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Studying the anisotropy of seismic wave velocity can provide a theoretical basis for understanding the characteristics of seismic wave propagation in anisotropic media, such as forward modeling of seismic wavefield and simultaneous inversion of anisotropic parameters. It is an important work to calculate the group velocities of three kinds of seismic waves (qP, qS1, and qS2) and the analytical expressions of the partial derivatives of the group velocities with respect to 21 elastic parameters in general anisotropic media. Therefore, a new relationship between the phase and group velocity in general anisotropic medium is introduced first, and then the analytical expressions of the group velocity of three kinds of waves are deduced. Then the analytical formulas of partial derivatives of group (or phase) velocity with respect to 21 elastic parameters are derived. Finally, the distribution of partial derivatives of group slowness with respect to 21 elastic parameters with varied ray angles is analyzed and discussed. The final analytical expressions of group velocity and its partial derivatives are relatively concise and can deal with the singular points and multivalued problems of qS waves. By comparing with the numerical solution of the eigenvector method, the accuracy of the analytical formula of group velocity and its partial derivatives with respect to elastic parameters are verified. The numerical simulation results show that the algorithm can accurately obtain the partial derivatives of group slowness with respect to 21 elastic parameters, and would provide a theoretical basis for seismic ray tracing and traveltime inversion in general anisotropic media.

In this highlight, the development of donor acceptor (D–A) MOF was briefly reviewed and summarized in the aspects of design, construction, and properties. Also, an outlook about the research and potential application of D–A MOF has been presented.

The real ray-tracing approach leads to an effective solution in the real space domain using a homogeneous ray velocity vector. However, it fails to yield solutions for quasi-S-waves, which suffer from triplications of the wavefronts. To address this challenging problem, a new real ray-tracing method and its two approximations are developed to solve the complex ray equation. The numerical results indicate that the new real ray-tracing method is superior to the common real ray-tracing method in the presence of triplications of the quasi-S-waves in the computation of ray velocity, ray attenuation, and ray quality factors, as well as the reflection and transmission coefficients in viscoelastic anisotropic media. Based on the assumptions of the real slowness direction and real polarization vectors, two new approximations of the new real ray-tracing method are developed for directly computing the homogeneous complex ray velocity vectors of three wave modes (qP, qS1, and qS2). These approximations significantly improve computational efficiency by avoiding the iterative process required by the new real ray-tracing method that is inherited from the common real ray-tracing method. The computational accuracies are verified through transversely isotropic and orthorhombic models with different strengths of attenuation and anisotropy. Incorporation of the new approximation into the shortest-path method turned out to be efficient and accurate for seismic ray tracing in heterogeneous viscoelastic and transversely isotropic media with a vertical axis of symmetry, even in the presence of strong attenuation and anisotropy.

In viscoelastic anisotropic media, the elastic moduli, slowness vector, phase, and ray velocity are all complex-valued quantities in the frequency domain. Solving the complex eikonal equation becomes computationally complex and time-consuming. We have developed two approximate methods to effectively calculate the ray velocity vector, attenuation, and quality factor in viscoelastic transversely isotropic media with a vertical symmetry axis (VTI) and in orthorhombic (ORT) anisotropy. The first method is based on the perturbation theory (PER) under the assumption of a homogeneous complex ray vector, which is obtained by applying the elastic background and viscoelastic perturbations to the real and imaginary components of the modulus tensor, respectively. The perturbations of the slowness vectors of the three wave modes (qP, qSV, and qSH) are determined through the vanishing Hamiltonian function. The second method is derived by applying a real slowness direction (RSD) to the inhomogeneous complex slowness vector and then approximately calculating the complex ray velocity vector with the condition of the homogeneous complex vector. The numerical results verify that the two approaches can produce accurate ray velocity vector, attenuation, and quality factors of the qP-wave in viscoelastic VTI and ORT media. The RSD method can yield high accuracies of ray velocity for the qSV- and qSH-wave in viscoelastic VTI models even at triplication of the qSV wavefronts, as well as qS1 and qS2 in a weak ORT medium ([Formula: see text] > 20), except for near the cusp of the qS1 wavefronts (errors approximately 6%) where the PER has more than 10% error.

