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Purpose Previous clinical studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest, but the results are conflicting and there is no uniform agreement regarding gender differences in survival and prognosis. The present study was aimed to investigate the interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest. Methods Asphyxia was induced by blocking the endotracheal tube in 120 adult Sprague–Dawley rats (60 males and 60 females) at the same age. Cardiopulmonary resuscitation (CPR) was started after 5 min of untreated cardiac arrest. Animals were randomized into one of the three post resuscitation care intervention groups (n = 40, 20 males) immediately after resuscitation: (1) normothermic control (NC): ventilated with 2% N2/98% O2 for 1 h under normothermia; (2) targeted temperature management (TTM): ventilated with 2% N2/98% O2 for 1 h under hypothermia; (3) hydrogen inhalation (HI): ventilated with 2% H2/98% O2 for 1 h under normothermia. Physiological variables were recorded during the 5 h post resuscitation monitoring period. Neurological deficit score (NDS) and accumulative survival were used to assess 96 h outcomes. Mutual independence analysis and Mantel–Haenszel stratified analysis were used to explore the associations among gender, intervention and survival. Results The body weights of female rats were significantly lighter than males, but CPR characteristics did not differ between genders. Compared with male rats, females had significantly lower mean arterial pressure, longer onset time of the electroencephalogram (EEG) burst and time to normal EEG trace (TTNT) in the NC group; relatively longer TTNT in the TTM group; and substantially longer TTNT, lower NDSs, and higher survival in the HI group. Mutual independence analysis revealed that both gender and intervention were associated with neurological outcome. Mantel–Haenszel stratified analysis demonstrated that female rats had significantly higher survival rate than males when adjusted for the confounder intervention. Conclusion In this rat model cardiac arrest and CPR, gender did not affect resuscitation but associated with neurological outcome. The superiority of female rats in neurological recovery was affected by post resuscitation interventions and female rats were more likely to benefit from hydrogen therapy.

Goal for the present research is investigating the effect of scale effect on free vibration of piezoelectric sandwich nanobeams on Winkler foundation. For this purpose, the effects of nonlocal parameters and strain gradient parameters on the free vibration of the model are studied. Based on the nonlocal strain gradient theory and Timoshenko beam theory, the nonlinear vibration of piezoelectric sandwich nanobeams on Winkler foundation is investigated. The nonlinear governing equations and boundary conditions are derived using the Hamilton's principle. The partial differential equation is transformed into ordinary differential equation by Galerkin's method, and then the nonlinear vibration of piezoelectric nanobeam is numerically analyzed using the Runge-Kutta method. The results show that the nonlinear frequency ratio decreases with the increase of length-to-thickness ratio. When the nonlocal parameter is not less than the strain gradient length scale parameter, the piezoelectric nanobeam exhibits stiffness softening effect. When the nonlocal parameter is not greater than the strain gradient length scale parameter, the piezoelectric nanobeam exhibits stiffness hardening effect. It is also observed that both large length-to-thickness ratios and shear deformation can attenuate the nonlocal strain gradient effect. In addition, changes in the external applied voltage have a significant effect on the natural frequency of the piezoelectric nanobeams and increasing the thickness of the piezoelectric layer can enhance the structural stiffness.

In this paper, considering the proven role of exosomes and the inevitable randomization within-host, we establish a hepatitis B virus (HBV) model with cell-to-cell transmission and CTL immune response from a deterministic framework to a stochastic differential equation (SDE). By introducing the reproduction number $ R_0 $, we prove that $ R_0 $ can be used to govern the stochastic dynamics of the SDE HBV model. Under certain assumptions, if $ R_{0}\leq1 $, the solution of the SDE model always fluctuates around the infection-free equilibrium of the deterministic model, which indicates that the HBV will eventually disappear almost surely; if $ R_{0} > 1 $, under extra conditions, the solution of the SDE model fluctuates around endemic equilibrium of the corresponding deterministic model, which leads to the stochastic persistence of the HBV with probability one. One of the most interesting findings is that the fluctuation amplitude is positively related to the intensity of the white noise, which can provide us some useful control strategies to regulate HBV infection dynamics.

