[Efficacy analysis of Venetoclax combined with TKI and dexamethasone-containing low-dose chemotherapy for relapsed/refractory Ph+acute B-lymphoblastic leukemia].

The clinical data of five cases of relapsed/refractory (R/R) Philadelphia chromosome-positive acute B-lymphocytic leukaemia (Ph+B-ALL) treated with Bcl-2 inhibitor venetoclax combined with tyrosine kinase inhibitor (TKI) and dexamethasone-containing low-dose chemotherapy regimen at Zhengzhou University Cancer Hospital were analyzed, and the efficacy and safety were evaluated. Ponatinib was used in two of the five patients with T315I mutation, and flumatinib was used in other three patients. The results showed that, of the four minimal residual disease (MRD) positive patients, three achieved complete molecular remission (CMR) in the short term and one was ineffective. Another patient with morphological recurrence reached CR in one month. The overall response rate was 80%. Treatment related adverse reactions included mild skin pigmentation, gastrointestinal reactions, fatigue, and grade Ⅰ-Ⅱ bone marrow suppression.

Experimental Simulation of Open Quantum System Dynamics via Trotterization.

Digital quantum simulators provide a diversified tool for solving the evolution of quantum systems with complicated Hamiltonians and hold great potential for a wide range of applications. Although much attention is paid to the unitary evolution of closed quantum systems, dissipation and noise are vital in understanding the dynamics of practical quantum systems. In this work, we experimentally demonstrate a digital simulation of an open quantum system in a controllable Markovian environment with the assistance of a single ancillary qubit. By Trotterizing the quantum Liouvillians, the continuous evolution of an open quantum system is effectively realized, and its application in error mitigation is demonstrated by adjusting the simulated noise intensities. High-order Trotter for open quantum dynamics is also experimentally investigated and shows higher accuracy. Our results represent a significant step toward hardware-efficient simulation of open quantum systems and error mitigation in quantum algorithms in noisy intermediate-scale quantum systems.

Impact of Spectators on a Two-Qubit Gate in a Tunable Coupling Superconducting Circuit.

Cross-resonance (CR) gates have emerged as a promising scheme for fault-tolerant quantum computation with fixed-frequency qubits. We experimentally implement an entangling CR gate by using a microwave-only control in a tunable coupling superconducting circuit, where the tunable coupler provides extra degrees of freedom to verify optimal conditions for constructing a CR gate. By developing a three-qubit Hamiltonian tomography protocol, we systematically investigate the dependency of gate fidelities on spurious qubit interactions and present the first experimental approach to the evaluation of the perturbation impact arising from spectator qubits. Our results reveal that the spectator qubits lead to reductions in CR gate fidelity dependent on ZZ interactions and particular frequency detunings between spectator and gate qubits. The target spectator demonstrates a more serious impact than the control spectator under a standard echo pulse scheme, whereas the degradation of gate fidelity is observed up to 22.5% as both the spectators are present with a modest ZZ coupling to the computational qubits. Our experiments uncover an optimal CR operation regime, and the method we develop here can readily be applied to improving other kinds of two-qubit gates in large-scale quantum circuits.

High-Efficiency Arbitrary Quantum Operation on a High-Dimensional Quantum System.

The ability to manipulate quantum systems lies at the heart of the development of quantum technology. The ultimate goal of quantum control is to realize arbitrary quantum operations (AQUOs) for all possible open quantum system dynamics. However, the demanding extra physical resources impose great obstacles. Here, we experimentally demonstrate a universal approach of AQUO on a photonic qudit with the minimum physical resource of a two-level ancilla and a log_{2}d-scale circuit depth for a d-dimensional system. The AQUO is then applied in a quantum trajectory simulation for quantum subspace stabilization and quantum Zeno dynamics, as well as incoherent manipulation and generalized measurements of the qudit. Therefore, the demonstrated AQUO for complete quantum control would play an indispensable role in quantum information science.

Insurance status and risk of suicide mortality among patients with cancer: a retrospective study based on the SEER database.

