Developing and evaluating a predictive model for neonatal hyperbilirubinemia based on UGT1A1 gene polymorphism and clinical risk factors.

Background: Neonatal hyperbilirubinemia (NHB) is one of the most common diseases in the neonatal period. Without timely diagnosis and treatment, it can lead to long-term complications. In severe cases, it may even result in fatality. The UGT1A1 gene and clinical risk factors play important roles in the development and progression of NHB. Methods: In this study, we conducted a cohort study and analyzed 3258 newborns from the Jilin Women And Children Health Hospital in northern China, including 372 children with hyperbilirubinemia. We established a predictive model using a logistic regression model based on clinical risk factors and the polymorphism of the G211A locus in the UGT1A1 gene of newborns. Furthermore, the performance of the prediction model was evaluated using the ROC curve. Results: The logistic regression model indicates that the following factors are associated with an increased risk of NHB: the time when stool turns yellow [P ≤ 0.001, OR 1.266 (95% CI: 1.125-1.425)]; neonatal cephalohematoma [P ≤ 0.001, OR 33.642 (95% CI: 21.823-51.861)]; hemolytic disease of newborn [P ≤ 0.001, OR 33.849 (95% CI: 18.589-61.636)]; neonatal weight loss [P ≤ 0.001, OR 11.275 (95% CI: 7.842-16.209)]; neonatal premature rupture of membranes (PROM) history [P = 0.021, OR 1.422 (95% CI: 1.056-1.917)]; genetic polymorphism at the UGT1A1 gene G211A locus. Gestational age is a protective factor [P ≤ 0.001, OR 0.766 (95% CI: 0.686-0.855)]. Compared to natural labor, cesarean section is a protective factor [P = 0.011, OR 0.711 (95% CI: 0.546-0.926)], while assisted delivery is a risk factor [P = 0.022, OR 2.207 (95% CI: 1.121-4.346)]. The area under the curve (AUC) of this prediction model is 0.804 (95% CI: 0.777-0.831), indicating good discrimination ability and value for predicting the risk of NHB after birth. Conclusion: We have developed and evaluated a predictive model that combines UGT1A1 gene polymorphism and clinical risk factors for the first time. By using this nomogram and taking into account the results of serum total bilirubin measurement or transcutaneous bilirubin measurement, early prediction of the risk of neonatal hyperbilirubinemia can be achieved.

Influences of Four Kinds of Surfactants on Biodegradations of Tar-Rich Coal in the Ordos Basin by Bacillus bicheniformis.

The biodegradation of tar-rich coal in the Ordos Basin was carried out by Bacillus licheniformis (B. licheniformis) under actions of four kinds of surfactants, namely, a biological surfactant (Rh), a nonionic surfactant (Triton X-100), an anionic surfactant (LAS), and a cationic surfactant (DTAB). The biodegradation rates under the actions of Triton X-100, LAS, Rh, DTAB, and the control group (without surfactant) were 59.8%, 54.3%, 51.6%, 17.3%, and 43.5%, respectively. The biodegradation mechanism was studied by examining the influences of surfactants on coal samples, bacteria, and degradation products in the degradation process. The results demonstrated that Rh, Triton X-100, and LAS could promote bacterial growth, while DTAB had the opposite effect. Four surfactants all increased the cell surface hydrophobicity (CSH) of B. licheniformis, and Triton X-100 demonstrated the most significant promotion of CSH. The order of improvement in microbial cell permeability by surfactants was DTAB > TritonX-100 > LAS > Rh > control group. In the presence of four surfactants, Triton X-100 exhibited the best hydrophilicity improvement for oxidized coal. Overall, among the four surfactants, Triton X-100 ranked first in enhancing the CSH of bacteria and the hydrophilicity of oxidized coal and second in improving microbial cell permeability; thus, Triton X-100 was the most suitable surfactant for promoting B. licheniformis's biodegradation of tar-rich coal. The GC-MS showed that, after the action of Triton X-100, the amount of the identified degradation compounds in the toluene extract of the liquid product decreased by 16 compared to the control group, the amount of dichloromethane extract decreased by 6, and the amount of ethyl acetate extract increased by 6. Simultaneously, the contents of alkanes in the extracts of toluene and dichloromethane decreased, lipids increased, and ethyl acetate extract exhibited little change. The FTIR analysis of the coal sample suggested that, under the action of Triton X-100, compared to oxidized coal, the Har/H and A(CH2)/A(CH3) of the remaining coal decreased by 0.07 and 1.38, respectively, indicating that Triton X-100 enhanced the degradation of aromatic and aliphatic structures of oxidized coal. Therefore, adding a suitable surfactant can promote the biodegradation of tar-rich coal and enrich its degradation product.

MicroRNA-204 silencing relieves pain of cervical spondylotic radiculopathy by targeting GDNF.