BACKGROUND Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be an ideal endpoint for antiviral therapy and a final therapeutic target for chronic hepatitis (CHB). This study aimed to evaluate the HBsAg kinetics in CHB patients during peginterferon-alpha (Peg-IFN-alpha) treatment. MATERIAL AND METHODS A retrospective cohort study was performed using a case database, which included 151 patients who received Peg-IFN-alpha treatment and with HBsAg load of no less than 4 time points from May 1, 2018 to January 31, 2019. The HBsAg kinetic pattern was analyzed by Q-type clustering, and a clinical prognostic empirical model was constructed based on the HBsAg kinetic pattern of uncured patients. RESULTS Changes of HBsAg in 13 functionally cured patients were attributed to 3 kinetic patterns by cluster analysis, and there was a significant positive correlation between functionally cure time and baseline HBsAg. For uncured 116 patients with treatment duration longer than or equal to 56 days, 5 HBsAg kinetic patterns were obtained by cluster analysis, and the clinical prognosis empirical model was established. Finally, 13 new functionally cured patients preliminarily confirmed the rationality of the proposed empirical model. CONCLUSIONS According to empirical model, we recommend that the therapeutic regime should be timely adjusted to improve sustained response rate and reduce patients' medical burden for patients with second (Z type) and fifth (Z+W type) kinds of patterns. While for the rest of patterns' patients, it is recommended to continue treatment for a longer period of time to achieve the desired therapeutic goal.

Immune thrombocytopenia (ITP) is an autoimmune disease which arises due to self-destruction of circulating platelets. Failure to respond or maintain a response to first-line treatment can lead to refractory/relapsed (R/R) ITP. The mechanism remains complicated and lacks a standard clinical treatment. Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Activation of the mTOR pathway in autoimmune diseases suggests that SRL might be a useful agent for treating ITP. Accordingly, we initiated an open-label, prospective clinical trial using SRL for patients with R/R ITP (ChiCTR-ONC-17012126). The trial enrolled 86 patients, each dosed with 2–4 mg/day of SRL. By the third month, 40% of patients (34 of 86) achieved complete remission (CR) and 45% of patients (39 of 86) achieved partial remission (PR), whereby establishing an overall response rate (ORR) of 85%. By 6 months of treatment, 41% of patients (32 of 78) achieved CR and 29% of patients (23 of 78) achieved PR, establishing an ORR of 70% without serious side effects. After 12 months follow-up, the ORR remained at 65%. We also found that SRL treatment exhibited higher efficacy in achieving CR in ITP patients who were younger than 40 years old or steroid dependent by univariate analysis. Importantly, in patients who responded, SRL treatment was associated with a reduction in the percentage of Th2, Th17 cells, and increase in the percentage of M-MDSCs and Tregs, indicating that SRL may reestablish peripheral tolerance. Taken together, Sirolimus demonstrated efficacy as a second-line agent for R/R ITP.

In this article, a non-classical shell model incorporating flexoelectric effect is presented to investigate the buckling behavior of piezoelectric cylindrical nanoshell based on the couple stress theory. This non-classical shell model contains both material length scale parameter and flexoelectric parameter and can capture the size effect and piezoelectricity of nanoscale shells. The closed-form solution of the critical buckling load is achieved by energy variational approach. Results show a significant dependence of the buckling modes of the nanoshell on the flexoelectric constant as well as the material length scale parameter. It is also found that the buckling load of the nanoshell is enhanced with the consideration of the flexoelectric effect and the couple stress theory due to their enhancement on the stiffness of the nanoshell. Although the effect of flexoelectricity is more pronounced in short shells, the influence of the material length scale parameter on the buckling load is remarkable even in long shells. In addition, the effects of flexoelectricity and the material length scale parameter on the critical buckling load are more evident for thicker shells.

