"Typhoidal Cells" Appear in a Woman with Hemophagocytic Syndrome Secondary To Brucellosis: A Case Report.

We report a case of hemophagocytic syndrome (HPS) secondary to brucellosis, in which typhoidal cells were found in bone marrow, suggesting typhoidal cells present not only in Salmonella typhi infections but also in other bacterial infections. Typhoidal cells in bone marrow can be used to quickly identify the presence of bacterial infection pending the results of bone marrow and/or blood cultures.

Extracellular Vesicle-Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models.

BACKGROUND: Stroke is a leading cause of adult disability that can severely compromise the quality of life of patients, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA (circRNA) molecules are known to function in ischemic brain injury. Lentivirus-based expression systems have been widely used in basic studies of circRNAs, but safety issues with such delivery systems have limited exploration of the potential therapeutic roles for circRNAs. METHODS: Circular RNA SCMH1 (circSCMH1) was screened from the plasma of patients with acute ischemic stroke by using circRNA microarrays. Engineered rabies virus glycoprotein-circSCMH1-extracellular vesicles were generated to selectively deliver circSCMH1 to the brain. Nissl staining was used to examine infarct size. Behavioral tasks were performed to evaluate motor functions in both rodent and nonhuman primate ischemic stroke models. Golgi staining and immunostaining were used to examine neuroplasticity and glial activation. Proteomic assays and RNA-sequencing data combined with transcriptional profiling were used to identify downstream targets of circSCMH1. RESULTS: CircSCMH1 levels were significantly decreased in the plasma of patients with acute ischemic stroke, offering significant power in predicting stroke outcomes. The decreased levels of circSCMH1 were further confirmed in the plasma and peri-infarct cortex of photothrombotic stroke mice. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that circSCMH1 treatment improved functional recovery after stroke in both mice and monkeys, and we discovered that circSCMH1 enhanced the neuronal plasticity and inhibited glial activation and peripheral immune cell infiltration. CircSCMH1 binds mechanistically to the transcription factor MeCP2 (methyl-CpG binding protein 2), thereby releasing repression of MeCP2 target gene transcription. CONCLUSIONS: Rabies virus glycoprotein-circSCMH1-extracellular vesicles afford protection by promoting functional recovery in the rodent and the nonhuman primate ischemic stroke models. Our study presents a potentially widely applicable nucleotide drug delivery technology and demonstrates the basic mechanism of how circRNAs can be therapeutically exploited to improve poststroke outcomes.

Male patients with primary Sjögren's syndrome have unique clinical manifestations and circulating lymphocyte profiles.

OBJECTIVES: We aimed to explore the relationship between clinical characteristics and circulating lymphocyte profiles in Chinese male patients with primary Sjögren's syndrome (pSS). METHOD: Data from 397 patients with pSS were analyzed retrospectively. 37 were male, which is a prevalence of 9.3%. The clinical, laboratory, and immunophenotypic profiles of peripheral blood lymphocyte subsets were compared between male and female pSS patients. RESULTS: Male patients with primary Sjögren's syndrome have unique clinical manifestations and circulating lymphocyte profiles. Male patients complained more about xerophthalmia and presented with more extra-glandular manifestations as compared with female patients. The CD4+/CD8+ ratio (P = 0.030), the prevalence of CD4-CD8- T cells in lymphocytes (P = 0.020), the absolute number of CD4-CD8- T cells (P = 0.035), the prevalence of CD4+ T cells in lymphocytes (P < 0.001), and the absolute number of CD4+ T cells (P = 0.023) were significantly lower in male patients compared to female patients. On the other hand, the prevalence of CD8+CD28+ T cells (P = 0.030) and CD4+CD25high T cells (P = 0.040) in lymphocytes was significantly higher in male patients than in female patients. Moreover, compared to females with pSS, an elevated serum IgG level, low C3 and C4 levels, anti-SSB positivity, and ANA titers of ≥ 1:160 positivity were more frequent in male with pSS. CONCLUSIONS: Male patients with pSS have distinctive peripheral blood lymphocyte subpopulations, present with more severe clinical symptoms and immunological features, and have an unfavorable prognosis. Key Points • Male patients with pSS have more severe clinical symptoms and specific characteristics of peripheral blood lymphocyte subsets. • Male pSS patients exhibit a higher intensity of the disease (as evaluated by ESSDAI). • Male patients with pSS require individualized treatment regimens and closer follow-up.

A pilot behavioural and neuroimaging investigation on photothrombotic stroke models in rhesus monkeys.

