Realizing Synthetic Dimensions and Artificial Magnetic Flux in a Trapped-Ion Quantum Simulator.

Synthetic dimension is a potent tool in quantum simulation of topological phases of matter. Here we propose and demonstrate a scheme to simulate an anisotropic Harper-Hofstadter model with controllable magnetic flux on a two-leg ladder using the spin and motional states of a single trapped ion. We verify the successful simulation of this model by comparing the measured dynamics with theoretical predictions under various coupling strength and magnetic flux, and we observe the chiral motion of wave packets on the ladder as evidence of the topological chiral edge modes. We develop a quench path to adiabatically prepare the ground states for varying magnetic flux and coupling strength, and we measure the chiral current on the ladder for the prepared ground states, which allows us to probe the quantum phase transition between the Meissner phase and the vortex phase. Our work demonstrates the trapped ion as a powerful quantum simulation platform for topological quantum matter.

[Best evidence summary for awake prone positioning in treating hypoxemic due to COVID-19 infection].

Objective: To retrieve, evaluate, and summarize the best evidence for the treatment of hypoxemia in patients with COVID-19 infection using the awake prone positioning, with the aim of guiding healthcare professionals in the standardized implementation of this therapy. Methods: A systematic search was conducted in databases including UpToDate, BMJ Best Practice, JBI Evidence-Based Healthcare Center, American Association of Critical-Care Nurses, Intensive Care Society, European Respiratory Society, World Health Organization website, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang. The retrieved literature was subjected to quality assessment and evidence extraction. Results: A total of ten publications were included, consisting of one thematic evidence summary, one guideline, two systematic reviews, three randomized controlled trials, and three expert consensus statements. This summary synthesizes thirty key pieces of evidence in five categories: organizational management and training, risk assessment, preparatory operations, implementation key points, and risk control. Conclusions: Awake prone positioning is beneficial for improving hypoxemia in patients with COVID-19 and is easy to implement. Medical institutions should develop nursing management systems, operational standards, and best practices for awake prone positioning based on evidence-based evidence in order to improve the quality of care management for such patients.

[Disease burden of acute viral hepatitis in Guangdong Province, 1990-2019].

Objective: To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province. Methods: Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden. Results: From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women. Conclusions: The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

Dual kinase inhibitor for EGFR mutants and ErbB2 limit breast cancer.

Mutations in the epidermal growth factor receptor (EGFR) have been found in more than 10% of non-small cell lung cancer (NSCLC) patients in North America. The vast majority of these differences are L858R point mutations in Exon 21. Currently, monoclonal antibodies directed against the extracellular domain of EGFR or small molecule/tyrosine kinase inhibitors (TKI) are the stalwarts of NSCLC therapy. Resistance, however, gradually develops because of the T790 mutation towards first and second generation TKIs. The third generation TKI AZD9291 (Osimertinib) has a high affinity for both activating and the acquired resistant mutation (T790 M) in EGFR, with a low affinity towards wild-type EGFR. Recent research, however, suggests that the EGFR (C797S) mutation in the tyrosine kinase domain is a likely cause of resistance to AZD9291. Another significant transformation mechanism associated with this resistance is erbB2 amplification. Our laboratory has developed a small kinase inhibitor, ER121 (MW: ∼500), that inhibits the erbB2/HER2 tyrosine kinases in addition to the EGFR C797S mutations. We have identified a TKI, ER121 targeting the mutant EGFR(T790 M). Using in vitro and in vivo models, examined the efficacy of ER121 on mutant EGFR cell lines. This has enabled us to establish that ER121 is well tolerated when administered orally and produces significant inhibitory activity against human cancers generated by mutant EGFR and amplified ErbB2.

Asperosaponin VI Protects Against Bone Loss Due to Hindlimb Unloading in Skeletally Growing Mice Through Regulating Microbial Dysbiosis Altering the 5-HT Pathway.

Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.

Inhibiting creep in nanograined alloys with stable grain boundary networks.