Vibration of nanotubes embedded in an elastic matrix is investigated by using the nonlocal Timoshenko beam model. Both a stress gradient and a strain gradient approach are considered. The Hamilton’s principle is adopted to obtain the frequencies of the nanotubes. The dependencies of frequency on the stiffness and mass density of the surrounding elastic matrix, the nonlocal parameter, the transverse shear stiffness and the rotary inertia of the nanotubes are obtained. The results show a significant dependence of frequencies on the surrounding medium and the nonlocal parameter. The frequencies are over-predicted by using the Euler beam model that neglects the shear stiffness and rotary inertia of the nanotubes. It is also found that the lower bound and the upper bound for the frequencies of nanotubes are, respectively, provided by the strain gradient model provides and the stress gradient theory. Explicit formulas for the frequency are obtained and therefore are easy to use by material scientists and engineers for the design of nanotubes and nanotubes based composites.

Community nurses play a crucial role in early detection and timely diagnosis of dementia. However, they are usually not prepared for the role through their formal education, particularly in low- and middle-income countries due to undeveloped nursing curriculum in dementia care. This paper describes a two-arm cluster-randomized controlled trial to improve community nurses' knowledge, attitudes, and practice changes using an innovative and interactive mobile phone applet-based activity in primary care settings. The intervention sites received dementia-specific training and control sites received care training for older people with disability. Both groups completed measures assessing dementia knowledge, attitudes, and intentions to make changes to achieve early detection and a timely diagnosis of dementia immediately after training and at 3-month follow-up. The intervention group provided feedback immediately after training and at 3-month follow-up. The main results show that the intervention group demonstrated significant improvement in dementia knowledge and attitudes from baseline immediately after training and at the 3-month follow-up. The intervention group also showed more intentions to make changes to achieve early detection of dementia. Feedback suggested the program was well-received. Overall, the program showed acceptability and feasibility in improving nurses' dementia knowledge, attitudes, and intentions to achieve early detection of dementia.

In this paper, a hepatitis B virus (HBV) infection model with logistic hepatocyte growth is investigated, and the basic reproduction number of HBV determining the extinction and the persistence of infection is obtained. When the basic reproduction number is less than one, the infection becomes extinct eventually; when the basic reproduction number is greater than one, the infection becomes persistent in vivo. Hopf bifurcation surface determining the stability of the chronic infection equilibrium is found, and the effect of all the parameters on stability of the chronic infection equilibrium is also discussed.

Hepatitis B virus (HBV) infection is an important health problem worldwide. In this paper, we introduce an improved HBV model with standard incidence function and cytokine-mediated ‘cure’ based on empirical evidences. By carrying out a global analysis of the modified model and studying the stability of the equilibria, we show that infection-free equilibrium is globally asymptotically stable if the basic reproduction number of virus is less than one and, conversely, the infection equilibrium is globally asymptotically stable if the basic reproduction number of virus is greater than one. The study and information derived from this model and other related models may have an important impact on preventing mortality due to hepatitis B virus in the future.

Routine targeted temperature management is recommended for comatose adult patients with return of spontaneous circulation after cardiac arrest. However, the role of targeted temperature management in patients resuscitated from nonshockable cardiac arrests remains uncertain. We conducted an updated systematic review and meta-analysis to evaluate the effects of targeted temperature management in this population. Medline, EMBASE, and Cochrane databases were systematically reviewed for studies published between January 2005 and March 2016, in which targeted temperature management was compared with standard care or normothermia for adult patients resuscitated from nonshockable cardiac arrests. A total of 25 trials that included 5715 patients were identified from 10985 relevant papers. Pooled data showed that targeted temperature management not only associated with improved short-term survival (RR = 1.42, 95% CI: 1.28–1.57) and neurological function (RR = 1.63, 95% CI: 1.39–1.91) but also associated with improved long-term survival (RR = 1.64, 95% CI: 1.27–2.12) and neurological recovery (RR = 1.42, 95% CI: 1.07–1.90) in observational cohort studies. However, more frequent infectious complications were reported in hypothermia-treated patients (RR = 1.46, 95% CI: 1.26–1.70) and the quality of the evidence ranged from moderate to very low.