In a viscoelastic anisotropic medium, velocity anisotropy and wave energy attenuation occur and are often observed in seismic data applications. Numerical investigation of seismic wave propagation in complex viscoelastic anisotropic media is very helpful in understanding seismic data and reconstructing subsurface structures. Seismic ray tracing is an effective means to study the propagation characteristics of high-frequency seismic waves. Unfortunately, most seismic ray-tracing methods and traveltime tomographic inversion algorithms only deal with elastic media and ignore the effect of viscoelasticity on the seismic raypath. We have developed a method to find the complex ray velocity that gives the seismic ray speed and attenuation in an arbitrary viscoelastic anisotropic medium, and we incorporate them with the modified shortest-path method to determine the raypath and calculate the real and imaginary traveltime (wave energy attenuation) simultaneously. We determine that the complex ray-tracing method is applicable to arbitrary 2D/3D viscoelastic anisotropic media in a complex geologic model and the computational errors of the real and imaginary traveltime are less than 0.36% and 0.59%, respectively. The numerical examples verify that the new method is an effective and powerful tool for accomplishing seismic complex ray tracing in heterogeneous viscoelastic anisotropic media.

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment, and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Background Most studies had used sufentanil and ropivacaine for intrathecal anesthesia in adults or children，but few studies had used sufentanil and ropivacaine for peripheral nerve block, especially in children. Brachial plexus block was one of the most commonly used nerve block methods in children. Therefore, the purpose of this study was to investigate whether 0.1µg/kg sufentanil combined with 0.25% ropivacaine can improve analgesia and prolong analgesia in children compared with ropivacaine alone.Methods 80 children, ASA I, aged 5-10 years old, undergoing upper limb surgery, were randomly divided into two groups: RS group(0.25% ropivacaine combined with 0.1µg/kg sufentanil) and R group (0.25% ropivacaine alone). The dosage of 0.25% ropivacaine administered in each group was 0.5ml/kg. After general anesthesia, all children underwent ultrasound-guided brachial plexus block and were performed by the same experienced anesthetist. The primary outcome measures were the FLACC score at 2, 4, and 6 h after surgery and the duration of analgesia in each group. Secondary outcome measures were the changes in vital signs during surgery in each group, the incidence of postoperative agitation, the postoperative awake time and the duration of stay in PACU. Results The FLACC scores at 2, 4 and 6 hours after surgery and the duration of analgesia showed no statistically significant difference. There were no statistically significant differences in the changes in vital signs during surgery in each group. The incidence of postoperative agitation was significantly lower in RS group than R group(20% vs 45%, PConclusion Compared with 0.25% ropivacaine alone, 0.1µg/kg sufentanil combined with 0.25% ropivacaine for pediatric brachial plexus block did not improve analgesia and prolong analgesia, but reduced postoperative agitation in the children.Trial RegistrationRegistration of Chinese Clinical Trial Registry(Date:19/04/2020, Number:ChiCTR2000032071).

Background: Evidence of lymphopoiesis, exhaustion, and premature aging in Chinese patients with human immunodeficiency virus (HIV) is very limited. Objective: To assess biological aging and immune senescence in Chinese healthy controls (HC) and ART-naïve HIV-infected men who have sex with men (MSM). Methods: This case-control study was conducted in Beijing Ditan Hospital from March 2018 to June 2019. The percentages of naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated memory (TemRA) subsets of CD4 and CD8 T cells were studied, along with markers of senescence (CD28-CD57+) and activation (HLA-DR+). Telomere length of naïve (CD45RA+) and memory (CD45RO+) CD8 T cells were quantified by real-time PCR. Results: A total of 26 HIV-infected and 20 age-matched HC MSM were included. Compared to the HC group, the CD4/CD8 ratio of the HIV-infected group was significantly reduced (0.30 vs. 1.70, P Conclusion: HIV-infected MSM exhibit signs of accelerated immune senescence and biological aging, which particularly affects the CD8 T-cell subsets.

A retrospective view of exaltation of refraction observed for many unsaturated and aromatic compounds demonstrates that this physical phenomenon is undeservedly considered only as a qualitative measure of conjugation. This mini-review discusses numerous papers by the author that have been published earlier in inaccessible periodicals and collections of scientific papers. Using a great number of illustrations, the author shows that this parameter can be successfully used for quantitative estimate of resonance effects in organic and polymer chemistry. The methods for derivation of strictly additive atomic and group refraction constants are described; these constants were subsequently used as a tool that allowed quantitative estimation of resonance effects in mono-, di-, tri- and polyalkylbenzenes, alkylnaphthalenes, some alkyl derivatives of unsaturated hydrocarbons. These effects cause strictly fixed increase in refraction of carbon atoms in different structural modifications (graphene, fullerene, diamond) and in polycyclic aromatic hydrocarbons. The relevant results regarding quantitative estimation of degree of steric inhibition of resonance in sterically hindered ortho-dialkylbenzenes, 1,2,3- trialkyl-, 1,2,3,4-tetraalkyl-, and 1,2,3,4,5-polyalkylbenzenes accumulated by the author are summarized.

