Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

Enhanced anaerobic digestion performance and sludge filterability by membrane microaeration for anaerobic membrane bioreactor application.

Slow dissolution/hydrolysis of insoluble/macromolecular organics and poor sludge filterability restrict the application potential of anaerobic membrane bioreactor (AnMBR). Bubble-free membrane microaeration was firstly proposed to overcome these obstacles in this study. The batch anaerobic digestion tests feeding insoluble starch and soluble peptone with and without microaeration showed that microaeration led to a 65.7-144.8% increase in methane production and increased critical flux of microfiltration membrane via driving the formation of large sludge flocs and the resultant improvement of sludge settleability. The metagenomic and bioinformatic analyses showed that microaeration significantly enriched the functional genes and bacteria for polysaccharide and protein hydrolysis, microaeration showed little negative effects on the functional genes involved in anaerobic metabolisms, and substrate transfer from starch to peptone significantly affected the functional genes and microbial community. This study demonstrates the dual synergism of microaeration to enhance the dissolution/hydrolysis/acidification of insoluble/macromolecular organics and sludge filterability for AnMBR application.

Role of endoscopic ultrasound in the evaluation of unexplained extrahepatic bile duct dilatation.

OBJECTIVE: This study was performed to assess the diagnostic performance of endoscopic ultrasonography (EUS) in patients with extrahepatic bile duct (EBD) dilatation and develop a novel model incorporating EUS-based signature with clinical parameters for distinguishing the malignant dilation of EBD. METHODS: The EUS data and clinical parameters of the patients were collected and analyzed retrospectively. First, we evaluated the diagnostic performance of EUS in detecting the cause of EBD dilatation. Then, we performed univariate and multivariate binary logistic regression analyses based on clinical and EUS features. Finally, a nomogram was established to aid in distinguishing between malignant dilation and noncalculous benign dilatation of EBD in patients. RESULTS: A total of 184 patients were enrolled. For the diagnosis of malignant dilation, EUS achieved an accuracy of 90.76%, sensitivity of 85.96%, and specificity of 92.91%. For the diagnosis of calculous dilation, EUS achieved an accuracy of 100%, sensitivity of 100%, and specificity of 100%. For the diagnosis of noncalculous benign dilatation, EUS achieved an accuracy of 90.76%, sensitivity of 90.90%, and specificity of 90.58%. Multivariable logistic regression analyses indicated that abnormal liver function test, elevated tumor markers, and EUS findings were the well-diagnostic factors of malignant EBD dilation. The nomogram established by these factors showed good calibration and discrimination. CONCLUSION: EUS is a useful examinational modality in the work-up of EBD dilatation. In combination with abnormal liver function test and elevated tumor markers, EUS may provide additional information for the detection of malignant dilation of EBD and should be further investigated.

Novel combined endoscopic and laparoscopic surgery for advanced T2 gastric cancer: Two case reports.

BACKGROUND: The standard treatment for advanced T2 gastric cancer (GC) is laparoscopic or surgical gastrectomy (either partial or total) and D2 lymphadenectomy. A novel combined endoscopic and laparoscopic surgery (NCELS) has recently been proposed as a better option for T2 GC. Here we describe two case studies demonstrating the efficacy and safety of NCELS. CASE SUMMARY: Two T2 GC cases were both resected by endoscopic submucosal dissection and full-thickness resection and laparoscopic lymph nodes dissection. This method has the advantage of being more precise and minimally invasive compared to current methods. The treatment of these 2 patients was safe and effective with no complications. These cases were followed up for nearly 4 years without recurrence or metastasis. CONCLUSION: This novel method provides a minimally invasive treatment option for T2 GC, and its potential indications, effectiveness and safety needs to be further evaluated in controlled studies.

[Formation and hemodynamics of pseudoaneurysm after rupture and bleeding of aneurysm: an experiment with dogs].

OBJECTIVE: To study the process and mechanism of the formation of pseudoaneurysm after the rupture of aneurysm. METHODS: A model of aneurysm (AN) of the left common carotid artery (CCA) was made in 20 dogs. One to 2 weeks after the formation of AN, a localized hematoma connected with the AN was formed as a model of pseudoaneurysm after the rupture of true aneurysm (false aneurysm caused by the ruptured true aneurysm, T + F) was established. The models were examined by using color Doppler, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and digital subtraction angiographies (DSA) 1, 2, 3, 4, and 8 weeks after the operation in all the animals. By the end of experiment the models of AN were taken out to undergo pathological examination by light and electron microscopy. The blood flow velocity, pressure on the walls and shear stress in the true and false aneurysm were analyzed by simulation of computational fluid dynamics (CFD) on these animal models. RESULTS: Experimental models of T + F were successfully created in the 11 dogs. CCA was successfully occluded in 3 dogs, true aneurysm was occluded in 2, and true aneurysms without pseudoaneurysm were produced in 4. The blood flow in the pseudoaneurysm was very slow. The pressure and shear stress were very high in the ends distal to the aneurysms and not high around the boundary between the true and false aneurysms. CONCLUSION: The formation and growth of pseudoaneurysm are probably correlated with the pressure within the vessels. T + F should be positively and definitely treated by surgery to prevent them from rupture and bleeding.

A minimal axiom group for rough set based on quasi-ordering.

Rough set axiomatization is one aspect of rough set study to characterize rough set theory using dependable and minimal axiom groups. Thus, rough set theory can be studied by logic and axiom system methods. The classic rough set theory is based on equivalent relation, but rough set theory based on reflexive and transitive relation (called quasi-ordering) has wide applications in the real world. To characterize topological rough set theory, an axiom group named RT, consisting of 4 axioms, is proposed. It is proved that the axiom group reliability in characterizing rough set theory based on similar relation is reasonable. Simultaneously, the minimization of the axiom group, which requires that each axiom is an equation and each is independent, is proved. The axiom group is helpful for researching rough set theory by logic and axiom system methods.

Neural decoding based on probabilistic neural network.

Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices, such as robot arms, computer cursors, and paralyzed muscles. A variety of neural decoding algorithms have been designed to explore relationships between neural activities and movements of the limbs. In this paper, two novel neural decoding methods based on probabilistic neural network (PNN) in rats were introduced, the PNN decoder and the modified PNN (MPNN) decoder. In the experiment, rats were trained to obtain water by pressing a lever over a pressure threshold. Microelectrode array was implanted in the motor cortex to record neural activity, and pressure was recorded by a pressure sensor synchronously. After training, the pressure values were estimated from the neural signals by PNN and MPNN decoders. Their performances were evaluated by a correlation coefficient (CC) and a mean square error (MSE). The results show that the MPNN decoder, with a CC of 0.8657 and an MSE of 0.2563, outperformed the traditionally-used Wiener filter (WF) and Kalman filter (KF) decoders. It was also observed that the discretization level did not affect the MPNN performance, indicating that the MPNN decoder can handle different tasks in BMI system, including the detection of movement states and estimation of continuous kinematic parameters.

[The evolution of related names of Bi syndrome and the theory of etiology and pathogenesis].

In the Traditional Chinese medical literature of ancient times, Bi referred to the pathogenesis, or the symptoms as well as the name of the disease. As the name of a disease, Bi has the different meanings of broad and narrow., joint-running, joint-running wind, white tiger joint-running, gout etc. referring to the narrow meaning of Bi disease. The theory of etiology and pathogenesis of the narrow meaning of Bi disease developed from damp-impediment, wind-cold-damp impediment to damp-hot impediment, stasis-hot impediment, which reflected the constant deepening of cognition.