BACKGROUND: Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans. RESULTS: The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke. COMPARISON WITH EXISTING METHODS: The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect. CONCLUSIONS: The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.

MicroRNA-21 and microRNA-155 promote the progression of Burkitt's lymphoma by the PI3K/AKT signaling pathway.

INTRODUCTION: Burkitt's lymphoma (BL) is a rare and highly aggressive B cell non-Hodgkin lymphoma. High toxicity of chemotherapy for BL treatment causes morbidity and mortality. Many miRNAs have been used as biomarkers for early detection or therapy targets for tumors. However, the roles of miR-21 and miR-155 in Burkitt's lymphoma remain unclear. METHODS: We collected 15 blood samples from patients with Burkitt's lymphoma and evaluated the expression of miR-21 and miR-155. Then, we knocked down miR-21 and miR-155 expression in Burkitt's lymphoma cell lines and assessed cell proliferation, cell cycle, and apoptosis. Furthermore, we detected the activation of PI3K/AKT pathway by qPCR and western blot. Finally, we predicted the target genes of miR-21 and miR-155 by publicly available databases. RESULTS: The expression of miR-21 and miR-155 in blood samples from patients with Burkitt's lymphoma were significantly upregulated. Knockdown of miR-21 and miR-155 significantly suppressed cell proliferation, and resulted in S phase arrest and cell apoptosis. The knockdown of miR-21 and miR-155 inhibited the activation of the PI3K/AKT pathway. We found that the target genes of miR-21 and miR-155 were C1RL and TCAP. CONCLUSION: miR-21 and miR-155 promote the progression of Burkitt's lymphoma through PI3K/AKT signaling by targeting C1RL and TCAP. Our findings will provide a novel biomarker and therapeutic strategies for Burkitt's lymphoma.

AKR1C1-3, notably AKR1C3, are distinct biomarkers for liver cancer diagnosis and prognosis: Database mining in malignancies.

Aldo-keto reductases, known as AKR1C1-AKR1C4 enzymes, are pivotal to NADPH-dependent reduction, and their expression is highly associated with the progression of malignant cancers. However, the expression and distinct prognostic value of the AKR1C family members in liver cancer are not well established. In the current study, the expression of AKR1C isoforms was studied using the Oncomine online databases. In addition, their expression profiles were analyzed in cancer cell lines using data from the Cancer Cell lines Encyclopedia (CCLE) database. Furthermore, the mRNA expression levels of AKR1C family members between liver cancer and normal liver samples were assessed by the Gene Expression Profiling Interactive Analysis (GEPIA) database. The AKR1C1-3 prognostic value was further investigated by the Kaplan-Meier plotter database in liver cancer patients. It was found that the expression levels of AKR1C3 were elevated significantly in liver cancer tissues and cells as demonstrated by the Oncomine, CCLE and GEPIA databases. The expression levels of AKR1C1 and AKR1C2 in liver cancer tissues did not increase significantly in the Oncomine database while expression was significantly high in CCLE and GEPIA databases. However, the expression levels of the AKR1C4 gene as determined by the CCLE, GEPIA and Oncomine databases were not consistent. Therefore, the Kaplan-Meier survival curves of liver cancer patients with the expression of AKR1C1-3 genes were next analyzed. The data indicated that high expression levels of AKR1C1-3 were correlated with lower overall survival in liver cancer patients. Using the co-expression and PPI network, AKR1C1-3 genes were identified that were involved in the same pathway displaying 44 total unique interactors. These results suggested that the increased AKR1C1-3, notably AKR1C3 expression levels served as possible diagnostic biomarkers and essential prognostic factors for liver cancer patients. The roles of AKR1C4 in liver cancer require further examination.

Peripheral blood lymphocyte subsets of newly diagnosed DLBCL patients and their dynamic changes with rituximab based immunochemotherapy.

The purpose of this study was to explore lymphocyte subsets of newly diagnosed DLBCL patients, and dynamics along with treatment of R-CHOP. A total of 40 DLBCL patients were enrolled. ALC of grade III-IV DLBCL patients was significantly lower than that of health controls (1.33*10E9/L vs 1.89*10E9/L, p = 0.003), mostly attributing to decreased CD4+ cells (p = 0.012). And serum LDH level of patients was negatively correlated with ALC (p = 0.033). ALC progressively decreased along with treatment, so as to CD3+, CD4+ and CD19+ cells, while proportion of CD4+ and CD8+ cells increased significantly after two cycles' treatment (p < 0.05). CR of ALC low (<1.18*10E9/L) group was lower than that of ALC high group (37.5% vs 73.3%), though not statistically significant (p = 0.179).

