealed abnormal signals in the occipital lobe in all patients, and signal changes suggestive of subcortical encephalomalacia were found in seven patients. Surgical treatment achieved favorable seizure control (Engel class I and II) in seven patients with an available follow-up period of 6.1 years., Significance: Prominent disorganization of cortical layering and lack of any other microscopically visible principle lesion in the surgical specimen would result in this neuropathological pattern hitherto being classified as FCD ILAE type Ib. However, perinatal hypoxia with distinctive MRI changes suggested primarily a hypoxemic lesion and acquired pathomechanism of neuronal cell loss in the occipital lobe of our patient series. We propose, therefore, classifying this distinctive clinicopathological pattern as a separate variant of FCD ILAE type IIId., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Thyroid cancer (TC) is the most common malignancy of the endocrine system. The relationship between iodine intake and TC risk is controversial always. We aim to figure out the relationship between iodine intake and TC using meta-analysis. Literature research in MEDLINE, Embase, China National Knowledge Infrastructure, and China BioMedicine was performed up to April 2016, searched for relevant case-control and cohort studies. The effect of iodine consumption on the risk of TC was assessed using the pooled odds ratio (OR) and 95% confidence interval (CI). The meta-analysis included 8 case-control studies (n = 4974; 2213 cases; 2761 controls). More than adequate or excess iodine intake (>300 μg/d) decreased the risk of TC (OR 0.74, 95% CI 0.60, 0.92). High consumption of saltwater fish or shellfish decreased the risk of TC (OR 0.72, 95% CI 0.55, 0.95; OR 0.70, 95% CI 0.52, 0.96; respectively). A higher intake of dietary iodine was as a protective factor for TC. However, the available data are very limited and more studies are required.

An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.

Acute lymphoblastic leukemia (ALL) is the most commonly diagnosed malignancy in children. It is a heterogeneous disease, and is determined by multiple gene alterations and chromosomal rearrangements. To improve current understanding of the underlying molecular mechanisms of ALL, the present study profiled genome‑wide digital gene expression (DGE) in a population of children with ALL in China. Using second‑generation sequencing technology, the profiling revealed that 2,825 genes were upregulated and 1,952 were downregulated in the ALL group. Based on the DGE profiling data, the present study further investigated seven genes (WT1, RPS26, MSX1, CD70, HOXC4, HOXA5 and HOXC6) using reverse transcription‑quantitative polymerase chain reaction analysis. Gene Ontology analysis suggested that the differentially expressed genes were predominantly involved in immune cell differentiation, metabolic processes and programmed cell death. The results of the present study provided novel insights into the gene expression patterns in children with ALL.

Inequalities of information entropic play a fundamental role in information theory and have been employed effectively in finding bounds on optimal rates of various information-processing tasks. In this paper, we perform the first experimental demonstration of the information-theoretic spin-1/2 inequality using the high-fidelity entangled state. Furthermore, we study the evolution of information difference of entropy when photons passing through different noisy channels and give the experimental rules of the information difference degradation. Our work provides an new essential tool for quantum information processing and measurement, and offers new insights into the dynamics of quantum correlation in open systems.

A 7-year-old girl was admitted to Xiangya Hospital due to systemic lymphadenectasis for 2 months and skin ecchymosis for 3 days. Nine months ago, the girl experienced painless nodules in the left lower extremity with no apparent causes. Three months later, dermatorrhagia and ecchymosis occurred in many regions such as the periocular areas, conjunctiva, oral mucosa, perineal area, and groin, with a "raccoon sign" in both eyes; superficial lymphadenectasis and hepatosplenomegaly were also observed in many regions. The pathological sections for the skin nodules showed malignant tumors in lymphohematopoietic cells, and in combination with clinical manifestations, immunohistochemistry, and positive results for CD4, CD56, and CD123 by bone marrow flow cytometry, the girl was diagnosed with blastic plasmacytoid dendritic cell neoplasm. Then high-risk ALL regimen was applied as the chemotherapy for this girl. At present, the girl has been followed up for 3 months; ecchymosis has disappeared, and the enlarged lymph nodes have shrunk. No abnormal cells have been found in bone marrow morphological examination, and bone marrow flow cytometry has shown that primitive precursor cells account for 1.5% and express CD33, CD34, CD123, and CD117.

The highest qubit Ardehali inequality violation with 203 standard deviations is first experimentally demonstrated using the hyper-entangled four-photon-eight-qubit Greenberger-Horne-Zeilinger (GHZ) state. Moreover, we experimentally investigate the robustness of the Ardehali inequality for the four-, six-, and eight-qubit GHZ states in a rotary noisy environment systematically. Our results first validate the Ardehali' theoretical statement of relation between violation of Ardehali inequality and particle number, and proved that Ardehali inequality is more robust against noise in larger number qubit GHZ states, and provided an experimental benchmark for us to estimate the safety of quantum channel in the noisy environment.

