ABSTRACT
Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: â The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. â¡Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. â¢Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. â£In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. â¤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). â¥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. â¦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, B-Cell , Female , Humans , Male , Aged , Middle Aged , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Prognosis , Immunohistochemistry , Immunoglobulin Heavy Chains/therapeutic useABSTRACT
BACKGROUND: Hepatitis B virus (HBV) infection is a major global public health concern. Although recent findings suggest an inverse relationship between HBV infection and multiple myeloma (MM), the true relationship between these two conditions remains unclear. AIM: The primary aim of this meta-analysis was to evaluate the association between HBV infection, defined as hepatitis B surface antigen positivity, and the incidence of MM. METHODS: We searched the PubMed/Medline, Cochrane Library and EMBASE databases from January 1975 to July 2014 and reviewed the reference lists of all retrieved articles. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed- and random-effects models. RESULTS: We identified nine case-control studies involving 30,646 patients with MM and 379,837 controls. HBV infection was not significantly associated with the development of MM (OR = 1.3; 95% CI: 0.92-1.82; P = 0.14). A similar risk of developing MM was present in different HBV-prevalent countries. However, significant heterogeneity was observed among studies (P = 0.01). A statistically significant relationship between HBV infection and increased MM risk was detected in sub-analyses evaluating high-quality studies and those with hospital-based controls (P < 0.05). CONCLUSION: HBV infection may be associated with an increased risk of MM. However, confirmation of this relationship and the specific molecular mechanisms involved in the association between HBV infection and the development of MM require further exploration.
Subject(s)
Hepatitis B/diagnosis , Hepatitis B/epidemiology , Multiple Myeloma/diagnosis , Multiple Myeloma/epidemiology , Case-Control Studies , Humans , Risk FactorsABSTRACT
Vascular endothelial growth factors (VEGFs) are crucial regulators of angiogenesis and vasculogenesis. The autocrine VEGF signaling is required for maintaining the homeostasis of vasculature. Dysregulation of angiogenesis is implicated in the development of many human cancers, especially in clear-cell renal cell carcinoma (ccRCC), a highly vascularized tumor. Meanwhile, antiangiogenesis has become a mainstay in the treatment of human cancers. In this study, we analyzed the functional roles of RKTG (Raf Kinase Trapping to Golgi), a negative regulator of mitogen-activated protein kinase (Raf/MEK/ERK) signaling, by sequestration of Raf kinase to the Golgi apparatus, in angiogenesis and ccRCC. Through a series of in vitro and in vivo experiments, we found that RKTG has a negative effect on cell proliferation, migration, sprouting and angiogenesis of endothelial cells. RKTG, by suppressing mitogen-activated protein kinase signaling, negatively regulates the transactivation activity of hypoxia-inducible factor 1α (HIF-1α) by inhibiting formation of HIF-1α/p300 complex and suppressing VEGF transcription, thereby reducing hypoxia-induced VEGF production. The expression level of RKTG is significantly downregulated in clinical ccRCC tumor samples, with an inverse correlation with VEGF expression level. These results highlight the functional roles of RKTG and its regulated Raf/ERK/MEK signaling cascade in angiogenesis and autocrine VEGF signaling. In addition, this study indicates that RKTG is likely implicated in the development of ccRCC through its regulation on angiogenesis.