[Study on active catheter for minimally invasive surgery based on large deflection theory].

A kind of active catheter used for minimally invasive surgery and actuated by shape memory alloy (SMA) was developed in this paper. The outer diameter of the catheter is 1.25 mm. The catheter was designed to consist of several bending units for achieving a large bending angle, but at the same time not increasing the outer diameter too much. It was considered that the deflection curve of axis of the catheter is determined by the output force of the SMA actuators. Based on large deflection theory, the deflection curve equation of the axis of the catheter was set up using precise form of the curvature. Through integral transform, the length and output force of each SMA actuator under the anticipative attitude of the tip of the active catheter were obtained, and the accurate coordinate of the center of the joint was givein. This study has provided great convenience to get control of the catheter, and has improved, to a certain extent, the design philosophy of problems such as active catheter.

Eosinophil Granulocyte and NK Cell-Mediated Platelet Destruction in Immune Thrombocytopenia.

To investigate the contribution and mechanism of eosinophil granulocytes and NK cells-mediated cytotoxicity to the pathogenesis of ITP. Mononuclear cells and platelets were prepared from the bone marrow of 16 ITP patients and 10 healthy controls. Separately, eosinophil granulocytes and NK cells were selected with magnetic microbeads. As the target cells, the autologous platelets were cultured with eosinophil granulocytes and NK cells respectively for 6 h and then stained with annexin V. Ratio of platelets expressing annexin V was determined by flow cytometry. The fraction of NK cells expressing perforin, granzyme B, FasL and TNF were determined by flow cytometry. Human eosinophil cationic protein (ECP) level in the bone marrow was determined by ECP ELISA kit. The annexin V positive platelet ratio of the ITP group was significantly higher than that of the control group; the expression rates of granzyme B, perforin, FasL on NK cells of the ITP group were significantly higher than those of the control group. Expression of human ECP in bone marrow of immune thrombocytopenia patients was higher than that of healthy controls. NK cells and eosinophil granulocytes are activated in ITP and might be involved in the pathogenesis of ITP.

Hip cartilage thickness measurement accuracy improvement.

Accurate measurement of the distance separating two adjacent sheet structures, such as femoral cartilage and acetabular cartilage in the hip joint is important in evaluation of osteoarthritis. A new method, insensitive to the influence of adjacent sheet structures, was developed to improve the accuracy of hip cartilage thickness measurement. A theoretical simulation for investigating the influence of adjacent sheet structures on the accuracy of cartilage thickness measurement in MR images was performed. The thickness is defined as the distance between zero-crossings of the second directional derivatives along the sheet surface normal direction. The simulation measurement showed considerable underestimation in thickness measurement occurred due to the influence of the adjacent sheet. A new method based on a model of the MR imaging process to eliminate the influence of adjacent sheet structure was developed and tested using phantoms and two cadaveric human hip joint MR scans. The new method reduced the influence of the adjacent sheet structure was more accurate than the conventional method for measuring hip cartilage thickness.

Design of a new haptic device and experiments in minimally invasive surgical robot.

In this paper, we designed a 8 degrees of freedom (DOFs) haptic device for applications in minimally invasive surgical robot. The device can provide three translational, three rotational and a grasping motion and force feedback capability. It is composed of three parts, including an arm mechanism, a redundant wrist mechanism and a grasper mechanism. The kinematics and gravity compensation algorithms are also detailed in the paper. In addition, the haptic device and a slave surgical robot for minimally invasive surgery (MIS) developed by our lab are integrated as a master-slave surgical robotic system in this paper. In the master-slave robotic system, a new control system is designed to realize real-time mater-slave control based on EtherCAT bus technology. Experiments show that the haptic device can effectively compensate gravity at any position in its workspace and successfully realize master-slave operation by the control method, which prove the haptic device designed in this paper can be used as a master manipulator to control the surgical robot.

A novel 4-DOF surgical instrument with modular joints and 6-Axis Force sensing capability.