Background The determination of angiogenesis time is the key prerequisite to obtaining a balance between valid repair and excessive angiogenesis in wound healing. The aim of the investigation was to establish a bio-mathematical model predicting corneal angiogenesis time after alkali burn by back propagation neural network (BP neural network). Methods The corneas of mice in 24 groups were burned by 0.01 mol/l NaOH. Five mice in each group were sacrificed at 6 h after alkali burn. The expression levels of vegf and tsp2, determined by real-time quantitive PCR, were used as input vectors in BP neural network. Meanwhile, the corneal angiogenesis of other mice, inspected every 3 h in 24 groups till the angiogenesis time were determined, served as output vectors. The data of 18 groups were randomly chosen for network adaptation while that of other 6 groups for simulation forecasting with functions of minmax (), postreg, prepca, trapca, respectively. Results A bio-mathematical model of two-level BP neural network was established, for its purpose to predict the angiogenesis time through the expression values of vegf and tsp2. The performance index (0.00999996) was smaller than the target value (0.01) after adapting 36,557 times and the accuracy rate of this predict system was 83.33%. Furthermore, the ideal regression line and the optimization regression line were almost coincident ( R = 0.988 in network adaptation and R = 0.793 in simulation forecasting). Conclusions The investigation indicated that the bio-mathematical model had available performance of simulation and forecasting. It might provide a novel method to solve clinical problems.

The aim of this study is to determine the prevalence and correlates of depressive symptoms in a school-based sample of 7–17-year-old children and adolescents in west-central China. A large cross-sectional sample survey of 10657 children and adolescents was conducted in Chongqing, a municipality in west-central China. Data were collected from the Children's Depression Inventory (CDI), Adolescent Self-Rating Life Events Checklist (ASLEC) and social-demographic variables which were evaluated with a structured scale. The total prevalence of depression risk was 23.9%. The risk factors for depressive symptoms included age older than 12 years, grade lower than 10, having unmarried parents, being taken care of by people other than two parents (single parent, grandparent(s), other relatives, or others), and living in a low-income family. The pressures of health and adaptation, interpersonal relationship, and study were also strong predictors of depressive symptoms. The prevalence of depressive symptoms among children and adolescents in Chongqing of China is relatively high compared with most figures reported in other cities. There is an urgent need to develop efficacious interventions aimed at the prevention and early recognition of childhood and adolescent depression.

Electrical defibrillation, which consists of delivering a therapeutic dose of the electrical current to the fibrillating heart with the aid of a defibrillator, is still the only effective way to treat life-threatening ventricular fibrillation (VF). However, the efficacy of electrical therapy for terminating VF is highly dependent on the waveform applied. When new defibrillation waveforms or techniques are developed, their efficacy needs to be accurately evaluated and compared to those in use. A common method for the comparison of defibrillation efficacy is to estimate and compare the individual defibrillation threshold (DFT) by constructing dose response curves or using an up-and-down method. Since DFT is calculated by repetitive and sequential shocks, there will be variability for each measurement and for each individual. This creates a considerable uncertainty for paired comparison. In this paper, a novel grouped up-and-down method is developed for the comparison of defibrillation efficacy between two different defibrillation waveforms or techniques. The efficacy of two commonly used biphasic defibrillation waveforms was compared in a porcine model of cardiac arrest using the developed method. Experimental results demonstrate that the proposed method is more sensitive for efficacy comparison and requires less defibrillation attempts compared with traditional DFT methods.