OBJECTIVE: Given that the presence of insurance may affect the risk of suicide mortality in cancer patients, we aimed to examine the association in a population-based study using the Surveillance, Epidemiologic, and End Results (SEER) database. STUDY DESIGN: A retrospective analysis of data from the SEER database. METHODS: We conducted a retrospective study using the SEER database. Hazard ratios (HRs), adjusted HRs (aHRs), and 95% confidence intervals (95% CIs) of suicide death were calculated using Cox proportional hazard models to evaluate the risk of suicide mortality among the cohorts. RESULTS: Multivariable analysis revealed that cancer patients without insurance had an increased risk of suicide death compared with patients with private insurance (aHR, 1.37; 95% CI, 1.01-1.72), whereas no significant result was observed in patients with any Medicaid (aHR, 1.10; 95% CI, 0.93-1.30; P = 0.27). In addition, the stratified analysis indicated that the risk of suicide death in patients in the uninsured and Medicaid groups presented with localized stage of disease (aHR, 1.32; 95% CI, 1.02, 1.69), White (aHR, 1.34; 95% CI, 1.05, 1.71), and American Indian/Alaska Native and Asian/Pacific Islander (aHR, 1.89; 95% CI, 1.08, 3.30) were greater than insured patients. CONCLUSION: Overall, our results indicated that insurance status was a statistically significant predictor of suicide death in patients with cancer. Healthcare providers should identify those patients at high risk of suicide and provide appropriate mental health and psychosocial oncology services in time.

[The prognostic factors of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia].

To analyze the prognostic factors of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute lymphoblastic leukemia (ALL).The clinical data of 33 relapsed patients in 95 ALL patients receiving allo-HSCT were analyzed retrospectively. The median time of relapse was 5.7 (0.7-52.3) months. Extramedullary relapse was recorded in 10 cases (10.5%), bone marrow relapse in 15 cases (15.8%), and both extramedullary and marrow relapse were seen in 8 cases (8.4%). The median time of EMR was 7.4(0.7-52.3) months. The most commonly involved organ was central nervous system, followed by testis and bone. The 3-year OS rate in EMR patients was (33.3±11.1) %. Univariate analysis showed that disease state before transplantation (P=0.026), extramedullary infiltration before transplantation (P=0.005), conditioning regimens (P=0.033) and acute graft-versus-host disease(aGVHD) (P=0.013) were significantly correlated with EMR. Multivariate analysis suggested that extramedullary infiltration (RR=5.067, 95%CI1.542-16.645, P=0.007) and aGVHD(RR=3.585, 95%CI1.245-10.320, P=0.018) were independent predictive factors of EMR in ALL patients after allo-HSCT.

[Risk factors of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemia].

Objective: To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia. Methods: A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively. Results: Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR (P<0.05). Multi-variable analysis revealed that CR2 or progressive disease (RR=3.468,95%CI 2.189-7.786), abnormal karyotype (RR=1.494,95%CI 1.020-2.189) and extramedullary disease before transplantation (RR=8.627,95%CI 3.921-18.452) were independent risk factors of EMR. Conclusions: The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.

[Adrenal adenoma presenting as serous chorioretinopathy complicated by exudative retinal detachment: a case report].

The case is presented on a 33-year-old woman with sudden vision loss for more than 20 days without a history of steroid use either locally or systemically. There was a history of connective tissue disease. The fundus fluorescein angiogram and optical coherence tomography showed multiple central serous chorioretinopathy (CSC) complicated by exudative retinal detachment (ERD). Meanwhile, the computed tomography of the adrenal suggested an adrenal adenoma. After complete tumor resection, the visual and anatomical functions of this patient have been significantly improved. Moreover, recurrence of CSC complicated by ERD was not observed during 9 months clinical follow-up after surgery. (Chin J Ophthalmol, 2021, 57: 784-786).

Manipulating Complex Hybrid Entanglement and Testing Multipartite Bell Inequalities in a Superconducting Circuit.

