Atorvastatin restores imbalance of cluster of differentiation 4 (CD4)+ T cells in immune thrombocytopenia in vivo and in vitro.

Immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease, in which the overactivation of T cells is crucial in the pathogenesis. Atorvastatin (AT), a lipid-lowering medicine, has shown promising immunomodulatory effects in certain inflammatory conditions. However, the immunoregulatory role of AT in ITP remains elusive. To investigate the effect of AT in the treatment of ITP, cluster of differentiation 4 (CD4)+ T cells were isolated from patients with ITP and cultured with different dosages of AT. We found that AT significantly inhibited cell proliferation, led to cell cycle arrest, induced apoptosis, and repressed the activation of CD4+ T cells in vitro. ITP murine models were then established, and results showed that AT treatment led to faster recovery of the platelet count to normal and exhibited comparable immunomodulatory function. Furthermore, we found the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), as well as activation of rat sarcoma virus (RAS) were all reduced dramatically after AT treatment in vitro. In conclusion, our present study demonstrated that AT could reinstate the functions of CD4+ T cells by inhibiting the excessive activation, proliferation, and survival of CD4+ T cells in ITP via the RAS/mitogen-activated protein kinase kinase (MEK)/ERK and the mTOR/phosphatidylinositol-3 kinase (PI3K)/AKT pathway. Therefore, we propose that AT could be used as a potential therapeutic option for ITP by restoring the over-activated cellular immunity.

Assessing the Use of Probes and Quenchers for Understanding the Reactive Species in Advanced Oxidation Processes.

Advanced oxidation processes (AOPs) are increasingly applied in water and wastewater treatment. Understanding the role of reactive species using probes and quenchers is one of the main requirements for good process design. However, much fundamental kinetic data for the reactions of probes and quenchers with reactive species is lacking, probably leading to inappropriate probe and quencher selection and dosing. In this work, second-order rate constants for over 150 reactions of probes and quenchers with reactive species such as •OH, SO4•-, and Cl• and chemical oxidants such as free chlorine and persulfate were determined. Some previously ill-quantified reactions (e.g., furfuryl alcohol and methyl phenyl sulfoxide reactions with certain chemical oxidants, nitrobenzene and 1,4-dioxane reactions with certain halogen radicals) were found to be kinetically favorable. The selection of specific probes can be guided by the improved kinetic database. The criteria for properly choosing dosages of probes and quenchers were proposed along with a procedure for quantifying reactive species free of interference from probe addition. The limitations of probe and quencher approaches were explicated, and possible solutions (e.g., the combination with other tools) were proposed. Overall, the kinetic database and protocols provided in this work benefit future research in understanding the radical chemistry in AOPs as well as other radical-involved processes.

Hyperlipidemia in immune thrombocytopenia: a retrospective study.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by low platelet count and bleeding manifestations. However, some patients also suffered from atherosclerosis or even infarction. Apart from activated platelets, lipid metabolism takes a large part in the formation of atherosclerosis and metabolic syndrome. The lipid metabolic state in ITP patients is still unknown. METHODS: We retrospectively reviewed 302 hospitalized ITP patients in our cohort, comparing their blood lipids, bleeding symptoms, metabolic diseases and treatment responses. RESULTS: We found a high proportion of ITP patients suffered from hyperlipidemia, and other metabolic diseases including cardiovascular or cerebral atherosclerosis or infarction, hypertension, and type 2 diabetes. Hyperlipidemia was associated with severe bleeding and treatment refractoriness in ITP. Statins could alleviate thrombocytopenia and bleeding severity, and facilitate ITP treatment, while improving hyperlipidemia in ITP patients. CONCLUSIONS: Our present study demonstrated that lipid metabolism might play an indispensable role in ITP pathogenesis and development.

Significance of anti-HBc serological status in primary immune thrombocytopenia.

The association of previous hepatitis B virus (HBV) exposure [hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (anti-HBc/HBcAb) positive] with disease severity and decision on treatment option in primary immune thrombocytopenia (ITP) patients remains unclear. Data from 725 patients diagnosed with ITP were analyzed to elucidate the association between anti-HBc serological status and disease severity. Data from a published prospective study [high-dose dexamethasone (HD-DXM), HD-DXM plus recombinant human thrombopoietin, NCT01734044] and two retrospective studies (standard-dose and low-dose rituximab) were rearranged to evaluate the impact of anti-HBc serological status on the response and outcome to ITP-specific treatments and the risk of HBV reactivation related to these treatments. The prevalence of HBsAg- HBcAb+ and HBsAg- HBcAb- in ITP patients was 51·03% and 48·97% respectively. Compared to the HBsAg- HBcAb- group, patients in the HBsAg- HBcAb+ group had lower platelet count, higher bleeding score, and longer hospitalization (P = 0·002, 0·033, and 0·008 respectively). Moreover, the initial complete response rate of HBsAg- HBcAb+ patients was lower than that of HBsAg- HBcAb- patients (45·2% vs 59·8%, P = 0·027). In conclusion, previous HBV exposure was correlated with disease severity and hospitalization in ITP patients. Anti-HBc positivity may be considered as a predictor for poor response to ITP-specific treatments.