Cervical spondylosis may cause chronic neck pain, radiculopathy and/or myelopathy, and consequently results in severe brain damage. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for motoneurons. Accumulating microRNAs (miRNAs) have highlighted as critical regulators of GDNF signaling in the mediation of neuroinflammation and neuropathic pain. Hence, we performed this study to investigate the potential role of miR-204 in the neuropathic pain of cervical spondylotic radiculopathy (CSR) by targeting GDNF. A rat model of spinal cord compression (SCC) was established to stimulate a pathologic lesion. RT-qPCR and western blot assays characterized the downregulation of GDNF and the upregulation of miR-204 in spinal cord tissues of rats under the conditions of SCC. Moreover, miR-204 could directly target GDNF, as evidenced by dual-luciferase reporter gene assay. In order to elucidate the roles of miR-204 and GDNF in SCC-induced neuropathic pain, miR-204 sponge, GDNF, or shRNA against GDNF was introduced to the rats, followed by measurements for SCC-induced neuroinflammation and neuropathic pain. GDNF upregulation or miR-204 silencing was identified to reduce the spontaneous pain score, gait scores and cell apoptosis. Furthermore, GDNF upregulation or miR-204 silencing resulted in elevated amplitude of sensory-evoked potentials (SEPs), number of motoneurons, release of pro-inflammatory factors, TNF-α, and IL-1ß in addition to an increase in the anti-inflammatory factor BDNF. Taken together, upregulation of GDNF induced by miR-204 silencing confers protection against SCC-induced pain in rat models, suggesting a potential therapeutic target for CSR treatment.

The Characteristics of Binary Spike-Time-Dependent Plasticity in HfO2-Based RRAM and Applications for Pattern Recognition.

A binary spike-time-dependent plasticity (STDP) protocol based on one resistive-switching random access memory (RRAM) device was proposed and experimentally demonstrated in the fabricated RRAM array. Based on the STDP protocol, a novel unsupervised online pattern recognition system including RRAM synapses and CMOS neurons is developed. Our simulations show that the system can efficiently compete the handwritten digits recognition task, which indicates the feasibility of using the RRAM-based binary STDP protocol in neuromorphic computing systems to obtain good performance.

Radiofrequency Thermocoagulation in Relieving Refractory Pain of Knee Osteoarthritis.

To investigate the efficacy of radiofrequency thermocoagulation (RFTC) in relieving refractory pain of knee osteoarthritis (OA), we selected 54 patients with chronic knee OA pain, 27 treated with RFTC (case group) and 27 receiving regular treatments (control group). Response evaluations were conducted before treatment, and at the termination of treatment, and 3-month follow-up, applying the visual analog scale, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and American Knee Society Score (AKSS). Data analyses were performed with SPSS 21.0. At the termination of treatments and 3-month follow-ups, cases gained significantly increased scores in vitality, bodily pain, general health perceptions, physical functioning, and social role functioning by SF-36 scaling and in pain, range of motion, stability, walking, and stair climbing by AKSS (all P < 0.05). Controls received higher scores by AKSS in pain at the termination of treatments and in pain, range of motion, and walking at the termination of 3-month follow-ups (all P < 0.05). Both cases and controls presented significant difference between visual analog scale scores before treatments and those at the termination of 3-month follow-ups (both P < 0.05). All patients felt less pain after treatments, cases presenting better improvement (P < 0.05). Pain was stronger in females compared with males and in a positive correlation with age while had no obvious relation to disease course. In conclusion, RFTC may have better efficacy in relieving refractory pain and promoting function recovery in patients with knee OA than regular treatment.

The Reinfusion of Autogenous Shed Blood After Unilateral Total Knee Arthroplasty Using the Perioperative Autologous Transfusion System OrthoPAT.

This study aims to explore the use of postoperative autogenous shed blood reinfusion using Orthopedic Perioperative Autotransfusion System (OrthoPAT) system in treating patients undergoing unilateral total knee arthroplasty (TKA). Fifty patients undergoing unilateral TKA were enrolled as the experimental group A and were treated with reinfusion of autologous shed blood within 6 hours after unilateral TKA using OrthoPAT. Accordingly, 50 patients undergoing unilateral TKA were selected as the experimental group B and were treated with allogeneic blood transfusion. Different indexes were observed at different times. Patients in both groups had relatively stable hemodynamics, and there was no postoperative coagulopathy. Prothrombin time, thrombin time, and activated partial thromboplastin time were lower, and fibrinogen was higher in group A than that in group B 24 hours after surgery (all P < 0.05). White blood cell, red blood cell, hemoglobin, hematocrit (Hct), and platelet count levels in group A were lower than those in group B 12 hours after surgery (all P < 0.05). The postoperative complications of the 2 groups have significant difference (P < 0.05). Postoperative autogenous shed blood reinfusion using OrthoPAT system in the treatment of patients undergoing unilateral TKA may improve the coagulation function of patients and reduce the rejection caused by standard allogeneic blood transfusion.

Establishment of a knock-in mouse model with the SLC26A4 c.919-2A>G mutation and characterization of its pathology.

Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4(tm1Dontuh/tm1Dontuh) mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4(tm1Dontuh/tm1Dontuh) mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4(tm1Dontuh/tm1Dontuh) mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4(tm1Dontuh/tm1Dontuh) mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4(tm1Dontuh/tm1Dontuh) mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4(-/-) mice and Slc26a4(loop/loop) mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains.

Transplantation of insulin-producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice.

Diabetes mellitus can be treated with islet transplantation, although there is a scarcity of donors. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord stroma could be induced to differentiate into insulin-producing cells and the effects of retro-orbital injection of human insulin-producing cells for the treatment of nonobese diabetic (NOD) mice. MSCs were isolated from human umbilical cord stroma and induced to differentiate into insulin-producing cells using differentiation medium. Differentiated cells were evaluated by immunocytochemistry, RT-PCR, and real-time PCR. C-peptide release, both spontaneous and after glucose challenge, was measured by ELISA. Insulin-producing cells were then transplanted into NOD mice. Blood glucose levels and body weights were monitored weekly. Human nuclei and C-peptide were detected in mouse livers by immunohistochemistry. Pancreatic ß-cell development-related genes were expressed in the differentiated insulin-producing cells. Differentiated cells' C-peptide release in vitro increased after glucose challenge. Further, in vivo glucose tolerance tests showed that blood sugar levels decreased after the cells' transplantation into NOD mice. After transplantation, insulin-producing cells containing human C-peptide and human nuclei were located in the liver. Thus, we demonstrated that differentiated insulin-producing cells from human umbilical cord stromal MSCs transplanted into NOD mice could alleviate hyperglycemia in diabetic mice.

[Clinical assessment of ProSeal laryngeal mask airway during total hip replacement operation].

OBJECTIVE: To assess the value of ProSeal-LMA (laryngeal mask airway) during hip replacement operation. METHODS: Sixty patients undergoing hip replacement operation were randomly divided into two groups with 30 cases in each. ProSeal-LMA was applied in Group I and normal endotracheal tube in Group II. The parameters of heart rate (HR), mean arterial blood pressure (MAP), partial pressure of carbon dioxide in end expiratory gas (PetCO2) and airway pressure (Paw) were monitored and recorded in both groups at time points of before and after placing ProSeal-LMA or tracheal tube, body turning-over, skin incision and extubating of ProSeal-LMA or tracheal tube. And also the cases with airway complications were reported. RESULTS: There was no significant changes of HR and MAP in Group I at time points of placing and extracting ProSeal-LMA (P > 0.05). However, there was significant difference of HR and MAP in Group II at time points of placing and extracting tracheal tube (P < 0.05), And it was significantly higher than that in Group I at the same time point (P < 0.05). No significant difference of these parameters was observed at other time points (P > 0.05). And also PetCO2 and Paw were not changed significantly between two groups at time points of before and after body turning over (P > 0.05). CONCLUSION: ProSeal-LMA can be applied in hip replacement operation because of its simple handling, lesser effects upon respiration and circulation and fewer post-operative complications.

A computational model of FGF-2 binding and HSPG regulation under flow.

A novel convection-diffusion-reaction model is developed to simulate fibroblast growth factor (FGF-2) binding to cell surface receptors (FGFRs) and heparan sulfate proteoglycans (HSPGs) under flow conditions within a cylindrical-shaped vessel or capillary. The model consists of a set of coupled nonlinear partial differential equations (PDEs) and a set of coupled nonlinear ordinary differential equations (ODEs). The time-dependent PDE system is discretized and solved by a second-order implicit Euler scheme using the finite volume method. The ODE system is solved by a stiff ODE solver VODE using backward differencing formulation (BDF). The transient solution of FGF-2, FGFR, HSPG, and their bound complexes for three different flow rates are computed and presented. Simulation results indicate that the model can predict growth factor transport and binding to receptors with/without the presence of heparan sulfate, as well as the effect of flow rate on growth factor-receptor binding. Our computational model may provide a useful means to investigate the impact of fluid flow on growth factor dynamics, and ultimately, signaling within the circulation.

Three-dimensional model on thermal response of skin subject to laser heating.

A three-dimensional (3D) multilayer model based on the skin physical structure is developed to investigate the transient thermal response of human skin subject to laser heating. The temperature distribution of the skin is modeled by the bioheat transfer equation, and the influence of laser heating is expressed as a source term where the strength of the source is a product of a Gaussian shaped incident irradiance, an exponentially shaped axial attenuation, and a time function. The water evaporation and diffusion is included in the model by adding two terms regarding the heat loss due to the evaporation and diffusion, where the rate of water evaporation is determined based on the theory of laminar boundary layer. Cryogen spray cooling (CSC) in laser therapy is studied, as well as its effect on the skin thermal response. The time-dependent equation is discretized using the finite difference method with the Crank-Nicholson scheme and the stability of the numerical method is analyzed. The large sparse linear system resulted from discretizing the governing partial differential equation is solved by a GMRES solver and the expected simulation results are obtained.