Quantum correlations in observables of multiple systems not only are of fundamental interest, but also play a key role in quantum information processing. As a signature of these correlations, the violation of Bell inequalities has not been demonstrated with multipartite hybrid entanglement involving both continuous and discrete variables. Here we create a five-partite entangled state with three superconducting transmon qubits and two photonic qubits, each encoded in the mesoscopic field of a microwave cavity. We reveal the quantum correlations among these distinct elements by joint Wigner tomography of the two cavity fields conditional on the detection of the qubits and by test of a five-partite Bell inequality. The measured Bell signal is 8.381±0.038, surpassing the bound of 8 for a four-partite entanglement imposed by quantum correlations by 10 standard deviations, demonstrating the genuine five-partite entanglement in a hybrid quantum system.

Demonstration of Controlled-Phase Gates between Two Error-Correctable Photonic Qubits.

To realize fault-tolerant quantum computing, it is necessary to store quantum information in logical qubits with error correction functions, realized by distributing a logical state among multiple physical qubits or by encoding it in the Hilbert space of a high-dimensional system. Quantum gate operations between these error-correctable logical qubits, which are essential for implementation of any practical quantum computational task, have not been experimentally demonstrated yet. Here we demonstrate a geometric method for realizing controlled-phase gates between two logical qubits encoded in photonic fields stored in cavities. The gates are realized by dispersively coupling an ancillary superconducting qubit to these cavities and driving it to make a cyclic evolution depending on the joint photonic state of the cavities, which produces a conditional geometric phase. We first realize phase gates for photonic qubits with the logical basis states encoded in two quasiorthogonal coherent states, which have important implications for continuous-variable-based quantum computation. Then we use this geometric method to implement a controlled-phase gate between two binomially encoded logical qubits, which have an error-correctable function.

Experimental Implementation of Universal Nonadiabatic Geometric Quantum Gates in a Superconducting Circuit.

Using geometric phases to realize noise-resilient quantum computing is an important method to enhance the control fidelity. In this work, we experimentally realize a universal nonadiabatic geometric quantum gate set in a superconducting qubit chain. We characterize the realized single- and two-qubit geometric gates with both quantum process tomography and randomized benchmarking methods. The measured average fidelities for the single-qubit rotation gates and two-qubit controlled-Z gate are 0.9977(1) and 0.977(9), respectively. Besides, we also experimentally demonstrate the noise-resilient feature of the realized single-qubit geometric gates by comparing their performance with the conventional dynamical gates with different types of errors in the control field. Thus, our experiment proves a way to achieve high-fidelity geometric quantum gates for robust quantum computation.

[Clonal heterogeneity and its prognostic significance in acute lymphoblastic leukemia].

Objective: To explore the characteristics and clinical significance of clonal heterogeneity in patients with acute lymphoblastic leukemia(ALL). Methods: From January 2016 to June 2019, 170 newly diagnosed ALL patients were enrolled in the Department of Hematology, Henan Cancer Hospital, including 93 males and 77 females, with a median age of 17 (2-80) years. Fifty-two ALL-related genes were detected by high-throughput sequencing technique. The clonal heterogeneity of mutations was analyzed according to the variant allele frequency (VAF) and the results of flow cytometry. The prognostic value of mutations was also evaluated. Results: Gene mutations were detected in 121 (71.2%, 121/170) patients, of which 2 or more clones were detected in 18 (52.9%, 18/34) T-cell acute lymphoblastic leukemia patients, while only 23 (16.9%, 23/136) B-cell acute lymphoblastic leukemia patients were positive of multiple mutations (P<0.01).Gene mutation-related clonal heterogeneity analysis showed that 2 or more clones were frequent in patients with NOTCH1 mutations (13/19 patients) (P<0.01). Event free survival (EFS) in patients with 3 or more clones was significantly lower than other patients (χ(2)=10.330, P=0.016). Child ALL patients had similar result, that multiple clones predicted lower overall survival (OS) and EFS (OS: χ(2)=7.974, P=0.047; EFS: χ(2)=10.860, P=0.013). Conclusion: Clonal heterogeneity in ALL patients is closely related to the different origin of lymphocyte lineages and the age of onset, which may reveal the nature of the disease and predict the clinical outcome.