Study Design: A retrospective study of modic changes (MCs) in degenerative lumbar scoliosis (DLS)., Objective: To investigate the prevalence of vertebral endplate MCs in DLS and explore their associated factors., Summary of Background Data: MCs are common in spinal degenerative diseases. Presently, most of the researches have been focused on investigating the relationship between MCs and chronic low back pain. Little has been known on the distribution of MCs in DLS and the relationship between MCs and scoliosis., Methods: The image data of 120 patients who had been diagnosed with DLS in our hospital from March 2005 to March, 2011 were retrospectively reviewed as the study group. The image data of 89 patients who had been diagnosed with degenerative lumbar diseases without scoliosis were selected as the control group. The prevalence, type, and distribution of MCs in 2 groups were observed and compared. Disc degeneration, Cobb angle, body weight, and smoking were recorded in the study group, and the relationship of MCs with these influential factors was analyzed., Results: Of 1440 endplates from 120 patients in the study group, 247 (17.2%) from 71 (59.2%) patients were found to have MCs. Compared with the control group, of 1068 endplates from 89 patients, 49 (4.5%) endplates from 21 (23.6%) patients were found to have MCs. The prevalence of MCs was significantly higher in the study group than that in the control group (P < 0.01). The MCs in DLS usually had asymmetric distribution with more frequent occurrence on the concave side than on the convex side of major or compensatory curve and mainly occurred at L2-L3, L4-L5, and L5-S1, which were in accordance with the common levels of apex vertebrae. Intervertebral disc degeneration, lumbar scoliosis, overweight and heavy smoking are considered as risk factors to MCs. By multinomial logistic regression analysis on these factors, the regression function was obtained: logit Y = -0.82 + 1.27D + 0.55S + 1.77 D × S (Y for MCs, D for intervertebral disc degeneration, S for scoliosis Cobb's angle and D × S for interaction of D and S)., Conclusion: The prevalence of MCs in patients with DLS was significantly higher than that of patients without DLS. Most of them were type 2 and usually located on the concave side of apex vertebrae. MCs were significantly associated with intervertebral disc degeneration and lumbar scoliosis.

Objective: To study the etiology and clinical significance of axial symptoms after posterior operative procedures for ossification of the posterior longitudinal ligament (OPLL)., Methods: From February 2005 to February 2010, 76 patients with OPLL treated were retrospectively experienced. There were 34 male and 42 female with average of 52.1 years (range from 37 to 74 years), the average duration of the disease was 32.1 months (range from 11 to 56 months). Nineteen patients underwent traditional laminectomy in group A, 33 patients received open-door laminoplasty in group B and 24 patients underwent lateral mass screw fixation in group C. All patients underwent X-ray examination pre- and post operative, computed tomography were used for diagnosis of OPLL, the recovery rate was calculated using pre- and postoperative Japanese Orthopedic Association (JOA) scores for each patient. Pre- and postoperative cervical curvature index and axial symptoms were measured and compared. χ(2) test and SNK test were used as statistical methods., Results: All patients were followed up for 14 - 35 months, average (21 ± 5) months. Loss of cervical curvature index was 4.2% ± 1.7% in group A, 2.9% ± 2.2% in group B and 2.3% ± 1.9% in group C. The difference was significant in loss of cervical curvature indice between group A and B (q = 2.94, P < 0.01), group A and C (q = 4.23, P < 0.01). The average JOA recovery rate was 58.3% for group A, 64.3% for group B and 66.7% for group C. There was no significant difference in JOA recovery rate among the three groups (P > 0.05). The rate of early evident axial symptoms was 7/19 in group A, 30.3% in group B and 33.3% in group C and the difference was not statistically significant (P > 0.05). The incidence of late evident axial symptoms was 5/19 in group A, 12.1% in group B and 8.3% in group C, the difference was not significant between group B and C (χ(2) = 13.762, P < 0.01), but of statistical difference between group A and B(χ(2) = 6.368, P < 0.01), group A and C (χ(2) = 11.481, P < 0.01). No kyphotic deformity in the group A, no "Close Door" phenomenon in group B and no internal failure in group C., Conclusion: The incidence of early axial symptoms are of no significant difference among the three groups, but late axial symptoms are higher in the laminectomy than other groups, which may be associated with loss of cervical lordosis.

Objective: To investigate the mechanism of decreasing the K562/ADM cells chemosensitivity by up-regulating expression of PTEN gene., Methods: K562/ADM cells were transient transfected with pGFP-PTEN or vector. The level of PTEN in K562/ADM cells was assayed by Western blot and RT-PCR. Cell viability on K562/ADM was determined by MTT assay. Cell apoptosis by flow cytometry. Activity of caspase-3 by Caspase Colorimetric Assay Kit. The proteins expression of LC3-I/II, Beclin1, p-Akt, p-p70S6K by Western blot. The autophagic vacuoles by MDC stain and Electron microscopy., Results: (1) The mRNA and protein levels of PTEN in K562/ADM cells transfected with pGFP-PTEN were significantly increased compared with the control (untreated and transfected with empty vector). (2) Enhanced expression of PTEN by gene transfection resulted in a reversal of resistance to ADM. Compared with empty vector group, cell viability decreased from (94.07 ± 2.6)% to (53.83 ± 4.2)%, the cell apoptotic rate increased from (11.89 ± 1.7)% to (43.69 ± 2.3)%, meanwhile, pretreated with caspase-3 inhibitor (Z-DEVE-FMK) didn't completely inhibit the cytotoxicity of ADM to K562/ADM cells. (3) After treated with ADM for 12 and 24 h, the activities of caspase-3 in PTEN-transfected K562/ADM cells increased compared with those in pGFP-transfected K562/ADM cells \[(2.27 ± 0.13) vs (1.19 ± 0.14)\] at 12h, \[(3.15 ± 0.08) vs (1.48 ± 0.05)\] at 24 h (P < 0.05). (4) The protein levels of LC3-II and Beclin1 in K562/ADM cells transfected with pGFP-PTEN were increased by 83% and 18% respectively, and the protein levels of p-Akt and p-p70S6K were declined by 96% and 87% respectively, compared with those in K562/ADM cells transfected with pGFP plasmid. (5) The upregulation of PTEN in K562/ADM cells improved the number of autophagic vacuoles compared with the empty vector group., Conclusion: The upregulation of PTEN expression increases the chemosensitivity of K562/ADM to ADM, which may related with the inhibition of PI3K/AKT/mTOR pathway induced by PTEN gene transfection.