BACKGROUND: It is difficult for surgeons to exert appropriate forces during delicate operations due to lack of force feedback in robot-assisted minimally invasive surgery (RMIS). A 4-DOF surgical grasper with a modular wrist and 6-axis force sensing capability is developed. METHODS: A grasper integrated with a miniature force and torque sensor based on the Stewart platform is designed, and a cable tension decomposition mechanism is designed to alleviate influence of the cable tension to the sensor. A modularized wrist consisting of four joint units is designed to facilitate integration of the sensor and eliminate coupled motion of the wrist. RESULTS: Sensing ranges of this instrument are ±10 N and ±160 N mm, and resolutions are 1.2% in radial directions, 5% in axial direction, and 4.2% in rotational directions. An ex vivo experiment shows that this instrument prototype successfully measures the interaction forces. CONCLUSIONS: A 4-DOF surgical instrument with modular joints and 6-axis force sensing capability is developed. This instrument can be used for force feedback in RMIS. Copyright © 2016 John Wiley & Sons, Ltd.

Experiments and kinematics analysis of a hand rehabilitation exoskeleton with circuitous joints.

Aiming at the hand rehabilitation of stroke patients, a wearable hand exoskeleton with circuitous joint is proposed. The circuitous joint adopts the symmetric pinion and rack mechanism (SPRM) with the parallel mechanism. The exoskeleton finger is a serial mechanism composed of three closed-chain SPRM joints in series. The kinematic equations of the open chain of the finger and the closed chains of the SPRM joints were built to analyze the kinematics of the hand rehabilitation exoskeleton. The experimental setup of the hand rehabilitation exoskeleton was built and the continuous passive motion (CPM) rehabilitation experiment and the test of human-robot interaction force measurement were conducted. Experiment results show that the mechanical design of the hand rehabilitation robot is reasonable and that the kinematic analysis is correct, thus the exoskeleton can be used for the hand rehabilitation of stroke patients.

Enhance photoelectrochemical hydrogen-generation activity and stability of TiO2 nanorod arrays sensitized by PbS and CdS quantum dots under UV-visible light.

We develop a composite photoanode by sensitizing TiO2 nanorod arrays with PbS quantum dots (QDs) and CdS QDs. Benefitted from additional introduced PbS QDs and CdS QDs onto TiO2, the absorption of the composite photoanodes are broaden from UV to visible region. The experimental results showed that the PbS sandwiched between TiO2 and CdS cannot only broad the absorption properties but also improve the stability. The stability can be explained by the hole facile transmission from PbS to CdS because of the valence band offsets between PbS and CdS which cause a small energy barrier and reduce the hole accumulation. The photocurrent density reached 1.35 mA cm(-2) at 0.9716 V vs. RHE (0 V vs. Ag/AgCl, under 60 mW cm(-2) illumination) for TiO2/PbS/CdS. The highest photocurrent of TiO2/PbS/CdS can be explained by the smallest of total resistance (138 Ω cm(-2)) compared to TiO2/CdS and pristine TiO2.

[Expression of XIAP gene in chronic myeloid leukemia and its clinical significance].

This study was purpose to investigate the expression of XIAP mRNA in chronic myeloid leukemia (CML) and to explore its significance in the advance and prognosis of CML. The chromosomal karyotype analysis and detection of XIAP mRNA were performed by the technique of chromosomal R banding and real time PCR in 71 patients with CML and 10 healthy controls. The results showed that there was a significant increase of XIAP mRNA expression in accelerated and blastic phase of the CML, compared with the patients in chronic phase (t = 9.10, 9.30, p < 0.01). Moreover, the difference of XIAP mRNA expression level was not statistically significant in different karyotype groups. It is concluded that the XIAP gene expression in accelerated and blastic phases of CML patients obviously increases, XIAP gene is closely related to the advance of CML.

Automatic identification of the reference system based on the fourth ventricular landmarks in T1-weighted MR images.

RATIONALE AND OBJECTIVES: The reference system based on the fourth ventricular landmarks (including the fastigial point and ventricular floor plane) is used in medical image analysis of the brain stem. The objective of this study was to develop a rapid, robust, and accurate method for the automatic identification of this reference system on T1-weighted magnetic resonance images. MATERIALS AND METHODS: The fully automated method developed in this study consisted of four stages: preprocessing of the data set, expectation-maximization algorithm-based extraction of the fourth ventricle in the region of interest, a coarse-to-fine strategy for identifying the fastigial point, and localization of the base point. The method was evaluated on 27 Brain Web data sets qualitatively and 18 Internet Brain Segmentation Repository data sets and 30 clinical scans quantitatively. RESULTS: The results of qualitative evaluation indicated that the method was robust to rotation, landmark variation, noise, and inhomogeneity. The results of quantitative evaluation indicated that the method was able to identify the reference system with an accuracy of 0.7 +/- 0.2 mm for the fastigial point and 1.1 +/- 0.3 mm for the base point. It took <6 seconds for the method to identify the related landmarks on a personal computer with an Intel Core 2 6300 processor and 2 GB of random-access memory. CONCLUSION: The proposed method for the automatic identification of the reference system based on the fourth ventricular landmarks was shown to be rapid, robust, and accurate. The method has potentially utility in image registration and computer-aided surgery.