[The genetic characteristics of BCR-ABL-negative myeloproliferative neoplasms].

Objective: To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV). Methods: A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients' general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed. Results: In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF. Conclusions: Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients' age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.

[Clinical analysis of gene mutation characteristics and mutation burden in myelodysplastic syndrome].

Objective: To investigate the relationship between gene mutation characteristics, mutation burden and general condition, disease subtype and karyotype of patients with myelodysplastic syndrome (MDS), and its clinical value. Methods: High-throughput sequencing was used to detect 65 blood tumor-related genes in 191 MDS patients and 9 secondary acute myelocytic leukemia patitents(SAML), and to analyze the characteristics of abnormal genes, mutation burden, as well as the relationship with disease subtypes, chromosome karyotypes and age. Results: Mutations were found in 148 patients (77.5%), including 47 abnormal genes and 186 mutation sites. And gene mutations were found in 9 SAML patients, the number of mutations was significantly higher than that in MDS patients (χ(2)=11.911, P=0.018). Among the abnormal genes, the mutation frequency of U2AF1 (37.3%) and ASXL1 (41.6%) were higher, and there were significant differences in mutation burden among different abnormal genes (F=91.946, P<0.001). There were differences in the number of gene mutations among different subtypes of MDS, and the number of EB-2 gene mutations was the highest (2.2±1.5). In SLD, MLD, EB-1 and EB-2, the proportion of carrying ≥ 3 mutations increased gradually (χ(2)=52.471, P=0.037). TP53 mutation was associated with abnormal karyotype (r(φ)=0.177, P=0.019), especially with complex karyotype (r(φ)=0.440, P<0.001), while NPM1 mutation is associated with normal karyotype (r(φ)=0.173, P=0.024). The number of mutations carried by patients under 30 years old was the least, and the number of mutations increased with the increase of age. The number of mutations was the most in patients aged 60 to 79 years old (P=0.017), and the mutation frequency of epigenetic related genes increased with the increase of age (P=0.041). Conclusions: The mutation characteristics and mutation load of MDS-related genes are closely related to clinical factors such as disease subtype, chromosome karyotype and patient age.

Witnessing Quantum Resource Conversion within Deterministic Quantum Computation Using One Pure Superconducting Qubit.

Deterministic quantum computation with one qubit (DQC1) is iconic in highlighting that exponential quantum speedup may be achieved with negligible entanglement. Its discovery catalyzed a heated study of general quantum resources, and various conjectures regarding their role in DQC1's performance advantage. Coherence and discord are prominent candidates, respectively, characterizing nonclassicality within localized and correlated systems. Here we realize DQC1 within a superconducting system, engineered such that the dynamics of coherence and discord can be tracked throughout its execution. We experimentally confirm that DQC1 acts as a resource converter, consuming coherence to generate discord during its operation. Our results highlight superconducting circuits as a promising platform for both realizing DQC1 and related algorithms, and experimentally characterizing resource dynamics within quantum protocols.

Observation of Topological Magnon Insulator States in a Superconducting Circuit.

Searching topological states in artificial systems has recently become a rapidly growing field of research. Meanwhile, significant experimental progress on observing topological phenomena has been made in superconducting circuits. However, topological insulator states have not yet been reported in this system. Here, for the first time, we experimentally realize a tunable dimerized spin chain model and observe the topological magnon insulator states in a superconducting qubit chain. Via parametric modulations of the qubit frequencies, we show that the qubit chain can be flexibly tuned into topologically trivial or nontrivial magnon insulator states. Based on monitoring the quantum dynamics of a single-qubit excitation in the chain, we not only measure the topological winding numbers, but also observe the topological magnon edge and defect states. Our experiment exhibits the great potential of tunable superconducting qubit chain as a versatile platform for exploring noninteracting and interacting symmetry-protected topological states.

[The safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with inermediate or higer-risk myelodysplastic syndrome].

