[Efficacy and Safety of Venetoclax-Based Induction Therapy in Acute Myeloid Leukemia].

AbstractObjective: To investigate the efficacy and safety of venetoclax-based induction chemotherapy in newly diagnosed (ND) patients ineligible for intensive therapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 51 newly diagnosed patients ineligible for intensive therapy and patients with R/R AML treated in the Department of Hematology of Xijing Hospital from February 1, 2021 to April 30, 2022 were retrospectively analyzed. The incidence of complete remission (CR)/CR with incomplete hematological recovery (CRi), objective remission rate (ORR), minimal residual disease (MRD) status, advense events (AE), overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: Among 51 patients, 32 patients were newly diagnosed patients unfit for intensive therapy, with a median age of 60 (29-88) years, and 19 patients were R/R patients, with a median age of 49 (22-92) years. The median cycles of VEN-based treatment in the two groups were both 2. The CR/CRi rates in the ND-AML and R/R-AML group after one course of induction treatment were 65.6% and 36.9%, respectively, and the ORR were 81.3% and 42.1%, respectively. The cumulative CR/CRi rates after 1-3 courses of VEN-based treatment were 71.9% and 47.4%, respectively. The MRD negativity rates of patients achieving CR/CRi were 69.6% and 33.3%, respectively. In the ND-AML and R/R-AML group, the median PFS were 8(5-11) and 3(1-5) months, and the median OS were 13 (6-20) and 5 (3-7) months, respectively. The median OS of patients achieving CR/CRi in both groups was significantly better than that of patients not achieving CR/CRi (13 months vs 4 months; OS not reached vs 4 months). During the first induction cycle, the incidence of grade 3 or higher granulocytopenia, anemia and thrombocytopenia was 96%, 90.2% and 84.3%, respectively. 30 patients (58.8%) had granulocytopenia with fever. The most common non-hematological AE was infection (12/51, 23.5%), followed by gastrointestinal symptoms (6/51, 11.8%). CONCLUSION: The VEN-based strategy has good treatment response and tolerance in newly diagnosed patients unfit for intensive therapy and R/R AML. The most common AEs are hematological toxicities and infection.

Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens.

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

[Clinical Characteristics and Prognosis of Systemic Anaplastic Large Cell Lymphoma].

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK+ patients while 53(15-73) years of the 30 ALK- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION: sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.

[Stable Isotope Characteristics and Vapor Source of Precipitation in the South and North Slopes of Wushaoling Mountain].

We analyze the stable isotope characteristics and vapor source of precipitation in a monsoon marginal area in the southern and northern slopes of Wushaoling Mountain, northwestern China, using 97 precipitation samples collected from October 2016 to October 2017. Correlation analysis and HYSPLIT model are used to study the characteristics of stable isotopes in precipitation, local meteoric water line equation, temperature and precipitation effects, and vapor source. The study found the following results. ① The slope and intercept of the southern slope local meteoric water line were lower than of those of the northern slope and global averages. ② Although the isotope temperature effects and seasonal effects of both slopes were obvious, the temperature effect of the northern slope was more obvious than of that of the southern slope. ③ The stable isotopes of precipitation during the summer on the northern slope and the precipitation on the southern slope<5 mm revealed that the precipitation effect was weak. There was no obvious precipitation effect in other seasons or in other precipitation levels on both slopes. ④ Vapor from the northwest and north accounted for>90% of the total. The northern slope was rarely affected by monsoon vapor, but the southern slope was affected by the southeast monsoon during the summer. Local water vapor recycling contributed to water vapor in the southern and northern slopes of Wushaoling Mountain. This study could improve the cognition of precipitation isotopic evolution in alpine regions, and lays a foundation for further research on isotope hydrology in cold and arid regions.

[Characteristics of Stable Isotopes and Analysis of Water Vapor Sources of Precipitation at the Northern Slope of the Qilian Mountains].

