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Objective To investigate the correlation between the serum levels of ischaemia-modified albumin (IMA) and disease severity in rats with acute pancreatitis (AP). Methods A rat AP model was established and blood samples from each group were analysed at different time points. After the experiment, the pancreatic tissues of the rats were collected for pathological examination and the measurement of protein levels of NF-κB and NF-κB p65. Serum levels of amylase (α-AMY), tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8 were also compared between groups of rats. Results The serum IMA concentration in the severe acute pancreatitis (SAP) group was greater than that in the mild acute pancreatitis (MAP) group. The levels of the NF-κB and NF-κB p65 proteins were increased in the MAP and SAP groups in a time-dependent manner. α-AMY, TNF-α and IL-6 were increased at all time points in the MAP and SAP groups. The increases were greatest at 24 h in the SAP group. In terms of pathological changes in the pancreas, renal and lung tissues, the damage in the SAP group was more obvious than that in the MAP group. Conclusions Serum IMA level was associated with inflammatory markers and NF-κB p65 in rats with AP.

Abstract The de‐embedding calibration method has been proposed to achieve high‐precision calibration for a single port electric field or magnetic field probe, which can effectively eliminate the calibration ripple. However, the method's effectiveness for a four‐port calibration system has not been verified yet. In this paper, a four‐port de‐embedding calibration method with a differential magnetic field probe is proposed, and its effectiveness is proved. Two symmetric grounded coplanar waveguide transmission lines are applied in the proposed method to solve the ABCD‐matrix of the embedded part of the calibrator. The de‐embedded S‐parameter model of the four‐port calibration system for differential magnetic field probe can be obtained. The calibration results indicate that the proposed method can also reduce the calibration ripple and compensate for the attenuation caused by the calibrator. Compared with the traditional calibration method using a microstrip line calibrator, the ripples of the proposed method can be reduced by 34%. The analysis results of the frequency interval of the ripple (FIR) in different methods show that the de‐embedding method can reduce the FIRs (except around 1.2 GHz) caused by the reflection of the calibrator and retain the FIR (about 1.2 GHz) caused by the reflection of the probe itself.

Previous studies have demonstrated an association between lymphatic vessels and diseases caused by bacterial infections. Listeria monocytogenes (LM) bacterial infection can affect multiple organs, including the intestine, brain, liver and spleen, which can be fatal. However, the impacts of LM infection on morphological and functional changes of lymphatic vessels remain unexplored. In this study, we found that LM infection not only induces meningeal and mesenteric lymphangiogenesis in mice, but also impairs meningeal lymphatic vessels (MLVs)-mediated macromolecules drainage. Interestingly, we found that the genes associated with lymphatic vessel development and function, such as Gata2 and Foxc2, were downregulated, suggesting that LM infection may affect cellular polarization and valve development. On the other hand, photodynamic ablation of MLVs exacerbated inflammation and bacterial load in the brain of mice with LM infection. Overall, our findings indicate that LM infection induces lymphangiogenesis and may affect cell polarization, cavity formation, and valve development during lymphangiogenesis, ultimately impairing MLVs drainage.

Abstract Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)—the cellular receptor of SARS-CoV-2—into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses.

We construct 3-Hom-Lie superalgebras on a commutative Hom-superalgebra by means of involution and even degree derivation. We construct a representation of induced 3-Hom-Lie superalgebras by means of supertrace.

In this study, the loess hill site of an elevated bridge section in Tongwei-Qin’an of the Baolan high-speed railroad was selected as the research object, and the vibration acceleration of the loess hill site under the elevated bridge was tested in the field under the train operating load. The results show that under the same intensity of train load, the time range of vibration acceleration observed by field test and numerical simulation decays linearly with increasing distance from the source, while the amplification effect appears in the loess hill site at a greater distance, and the vibration duration also appears to increase. The vibration acceleration waveforms at each observation point observed by field tests and numerical simulations are similar, and the peak vertical acceleration at each observation point obtained from numerical simulations is overall greater than the peak acceleration at each point obtained from field tests, with aSimulated− max/aObservated− max values ranging from 1.04 to 1.63. The Fourier spectrum frequencies recorded by numerical simulation and field test are mainly concentrated in the range of 1∼40 Hz, but the difference between the main frequencies recorded by the two is large. The main frequency of the energy spectrum recorded by the numerical simulation is around 15 Hz, which is the same as the main frequency of the energy spectrum vibration of the input vibration wave, and the main frequency of the energy spectrum vibration recorded by the field test is around 25 Hz.