Background: Degenerative lumbar scoliosis is common in older patients. Decreased bone density and the degeneration of intervertebral discs are considered to be correlated with degenerative lumbar scoliosis. A means of quantifying the relative signal intensity for degenerative disc disease has not been previously discussed. The purpose of this study was to compare bone mineral density and intervertebral disc degeneration between degenerative lumbar scoliosis and lumbar spinal stenosis patients in a nine-year retrospective study., Methods: From January 2001 to August 2010, 96 patients with degenerative lumbar scoliosis were retrospectively enrolled and 96 patients with lumbar spinal stenosis were selected as controls. Cobb angle, height of the apical disc and the contiguous disc superiorly and inferiorly on convex and concave sides, the height of the convex and concave side of the apical and the contiguous vertebral body superiorly and inferiorly were measured in the scoliosis group. The height of L2/L3, L3/L4, L4/L5 discs and the height of L2/L4 vertebral body was measured in the control group. The grade of intervertebral disc degeneration was evaluated using T2WI sagittal images in both groups. The bone density of lumbar vertebrae was measured with dual-energy X-ray., Results: In scoliosis group, the intervertebral disc height on the convex side was greater than the height on the concave side (P < 0.001). The vertebral body height on the convex side was greater than the height on the concave side (P = 0.016). There was a significant difference between the scoliosis group and the control group (P = 0.003), and between T-value and the rate of osteoporosis between the two groups (both P < 0.001)., Results: were verified using multiple linear regression analysis., Conclusions: Degenerative lumbar scoliosis is accompanied by height asymmetry between the intervertebral disc and vertebral body regarding the convex and concave surfaces. There is a positive correlation between the angle of scoliosis and the disc index, the degree of degeneration of the intervertebral disc, and a negative correlation between the angle of scoliosis and bone density.

Objectives: To analyze the correlation between intervertebral disc-endplate degeneration and bony construction parameter and to explore its roles in adult degenerative scoliosis., Methods: The imaging data of 79 patients with adult degenerative scoliosis from March 2005 to March 2010 were retrospectively reviewed as the study group. The imaging data of 41 patients with adolescent idiopathic scoliosis were selected as the control group. The vertebral body and intervertebral height in both sides on frontal X-ray, and the facet joint orientation in both sides on CT scan were measured respectively. The average vertebral body height, average intervertebral disc height and average facet orientation were regarded as bony structural parameters. The quantitative grading methods were used in the intervertebral disc and endplate degeneration. The relationship of bony construction parameter and intervertebral disc-endplate degeneration, and the relationship of bony construction parameter and Cobb's angle of scoliosis were analyzed by comparing all bony construction parameters in both groups., Results: Analyzed by paired-t test, the intervertebral height, vertebral body height and facet joint orientation between convex and concave sides of the study group were of significant difference (t = 3.411, 2.623 and 2.085, P < 0.05). The intervertebral height between convex and concave sides of the control group were of significant difference (t = 3.276, P < 0.01), while the vertebral body height and the facet joint orientation were of no statistical significance (t = 1.572 and 1.493, P > 0.05). By linear correlation and regression analysis, the asymmetric degree of bony construction parameter showed good correlation with the score of intervertebral disc-endplate degeneration (-1 < r < 1, P < 0.05), which was positively correlated with Cobb's angle of scoliosis (0 < r < 1, P < 0.05). Linear regression existed between asymmetric degree of bony construction parameter and Cobb's angle (F = 427.342, P < 0.01). The regression function was obtained: Cobb's angle = -8.904+8.136 × IAD + 3.274 × VAD-0.713 × FAD (IAD: intervertebral asymmetry degree, VAD: vertebral asymmetry degree, FAD: facet joint asymmetry degree)., Conclusions: The asymmetric change of bony construction exists in adult degenerative scoliosis, which significantly correlated with intervertebral disc-endplate degeneration and Cobb's angle of scoliosis. The asymmetric bony construction parameter probably plays a biomechanical role in the progression of scoliosis, which maybe the reason for the asymmetric degeneration of intervertebral disc-endplate.