Creep, the time-dependent deformation of materials stressed below the yield strength, is responsible for a great number of component failures at high temperatures. Because grain boundaries (GBs) in materials usually facilitate diffusional processes in creep, eliminating GBs is a primary approach to resisting high-temperature creep in metals, such as in single-crystal superalloy turbo blades. We report a different strategy to inhibiting creep by use of stable GB networks. Plastic deformation triggered structural relaxation of high-density GBs in nanograined single-phased nickel-cobalt-chromium alloys, forming networks of stable GBs interlocked with abundant twin boundaries. The stable GB networks effectively inhibit diffusional creep processes at high temperatures. We obtained an unprecedented creep resistance, with creep rates of ~10-7 per second under gigapascal stress at 700°C (~61% melting point), outperforming that of conventional superalloys.

Observation of Non-Markovian Spin Dynamics in a Jaynes-Cummings-Hubbard Model Using a Trapped-Ion Quantum Simulator.

The Jaynes-Cummings-Hubbard (JCH) model is a fundamental many-body model for light-matter interaction. As a leading platform for quantum simulation, the trapped ion system has realized the JCH model for two to three ions. Here, we report the quantum simulation of the JCH model using up to 32 ions. We verify the simulation results even for large ion numbers by engineering low excitations and thus low effective dimensions; then we extend to 32 excitations for an effective dimension of 2^{77}, which is difficult for classical computers. By regarding the phonon modes as baths, we explore Markovian or non-Markovian spin dynamics in different parameter regimes of the JCH model, similar to quantum emitters in a structured photonic environment. We further examine the dependence of the non-Markovian dynamics on the effective Hilbert space dimension. Our Letter demonstrates the trapped ion system as a powerful quantum simulator for many-body physics and open quantum systems.

Quantum Simulation of the Two-Dimensional Weyl Equation in a Magnetic Field.

Quantum simulation of 1D relativistic quantum mechanics has been achieved in well-controlled systems like trapped ions, but properties like spin dynamics and response to external magnetic fields that appear only in higher dimensions remain unexplored. Here we simulate the dynamics of a 2D Weyl particle. We show the linear dispersion relation of the free particle and the discrete Landau levels in a magnetic field, and we explicitly measure the spatial and spin dynamics from which the conservation of helicity and properties of antiparticles can be verified. Our work extends the application of an ion trap quantum simulator in particle physics with the additional spatial and spin degrees of freedom.

Observation of supersymmetry and its spontaneous breaking in a trapped ion quantum simulator.

Supersymmetry (SUSY) helps solve the hierarchy problem in high-energy physics and provides a natural groundwork for unifying gravity with other fundamental interactions. While being one of the most promising frameworks for theories beyond the Standard Model, its direct experimental evidence in nature still remains to be discovered. Here we report experimental realization of a supersymmetric quantum mechanics (SUSY QM) model, a reduction of the SUSY quantum field theory for studying its fundamental properties, using a trapped ion quantum simulator. We demonstrate the energy degeneracy caused by SUSY in this model and the spontaneous SUSY breaking. By a partial quantum state tomography of the spin-phonon coupled system, we explicitly measure the supercharge of the degenerate ground states, which are superpositions of the bosonic and the fermionic states. Our work demonstrates the trapped-ion quantum simulator as an economic yet powerful platform to study versatile physics in a single well-controlled system.

Experimental Realization of the Rabi-Hubbard Model with Trapped Ions.

Quantum simulation provides important tools in studying strongly correlated many-body systems with controllable parameters. As a hybrid of two fundamental models in quantum optics and in condensed matter physics, the Rabi-Hubbard model demonstrates rich physics through the competition between local spin-boson interactions and long-range boson hopping. Here, we report an experimental realization of the Rabi-Hubbard model using up to 16 trapped ions and present a controlled study of its equilibrium properties and quantum dynamics. We observe the ground-state quantum phase transition by slowly quenching the coupling strength, and measure the quantum dynamical evolution in various parameter regimes. With the magnetization and the spin-spin correlation as probes, we verify the prediction of the model Hamiltonian by comparing theoretical results in small system sizes with experimental observations. For larger-size systems of 16 ions and 16 phonon modes, the effective Hilbert space dimension exceeds 2^{57}, whose dynamics is intractable for classical supercomputers.