Abstract The evaluation of soil quality can provide new insights into the sustainable management of forests. This study investigated the effects of three types of forest management intensities (non-management (CK), extensive management (EM), and intensive management (IM)), and five management durations (0, 3, 8, 15, and 20 years) on the soil quality of a Carya dabieshanensis forest. Further, minimum data sets (MDS) and optimized minimum data sets (OMDS) were established to evaluate the soil quality index (SQI). A total of 20 soil indicators representing its physical, chemical, and biological properties were measured for the 0–30 cm layer. Using one-way ANOVA and principal component analysis (PCA), the total data set (TDS), the minimum data set (MDS), and optimized minimum data set (OMDS) were established. The MDS and OMDS contained three (alkali hydrolyzed nitrogen (AN), soil microbial biomass nitrogen (SMBN), and pH) and four (total phosphorus (TP), soil organic carbon (SOC), AN, and bulk density (BD)) soil indicators, respectively. The SQI derived from the OMDS and TDS exhibited a stronger correlation (r = 0.94, p

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H2O2-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H2O2, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H2O2 levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H2O2-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

The clinical use of anti-EGFR antibody-based cancer therapy has been limited by antibody-EGFR binding in normal tissues, so developing pH-dependent anti-EGFR antibodies that selectively bind with EGFR in tumors—by taking advantage of the acidity of tumor microenvironment relative to normal tissues—may overcome these limitations. Here, we generated pH-dependent anti-EGFR antibodies with cross-species reactivity for human and mouse EGFR, and we demonstrate that pH-dependent antibodies exhibit tumor-selective binding by binding strongly to EGFR under acidic conditions (pH 6.5) but binding weakly under neutral (pH 7.4) conditions. Based on screening a non-immune human antibody library and antibody affinity maturation, we initially generated antibodies with cross-species reactivity for human and mouse EGFR. A structure model was subsequently constructed and interrogated for hotspots affecting pH-dependent binding, which supported development of a cross-reactive pH-dependent anti-EGFR antibody, G532. Compared with its non-pH-dependent antibody variant, G532 exhibits improved tumor selectivity, tumor penetration, and antitumor activity. Thus, beyond showing that pH-dependent anti-EGFR antibodies can overcome multiple limitations with antibody-based cancer therapies targeting EGFR, our study illustrates a structure-guided antibody-antigen binding pH-dependency engineering strategy to enhance antibody tumor selectivity and tumor penetration, which can inform the future development of antibody-based cancer therapies targeting other ubiquitously expressed molecules.

Abstract Boron and boron-based nanoclusters exhibit unique structural and bonding patterns in chemistry. Extensive density functional theory calculations performed in this work predict the mononuclear walnut-like C i C50B54 (1) (C2B10@C48B44), C 1 C50B54 (2) (CB11@C49B43), and S 10 C50B54 (3) (B12@C50B42) which contain one icosahedral-C n B12-n core (n = 0, 1, 2) at the center following the Wade’s skeletal electron counting rules and the approximately electron sufficient binuclear peanut-like C s C88B78 (4) ((C2B10)2@C84B58), C s C88B78 (5) ((CB11)2@C86B56), C s C88B78 (6) ((B12)2@C88B54), C s B180 (7) ((B12)2@B156), C s B182 (8) ((B12)2@B158), and C s B184 (9) ((B12)2@B160) which encapsulate two interconnected C n B12-n icosahedrons inside. These novel core–shell borafullerene and borospherene nanoclusters appear to be the most stable species in thermodynamics in the corresponding cluster size ranges reported to date. Detailed bonding analyses indicate that the icosahedral B12 2−, CB11 −, and C2B10 cores in these core–shell structures possess the superatomic electronic configuration of 1S21P61D101F8, rendering spherical aromaticity and extra stability to the systems. Such superatomic icosahedral-C n B12-n stuffed borafullerenes and borospherenes with spherical aromaticity may serve as embryos to form bulk boron allotropes and their carbon-boron binary counterparts in bottom-up approaches.