Skeleton-based active catheter navigation.

BACKGROUND: The emergence of the active catheter has prompted the development of catheterization in minimally invasive surgery. However, it is still operated using only the physician's vision; information supplied by the guiding image and tracking sensors has not been fully utilized. METHODS: In order to supply the active catheter with more useful information for automatic navigation, we extract the skeleton of blood vessels by means of an improved distance transform method, and then present the crucial geometric information determining navigation. With the help of tracking sensors' position and pose information, two operations, advancement in the proximal end and direction selection in the distal end, are alternately implemented to insert the active catheter into a target blood vessel. RESULTS: The skeleton of the aortic arch reconstructed from slice images is extracted fast and automatically. A navigation path is generated on the skeleton by manually selecting the start and target points, and smoothed with the cubic cardinal spline curve. Crucial geometric information determining navigation is presented, as well as requirements for the catheter entering the target blood vessel. Using a shape memory alloy active catheter integrated with magnetic sensors, an experiment is carried out in a vascular model, in which the catheter is successfully inserted from the ascending aorta, via the aortic arch, into the brachiocephalic trunk. CONCLUSIONS: The navigation strategy proposed in this paper is feasible and has the advantage of increasing the automation of catheterization, enhancing the manoeuvrability of the active catheter and providing the guiding image with desirable interactivity.

Computer-assisted automatic localization of the human pedunculopontine nucleus in T1-weighted MR images: a preliminary study.

BACKGROUND: The pedunculopontine nucleus (PPN) is a new promising target of deep brain stimulation (DBS) for the treatment of Parkinson's disease. This study was to develop a method of computer-assisted automatic localization of the PPN in T1-weighted MR images. METHODS: A 3D template of a segment of the brainstem containing the PPN was constructed. A knowledge-based, hierarchical method of template-to-subject registration was proposed to register the template to the subject's data to locate the subject's PPN. RESULTS: Experiments were performed with both T1-weighted and proton density MR images acquired from 12 people. Preliminary results show that the proposed method can locate the PPN with an error of 1.83 +/- 0.42 mm for its rostral pole and 1.57 +/- 0.34 mm for its caudal pole. CONCLUSION: The proposed method is automatic, robust and accurate in the localization of the PPN, which demonstrates utility for preoperative surgical planning.

Steerable catheters in minimally invasive vascular surgery.

BACKGROUND: Remote-controlled catheter navigation systems have recently been introduced into minimally invasive vascular surgery and some of them have already been applied in clinical practice. Steerable catheters with improved manoeuvrability play an important role in these innovations for conventional catheterization. METHODS: This review details the development of various steerable catheters, both in use clinically and under investigation. Comprehensive comparison and analysis in several key aspects are followed to reveal both the advantages and limitations of these catheters, as well as the requirements for relevant techniques. RESULTS: Steerable catheters are able to select direction in the distal end, and superior to conventional counterparts in many aspects. Differences between magnetic and active catheters mainly lie in function, safety, configuration of operating room and cost. They have similar requirements for miniaturization and slave insertion mechanisms. CONCLUSIONS: Steerable catheters are rapidly evolving and still require technological refinements to extend current capabilities.

Research on the axis shape of an active catheter.

BACKGROUND: An active catheter is a minimally invasive surgery catheter that can perform deflectable motions. The active catheter can be controlled from outside the body and moves like a snake, utilizing a multi-joint mechanism with distributed shape memory alloy (SMA) actuators. METHODS: It was considered that the deflection curve of the axis of the catheter is determined by the output force of the SMA actuators. Based on the large deflection theory, the deflection curve equation of the axis of the catheter was derived, using the precise form of the curvature. RESULTS: Through experimentation, the axial bending curve shape of the blended active catheter was measured precisely, and the experimental results were compared with the calculation results obtained from the large deflection theory and the circular arc hypothesis. The experimental results show that the curves calculated by large deflection theory are very close to the actual axis curves. CONCLUSIONS: An active catheter prototype has been designed using the theory presented in this paper. Utilizing a vascular model, the active catheter-based invasive surgery was simulated. The experiment confirmed that the large deflection theory calculation method can be used to guide the design of the active catheter.