Global burden and attributable risk factors of acute lymphoblastic leukemia in 204 countries and territories in 1990-2019: Estimation based on Global Burden of Disease Study 2019.

To provide a foundational guideline for policy-makers to efficiently allocate medical resources in the context of population aging and growth, the latest spatial distribution and temporal trend of acute lymphoblastic leukemia (ALL) along with attributable risk factors by sex and age were mapped. Based on the Global Burden of Disease Study 2019, estimated annual percentage change (EAPC) was calculated according to the relativity between age-standardized rate and calendar year, to quantify temporal trends in morbidity and mortality of ALL. We used applied Spearman rank correlation to estimate the relationship between the EAPC and potential influence factors. The population attributable fraction of potential risk factors for ALL-related disability-adjusted life years were estimated by the comparative risk assessment framework. As a result, we found that new ALL cases increased significantly by 1.29% worldwide, and the age-standardized incidence rate increased by 1.61% annually. The proportion of elder patients sharply increased, especially within the higher socio-demographic index (SDI) region. Smoking and high body mass index remained the predominant risk factors for ALL-related mortality. Notably, the contribution of high body mass index presented an increasing trend. In conclusion, the global burden of ALL has steadily increased, especially in Middle SDI region. Health measures and new drugs should be taken into consideration to improve the management and treatment of elders with ALL due to an increasing proportion in the higher SDI region. For Low SDI areas, attention should be paid to the environmental problems caused by industrial development.

Single-dose versus low-dose rituximab in corticosteroid-resistant or relapsed ITP: A multicenter, randomized, controlled study.

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder, in which rituximab (RTX) induces the best long-term effect among recommended second-line treatments. Nevertheless, the optimal regimen of RTX remains unclear. We herein conducted a prospective, multicenter, open-label, randomized controlled trial to compare the efficacy and safety of RTX at two different dosage regimens in patients with corticosteroid-resistant or relapsed ITP. Recruited patients were randomly assigned (1:1) to receive either RTX at a repeated low dose (100 mg weekly for 4 weeks, LD-RTX) or at a single dose (375 mg/m2 , S-RTX). Overall response was achieved in 64.3% of patients who received LD-RTX versus 67.4% of those receiving S-RTX (p = .759). The complete response (CR) rate was 23.8% after LD-RTX and 28.3% after S-RTX (p = .635). In health-related quality of life, S-RTX improved patients' psychological status, quality of life, social activities, and work compared with LD-RTX. Furthermore, S-RTX significantly reduced physician visits without compromising efficacy. Our findings demonstrate that a S-RTX is comparable to LD-RTX in effectiveness and safety for treatment of corticosteroid-resistant or relapsed ITP. The single-dosage regimen optimizes the use of medical resources, improves the cost-effectiveness of RTX, and represents a promising and more convenient replacement for LD-RTX in ITP. This study has been completed and is registered with ClinicalTrials.gov, number NCT03258866.

Experimental demonstration of a local active phase compensation method for a phase encoding quantum key distribution system.

An efficient phase stabilization method is required in quantum key distribution (QKD) systems for stability in practical applications. The existing active phase compensation method has limitations in multi-node network applications, especially in network-scale applications based on measurement-device-independent QKD systems. In this study, we propose a local active phase compensation scheme that can realize phase compensation independently for each interferometer node. We performed experimental demonstrations in the BB84 phase encoding system based on a Faraday-Michelson interferometer. The average QBER rates of the system under two different forms of the reference light were found to be 1.9% and 1.6%. This scheme can also be applied to other QKD systems and has potential for application in future quantum communication networks.

Platelet autoantibody specificity and response to rhTPO treatment in patients with primary immune thrombocytopenia.

This retrospective study aimed to evaluate the relationship between plasma autoantibody species and rhTPO response in adult ITP patients who failed the first-line treatments. Plasma anti-glycoprotein (GP) IIb/IIIa and anti-GPIb/IX autoantibodies were detected in 47·2% and 40·6% of the 123 patients, respectively. Overall response rate to rhTPO treatment in patients without anti-GPIb/IX autoantibodies was significantly higher than patients with anti-GPIb/IX autoantibodies (82·2% vs. 60·0%, P = 0·006). By contrast, no statistical difference in response rate was observed between patients with or without anti-GPIIb/IIIa autoantibodies (74·1% vs. 72·3%, P = 0·819). Therefore, the presence of anti-GPIb/IX autoantibodies might serve as a predictive factor for poor response to rhTPO treatment in ITP.