Abstract Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs. Graphical Abstract

With the advent of the information epoch and the development of Big Data, users are constantly overwhelmed in massive information online. As an effective method to deal with this dilemma of information overload, recommendation system has become a popular area of research for the past few years. However, most of the current recommendation models fail to make the most of the ample resources hidden behind auxiliary data and user reviews. For this reason, we put forward the FHRec model. We try to combine heterogeneous information network with deep learning technology to improve recommendation performance. The working mechanism is to represent the rich auxiliary data by using heterogeneous information network, learning the features of entities through network embedding; in the meantime, by adopting deep learning technology to mine the features of entities from review texts, using the attention mechanism to fuse feature vectors of entities, inputting them into the neural network for recommendation; the last step is that we use Yelp dataset and Douban movie dataset to verify the FHRec model. The experimental results show that the FHRec behaves better than the traditional comparison algorithm on the Yelp dataset and Douban movie dataset.

The rapid mutations on hemagglutinin (HA) of influenza A virus (IAV) can lead to significant antigenic variance and consequent immune mismatch of vaccine strains. Thus, rapid antigenicity evaluation is highly desired. The subtype-specific antigenicity models have been widely used for common subtypes such as H1 and H3. However, the continuous emerging of new IAV subtypes requires the construction of universal antigenic prediction model which could be applied on multiple IAV subtypes, including the emerging or re-emerging ones. In this study, we presented Univ-Flu, series structure-based universal models for HA antigenicity prediction. Initially, the universal antigenic regions were derived on multiple subtypes. Then, a radial shell structure combined with amino acid indexes were introduced to generate the new three-dimensional structure based descriptors, which could characterize the comprehensive physical–chemical property changes between two HA variants within or across different subtypes. Further, by combining with Random Forest classifier and different training datasets, Univ-Flu could achieve high prediction performances on intra-subtype (average AUC of 0.939), inter-subtype (average AUC of 0.771), and universal-subtype (AUC of 0.978) prediction, through independent test. Results illustrated that the designed descriptor could provide accurate universal antigenic description. Finally, the application on high-throughput antigenic coverage prediction for circulating strains showed that the Univ-Flu could screen out virus strains with high cross-protective spectrum, which could provide in-silico reference for vaccine recommendation.

Herein, a simple and efficient strategy was proposed to improve the gas barrier properties of waterborne polyurethane (WPU). Graphene oxide was first modified with dopamine and then cross-linked by boric acid (BA) to bring the graphene sheets closer together, thereby increasing the complexity of the gas pathway. FTIR, XPS, and SEM analyses proved that boric acid was uniformly dispersed into WPU, meanwhile, SEM images demonstrated the defects between the composites that were filled by the boric acid network. In addition, the mechanical properties of the composite were also enhanced. The tensile strength of the material increased from 25.2 to 34.2 MPa, and Young’s modulus increased from 63.3 to 93.7 MPa. The helium gas permeability of the composites was reduced by 85%, compared with the unmodified WPU film. The arrangement structure of GO modified with dopamine (DGO) in polyurethane is the main reason for the excellent gas barrier performance of the material This work provides great potential with GO/polyurethane for industrial application.

It is important to detect foodborne pathogens in food and water, such as Listeria monocytogenes (L.monocytrogenes), which can cause foodborne illness in people with compromised immune systems. Volatile organic compounds (VOC) and 3‑hydroxy-2-butanone (3H-2B) produced by L.monocytrogenes can be used as biomarkers for indirect detection of microbial contamination. In this study, the mesoporous ZnO@CO3O4 nanosphere was prepared through the simple hydrothermal synthesis method of ZIF-l-Zn@Co, the cage construction of mesoporous ZnO@CO3O4 nanosphere was remained unchanged after the calcination of the ZIF-l-Zn@Co at 600 °C for 2 h in air. The mesoporous ZnO@CO3O4 nanosphere was selected as the gas sensor showed the strongest response to 3H-2B, and 7–12 times higher than the response of other test gases. In addition, compared with ZnO and Co3O4 single metal oxide gas sensor, the ZnO@CO3O4 sensor possessed better repeatability and stability after repeated repeatability tests under the same conditions.