Objectives: To investigate the correlation between scoliosis angle and the asymmetric index of degenerative lumbar scoliosis, the degree of intervertebral disc degeneration, decreased bone density., Methods: As a retrospectively study, a total of 96 patients with degenerative lumbar scoliosis were retrospectively enrolled from January 2002 to August 2010 as scoliosis group, meanwhile 96 patients with lumbar spinal stenosis matched in gender, age and body mass index (BMI) were selected as control group. All patients were studied with plain radiographs, MRI and dual energy X-ray absorptiometry at presentation. Radiographic measurements include Cobb angle, the height of the convex and concave side of the apical disc and the contiguous disc superiorly and inferiorly, the height of the convex and concave side of the apical and the contiguous vertebral body superiorly and inferiorly in scoliosis group, the height of L(2-3), L(3-4), L(4-5) discs and the height of L(2-4) vertebral body in control group. The average relative signal intensity of lumbar intervertebral disc and cerebrospinal fluid in T2WI sagittal image was measured in apex intervertebral disc and adjacent discs by Adobe Photoshop 6.0 in scoliosis group, which was measured in L(2-3), L(3-4), L(4-5) disc in control group. The bone density of lumbar, femoral neck, trochanter, and Ward's triangle regions were measured with dual-energy X-ray absorptiometry., Results: The intervertebral disc height in convex side was greater than the height in the concave side [(40 ± 7) mm vs. (28 ± 7) mm, P < 0.01], the vertebral body height in convex side was greater than the height in the concave side [(76 ± 12) mm vs. (72 ± 10) mm, P = 0.016] in scoliosis group. There was significant statistically difference in the degenerative degree of intervertebral discs between two groups (P = 0.003). There was significant statistically difference of the average T-value and the rate of osteoporosis between two groups (P < 0.01). Multiple linear regression analysis showed that the asymmetric disc index, the degenerative degree of intervertebral disc and osteoporosis were the predominant correlative factors, which affected the development of degenerative lumbar scoliosis., Conclusions: Degenerative lumbar scoliosis is always accompanied by the height asymmetry of intervertebral discs and vertebral body from convex and concavity sides. There is positive correlation between the angle of scoliosis and the asymmetric disc index, the degeneration of intervertebral disc, and negative correlation between the angle of scoliosis and the bone density (T-value).

For children with acute myeloblastic leukemia (AML), multidrug resistance (MDR) reduces treatment effectiveness, and often leads to poor patient survival. While a number of factors have been described that affect MDR, the mechanisms underlying this effect remain unclear. In this study, the role of WAVE1 in MDR was investigated. Among 62 children with AML, high levels of WAVE1 were associated with poor patient outcomes. Proteomic techniques were used to identify novel WAVE1-interacting proteins from leukemia cells, one of which was the cytoskeleton regulator Ezrin. In leukemia cells, WAVE1 co-localized with both Ezrin and P-glycoprotein (P-gp), a critical regulator of the MDR phenotype. Overexpression of WAVE1 in K562 leukemia cells up-regulated P-gp and Ezrin, and reduced K562 cells' sensitivity to the chemotherapy drug adriamycin. The opposite effect was seen when WAVE1 expression was reduced via RNA interference. Critically, overexpression of WAVE1 in the absence of Ezrin did not affect P-gp levels or MDR. These data suggest that WAVE1 affects P-gp and MDR of leukemia cells through Ezrin.

We report a successful observation of pressure-induced superconductivity in a topological compound Bi(2)Te(3) with T(c) of ∼3 K between 3 to 6 GPa. The combined high-pressure structure investigations with synchrotron radiation indicated that the superconductivity occurred at the ambient phase without crystal structure phase transition. The Hall effects measurements indicated the hole-type carrier in the pressure-induced superconducting Bi(2)Te(3) single crystal. Consequently, the first-principles calculations based on the structural data obtained by the Rietveld refinement of X-ray diffraction patterns at high pressure showed that the electronic structure under pressure remained topologically nontrivial. The results suggested that topological superconductivity can be realized in Bi(2)Te(3) due to the proximity effect between superconducting bulk states and Dirac-type surface states. We also discuss the possibility that the bulk state could be a topological superconductor.

Objective: Multidrug resistance (MDR) is one of the primary causes of suboptimal outcomes in chemotherapy of children with acute myeloblastic leukemia (AML). The mechanisms of drug transport resistance may chiefly contribute to MDR. Expression and/or activity of P-glycoprotein (P-gp), multiple resistance-associated protein-1 (MRP1), lung-resistance related protein (LRP) and breast cancer resistance protein (BCRP) have been considered to be associated with unfavourable outcomes in pediatric AML patients. In previous studies, we found WASP-family verprolin-homologous protein-1 (WAVE1) was involved in the MDR mechanisms in K562/A02 leukemia cells. To investigate the expression of WAVE1, P-gp, MRP1, LRP/MVP and BCRP; and if WAVE1 is involved in MDR of human leukemia cell., Methods: WAVE1, P-gp, MRP1, LRP, BCRP mRNA and protein expression in bone marrow mononuclear cells (BMMCs) were measured by real-time fluorescence quantitative PCR (RQ-PCR) and Western blot in a cohort of 52 children with acute myeloblastic leukemia. During follow-up, of the 52 patients, 21 were documented as being relapsing or refractory, and 31 were induced into complete continuous remission. Furthermore, HL60 cells and HL60/ADR cells were transiently transfected with PCDNA3.1-WAVE1 reconstructed plasmid and specifically siRNA to WAVE1 respectively, and the expression of WAVE1, MRP1 and BCRP before and after transfection was assessed by real-time PCR and Western blot analysis., Results: (1) The expression levels of WAVE1, P-gp, MRP, LRP and BCRP in refractory/relapsing group were much higher than that in complete continuous remission (CCR) group. (2) WAVE1 mRNA and protein expression in BMMCs of children were at higher levels when they were newly diagnosed or relapsed, compared with complete continuous remission. (3) The WAVE1 expression at mRNA and protein level in HL60/ADR cells was increased by about 353% and 95% respectively as compared with that in HL60 cells. (4) Overexpression of WAVE1 in HL60 cell lines upregulated the expression levels of MRP and BCRP (MRP mRNA and protein level were increased by about 16.54 times and 129% respectively, BCRP was increased by 4.93 times and 96%); whereas suppression of WAVE1 expression by RNA interference downregulated the expression levels of MRP1 and BCRP (MRP mRNA and protein level was only 11% and 43% of pre-disturbance respectively, BCRP was 14% and 71%)., Conclusions: Higher levels of WAVE1 in the BM indicate an unfavorable prognosis in children with AML. WAVE1 is related to the development of AML and involved in the MDR mechanisms, and regulates the level of MRP1 and BCRP.