Experimental Realization of Multi-ion Sympathetic Cooling on a Trapped Ion Crystal.

Trapped ions are one of the leading platforms in quantum information science. For quantum computing with large circuit depth and quantum simulation with long evolution time, it is of crucial importance to cool large ion crystals at runtime without affecting the internal states of the computational qubits, thus the necessity of sympathetic cooling. Here, we report multi-ion sympathetic cooling on a long ion chain using a narrow cooling beam focused on two adjacent ions, and optimize the choice of the cooling ions according to the collective oscillation modes of the chain. We show that, by cooling a small fraction of ions, cooling effects close to the global Doppler cooling limit can be achieved. This experiment therefore demonstrates an important enabling step for quantum information processing with large ion crystals.

[Literature research of Compendium of Materia Medica quoted from Bencao Tujing].

According to the content of Compendium of Materia Medica quoted from Bencao Tujing(, Illustration Classics for Materia Medica), this paper analyzed Li Shizhen's treatment methods of Bencao Tujing, such as description mode, the first record of drug varieties, distinction of related drugs, the purpose of specific citation content, and the characteristics of citation literature. It is believed that Li Shizhen's citation on Bencao Tujing is comprehensive, scientific, and absorbed the essence of Bencao Tujing. It was a great contribution to Li Shizhen's successful compilation of Compendium of Materia Medica, and Li Shizhen insisted on the principle of treating repetition with deletions, treating deficiency with addition, and treating errors with correction. Li Shizhen corrected realistically the deficiency of "The pictures and annotations are different, the two are not matched with each other, or there are pictures without annotations, or there are articles without pictures,or there are right annotations with the wrong pictures" in Bencao Tujing.

Observation of a quantum phase transition in the quantum Rabi model with a single trapped ion.

Quantum phase transitions (QPTs) are usually associated with many-body systems in the thermodynamic limit when their ground states show abrupt changes at zero temperature with variation of a parameter in the Hamiltonian. Recently it has been realized that a QPT can also occur in a system composed of only a two-level atom and a single-mode bosonic field, described by the quantum Rabi model (QRM). Here we report an experimental demonstration of a QPT in the QRM using a 171Yb+ ion in a Paul trap. We measure the spin-up state population and the average phonon number of the ion as two order parameters and observe clear evidence of the phase transition via adiabatic tuning of the coupling between the ion and its spatial motion. An experimental probe of the phase transition in a fundamental quantum optics model without imposing the thermodynamic limit opens up a window for controlled study of QPTs and quantum critical phenomena.

CUL4A promotes the invasion of cervical cancer cells by regulating NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effects of cullin 4A (CUL4A) on promoting the proliferation and inhibiting the apoptosis of cervical cancer (CC) cells by regulating the nuclear factor-kappa B (NF-κB) signaling pathway. PATIENTS AND METHODS: The protein expressions of CUL4A and NF-κB in 75 CC tissues were detected through immunohistochemistry. The correlation between the expressions of the two proteins in CC tissues was analyzed via Spearman's correlation test. Meanwhile, the prognostic significance of CUL4A expression for CC patients was analyzed by Kaplan-Meier curve. CUL4A small interfering ribonucleic acid (siRNA) was transfected into CC cells (HeLa) to downregulate the expression level of CUL4A. Subsequently, the effects of CUL4A on the proliferation and apoptosis of HeLa cells were detected by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Finally, the effect of CUL4A on the activity of the NF-κB signaling pathway was analyzed through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: The protein expressions of CUL4A and NF-κB in CC tissues were significantly higher than those in normal tissues (p<0.01). The results of the survival curve showed that the prognosis of CC patients with highly expressed CUL4A is poor (p<0.001). Meanwhile, lowly expressed CUL4A protein significantly inhibited the proliferation and promoted the apoptosis of HeLa cells (p<0.01). QRT-PCR results indicated that the relative messenger RNA (mRNA) expression levels of downstream genes of the NF-κB signaling pathway were significantly lower in CC cells than those in the control group (p<0.001). In addition, CUL4A expression was positively correlated with NF-κB expression in CC (p<0.001). CONCLUSIONS: CUL4A promotes the invasion of CC cells through the NF-κB signaling pathway.