Compared with paclitaxel, sirolimus has been more used in the treatment of vascular restenosis gradually as an anti-proliferative drug, but few basic studies have elucidated its mechanism. The anti-proliferative effects of sirolimus or paclitaxel have been demonstrated by numerous studies under normoxia, but few studies have been achieved focusing hypoxia. In this study, porcine carotid artery injury model and classical cobalt chloride hypoxia cell model were established. Sirolimus nanoparticles (SRM-NPs), paclitaxel nanoparticles (PTX-NPs) and blank nanoparticles (Blank-NPs) were prepared respectively. The effect of RPM-NPs on the degree of stenosis, proliferative index and the expression of PCNA after 28 days of porcine carotid artery injury model was evaluated. Compared with saline group and SRM groups, SRM-NPs group suppressed vascular stenosis, proliferative index and the expression of PCNA (P

In this paper, an electrochemical sensing platform based on gold nanoparticle modified carbon nanofiber (CNF@AuNPs) as working electrode is proposed for the high sensitivity and selective determination of metronidazole. Meanwhile, the sensor has a large linear response range from 0.1 to 2000 μM, the limit of detection for metronidazole (MNZ) is as low as 0.024 μM. The sensor is simple to prepare and reproducible, and it shows good results in MNZ analysis of tap water.

The hybrid boundary-integral equation and finite-element method (BIE/FEM) is efficient for signal/power integrity analysis of multiple vias in a shared antipad (labeled as compact vias) in an arbitrarily shaped power/ground plate pair. According to field distribution between the parallel plate pair, the computation domain of plate pair is decomposed into via domains and plate domain by using a domain decomposition approach. The higher order modes in the proximity of the antipads, which attenuate exponentially along the propagating direction and are confined in the via domains, are calculated by 3-D FEM. On the other hand, in the region outside the via domains, namely, the plate domain, only the zero-order parallel plate modes need to be considered. The network parameters of the plate domain are solved by the boundary-integral method. By enforcing the field continuity conditions along with the segmentation interfaces between via domains and plate domain, the connection of the multi-mode networks of via domains and the impedance matrix of plate domain yields the S-parameter of the entire plate pair, which characterizes the complete noise coupling path from one via structure to another one. The accuracy and efficiency of the hybrid method are verified by comparing with a commercial full-wave solver.

Flower color is an important trait in plants. However, genes responsible for the white flower trait in Chinese cabbage are rarely reported. In this study, we constructed an F2 population derived from the Y640-288 (white flower) and Y641-87 (yellow flower) lines for the fine mapping of the white flower gene BrWF3 in Chinese cabbage. Genetic analysis indicated that BrWF3 was controlled by a single recessive gene. Using BSA-seq and KASP assays, BrWF3 was fine-mapped to an interval of 105.6 kb. Functional annotation, expression profiling, and sequence variation analyses confirmed that the AtPES2 homolog, Bra032957, was the most likely candidate gene for BrWF3. Carotenoid profiles and transmission electron microscopy analysis suggested that BrWF3 might participate in the production of xanthophyll esters (particularly violaxanthin esters), which in turn disrupt chromoplast development and the formation of plastoglobules (PGs). A SNP deletion in the third exon of BrWF3 caused the loss of protein function, and interfered with the normal assembly of PGs, which was associated with reduced expression levels of genes involved in carotenoid metabolism. Furthermore, we developed and validated the functional marker TXBH83 for BrWF3. Our results provide insight into the molecular mechanism underlying flower color pigmentation and reveal valuable information for marker-assisted selection (MAS) breeding in Chinese cabbage.

Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. We have previously reported that compound fuling granule (CFG), a traditional Chinese medicinal preparation used to treat ovarian cancer in China for over 20 years, significantly promotes cell cycle arrest, apoptosis, senescence, TGFβ-induced invasion and migration, tumor growth, and distant metastasis in ovarian cancer cells. However, the underlying mechanisms are not clear. In the present study, we found that PHF19 expression in ovarian cancer cells positively correlated with their resistance ability to CFG. In addition, PHF19 overexpression increased the resistance of HEY-T30 and SKOV3 cells to CFG, while knockdown of PHF19 enhanced their sensitivity to CFG. Moreover, CFG significantly inhibited the expression of PHF19 both in mRNA and protein levels in these cells. Gain of function and loss of function experiments further proved that PHF19 is a crucial mediator involved in the ovarian cancer progression, including cell proliferation, invasion, migration, and stemness. Importantly, rescue the expression of PHF19 reverted CFG-induced suppression in ovarian cancer cell growth, EMT and stemness, while PHF19 knockdown accelerated CFG’s anti-tumor effect. Overall, our results provide a series of evidence to reveal that PHF19 is critical suppressor for CFG’s anti-tumor effect in ovarian cancer.