Tunable high-order sideband generation in a coupled double-cavity optomechanical system.

Tunable high-order sideband generation has important applications in the realization of the optical frequency comb with a varying spectral region (corresponding to the sideband range) and frequency resolution (corresponding to the sideband interval). In this paper, we propose a theoretical scheme to tune both the range and the interval of the high-order sidebands in a coupled double-cavity optomechanical system, which consists of an optomechanical cavity and an auxiliary cavity. Our proposal can be realized by driving the optomechanical cavity with a control field and a probe field simultaneously, driving the auxiliary cavity with a pump field. Furthermore, we assume that the frequency detuning between the control field and the probe field (the pump field) equals ωb/n (ωb/m), where ωb is the mechanical frequency, m and n are integers. When n = m = 1, we find that the sideband range can be effectively enlarged by increasing the pump amplitude or the photon-hopping coupling rate, or by decreasing the auxiliary cavity damping rate. When n = 1 and m > 1, the output spectrum consists of a series of integer-order sidebands, fraction-order sidebands, and the sum and difference sidebands, and the sideband interval becomes ωb/m and can be diminished by simultaneously increasing m and the pump amplitude.

Rate Constants and Mechanisms for Reactions of Bromine Radicals with Trace Organic Contaminants.

Bromine radicals can pose great impacts on the photochemical transformation of trace organic contaminants in natural and engineered waters. However, the reaction kinetics and mechanisms involved are barely known. In this work, second-order reaction rate constants with Br• and Br2•- were determined for 70 common trace organic contaminants and for 17 model compounds using laser flash photolysis and steady-state competition kinetics. The kBr• values ranged from <108 to (2.86 ± 0.31) × 1010 M-1 s-1 and the kBr2•- values from <105 to (1.18 ± 0.09) × 109 M-1 s-1 at pH 7.0. Six quantitative structure-activity relationships were developed, which allow predicting additional unknown kBr• and kBr2•- values. Single-electron transfer was shown to be a favored pathway for the reactions of Br• and Br2•- with trace organic contaminants, and this was supported by transient spectroscopy and quantum chemical calculations. This study is essential in advancing the scientific understanding of halogen radical-involved chemistry in contaminant transformation.

Proof-of-principle demonstration of measurement-device-independent quantum key distribution based on intrinsically stable polarization-modulated units.

The experimental demonstration of measurement-device-independent quantum key distribution (MDI-QKD) has been widely demonstrated. Thus far, several experimental groups have implemented polarization encoding MDI-QKD but with manual polarization controllers, or polarization modulators that make circular polarization states unstable. Here, we apply an intrinsically stable polarization-modulated unit (PMU) to MDI-QKD so that Alice and Bob can modulate four BB84 polarization states, all of which can be kept stable from even the harsh environment. Moreover, our PMU can provide two operational polarization encoding modes suitable to different application scenarios. A proof-of-principle demonstration of MDI-QKD based on our PMU is implemented with an interference visibility of 46.6%, an average quantum bit error rate of 1.49% for the Z basis and the secure key rate of 4.25 × 10-6 bits per pulse. The proposed study is helpful for building polarization encoding MDI-QKD systems with better stability.

Fraction-order sideband generation in an optomechanical system.

We propose a scheme for generating a new kind of sideband, i.e., the fraction-order sideband, in an optomechanical system. In the conventional scheme of high-order sideband generation [Opt. Lett.38, 353 (2013)OPLEDP0146-959210.1364/OL.38.000353], the sideband interval has a minimum frequency limitation, which is equal to the mechanical frequency ωb, and this limits the precision of the sideband comb. With our proposed fraction-order sidebands, the sideband interval can break that limitation and reach ωb/n (n is an integer). The scheme we propose can be realized by driving the optomechanical system with three laser fields, including a control field (ωc) and two probe fields (ωp, ωf), in which the detuning between ωc and ωp is equal to the mechanical frequency ωb, while the detuning between ωc and ωf is equal to ωb/n. In this case, we find that not only the integer-order (high-order) sidebands, but also the fraction-order sidebands, and the sum and difference sidebands between the integer- and fraction-order sidebands, will appear in the output spectrum. Moreover, the sideband interval becomes ωb/n, and it can be decreased by increasing n. Our work paves the way to achieve a tunable optical frequency comb based on the optomechanical system.

Digital Simulation of Topological Matter on Programmable Quantum Processors.