Subject(s)
Carcinoma, Renal Cell/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Kidney Neoplasms/metabolism , MAP Kinase Signaling System/physiology , Membrane Proteins/metabolism , Signal Transduction/physiology , Autocrine Communication/drug effects , Carcinoma, Renal Cell/pathology , Cell Proliferation/drug effects , Down-Regulation , Humans , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinase Kinases/pharmacology , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Mitogen-Activated Protein Kinases/pharmacology , Vascular Endothelial Growth Factors/metabolism , Vascular Endothelial Growth Factors/pharmacology , raf Kinases/metabolismABSTRACT
Three cyano-bridged bimetallic assemblies, [NiL(1)](3)[Cr(CN)(6)](2).7H(2)O (1), [NiL(2)](3)[Cr(CN)(6)](2).9H(2)O (2), and [NiL(2)](3)[Cr(CN)(5)(NO)](2).9H(2)O (3) (L(1) = 3,10-dimethyl-1,3,5,8,10,12-hexaazacycloctadecane and L(2) = 3,10-diethyl-1,3,5,8,10,12-hexaazacycloctadecane), have been prepared and characterized structurally and magnetically. Complex 1 crystallizes in the monoclinic space group of C2/c with a = 25.929 A, b = 15.442(3) A, c = 19.553(4) A, beta = 106.21(3) degrees, and Z = 4, while 2 and 3 are in the trigonal space group P3 with a = b = 14.919(2) A, c = 9.5246(19) A, gamma = 120 degrees, and Z = 1 for 2 and a = b = 14.863(2) A, c = 9.3134(19) A, gamma = 120 degrees, and Z = 1 for 3. The structures of 1-3 are similar and consist of cyano-bridged two-dimensional (2D) honeycomb-like neutral Ni(3)Cr(2) layers. In each complex, [Cr(CN)(6)](3-) or [Cr(CN)(5)(NO)](3-) coordinates to three trans-[Ni(macrocycle)](2+) groups using three fac-CN(-) ligands, providing a 2D layered network. The NO group in [Cr(CN)(5)(NO)](3-) remains monodentate. Magnetic studies show the existence of a short-range ferromagnetic interaction in all of the complexes. Complexes 1 and 2 exhibit long-range antiferromagnetic ordering at 13.0 and 11.9 K, respectively, and a metamagnetic transition with critical field of ca. 1.6 kOe for 1 and 1.5 kOe for 2 at 1.8 K. Complex 3 exhibits long-range ferromagnetic ordering below 4.3 K.
ABSTRACT
This paper introduces a parametric method for identifying the somatosensory evoked potentials (SEPs). The identification was carried out by using pole-zero modeling of the SEPs in the discrete cosine transform (DCT) domain. It was found that the DCT coefficients of a monophasic signal can be sufficiently approximated by a second-order transfer function with a conjugate pole pair. The averaged SEP signal was modeled by the sum of several second-order transfer functions with appropriate zeros and poles estimated using the least square method in the DCT domain. Results of the estimation demonstrated that the model output was in an excellent agreement with the raw SEPs both qualitatively and quantitatively. Comparing with the common autoregressive model with exogenous input modeling in the time domain, the DCT domain modeling achieves a high goodness of fitting with a very low model order. Applications of the proposed method are possible in clinical practice for feature extraction, noise cancellation and individual component decomposition of the SEPs as well as other evoked potentials.
Subject(s)
Evoked Potentials, Somatosensory , Models, Neurological , Adolescent , Adult , Biomedical Engineering , Electroencephalography/statistics & numerical data , Humans , Models, Statistical , Signal Processing, Computer-AssistedABSTRACT
As some functional diseases in the brain, such as cerebellum dysfunction and Parkinson's disease, cause the disability related to human movement control, a compensation method was developed for improving the performance of hand movement. The compensation can be carried out by adding assistant force, which is generated from artificial equipment attached to a human arm. From the experiment of visual target tracking, the tracking trajectories recorded from both healthy persons and patients with movement disability were analyzed. It was found that the tracking trajectories were represented sufficiently by a dynamic model of a robot arm in which the differences between healthy persons and patients were characterized by the model parameters. Based on the model, it was demonstrated that the hand movement of patients could be improved by introducing an appropriate compensation. The effectiveness of the proposed compensation method was verified from a simulation study of a robot arm. The design of artificial equipment for compensating the hand movement was also presented and discussed.
Subject(s)
Cerebellar Diseases/rehabilitation , Electric Stimulation Therapy/instrumentation , Functional Laterality/physiology , Motor Skills/physiology , Parkinson Disease/rehabilitation , Psychomotor Performance/physiology , Robotics/instrumentation , Biofeedback, Psychology/physiology , Brain/physiopathology , Cerebellar Diseases/physiopathology , Computer Simulation , Equipment Design , Humans , Parkinson Disease/physiopathology , Range of Motion, Articular/physiologyABSTRACT
The Markov process amplitude (MPA) EEG model effectively representing spontaneous brain activity of the EEG was introduced. The relationship between the electrical mechanism for EEG generation and the proposed model was also investigated. The MPA EEG model was described by the sinusoidal waves with the randomly fluctuating amplitude of the first-order Markov process. The parameters of the MPA EEG model were determined optimally based on the real EEG records. The results of model outputs in the frequency domain demonstrated an excellent fit with the power spectrum of the corresponding EEG. The simulated model signal in the time domain also showed good agreement with the EEG time series. The satisfactory results from the MPA EEG model suggest its possible applicability in clinical practice. Furthermore, from the high goodness of fit, the authors think that the neurons oscillate at fixed frequencies and are modulated by synaptic interactions in accordance with the first-order Markov process.