Acute burn injuries are among the most devastating forms of trauma and lead to significant morbidity and mortality. Appropriate fluid resuscitation after severe burn, specifically during the first 48 hours following injury, is considered as the single most important therapeutic intervention in burn treatment. Although many formulas have been developed to estimate the required fluid amount in severe burn patients, many lines of evidence showed that patients still receive far more fluid than formulas recommend. Overresuscitation, which is known as “fluid creep,” has emerged as one of the most important problems during the initial period of burn care. If fluid titration can be personalized and automated during the resuscitation phase, more efficient burn care and outcome will be anticipated. In the present study, a dynamic urine output based infusion rate prediction model was developed and validated during the initial 48 hours in severe thermal burn adult patients. The experimental results demonstrated that the developed dynamic fluid resuscitation model might significantly reduce the total fluid volume by accurately predicting hourly urine output and has the potential to aid fluid administration in severe burn patients.

We use the Hill function to analyze the dynamics of Tc-99m 2 methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy data and to examine the earlier lower extremity microvascular perfusion of diabetic patients without typical clinical symptoms and with the preserved normal ankle-brachial index (ABI). Eighty-eight participants (30 healthy control, 34 diabetic patients, and 24 diabetic patients with peripheral arterial disease [PAD]) were recruited and applied 99mTc-MIBI scintigraphy. Fourteen diabetic patients with PAD also underwent computed tomography angiography (CTA) examination and were performed endovascular interventions. Diabetic patients with normal ABI already have significantly impaired maximum 99mTc-MIBI muscle perfusion counts (P

The contribution of covalently closed circular DNA (cccDNA) and dendritic cells (DCs) to the progression of chronic hepatitis B virus (HBV) infection remains largely unknown. A dynamic model with seven cell types was proposed based on the biological mechanisms of viral replication and the host immune response. The cccDNA self-amplification rate was found to be closely related to both the basic reproduction number of the virus and the immune response. The combination of the cccDNA self-amplification rate and the initial activated DC count induces rich dynamics. Applying our model to the clinical data of untreated patients, we found that chronic patients have a high cccDNA self-amplification rate. For antiviral treatment, an overall drug effectiveness was introduced and the critical drug effectiveness was obtained. The model predicts that timely long-term therapy is needed to reduce the symptoms of HBV and to maintain the benefits of treatment.

The most frequent initial rhythm in out-of-hospital witnessed cardiac arrest is ventricular fibrillation (VF) and electrical defibrillation is still the only effective therapy for the termination of this life-threatening cardiac arrhythmia. Even though earlier defibrillation is greatly emphasized during cardiopulmonary resuscitation (CPR), unnecessary or repetitive high energy defibrillations are associated with decreased post-resuscitation myocardial function. Optimizing the timing of defibrillation is of great importance in order to discriminate patients should receive immediate defibrillation versus alternate therapies such as CPR. Since characteristics of VF waveform changes over time and with CPR, which exhibit predictable ability of defibrillation success, quantitative analysis of VF waveform has the potential to guide defibrillation. This article reviewed methods developed for VF waveform analysis (including time domain, frequency domain, time-frequency domain, nonlinear analysis, and combination analysis techniques) and their performances for the prediction of defibrillation outcomes in clinical settings. The retrospective meta-analysis confirmed that VF waveform could predict the return of organized electrical activity, restoration of spontaneous circulation, and survival reliably. Additionally, predictors based on time-frequency and nonlinear methods were superior to other methods on the whole. However, no prospective studies have been performed to identify the optimal time of defibrillation utilizing VF waveform analysis until now. Therefore, the value of VF waveform analysis to guide clinical countershock management still needs further investigation.