This study is based on precipitation samples from eight sites at the northern slope of the Qilian Mountains, combined with meteorological factors over the same period. Precipitation isotope characteristics, influence factors and the vapor sources of precipitation were analyzed, and the results show that:① The stable isotopes of precipitation in the study area show obvious seasonal changes, which are characterized by enrichment in the summer half-year and depletion in the winter half-year. The spatial precipitation δ18O value shows a significant downward trend with increasing altitude, and the altitude effect of the annual precipitation δ18O is -0.19‰/100 m, respectively;② At all stations, the slope and intercept of local meteoric water lines show an increasing trend from low altitude to high altitude. The high-altitude mountains above 2000 m are affected by local water vapor recirculation;③ The temperature effect is more significant and the temperature effect of δ18O is 0.64‰, and there is only a weak precipitation effect in summer;④ The results indicate that sub-cloud evaporation has a great influence on the δ18O of precipitation; the average raindrop evaporation rate of δ18O is 23%, 11%, 12%, and 16%,and the δ18O composition has been enriched by 46%, 27%, 38%, and 32% in May, June, July, and August from cloud base to ground, respectively.⑤ Under the condition of continuous rainfall in summer, the vapor sources of precipitation mainly come from the west and are affected by local evaporation of water vapor. The study enhances knowledge of isotopic evolution of precipitation and provides a basis for further study of isotopic hydrology in arid regions.

Conservative discrete-velocity method for the ellipsoidal Fokker-Planck equation in gas-kinetic theory.

A conservative discrete velocity method (DVM) is developed for the ellipsoidal Fokker-Planck (ES-FP) equation in prediction of nonequilibrium neutral gas flows in this paper. The ES-FP collision operator is solved in discrete velocity space in a concise and quick finite difference framework. The conservation problem of the discrete ES-FP collision operator is solved by multiplying each term in it by extra conservative coefficients whose values are very close to unity. Their differences to unity are in the same order of the numerical error in approximating the ES-FP operator in discrete velocity space. All the macroscopic conservative variables (mass, momentum, and energy) are conserved in the present modified discrete ES-FP collision operator. Since the conservation property in a discrete element of physical space is very important for the numerical scheme when discontinuity and a large gradient exist in the flow field, a finite volume framework is adopted for the transport term of the ES-FP equation. For nD-3V (n<3) cases, a nD-quasi nV reduction is specifically proposed for the ES-FP equation and the corresponding FP-DVM method, which can greatly reduce the computational cost. The validity and accuracy of both the ES-FP equation and FP-DVM method are examined using a series of 0D-3V homogenous relaxation cases and 1D-3V shock structure cases with different Mach numbers, in which 1D-3V cases are reduced to 1D-quasi 1V cases. Both the predictions of 0D-3V and 1D-3V cases match well with the benchmark results such as the analytical Boltzmann solution, direct full-Boltzmann numerical solution, and DSMC result. Especially, the FP-DVM predictions match well with the DSMC results in the Mach 8.0 shock structure case, which is in high nonequilibrium, and is a challenge case of the model Boltzmann equation and the corresponding numerical methods.

[Space-time Characteristics and Environmental Significance of Stable Isotopes in Precipitation at an Arid Inland River Basin].

This study was based on one complete hydrological year sampling of precipitation and meteorological data of the Shiyang River Basin in the Wuwei Station (1531 m a.s.l.), Minqin Station (1389 m a.s.l.), and Xidahe Station(2897 m a.s.l.) from July 2013 to July 2014. This paper aims to analyze temporal and spatial variation of stable isotopes in local precipitation, and discuss the impact of environmental factors during precipitation. The stable isotope evolution correlation with temperature, humidity, precipitation, vapor pressure, and average relative humidity is analyzed. The results show that:①During the study period, the stable isotope of precipitation showed significant seasonal changes, lower in the winter and spring, higher in the summer and autumn;②The monthly average D-excess of Wuwei Station is lower than that of Xidahe Station. In addition to the possibility of different water vapor sources, the high-altitude mountain areas are more affected by local recirculating water vapor, and the secondary evaporation under the clouds in low-altitude plain areas is stronger;③The stable isotope of precipitation in the basin shows a significant temperature effect, and the precipitation effect is reflected on the weather scale, which may be affected by leaching or monsoon circulation;④The δ18O value of precipitation is negatively correlated with the average relative humidity. It may be that the secondary evaporation under the cloud is weakened by the increase of precipitation and humidity.

Climate background, relative rate, and runoff effect of multiphase water transformation in Qilian Mountains, the third pole region.