Seismic ray-tracing methods are widely used in seismology, with most such algorithms being executed in Cartesian or spherical coordinate systems. However, the actual Earth is not a perfect sphere but rather an ellipsoid, meaning that results calculated in spherical coordinates may be different from the actual situation. The general approach is to first calculate traveltimes in a spherical Earth model, then apply ellipsoidal time corrections to obtain more accurate traveltime data. Alternatively, one may directly conduct the ray tracing in the ellipsoidal Earth model without any time corrections. In this paper, we extend the functional of the multistage irregular shortest-path method, previously formulated for a spherical Earth model, to an ellipsoidal Earth model in order to trace multiphase global seismic arrivals. The results of two models indicate that the proposed algorithm has high computational accuracy, which can be further tuned by decreasing the secondary node spacing. Comparison tests indicate that the traveltime differences between the ellipsoidal and spherical coordinate ray-tracing methods cannot be ignored for direct P and S arrivals, reflected PcP and ScS arrivals, and reflected and converted PcS and ScP arrivals. The traveltime differences (TE − TS) computed by the ellipsoidal and spherical ray-tracing methods have different distribution patterns, being dependent on the source locations. However, in general, these traveltime differences (TE − TS) have relatively large negative values near the polar region and positive values near the equatorial region, except for sources located near the polar region. For ellipsoidal time correction in a specific case, the maximum differences between the traveltimes computed by the ellipsoidal coordinate ray-tracing method and the AK135 Traveltime Table after application of ellipsoidal time corrections are less than 0.1 s. Meanwhile, the maximum differences between the traveltimes predicted by the ellipsoidal coordinate ray-tracing method and by the spherical coordinate ray-tracing method after application of ellipsoidal time corrections are only 0.075 s for the six stated phases. These results indicating that ray tracing could be conducted directly in the ellipsoidal Earth model.

Background The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. Methods Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People’s Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-β1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. Results The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P 0.05). Serum TGF-β1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-β1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). Conclusions Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-β1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

To realize the photothermal therapy ability of Prussian blue-modified ferritin nanoparticles (PB-Ft NPs) and its synergistic effect with chemotherapy, PB-Ft NPs were synthesized by a simple surface double decomposition reaction. Mean sizes of ferritin and PB-Ft NPs were 10.4 nm and 12.6 nm, respectively. The obtained PB-Ft NPs were verified to have both the photothermal conversion ability of Prussian blue and the morphology of ferritin. The in vitro and in vivo photothermal therapy results confirm PB-Ft NPs can successfully inhibit the growth of murine breast cancer cell line (4T1) without any obvious side effect. Moreover, taking use of the peroxidase-like activity of PB-Ft NPs, the photothermal therapy effect of PB-Ft NPs effectively improved the curative effect of gemcitabine (GEM) via enhancing reactive oxygen species production. The obtained PB-Ft NPs can be served as a useful and safe photothermal therapy agent in breast cancer. Moreover, PB-Ft NPs-assisted photothermal therapy can be applied as an adjunctive therapy with various established cancer treatments such as chemotherapy.

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans. Key words: Bat-origin; Coronavirus; Zoonotic transmission; Pneumonia; Etiology; Next-generation sequencing

MicroRNAs (miRNAs) are endogenous, time sequencing, conserved and small non-coding RNA molecules (19-25 bp long) that regulate gene expression at the post-transcriptional level by binding to the partial sequence homology of the 3'-untranslated region of target messenger (m)RNA. The miRNA-27 family consists of miR-27a and miR-27b, which are transcribed from different chromosomes and different in nucleotide at the 3' end. It has been reported that miR-27a was located on chromosome 19 and played a vital role in tumor development. Increasing evidences support a vital role for miR-27a in modulating polymorphisms, tumorigenesis, proliferation, apoptosis, invasion, migration and angiogenesis. Apart from it, miR-27a could affect drug sensitivity, treatment of cancer and patients prognosis. The miR-27a could be an oncogene or a tumor suppressor in several types of cancer, including colon cancer, pancreatic cancer, breast cancer, bladder cancer and hepatocellular carcinoma. In this review, we discuss the role of miR-27a in tumor biology and clinical significance in detail and offer novel insights into molecular targeting therapy for human cancers.