The characteristics of the vibrations induced by the passage of a high-speed train do not only depend on the train speed, axle load, and track irregularity but also depend on the properties of the foundation soil and the surrounding topography. Estimating the vibration characteristics in different terrains is therefore essential. This study investigates the characteristics of propagation and attenuation of the vibrations induced by high-speed trains in loess-terraced slopes. The influence of the soil mechanical properties on the propagation of vibrations is analyzed through a numerical simulation. Field experiments are conducted to measure the vibration induced by a high-speed train at a loess-terraced slope site in Qin’an, Gansu, China. The measured acceleration time history is analyzed in the time domain and frequency domain. The results show that, at the edge of each terrace level, the vibration in the Y direction is the strongest, followed by those in the X and Z directions. The peak ground acceleration values are amplified in all three directions at the fourth terrace level. A model describing the vehicle-roadbed-foundation-terraced slope system is established to study the influence of the elastic modulus of the soil on the vibration characteristics. A change in the elastic modulus of the foundation soil is found to have an evident influence on the horizontal and vertical vibrations in each terrace level. However, a change in the elastic modulus of the soil in a terrace only affects the vibration in that terrace and in the adjacent ones, whereas it has no effect on the vibrations in terraces located farther away. This study can provide some reference values for slope reinforcement along railways.

Drug-resistant cases of human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitors (NRTI) are constantly accumulating due to the frequent mutations of the reverse transcriptase (RT). Predicting the potential drug resistance of HIV-1 NRTIs could provide instructions for the proper clinical use of available drugs. In this study, a novel proteochemometric (PCM) model was constructed to predict the drug resistance between six NRTIs against different variants of RT. Forty-seven dominant mutation sites were screened using the whole protein of HIV-1 RT. Thereafter, the physicochemical properties of the dominant mutation sites can be derived to generate the protein descriptors of RT. Furthermore, by combining the molecular descriptors of NRTIs, PCM modeling can be constructed to predict the inhibition ability between RT variants and NRTIs. The results indicated that our PCM model could achieve a mean AUC value of 0.946 and a mean accuracy of 0.873 on the external validation set. Finally, based on PCM modeling, the importance of features was calculated to reveal the dominant amino acid distribution and mutation patterns on RT, to reflect the characteristics of drug-resistant sequences.

BackgroundData regarding human papillomavirus (HPV) prevalence and genotype distribution are limited in Shandong Province, China. Therefore, we investigated the recent HPV prevalence and genotype distribution among females in Shandong and aimed to provide comprehensive data to guide HPV-based cervical cancer screening and HPV vaccination for this population of Chinese women.MethodsHPV testing results of 94,489 females were retrospectively reviewed and extracted from the database of Jinan KingMed Diagnostics, the largest independent pathology laboratory in Shandong Province, China. HPV was detected by a HPV genotyping panel from January 2011 to June 2017. The overall prevalence, age-specific prevalence, and genotype distribution were analyzed.ResultsA total of 26,839 cases (28.4%) were HPV-positive, with 4.3% positive for low- or undetermined-risk HPV (lr-/urHPV)-only, 18.1% positive for high-risk HPV (hrHPV)-only, and 6.1% positive for mixed lr-/urHPV and hrHPV infections. Single HPV infections accounted for 62.8%, while the rest were multiple HPV infections of two or more genotypes. HPV16 (5.8%), HPV52 (5.1%), HPV58 (3.5%), HPV51 (2.6%), and HPV56 (2.3%) were the five most common hrHPV genotypes; while HPV81 (2.8%), HPV53 (2.8%), and HPV6 (2.3%) were the three most common lr-/urHPV genotypes. HPV18 (1.7%) was only the ninth most common hrHPV genotype. HPV16 but not HPV52 was more common in single infections than in multiple infections. The distribution of both mixed lr-/urHPV and hrHPV as well as overall HPV infections demonstrated a bimodal pattern across age groups, of which the first peak appeared in the younger group and the second peak was found in older women. A similar age-specific distribution was observed in multiple infections of three or more subtypes as well. Moreover, the proportion of mixed lr-/urHPV and hrHPV infection significantly increased, while those of lr-/urHPV-only and hrHPV-only infections declined as the number of co-infections increased during the study period.ConclusionThis large daily clinical practice report shows that HPV prevalence and genotype distribution are different in this population, who had limited cervical cancer screening service, compared to those in developed countries. Therefore, different strategies should be developed for HPV-based cervical cancer screening and vaccine-based HPV prevention in Shandong Province.