This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides., (© 2009 Blackwell Publishing Ltd.)

Objective: To investigate role of WASP family verprolin homologous protein 1 (WAVE1) in K562 leukemia cell invasion and its mechanism., Methods: Immunofluorescence method was used to detect the distribution of WAVE1 and MMP-2 in the cells. K562 cells were transfected with pcDNA3. 1-WAVE1 reconstructed plasmid or with specific siRNA to WAVE1 gene. The invasion ability of K562 cells was examined by Transwell assay. The expression level of WAVE1 and MMP-2 in K562 cells was assayed by real-time PCR and Western blot., Results: (1) WAVE1 and MMP-2 mainly expressed and co-localized in the cell membrane; (2) 24 h and 48 h after transfected with pcDNA3. 1-WAVE1, the MMP-2 mRNA level in K562 cells increased by 295% and 198% while its protein increased by 80% and 23% respectively as compared with control K562 cells. At the same time point after transfected with specific siRNA, the MMP-2 mRNA level decreased by 81% and 28%, and its protein decreased by 36% and 53% respectively as compared with control. (3) The invasion ability of K562 cells was enhanced after transfected with pcDNA3. 1-WAVE1 and depressed after transfected with the specific siRNA., Conclusion: The co-localization of WAVE1 and MMP-2 in K562 cells suggests they coordinate in functions; WAVE1 may involve in the migration and invasion of K562 cells through regulating the expression level of MMP-2.

Objective: To study the expression of WAVE1 and p22phox in peripheral blood mononuclear cells (PBMCs) in children with acute lymphocytic leukemia (ALL) and the relationship of WAVE1 with oxidative stress., Methods: Real-time PCR was used for detecting WAVE1 and p22phox expression in PBMCs in 41 children with ALL and 10 normal controls. Plasma activity of superoxide dismutase (SOD) was measured by the xanthine oxidase method. Plasma activity of GSH-Px was measured by the DTNB reaction test., Results: The expression of WAVE1 and p22phox was significantly higher in the active ALL groups (newly diagnosed and relapse ALL) than that in the normal control and the complete remission (CR) ALL groups (<0.01). The CR ALL group showed increased WAVE1 and p22phox expression than those in the normal control group (<0.05). Plasma activities of SOD (22.62+/-7.39 U/mL) and GSH-Px (91.73+/-28.88 micromol/L) in the active ALL group were significantly lower than those in the normal control (166.35+/-27.93 U/mL and 490.94+/-39.38 micromol/L, respectively) and the CR ALL groups (107.11+/-28.57 U/mL and 267.56+/-82.64 micromol/L, respectively) (<0.01). WAVE1 expression was positively correlated with p22phox expression (r=0.34, <0.05) but negatively correlated with plasma activities of SOD and GSH-Px ( r=-0.336 and-0.408, respectively; <0.05)., Conclusions: WAVE1 and p22phox expression in PBMCs increased and was associated with the disease course in children with ALL. Oxidative stress may be involved in the regulation of WAVE1 expression in ALL children.

Objective: To investigate whether WASP/Verprolin homologous protein 1 (WAVE1) plays a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL)., Methods: WAVE1 mRNA and protein expression in bone marrow mononuclear cells (BMMCs) was measured by RT-PCR and Western blotting respectively in 4 children with ALL relapse, 15 children with ALL in complete remission (CR) and 40 children with newly diagnosed ALL. Ten normal bone marrow samples were used as controls. Jurkat cells were treated with different concentrations of adriamycin (ADM). The cell proliferation was detected with MTT. The apoptosis rate was measured by flow cytometry. WAVE1 mRNA and protein expression of Jurkat cells treated with ADM was detected by RT-PCR and Western blotting respectively., Results: WAVE1 was not expressed or weakly expressed in BMMCs from normal controls and patients with ALL in CR. Higher WAVE1 mRNA and protein expression was found in BMMCs from patients with newly diagnosed ALL and patients with relapse ALL when compared with the controls and the patients in CR (P<0.01). ADM significantly inhibited the proliferation of the Jurkat cells and the inhibitory effect was dose-and time-dependent (P<0.05). After ADM treatment for 24 hrs, the percentage of apoptosis cells increased significantly and WAVE1 mRNA and protein expression of Jurkat cells decreased significantly when compared with the untreated controls (P<0.05)., Conclusions: The WAVE1 expression increased in children with ALL. WAVE1 may be related to the development of ALL and may be severed as a marker for the evaluation of the severity of ALL in children.