To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with intermediate or high-risk myelodysplastic syndrome (MDS). Three of the total 11 MDS patients achieved complete remission (CR) and 6 achieved hematological improvement (HI), 1 stable disease (SD), and 1 progressive disease (PD). One patient was treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median follow-up time was 413(90-1 275) d. Nine patients were still alive. Low dose subcutaneous decitabine combined with arsenic trioxide can be an alternative regimen for intermediate or high-risk MDS patients.

[Clinical analysis of 9 patients with transplant-related thrombotic microangiopathy].

Objective: To analyze the clinical features, efficacy and outcomes in patients with transplantation associated thrombotic microangiopathy (TA-TMA). Methods: The clinical data of 9 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed from January 2011 to August 2018 in Affiliated Tumor Hospital of Zhengzhou University. Results: There were 6 male and 3 female patiens with a median age of 31 (12-38) years. The median time from transplantation to TA-TMA was 76 (24-155) days. The baseline blood and biochemical parameters at diagnosis of TA-TMA included median hemoglobin (Hb) 66 (58-77) g/L,platelet (PLT) count 22 (4-38) × 10(9)/L,serum lactic dehydrogenase (LDH) 655 (305-4 238) U/L,blood urine nitrogen (BUN) level 15.9 (4.8-26.2) mmol/L,blood creatinine (Cr) level 118 (24-380) µmol/L. The proportion of median peripheral blood schistocytes was 2.6%(1.2%-9%). All patients had positive urinary occult blood tests,and urinary protein was seen in 4 patients. Three patients had mental symptoms. Coombs tests were all negative. The main treatments of TA-TMA composed of reduction and withdrawal of calcineurin inhibitor,steroids and plasma exchange. Response was seen in 4 patients. Patients who did not response to the treatment had a higher proportion of schistocytes,more severe acute graft-versus-host disease (aGVHD),more elevated serum LDH and other transplant-related complications. Conclusions: TA-TMA after allo-HSCT is a serious complication with high mortality rate. The proportion of schistocytes in peripheral blood, serum LDH level and comorbidities are prognostic factors of clinical outcome.

[The influence of additive clonal chromosome abnormalities in Ph negative cells on the efficacy of chronic myeloid leukemia].

Objective: To investigate the influence of additional clonal chromosome abnormalities in Ph negative cells (CCA/Ph(-)) on the efficacy of chronic myeloid leukemia (CML) after tyrosine kinase inhibitors (TKI) treatment. Methods: The clinical data of 28 CML patients with CCA/Ph(-) treated in Henan Cancer Hospital from July 2014 to December 2017 were analyzed retrospectively. The univariate analysis was carried out by Kaplan-Meier method. Multivariate analysis was done by Cox proportional risk model. Results: A total of 28 CCA/Ph(-)patients were recruited including 17 males and 11 females with median age of 42.5 years old. The most common CCA/Ph(-)were trisomy 8 (60.7%), monosomy 7 (14.3%). 64.3% CCA/Ph(-)were transient and 35.7% recurrent (more than 2 times). Cytopenia in two or three lineages of peripheral blood was seen in 42.9% patients. As to the efficacy, 89.3% patients achieved major cytogenetic response (MCyR), 25% with major molecular response (MMR). The median follow-up time was 26.5 months. Treatment failure (TF) of TKI occurred in 32.1% patients with median duration of response 8 (1-41) months. Univariate analysis showed that TF rate was significantly correlated with the frequency of CCA/Ph(-)and cytopenia (all P<0.05). The MMR rate was also significantly correlated with cytopenia (P<0.05). Cytopenia of two lineages or pancytopenia was an independent risk factor related to MMR rate (RR=3.868, 95%CI 1.216-12.298, P=0.022) . Conclusions: Cytopenia in CCA/Ph(-)appears to be an independent risk factor of MMR in CML patients with TKI treatment. The recurrent CCA/Ph(-)may link to higher treatment failure rate. Drug withdrawal or alternative strategy should be considered according to response and the ABL kinase mutations.

[The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells combined with umbilical mesenchymal stem cells in patients with refractory severe aplastic anemia-â ¡].

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.