Protective effect of sonic hedgehog signaling pathway activation on acute myocardial infarction.

To study changes in the sonic hedgehog (Shh) signaling pathway in acute myocardial infarction (AMI) and the protective effect of changes in Shh signaling pathway activity on AMI, specific pathogen-free (SPF) C57BL/6 mice were treated with left anterior descending (LAD) ligation to establish an AMI model. The samples were collected on the 1st, 3rd, 14th, and 21st days after AMI induction. After the operations, the mice were administered the Shh signaling pathway receptor agonist SAG1.3 (5 mg/kg/d) and antagonist SANT-1 (3.3 mg/kg/d) by intraperitoneal injection. The myocardial ischemia model was established by oxygen glucose deprivation (OGD) in vitro. The AMI mouse model and the in vitro OGD-induced myocardial ischemia model were established. The Smo agonist SAG1.3 was used to activate the Shh signaling pathway, thereby reducing the expression of Bcl-2 and Bax. The number of apoptotic cells was reduced. Administration of the antagonist SANT-1 inhibited Shh signaling pathway activity by increasing the expression of Bcl-2 and Bax, and the number of apoptotic cells increased. In conclusion, activation of the Shh signaling pathway improved cardiac functions and myocardial remodeling and reduced the apoptosis of myocardial cells.

PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targeted p185erbB2/neu Tumor Immunotherapy.

Regulatory T cells (Tregs) are a subpopulation of T cells that are specialized in suppressing immune responses. Here we show that the arginine methyl transferase protein PRMT5 can complex with FOXP3 transcription factors in Tregs. Mice with conditional knock out (cKO) of PRMT5 expression in Tregs develop severe scurfy-like autoimmunity. In these PRMT5 cKO mice, the spleen has reduced numbers of Tregs, but normal numbers of Tregs are found in the peripheral lymph nodes. These peripheral Tregs that lack PRMT5, however, display a limited suppressive function. Mass spectrometric analysis showed that FOXP3 can be di-methylated at positions R27, R51, and R146. A point mutation of Arginine (R) 51 to Lysine (K) led to defective suppressive functions in human CD4 T cells. Pharmacological inhibition of PRMT5 by DS-437 also reduced human Treg functions and inhibited the methylation of FOXP3. In addition, DS-437 significantly enhanced the anti-tumor effects of anti-erbB2/neu monoclonal antibody targeted therapy in Balb/c mice bearing CT26Her2 tumors by inhibiting Treg function and induction of tumor immunity. Controlling PRMT5 activity is a promising strategy for cancer therapy in situations where host immunity against tumors is attenuated in a FOXP3 dependent manner.

Chemoembolisation with polyvinyl alcohol for advanced hepatocellular carcinoma with portal vein tumour thrombosis and arterioportal shunts: efficacy and prognostic factors.