Multiphase water transformation has great effects on alpine hydrology, but these effects remain unclear in the third pole region. Taking the Qilian Mountains as an example, the climate background and relative rates of multiphase water transformation were analyzed, and the runoff effect was evaluated based on long-term field observations. There are three climatic aspects driving multiphase water transformation, including lengthening ablation period, accelerative warming after 1990, and larger warming in the cryosphere belt than in the vegetation belt. The accelerative multiphase water transformation was quantified by three facts: the glacier area retreat rate accelerated by 50% after 1990, the percentage of snowfall in precipitation decreased by 7% after 1990, and the contribution from recycling moisture to precipitation increased by 60% from 1961-1990 to 1991-2016. Under the multiphase water transformation, the outlet runoff for three inland rivers increased by 5 × 108 m3/10 a after 1990. This runoff increase was concentrated mainly in the ablation period. For the seasonal runoff pattern, maximum runoff lagged maximum precipitation by one month under increasing glacier snow meltwater and thickening permafrost active layer. Meltwater from the cryosphere is a crucial runoff component in the Qilian Mountains. At present, these multiphase water transformations are accelerating, along with the yearly runoff increase, which will obviously have a profound impact on water resources management and flood control in the third pole region.

[Space-Time Characteristics and Environmental Significance of the Stable Isotopes in Precipitation in the Gulang River Basin].

Based on the precipitation samples and meteorological data simultaneously collected during individual precipitation events at the Gulang (2085 m a.s.l.) and Anyuan stations (2700 m a.s.l.) in Gulang, this article analyzes the temporal variation and local meteroic water lines and discusses the relationship between precipitation stable isotopes and temperature and precipitation and relative humidity. The results show that:① Gulang and Anyuan have higher δ18O values in summer and autumn and lower δ18O values in spring and winter, respectively; ② The vaule of δ18O decreases with increasing altitude, while the value of the d-excess increases, reflecting the gradual depletion of stable isotopes of precipitation when the air mass is rising along the slope; ③ The slope and intercept of the local meteroic water lines deviate from that of the global meteroic water lines, showing that they may also be affected by local water vapor recirculation, except for the dry environment and strong evaporation effect; and ④ The temperature effect of Gulang in the low-altitude area is more significant than that of the Anyuan station and the Gulang River Basin does not show a precipitation effect. It has been proven that precipitation is not the fundamental factor determining the δ18O of the precipitation in arid areas. The results of this study are helpful to further understand the water circulation mechanism in the Gulang River Basin.

[Environmental Significance of the Stable Isotopes in Precipitation at Different Altitudes in the Tuolai River Basin].

Precipitation samples and meteorological data were collected simultaneously during individual precipitation events at Tuole station (3367 m a.s.l.) and Jiayuguan station (1658 m a.s.l.) in the Tuolai River Basin. A study of temporal variation, Local Meteoric Water Lines, and altitude change on precipitation stable isotopes was conducted. The relationships between precipitation stable isotopes and temperature, precipitation, average vapor pressure, and relative humidity were determined in order to explore the environmental significance of the stable isotopes at different altitudes in the middle reaches of the Qilian Mountains. The analysis indicated that the stable isotopes of the precipitation in Tuole and Jiayuguan station were characterized by pronounced seasonal variation, with Tuole having higher δ18O values in summer and autumn and lower δ18O values in spring and winter, while Jiayuguan displays higher δ18O values in spring and lower in other seasons. The d-excess was correlated negatively with δ18O, and the correlation coefficients between δ18O and d-excess decreased with increasing altitude due to weakening sub-cloud evaporation. The slope and intercept of the Local Meteoric Water Lines from Jiayuguan to Tuole rose significantly, showing an increasing trend from low altitude to high altitude. For the precipitation events above 10℃, δ18O of Tuole was positively correlated with the temperature, but the Jiayuguan results indicated the opposite. Sub-cloud evaporation weakened with high precipitation events in Jiayuguan. δ18O and d-excess were positively correlated with the average vapor pressure, which declined from Tuole to Jiayuguan. Since the water vapor pressure and saturated water vapor pressure increased, it was difficult to form precipitation with decreasing altitude. The local strong sub-cloud evaporation caused δ18O and δD was positive at low altitude, while the effect of moisture recycling is obvious, such that δ18O and δD are negative in high altitude areas. There is no significant positive correlation between the δ18O and the relative humidity of the precipitation in Jiayuguan, while Tuole displays an opposite pattern. The results of the study will provide a scientific basis for further study of precipitation isotopes in the Tuolai River basin.

[Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.