To overcome a major problem in current ray tracing methods, which are only capable of tracing first arrivals, and occasionally primary reflections (or mode conversions) in regular cell models, we extend in this paper the multistage triangular shortest-path method (SPM) into 3D titled transversely isotropic (TTI) anisotropic media. The proposed method is capable of tracking multi-phase arrivals composed of any kind of combinations of transmissions, mode conversions and reflections. In model parameterization, five elastic parameters, plus two angles defining the titled axis of symmetry of TTI media are sampled at the primary nodes of the tetrahedral cell, and velocity value at secondary node positions are linked by a tri-linear velocity interpolation function to the primary node velocity value of that of a tetrahedral cell, from which the group velocities of the three wave modes (qP, qSV and qSH) are computed. The multistage triangular SPM is used to track multi-phase arrivals. The uniform anisotropic test indicates that the numerical solution agrees well with the analytic solution, thus verifying the accuracy of the methodology. Several simulations and comparison results for heterogeneous models show that the proposed algorithm is able to efficiently and accurately approximate undulating surface topography and irregular subsurface velocity discontinuities. It is suitable for any combination of multi-phase arrival tracking in arbitrary tilt angle TTI media and can accommodate any magnitude of anisotropy.

To conduct forward and simultaneous inversion in a complex geological model, including an irregular topography (or irregular reflector or velocity anomaly), we in this paper combined our previous multiphase arrival tracking method (referred as triangular shortest-path method, TSPM) in triangular (2D) or tetrahedral (3D) cell model and a linearized inversion solver (referred to as damped minimum norms and constrained least squares problem solved using the conjugate gradient method, DMNCLS-CG) to formulate a simultaneous travel time inversion method for updating both velocity and reflector geometry by using multiphase arrival times. In the triangular/tetrahedral cells, we deduced the partial derivative of velocity variation with respective to the depth change of reflector. The numerical simulation results show that the computational accuracy can be tuned to a high precision in forward modeling and the irregular velocity anomaly and reflector geometry can be accurately captured in the simultaneous inversion, because the triangular/tetrahedral cell can be easily used to stitch the irregular topography or subsurface interface.

Earthquake hypocenter determination and traveltime tomography with local earthquake data are normally conducted using a Cartesian coordinate system and assuming a flat Earth model, but for regional and teleseismic data Earth curvature is incorporated and a spherical coordinate system employed. However, when the study region is from the local to near-regional scale (1°–4°), it is unclear what coordinate system to use and what kind of incorrect anomalies or location errors might arise when using the Cartesian coordinate frame. In this paper we investigate in a quantitative sense through two near-regional crustal models and five different inversion methods, the hypocenter errors, reflector perturbation and incorrect velocity anomalies that can arise due to the selection of the wrong coordinate system and inversion method. The simulated inversion results show that the computed traveltime errors are larger than 0.1 s when the epicentral distance exceeds 150 km, and increases linearly with increasing epicentral distance. Such predicted traveltime errors will result in different patterns of incorrect velocity anomalous structures, a perturbed Moho interface for traveltime tomography and source position which deviate for earthquake locations. The maximum magnitude of a velocity image artifact is larger than 1.0% for an epicentral distance of less than 500 km and is up to 0.9% for epicentral distances of less than 300 km. The earthquake source location error is more than 2.0 km for epicentral distances less than 500 km and is up to 1.5 km for epicentral distances less than 300 km. The Moho depth can be in error by up 1.0 km for epicentral distances of less than 500 km but is less than 0.5 km at distances below 300 km. We suggest that spherical coordinate geometry (or time correction) be used whenever there are ray paths at epicentral distances in excess of 150 km.