AIM: To evaluate the efficacy and to identify prognostic factors of polyvinyl alcohol (PVA) chemoembolisation for treating advanced hepatocellular carcinoma (HCC) with portal vein (PV) tumour thrombosis (PVTT) and arterioportal shunts. MATERIALS AND METHODS: The clinical data of 145 advanced HCC patients with PVTT and arterioportal shunts were collected. The patients were divided into two groups: group A, with main PV invasion, (n=56) and group B, with PV branch invasion, (n=89). Based on arterioportal shunt types, different particle sizes of PVA were used for chemoembolisation. The overall survival (OS), time to progression (TTP), and postoperative complications were analysed retrospectively. RESULTS: The median OS of all patients was 10.1 months. The median OS of group A and group B was 8.2 and 12.5 months, respectively (χ2=6.03, p=0.01). The overall 6-, 12-, and 18-month survival rates of groups A and B were 63.8%, 24.9%, and 6.3%, and 78.1%, 55.2%, and 23.7%, respectively. After embolisation, there were two cases of acute liver failure and three cases of upper gastrointestinal bleeding. Cox multivariate survival analysis revealed that main PVTT (HR [hazard ratio]=1.75, p=0.01), Child-Pugh B class (HR=1.99, p=0.003) and tumour burden ≥50% (HR=3.25, p<0.001) were independent risk factors. A dose of oxaliplatin >100 mg (HR=0.48, p<0.001) was an independent protection factor. CONCLUSION: Treatment of advanced HCC with PVTT and arterioportal shunts by PVA chemoembolisation is safe and effective. The patients achieved a better prognosis with the dose of oxaliplatin >100 mg, while main PVTT, Child-Pugh B class, and tumour burden ≥50% were poor prognostic indicators.

A targeted immunotherapy approach for HER2/neu transformed tumors by coupling an engineered effector domain with interferon-γ.

Despite substantial clinical progress with targeted therapies, current antibody-based approaches have limited efficacy at controlling HER2/neu-positive breast cancers, especially in the absence of chemotherapies. Previously, we showed that the combination of IFNγ and anti-HER2/neu antibody synergistically reduces tumor growth in an in vivo implanted mammary tumor model. Here, we report a recombinant approach to produce an anti-HER2/neu scFv and IFNγ fusion protein using an engineered effector domain (EED) scaffold. The new molecule induces in vitro apoptosis in an IFNγ receptor-dependent manner. At a very low dose in the in vivo xenografted tumor models, the new EED-IFNγ fusion protein demonstrates superior activity over the anti-HER2/neu antibody and is even active on tumors that are resistant to anti-HER2/neu antibody therapy. Examination of tumor infiltrated macrophages and lymphocytes reveals that the fusion protein can induce changes in tumor microenvironment to support immune reactivity against tumors. Our studies have defined a targeted immunotherapy approach for the treatment of cancers.

[Retrospectively analysis on 95 postpartum hemorrhage women treated with obstetrics and gynecology in intensive care unit].

Objective: To review the clinical aspects and pathogenesis of postpartum hemorrhage (PPH) and investigate the optimal protocols for intervention. Methods: From February 2009 to December 2015, data of normal labour and casearean birth women admitted to intensive care unit (ICU) in our hospital because of hematobilia were selected. 95 patients were divided into three groups (e. g ≥500-1 000 ml, ≥1 000-1 500 ml, ≥1 500-2 500 ml and ≥2 500 ml group) according to the bleeding volume. A retrospective analysis was performed to study the pathogenesis of PPH, organ function, surgical intervention and clinical prognosis on hemorrhage. Results: The data comprised 20 504 women over the 6-year period. 95 (0.463%) of which resulted in PPH and were admitted to ICU. 9 of these patients with PPH unsurvived. The value of creatinine and urea nitrogen, the score of APACHE Ⅱ and the possibility of multiple organ dysfunction syndromethe (MODS) increased with the amount of bleeding (P<0.05). For patients with PPH caused by injury of birth canal and/or placenta factors, there was significant difference among three groups on amount of bleeding (P<0.05). For patients with surgical intervention such as vaginal packing, interventional treatment and exploratory laparotomy conducted in 6 hours, the volume of transfusion was(759±114) ml. The volume of transfusion was (2 000±829) ml and (4 999±1 699) ml in 6 to 12 hours intervention group and in greater than 12 hours intervention group, respectively. The volume of transfusion significant increased over intervention time. There was a statistically significant difference in all groups (P<0.05). Conclusions: Classified treatment should be conducted according the classification on the amount of bleeding. Patients with severe PPH and/or tendency of organ failure should be admitted to ICU. Measures for maintenance of the function of organs are necessary, while appropriate surgical intervention is also needed based on the cooperation between ICU and obstetrical department, and the cure rate could be improved.