Subject(s)
Cerebral Cortex/physiopathology , Electroencephalography/statistics & numerical data , Epilepsy/physiopathology , Markov Chains , Models, Statistical , Adult , Brain Mapping , Epilepsy/diagnosis , Evoked Potentials/physiology , Fourier Analysis , Humans , Signal Processing, Computer-AssistedABSTRACT
This study introduces a method for accurate identification of the waveform of the evoked potentials by decomposing the component responses. The decomposition was achieved by zero-pole modeling of the evoked potentials in the discrete cosine transform (DCT) domain. It was found that the DCT coefficients of a component response in the evoked potentials could be modeled sufficiently by a second order transfer function in the DCT domain. The decomposition of the component responses was approached by using partial expansion of the estimated model for the evoked potentials, and the effectiveness of the decomposition method was evaluated both qualitatively and quantitatively. Because of the overlap of the different component responses, the proposed method enables an accurate identification of the evoked potentials, which is useful for clinical and neurophysiological investigations.
Subject(s)
Electroencephalography , Evoked Potentials, Somatosensory , Signal Processing, Computer-Assisted , Adolescent , Adult , Humans , Models, Theoretical , PainABSTRACT
A method for eliminating blink artifacts that contaminate electroencephalographic (EEG) records is introduced. The proposed method enables a direct estimation of blink artifacts without the use of the simultaneously recorded electroculargraphic (EOG) signal. The estimation of blink artifacts in the EEG was achieved by modeling in the discrete cosine transform (DCT) domain. The DCT coefficients of the blink artifact were sufficiently represented by a system transfer function with a low model order of 4. Two cases were investigated: one was blink artifact elimination for the background EEG and the other was for the somatosensory evoked potentials. The effectiveness of the proposed method was demonstrated in an experimental study based on actual EEG data of 11 healthy subjects. The simplicity and effectiveness of the proposed method suggest that blink artifact elimination using DCT domain modeling can possibly be applied in various areas of neuroscience for improving EEG quality.
Subject(s)
Electroencephalography/statistics & numerical data , Adolescent , Adult , Biomedical Engineering , Blinking , Evoked Potentials, Somatosensory , Humans , Models, Neurological , Models, StatisticalABSTRACT
To develop an appropriate model for representing spontaneous electroencephalography (EEG) is an important and necessary work in the field of neuroscience. The Markov process amplitude (MPA) EEG model has been proposed in our previous work for representing the features of the EEG in terms of a few parameters. However, being a linear model, the linear MPA EEG model cannot perfectly describe the spontaneous EEG that displays nonlinear phenomena. In this paper, the nonlinear Markov process amplitude (nonlinear MPA) EEG model that includes nonlinear components is introduced. The consistent consideration of the nonlinear features of the EEG investigated by N. Wiener and P. L. Nunez can be seen from the nonlinear MPA EEG model. The similarity in the time domain and the goodness of fitting in the frequency domain with respect to the ongoing EEG are shown. As a result, the EEG power spectrum can be decomposed into the spontaneous components and the nonlinearly coupled components by use of the nonlinear MPA EEG model, which is useful for a better understanding the mechanism of the EEG generation.
Subject(s)
Electroencephalography/statistics & numerical data , Biomedical Engineering , Humans , Markov Chains , Models, Neurological , Nonlinear DynamicsABSTRACT
Automatic detection of open and closed eye states in electroencephalographic (EEG) records was investigated in this study as a part of procedures for the precise interpretation of the background EEG to achieve a comprehensive automatic EEG interpretation system. The features of eye open and closure were extracted from the EEG using a Markov process amplitude (MPA) EEG model, which could efficiently express the features of the EEG using a small number of parameters. A new technique, named the trigger method, was also developed to overcome the difficulty resulting from large differences in the EEG features among different subjects, because an accurate detection could not be obtained by using the conventional threshold method. The proposed method gave satisfactory results which conformed with those of visual inspection by a qualified EEGer and could be clinically used as a preprocessing method for the automatic interpretation of the awake background EEG.
Subject(s)
Brain/physiology , Electroencephalography/methods , Image Processing, Computer-Assisted/methods , Ocular Physiological Phenomena , Adult , Aged , Automation , Humans , Markov Chains , Middle AgedABSTRACT
The immunoglobulins content was measured in blood serum of 233 individuals who took part in the elimination of effects of ChNPP breakdown. Distributive patterns of phenotypes, antigens and genes of HLA system depending on levels of Igs G, A and M have been studied. A positive association of some HLA antigens with concentration of immunoglobulins of certain isotypes was found out.