Background & Objective: High mobility group box l (HMGB1), a nuclear DNA-binding protein, stabilizes the structure and function of chromatin, regulates gene transcription. Recent studies found that HMGB1 is associated with the proliferation and metastasis of many tumors, including breast cancer, colon carcinoma, and melanoma, and is rich in various solid cancer tissues and immature cells. This study was to explore the role of HMGB1 in adriamycin (ADM)-induced apoptosis in leukemia K562 cells., Methods: K562 cells were transiently transfected with recombinant plasmid pcDNA3.1-HMGB1. The expression of HMGB1 in K562 cells were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The 50% inhibition concentration (IC(50)) of ADM for K562 cells was determined by WST-8 assay. Cell apoptosis was assessed by flow cytometry. The protein level of Bcl-2 was detected by Western blot. The activities of Caspase-3 and Caspase-9 were assayed with Caspase Colorimetric Assay Kit., Results: The mRNA and protein levels of HMGB1 in K562 cells transfected with pcDNA3.1-HMGB1 were increased by about 85% and 56% respectively as compared with those in K562 cells transfected with pcDNA3.1. Overexpression of HMGB1 in K562 cells by transient transfection significantly increased the resistance to ADM; the IC(50) of ADM was increased from (0.06+/-0.00) microg/mL to (3.46+/-0.06) microg/mL. When treated with 1 microg/mL ADM, the apoptosis rate was significantly lower in HMGB1-transfected K562 cells than in pcDNA3.1-transfected K562 cells [(12.00+/-1.26)% vs. (44.50+/-1.87)%, P<0.05]. Overexpression of HMGB1 in K562 cells significantly inhibited ADM-induced down-regulation of Bcl-2 protein. After treatment of ADM, the activities of Caspase-3 and Caspase-9 in HMGB1-transfected K562 cells were inhibited as compared with those in pcDNA3.1-transfected K562 cells (Caspase-3: 1.55+/-0.06 vs. 2.55+/-0.06 at 12 h, 1.86+/-0.10 vs. 2.85+/-0.06 at 24 h, P<0.05; Caspase-9: 1.40+/-0.08 vs. 2.03+/-0.05 at 12 h, 1.55+/-0.06 vs. 2.22+/-0.05 at 24 h, P<0.05)., Conclusion: HMGB1 overexpression could inhibit ADM-induced apoptosis in leukemia K562 cells through regulating the protein level of Bcl-2 and the activities of Caspase-3 and Caspase-9.

Objective: To investigate the effect of high mobility group boxl (HMGBI) gene silence on adriamycin (ADM)-induced apoptosis in K562/A02 drug resistance leukemia cells., Methods: K562/ A02 cells were transient transfected with HMGB1- small interference RNA(siRNA) vector, and the levels of HMGB1 gene differential expression pre-and post-transfection were measured by RT-PCR and Western blotting. 50% inhibition concentration (IC50) of ADM on K562/A02 was determined by WST-8 assay. Cell apoptosis was assessed by flow cytometry. The release of Smac/DIABLO from the mitochondria to the cytoplasm was assayed by Western blotting. Activity of Caspase-3 was assayed with a Caspase Colorimetric Assay Kit., Results: (1) The HMGB1 expression at mRNA and protein levels in HMGB1 siRNA transfected K562/A02 cells were decreased by 86% and 71% respectively compared with control. (2) Suppression of HMGB1 by siRNA in K562/A02 cells resulted in a reversal of the resistance to ADM, and decreased IC50 from (4.83 +/- 0.08) microg/ml to (1.33 +/- 0.10) microg/ml. 1 microg/ml and 5 microg/ml of ADM treatment increased cell apoptotic rate by 27% and 32% respectively. (3) HMGB1 suppression in K562/A02 cells significantly promoted ADM- induced Smac/DIABLO release from the mitochondria to the cytoplasm, and increased the activities of Caspase-3., Conclusion: HMGB1 gene silence can enhance sensitivity of K562/A02 cells to ADM and reverse cell resistant to ADM.

Objective: To analyze the therapeutic effect and the influencing factors of event-free survival (EFS) of childhood acute lymphoblastic leukemia (ALL) in Xiangya Hospital of Central South University and the First Affiliated Hospital of Guangxi Medical University., Methods: All the patients adopted chemotherapy according to therapeutic guideline revised by the Subspecialty Group of Hematology, The Society of Pediatrics, Chinese Medical Association for the second-time in 1998 (the Rongcheng ALL-98 Protocol). Kaplan-Meier method was used to estimate the survival rates of 188 patients who received therapy with good compliance. The differences of EFS between groups were assessed by Log-rank test. The independent influencing factors on EFS were analyzed by the Cox proportional hazards regression model., Results: After receiving inductive treatment, 354 of 374 (93.6%) patients demonstrated a complete remission; 188 patients who received complete courses of treatment with good compliance showed (68.1 +/- 5.6)% five-year EFS. Meanwhile, the five-year EFS in standard-risk (SR) group and high-risk (HR) group were (75.2 +/- 6.0)% and (47.6 +/- 11.6)%, respectively. The total relapse rate was 10.6% and the median time to relapse was 13 months. Twenty-nine of 188 patients (15.4%) were dead, and 13 patients (7.0%) died from treatment-related complications. Independent adverse prognostic factors included risk grouping, t (9; 22)/bcr-abl gene and leukocyte count., Conclusions: The total EFS of childhood ALL patients treated with Rongcheng ALL-98 Protocol in two hospitals was close to 70%. Therefore, it is necessary to evaluate risk factors and consider the grouping in more detail to reduce the treatment-related mortality and to increase the compliance of treatment which can ultimately improve the EFS.