In this paper, mathematical analysis of the global dynamics of a viral infection model in vivo is carried out. Though the model is originally to study hepatitis C virus (HCV) dynamics in patients with high baseline viral loads or advanced liver disease, similar models still hold significance for other viral infection, such as hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection. By means of Volterra-type Lyapunov functions, we know that the basic reproduction number [Formula: see text] is a sharp threshold para-meter for the outcomes of viral infections. If [Formula: see text], the virus-free equilibrium is globally asymptotically stable. If [Formula: see text], the system is uniformly persistent, the unique endemic equilibrium appears and is globally asymptotically stable under a sufficient condition. Other than that, for the global stability of the unique endemic equilibrium, another sufficient condition is obtained by Li–Muldowney global-stability criterion. Using numerical simulation techniques, we further find that sustained oscillations can exist and different maximum de novo hepatocyte influx rate can induce different global dynamics along with the change of overall drug effectiveness. Finally, some biological implications of our findings are given.

Human immunodeficiency virus 1 (HIV-1) drug resistance is a grave problem in highly active antiretroviral therapy (HAART) and neutral mutation is an important factor in the evolution of HIV-1. We consider the process of HIV-1 quasispecies transition in HAART to be transformation among three viral phenotypes: wild-type HIV-1, neutral-type HIV-1 and resistant-type HIV-1. A new model is proposed to study the transition dynamics of resistant-type HIV-1 induced by neutral mutation. The colonized time, the stable time and the stable size of the resistant species are simulated with the model. The results indicate that neutral mutation is closely related to the colonized pattern of resistant-type HIV-1 quasispecies which may lead to important strategies for predicting or checking HIV-1 drug resistance. Key words: Human immunodeficiency virus -1, neutral mutation, drug resistance, highly active antiretroviral therapy, stability delay, stability.

Objectives: Fluctuation profile has been observed in chronic hepatitis B patients who are untreated or interrupt therapy. A mathematical model and its parameters could be used to diagnose the assumption of superinfection of hepatocytes and to understand the causes for the spontaneous fluctuation pattern of HBV DNA loads in chronically infected patients. Methods: We propose a new conceptual model in terms of chemical kinetics, which is based on the assumption that hepatocytes can be superinfected with hepatitis B virus (HBV). Minimizing the sum of squares of the deviations, we fitted the model to the HBV DNA trajectories from clinical data and obtained the model parameters. Results: The model with the fitted parameters can capture the tendency of HBV DNA trajectories. The mean value of the fitted number of virions that enter a single hepatocyte at the beginning stage of an invasion is 2.10 ± 0.18. The dynamics patterns may correlate with the clinical phenotypes of patients and the value of clinical parameters, such as α-fetoprotein, hepatitis B e-antigen, hepatitis B e-antibody, total bilirubin and alanine transaminase. Conclusions: The superinfection scenario is possible in HBV infection and it may induce HBV DNA fluctuation in the host.

In this paper we model and analyze the hepatitis B virus (HBV) infection in a diffusion model confined to a finite domain, induced by intracellular time delay between infection of a cell and production of new virus particles. The equilibrium solutions are obtained and the stability is analyzed if the space is assumed as homogeneous. When the space is inhomogeneous, the effects of diffusion and intracellular time delay are obtained by computer simulations.

A mathematical model is proposed to simulate the hepatitis B virus (HBV) infection with spatial dependence. The existence of traveling waves is established via the geometric singular perturbation method. Numerical simulations show that the model admits non-monotone traveling profiles. Influences of various parameters on the minimum wave speed are also discussed.

To study the transition dynamics of resistant-type human immunodeficiency virus 1 (HIV-1) in highly active antiretroviral therapy (HAART) and the affect of neutral mutation in the evolution of HIV-1, a mathematical model is proposed when mutation occurs mainly during reproduction. The derived results show that the resistant-type will certainly colonize in patients once mutation occurs. Furthermore, a neutral mutation is closely related to the colonized pattern of resistant-type HIV-1 quasispecies and there are some changes in the pattern of transmission dynamics when mutation occurs mainly during reproduction or in the absence of reproduction, which may lead to significant strategies for predicting or checking HIV-1 drug resistance in HAART.