Background The aim of this bibliometric analysis was to evaluate the clinical trials of randomized controlled trials (RCTs) of colorectal cancer all the world over the past decade. Methods The PubMed and Web of Science database were searched to obtain a randomized controlled trial of colorectal cancer from January 1, 2008 to January 1, 2018.The included literatures were analyzed with the bibliometric analysis. Results In the past 10 years, Randomized controlled trials of colorectal cancer have shown an upward trend; Most of the top ten research institutions in the literature are from the USA, the UK and other regions which has the high incidence of colorectal cancer; Most of the related research journals are also sponsored by European and American countries; the frequently cited top 15 literatures are mostly international multi-center clinical research, and there are fewer participants in Chinese research institutions. By keyword co-occurrence, colorectal cancer research mostly involves screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life and prognosis; The results of the co-authorship network analysis show that Chinese researchers are less involved in international cooperation. Conclusions High-quality randomized controlled trials are increasingly favored by top international journals. However, there is still a large gap in clinical research between China and abroad. Researchers should gradually implement the standardization and accuracy of clinical trials, strengthen international multi-center cooperation and emphasize quality control.

Background This study investigated and analyzed rectal cancer-related clinical trials registered on Chinese Clinical Trial Registry (Chi-CTR) by the end of 2018. We aimed to discuss the characteristics and developmental trends. Methods The Chi-CTR database was searched and all clinical trials related to rectal cancer extracted. The time limit for the search was from the establishment of the data library to December 31, 2018. The characteristics of registered clinical trials were then analyzed. Results A total of 70 clinical trials were retreived. Beijing, Shandong, and Guangzhou accounted for 47.1% of the total number of registered clinical trials. Sichuan and Sun Yat-sen Universities having the highest number of registrations. The registration status of the 55 trials was prospective registration. The top sources of funding were self-financing (41.4%), hospital funding (22.9%) and local finance (15.7%). Out of the 43 randomized controlled trials, 39 were either blank or missing in the blinded section. The sample size of clinical trials was high in 100 to 199 cases. Only eight of the 70 trials were multicenter clinical trials. Conclusions Relevant departments should increase the registration of clinical trials, increase the awareness of registration, and promote the development of high-quality clinical trials. At the same time, researchers should raise the awareness of clinical trial registration, and actively carry out multi-center clinical trials.

Traditional traveltime inversion for anisotropic medium is, in general, based on a “weak” assumption in the anisotropic property, which simplifies both the forward part (ray tracing is performed once only) and the inversion part (a linear inversion solver is possible). But for some real applications, a general (both “weak” and “strong”) anisotropic medium should be considered. In such cases, one has to develop a ray tracing algorithm to handle with the general (including “strong”) anisotropic medium and also to design a non-linear inversion solver for later tomography. Meanwhile, it is constructive to investigate how much the tomographic resolution can be improved by introducing the later arrivals. For this motivation, we incorporated our newly developed ray tracing algorithm (multistage irregular shortest-path method) for general anisotropic media with a non-linear inversion solver (a damped minimum norm, constrained least squares problem with a conjugate gradient approach) to formulate a non-linear inversion solver for anisotropic medium. This anisotropic traveltime inversion procedure is able to combine the later (reflected) arrival times. Both 2-D/3-D synthetic inversion experiments and comparison tests show that (1) the proposed anisotropic traveltime inversion scheme is able to recover the high contrast anomalies and (2) it is possible to improve the tomographic resolution by introducing the later (reflected) arrivals, but not as expected in the isotropic medium, because the different velocity (qP, qSV and qSH) sensitivities (or derivatives) respective to the different elastic parameters are not the same but are also dependent on the inclination angle.

Currently, it is still controversial that if the pathogenicity of EV-A71 causing severe or mild hand, foot, and mouth disease (HFMD) is associated with viral nucleotide or amino acid sequence(s). In this study, 19 clinical strains were detected in samples from diagnosed patients of EV-A71-caused HFMD with mild or severe symptoms. Then, VP1-2A fragment sequences of 19 EV-A71 isolates were determined, the phylogenetic analysis, based on VP1 sequences of 19 EV-A71 stains in this study and which of 62 EV-A71 strains with different clinical phenotypes reported before, were carried out. Our results showed that no difference in the genotype and evolution distribution was observed among the EV-A71 strains mentioned above. Furthermore, two EV-A71 isolates, which with much close evolutionary relationship but different clinical manifestations, were purified by plaque assay, the complete genome sequencing was done, and deduced amino acid sequence analysis of 11 proteins coded by EV-A71 was carried out. Eight variable amino acid sites were found and further verified with those of 62 strains reported before. Our study provides further evidence that the potential pathogenicity of EV-A71 causing severe or mild HFMD seems not to be associated with viral genotype and even the amino acid substitution.