Currently, available data regarding previous cervical cytology and high-risk human papillomavirus (hrHPV) test results to detect invasive cervical cancer are limited and controversial in China. Therefore, this retrospective study in a population of Chinese women with invasive cervical carcinoma aimed to gain further insight into the roles of cytology and hrHPV testing in cervical cancer screening.A total of 1214 cases with a histological diagnosis of invasive cervical cancer were retrieved from the Pathology Database of Jinan KingMed Diagnostics (JKD) over a 5-year period. Previous cytology and hrHPV test results of 469 patients carried out within the year before cancer diagnosis were documented.A higher percentage of patients who had undergone prior screening had micro-invasive cervical carcinoma than patients who had no prior screening (25.4% vs. 12.1%, P < 0.001). Of the 469 patients with available prior screening results, 170 had cytology alone, 161 had hrHPV testing alone, and 138 had both cytology and hrHPV testing. There was a significantly lower percentage of hrHPV-positive cases with adenocarcinoma than with squamous cell carcinoma (77.8% vs. 96.4%, P = 0.001). The hrHPV test showed a significantly higher sensitivity than cytology alone (94.4% vs. 85.3%, P = 0.006). The overall sensitivity of the combination of cytology and hrHPV testing (98.6%) was much higher than that of cytology alone (P < 0.001) but only marginally higher than that of hrHPV testing alone (P = 0.058).The results revealed that prior cervical screening can detect a significantly larger number of micro-invasive cervical cancers. The hrHPV test can provide a more sensitive and efficient strategy than cytology alone. As the addition of cytology to hrHPV testing can only marginally increase the efficiency of the hrHPV test, hrHPV testing should be used as the primary screening approach, especially in the low-resource settings of China.

The global stability for a delayed HBV infection model with CTL immune response is investigated. We show that the global dynamics is determined by two sharp thresholds, basic reproduction number $Re_0$ and CTL immune-response reproduction number $Re_1$. When $Re_0 leq 1$, the infection-free equilibrium is globally asymptotically stable, which means that the viruses are cleared and immune is not active; when $Re_1 leq 1 < Re_0$, the CTL-inactivated infection equilibrium exists and is globally asymptotically stable, which means that CTLs immune response would not be activated and viral infection becomes chronic; and when $Re_1 > 1$, the CTL-activated infection equilibrium exists and is globally asymptotically stable, in this case the infection causes a persistent CTLs immune response. Our model is formulated by incorporating a Cytotoxic T lymphocytes (CTLs) immune response to recent work [Gourley, Kuang, Nagy, J. Bio. Dyn., 2(2008), 140-153] to model the role in antiviral by attacking virus infected cells. Our analysis provides a quantitative understandings of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection.

We formulate a (2n+2)-dimensional viral infection model with humoral immunity, n classes of uninfected target cells and n classes of infected cells. The incidence rate of infection is given by nonlinear incidence rate, Beddington-DeAngelis functional response. The model admits discrete time delays describing the time needed for infection of uninfected target cells and virus replication. By constructing suitable Lyapunov functionals, we establish that the global dynamics are determined by two sharp threshold parameters: R0 and R1. Namely, a typical two-threshold scenario is shown. If R0≤1, the infection-free equilibrium P0 is globally asymptotically stable, and the viruses are cleared. If R1≤11, the endemic equilibrium P2 is globally asymptotically stable, and the infection is chronic with persistent antibody immune response.