Measurements of thermopower S(a)(T) along the highly conducting a axis and specific heat of the Bechgaard salts (TMTSF)(2)ClO(4) for various cooling rates through the anion ordering temperature T(a) = 24 K were carried out. Sign reversal in S(a)(T) is found below T(a) and it decreases with increasing cooling rate, which is attributed to the change of a narrow band filling level as the temperature and the cooling rates change. The crossover from 2D to 3D in S(a)(T) is observed around 15 K. The onset temperature of anion ordering in S(a)(T) decreases from 29.8 to 24.2 K as the cooling rate increases. Meanwhile, the electronic specific heat coefficient γ has a pronounced change within this temperature region, giving strong evidence for a narrow band contribution. The difference in the specific heat between the quenched and relaxed states follows a T-cubic law from 5 to 24 K, implying a lattice distortion by the ordered anion only. The entropy estimated from the specific heat peak between 28 and 15 K is Rln (4/3) lower than the value Rln2, consistent with the thermopower result that some anions have been ordered far above T(a) for the relaxed state.

Objective: To explore the relationship between human cyclin C (CCNC) gene and childhood acute lymphocytic leukemia (ALL)., Methods: The total RNA isolated from myeloid tissues of normal children and of children with newly diagnosed ALL and from ALL cell line 6T-CEM was reversely transcribed into cDNA. Real-time fluorescence quantitative PCR method was used to detect CCNC gene expression., Results: CCNC was expressed in myeloid tissues of normal children and of children with newly diagnosed ALL as well as 6T-CEM. The relative expression level of CCNC gene in children with newly diagnosed ALL was significantly lower than in normal controls (2.35 +/- 0.83 vs 13.5 +/- 0.30; P <0.05)., Conclusions: CCNC gene shows lower expression in children with newly diagnosed ALL, suggesting that it may be a tumor suppressing gene in childhood ALL.

Laron syndrome is an autosomal recessive disorder caused by defects of growth hormone receptor (GHR) gene. It is characterized by severe postnatal growth retardation and characteristic facial features as well as high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). This report described the clinical features and GHR gene mutations in 2 siblings with Laron syndrome in a Chinese family. Their heights and weights were in the normal range at birth, but the growth was retarded after birth. When they presented to the clinic, the heights of the boy (8 years old) and his sister (11 years old) were 80.0 cm (-8.2 SDS) and 96.6 cm (-6.8 SDS) respectively. They had typical appearance features of Laron syndrome such as short stature and obesity, with protruding forehead, saddle nose, large eyes, sparse and thin silky hair and high-pitched voice. They had higher basal serum GH levels and lower serum levels of IGF-I, IGFBP-3 and growth hormone binding protein (GHBP) than normal controls. The peak serum GH level after colonidine and insulin stimulations in the boy was over 350 ng/mL. After one-year rhGH treatment, the boy's height increased from 80.0 cm to 83.3 cm. The gene mutation analysis revealed that two patients had same homozygous mutation of S65H (TCA -->CCA) in exon 4, which is a novel gene mutation. It was concluded that a definite diagnosis of Laron syndrome can be made based on characteristic appearance features and serum levels of GH, IGF-I, IGFBP-3 and GHBP. The S65H mutation might be the cause of Laron syndrome in the two patients.

Objective: To investigate the diagnostic value of heat shock protein 70 (HSP70) in central nervous system infection (CNSI) in children., Methods: The level of HSP70 in the cerebrospinal fluid (CSF) was determined in children with CNSI of different etiology. The concentration of HSP70 was determined in the CSF of 104 children, among them 13 patients had purulent meningitis (PM), 38 patients had acute viral meningitis (VM), 7 patients had tuberculous meningitis (TM), and 46 with no CNSI to serve as controls. The concentration of HSP70 was determined by Western blotting assay. The CSF specimens were also analyzed for the total cellular score (TCS), white blood cell count (WBC), lactate dehydrogenase (LDH), protein content (PC), adenosine deaminase (ADD), glucose, chloride content (Cl(í)), and pressure., Results: The CSF level of HSP70 was significantly higher in the PM, TM and VM groups [76.61+/-27.69, 65.85+/-33.16, 33.65+/-16.93] compared with the control group (23.28+/-19.77) (P<0.05 or P<0.01). The HSP70 concentration was markedly higher in the CSF of patients with PM and TM than patients with VM (both P<0.01). No significant difference was found between PM group and TM group in HSP70 level in CSF (P>0.05). The concentration of HSP70 in the CSF was positively correlated to TCS (r=0.298, P=0.002), WBC (r=0.274, P=0.005), LDH (r=0.322, P=0.001), PC (r=0.629, P<0.001), ADD (r=0.363, P<0.001), and negatively correlated to the glucose (r=-0.443, P<0.001) in CSF. The HSP70 concentration was not correlated to the Cl(í) (r=0.148, P=0.133) and pressure (r=0.001, P=0.993) of CSF., Conclusion: HSP70 is increased in the CSF of patients with CNSI. It may be one of the pathophysiological mechanisms of acute infection of the central nervous system. The level of HSP70 in CSF may be a valuable index in the differential diagnosis of CNSI, and it may be helpful in differentiating PM and TM from VM.