Simulating the topological phases of matter in synthetic quantum simulators is a topic of considerable interest. Given the universality of digital quantum simulators, the prospect of digitally simulating exotic topological phases is greatly enhanced. However, it is still an open question how to realize the digital quantum simulation of topological phases of matter. Here, using common single- and two-qubit elementary quantum gates, we propose and demonstrate an approach to design topologically protected quantum circuits on the current generation of noisy quantum processors where spin-orbital coupling and related topological matter can be digitally simulated. In particular, a low-depth topological quantum circuit is performed on both the IBM and Rigetti quantum processors. In the experiments, we not only observe but also distinguish the 0 and π energy topological edge states by measuring the qubit excitation distribution at the output of the circuits.

High-dose dexamethasone plus recombinant human thrombopoietin vs high-dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective, multicenter, randomized trial.

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.

Nonreciprocal transmission and fast-slow light effects in a cavity optomechanical system.

We study the nonreciprocal transmission and the fast-slow light effects in a cavity optomechanical system, in which the cavity supports a clockwise and a counter-clockwise circulating optical mode; both the modes are driven simultaneously by a strong pump field and a weak signal field. We find that the system reveals a nonreciprocal transmission of the signal fields when the intrinsic photon loss of the cavity is equal to the external coupling loss of the cavity. However, when the intrinsic photon loss is much less than the external coupling loss, the nonreciprocity about the transmission properties almost disappears, the nonreciprocity is shown in the group delay properties of the signal fields, and the system exhibits a nonreciprocal fast-slow light propagation phenomenon.

Improving the phase sensitivity of an SU(1,1) interferometer with photon-added squeezed vacuum light.

We study the phase sensitivity of an SU(1,1) interferometer from two aspects, i.e., the phase estimation determined by the error propagation formula and that by the quantum Cramér-Rao bound (QCRB). The results show that the phase sensitivity by using the intensity detection reaches the sub-shot-noise limit with a coherent state and an m-photon-added squeezed vacuum state (m-PA-SVS) as inputs. The phase sensitivity gradually approaches the Heisenberg limit for increasing m, and the ultimate phase precision improves with the increase of m. In addition, the QCRB can be saturated by the intensity detection with inputting the m-PA-SVS.

Quantum squeezing in a modulated optomechanical system.

Quantum squeezing, as a typical quantum effect, is an important resource for many applications in quantum technologies. Here we propose a scheme for generating quantum squeezing, including the ponderomotive squeezing and the mechanical squeezing, in an optomechanical system, in which the radiation-pressure coupling and the mechanical spring constant are modulated periodically. In this system, the radiation-pressure interaction can be enhanced remarkably by the modulation-induced mechanical parametric amplification. Moreover, the effective phonon noise can be suppressed completely by introducing a squeezed vacuum reservoir. This ultimately leads to that our scheme can achieve a controllable quantum squeezing. Numerical calculations show that our scheme is experimentally realizable with current technologies.

Entangling cavity optomechanical systems via a flying atom.

We propose a novel scheme to generate the entanglement between two cavity optomechanical systems (COMSs) via a flying two-level atom. We derive the analytical expressions for the generated entangled states. We find that there exist two processes for generating entanglement: one is the entanglement transfer between the two phonon-modes, and the other is the entanglement swapping-like process among the two photon-modes and the two phonon-modes. We analyze these two kinds of phenomena, respectively, by adjusting the distance between the two COMSs. Then we discuss the verification of the generated entangled states of the two COMSs, and analyze the decoherence of the generated entangled states. Finally, we discuss the experimental feasibility of our proposal.

Mechanical squeezing and photonic anti-bunching in a coupled two-cavity optomechanical system.

We propose a scheme for generating the squeezing of a mechanical mode and the anti-bunching of photonic modes in an optomechanical system. In this system, there are two photonic modes (the left cavity-mode and the right cavity-mode) and one mechanical mode. Both the left cavity-mode and the right cavity-mode are driven by two lasers, respectively. The power of the driving lasers and the detuning between them play a key role in generating squeezing of the mechanical mode. We find that the squeezing of the mechanical mode can be achieved even at a high temperature by increasing the power of the driving lasers. We also find that the cavity-modes can show photonic anti-bunching under suitable conditions.

Controllable optomechanically induced transparency and ponderomotive squeezing in an optomechanical system assisted by an atomic ensemble.

We propose a system for realizing controllable optomechanically induced transparency (OMIT) and ponderomotive squeezing. In this system, an atomic ensemble driven by an external optical field couples with the cavity field in a typical optomechanical cavity. When the cavity is driven by a coupling laser and a probe laser, we can produce a switch for the probe field and adjust the width of the transparency window flexibly by manipulating the coupling strength between the atomic ensemble and the external optical field. We also investigate the ponderomotive squeezing properties of the transmitted field by analyzing its spectrum. Interestingly, the coupling strength between the atomic ensemble and the cavity field plays an important role in controlling the squeezing properties and the squeezing spectrum presents distinct features at red-detuned and blue-detuned frequencies by adjusting the coupling strength.