Objective: To investigate if WAVE1 is involved in mult drug-resistance (MDR) of human leukemia cell line K562/A02., Methods: The level of WAVE1 in K562 and K562/A02 cells was assayed by Western blot and RT-PCR; K562 cells and K562/A02 cells were transient transfected with pEFBOS-WAVE1 reconstructed plasmid or specifically siRNA to WAVE1. 50% inhibition concentration (IC50) of doxorubicin on K562/A02 was determined by WST-8 assay. Hoechst33258 staining was used to examine cell morphological changes and to calculate percentage of apoptotic nuclei. The mRNA level of mdrl was assayed by RT-PCR. The Bcl-2 protein was assayed by Western blot., Results: 1. The WAVE1 expression at mRNA and protein level in K562/A02 cells was increased by about 70% and 63% respectively as compared with that in K562 cells. 2. Overexpression of WAVE1 in K562 cells by transient transfection significantly increased the resistance to doxorubicin, and increased IC50 from (0.05 +/- 0.00) microg/ml to (2.99 +/- 0.12) microg/ml, and at 1 microg/ml or 5 microg/ml of doxorubicin treatment, cell apoptotic nuclei rate was decreased by 30% or 35% respectively. 3. Suppression of WAVE1 in K562/A02 cells by siRNA resulted in a reversal of MDR to doxorubicin, and decreased IC50 from (4.29 +/- 0.15) microg/ml to (1.85 +/- 0.07) microg/ml, and at 1 microg/ml or 5 microg/ml of doxorubicin treatment, cell apoptotic nuclei rate was increased by 24% or 21% respectively. 4. Overexpression of WAVE1 in K562 cells significantly increased the mdrl mRNA and the Bcl-2 protein, and suppression of WAVE1 in K562/A02 cells by siRNA decreased the mRNA and the protein., Conclusion: WAVE1 involves in the MDR mechanisms in K562/A02 leukemia cells through regulation the level of mdrl and Bcl-2.

Objective: This study analyzed the clinical data of newly diagnosed childhood leukemia from various hospitals in the cities or counties of Hunan Province between 2002 and 2005 in order to provide references for further epidemiologic survey of childhood leukemia., Methods: The clinical data of children with newly diagnosed leukemia from hospitals of various cities or counties of Hunan Province between 2002 and 2005 were collected and reviewed., Results: There were 803 children with leukemia during 2002-2005. Acute lymphoid leukemia was most commonly seen (597/803, 74.35%), followed by acute non-lymphoid leukemia (192/803, 23.91%) and chronic myelocytic leukemia (14/803, 1.74%). There were no significant differences in the clinical type and the prevalence of leukemia between males and females. The prevalence of newly diagnosed childhood leukemia in the urban area was noticeably higher than that in the rural area (2.02/10(5) vs 1.50/10(5), P < 0.05). 41.79% of children with newly diagnosed leukemia from the urban area received treatments but only 22.80% of patients from the rural area received treatments (P < 0.05)., Conclusions: This study of patients-based hospitals showed some features of the morbidity of childhood leukemia in Hunan Province. It provides references for further epidemiologic investigation of this disease in Hunan Province.

Objective: Cytokine mediated cell immunity is the main mode of anti-tumor immunity in organism, and the disequilibrium of cytokine network is the main cause of tumor cells escaping immunologic surveillance. High mobility group box 1 (HMGB1), a nuclear protein, has recently been identified as an important mediator of local and systemic inflammatory diseases when released into the extracellular milieu. In the present study, the investigators explored the clinical significance of alteration in the serum levels of HMGB1 in childhood acute lymphocytic leukemia (ALL) and the mechanism of HMGB1-induced tumor necrosis factor (TNF)-alpha secretion in leukemic cells., Methods: The serum levels of HMGB1 in healthy children and childhood ALL were assayed by Western blotting. K562 leukemic cells were stimulated with recombinant HMGB1 protein in vitro, and the secretion of TNF-alpha was determined by using ELISA. The effects of HMGB1 on activation of p38, c-Jun amino-terminal kinase (JNK), and extracellular-signal regulated protein kinase (ERK) and mitogen-activated protein kinase (MAPK) in K562 cells were assayed by using Western blotting. The effects of inhibitors specific for the MAPK on HMGB1-induced TNF-alpha secretion were assayed by using ELISA., Results: The serum levels of HMGB1 were significantly higher in ALL initial treatment group (n = 15, 43.78 +/- 4.62 microg/ml) than those in healthy control group (n = 15, 0.60 +/- 0.48 microg/ml, P < 0.01) and ALL complete remission group (n = 15, 0.89 +/- 0.62 microg/ml, P < 0.01). No significant difference was found between the healthy control group and ALL complete remission group in HMGB1 levels (P > 0.05). TNF-alpha started to become detectable at 2 h and was still increasing at 16 h after HMGB1 (1 microg/ml) treatment in K562 cell culture. TNF-alpha was also secreted from K562 cells in a dose-dependent manner after HMGB1 (1 ng/ml-1 microg/ml) exposure. HMGB1 induced the phosphorylation of p38, JNK and ERK in k562 cells. Inhibitors specific for the JNK (SP600125), MEK (PD98059), and p38 MAPK (SB203580), abrogated HMGB1-induced TNF-alpha secretion., Conclusions: The measurement of serum HMGB1 is helpful to evaluate the prognosis of the childhood ALL. HMGB1 stimulates leukemic cells to secrete TNF-alpha through a MAPK-dependent mechanism.