Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT0279955

Expert Consensus on Microtransplant for Acute Myeloid Leukemia in Elderly Patients -Report From the International Microtransplant Interest Group

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment

Host and Tissue Affiliations of Culturable Endophytic Fungi Associated with Xerophytic Plants in the Desert Region of Northwest China

Endophytic fungi isolated from plants under drought stress have been evidenced to confer hosts adaptive benefits to withstand drought. In this study, endophytic fungi associated with five typical desert shrubs in different tissue from extremely arid desert in Northwest China were investigated based on ITS sequence analysis. A total of 158 endophytic fungal stains were isolated from 1088 tissue segments of 12 samples, and 28 taxa represented by 25 species and 15 genera were identified as Ascomycetes. Alternaria sp. was the dominant genus with generic abundance ranging from 20% to 65%. The colonization rate of root was significantly lower, but the root-endophytic fungi (19 species) conversely presented a higher diversity than stem and leaf (11 and 7 species, respectively). Endophytic fungi had pronounced relative host and tissue preferences, while tissue explained more endophytic fungal variation than plant species. Additionally, soil pH, organic carbon, and phosphatase elicited significant responses from fungal species, which significantly affected the species richness of Fusarium redolens, Alternaria chlamydospore, Didymella glomerata, and Xylariales sp. This research provides a basis for the further understanding of the ecological distribution of endophytic fungi associated with xerophytic plants and their potential application for vegetative restoration and agricultural cultivation in drylands

Active Bearing Technology of Foot Steel Pipe Applied in Controlling the Large Deformation of Tunnels: A Case Study

Foot steel pipe was the main arch foot supporting structure to control large deformation of loess tunnels, but the supporting effect was not ideal. Taking Yulinzi Tunnel in Qingyang, Gansu Province, as the engineering background, the design concept and implementation scheme of a foot steel pipe active bearing was put forward. The purpose was to solve the problem that it was difficult to control the surrounding rock settlement with the foot steel pipe. Numerical simulation and field experiments were used to verify the effect of the active bearing technology of the foot steel pipe. The main conclusions were as follows: (1) The effect of increasing the diameter of the foot steel pipe is better than that of increasing the number of foot steel pipes. (2) The active bearing mode of exerting its bearing capacity in advance by prepressing the foot steel pipe can effectively reduce the settlement of the vault. The settlement rate of the vault can be reduced by about 70% in 1–2 days and more than 50% in 1–3 days. (3) At the initial stage of surrounding rock deformation, this technology can provide a large bearing capacity, thereby reducing the overall deformation of the surrounding rock, slowing down the release of the surrounding rock pressure, and playing a positive role in the settlement control of the vault

Experimental Investigation on the Mechanical Properties of Vault Void Lining in Highway Tunnels and Steel Plate Strengthening

In the present study, large-scale specimens based on the tunnel prototype were prepared and static load tests were carried out to investigate the damage caused by lining voids. Based on the strengthening scheme of the tunnel, the strengthened specimens were prepared to explore the strengthening effect on the strengthening structure. The strengthening structure is made of a steel plate fixed with chemical anchor bolts and two-component epoxy adhesive. By analyzing the failure mode, structural deformation, and the relationship between load and strain, the damage caused by vault void with various void heights was analyzed and the obtained results were verified through the experiment. Moreover, the enhancement of the bearing capacity and stiffness of the structure strengthened by surface bonding steel was studied. The obtained results show that the damage caused by the lining void mainly occurs at the void boundary. The damage appears as multiple longitudinal cracks. The crack starts from the lower surface and develops radially. Using chemical anchor bolts and two-component epoxy adhesive to bond the steel plate on the lining surface, the damage can be reduced, and the bearing capacity of the structure can be improved effectively when the void height is a quarter of the second lining thickness, the number of cracks is reduced from 14 to 5 after steel plate strengthening, and the length of the longest crack is reduced from 13.2 cm to 8.3 cm, reduced by 37.12%. The steel plate strengthening also reduces the strain of the lower steel bar at the void boundary from 1130.58 με to 555.12 με, and the strain decreases by 50.89%. The experimental results show that the position where the void has the greatest impact on the lining is at the void boundary. Therefore, when steel plates are used to strengthen the void lining, the void boundary should be emphasized, which makes the strengthening more accurate and saves the cost of treatment

Active Bearing Technology of Foot Steel Pipe Applied in Controlling the Large Deformation of Tunnels: A Case Study

Foot steel pipe was the main arch foot supporting structure to control large deformation of loess tunnels, but the supporting effect was not ideal. Taking Yulinzi Tunnel in Qingyang, Gansu Province, as the engineering background, the design concept and implementation scheme of a foot steel pipe active bearing was put forward. The purpose was to solve the problem that it was difficult to control the surrounding rock settlement with the foot steel pipe. Numerical simulation and field experiments were used to verify the effect of the active bearing technology of the foot steel pipe. The main conclusions were as follows: (1) The effect of increasing the diameter of the foot steel pipe is better than that of increasing the number of foot steel pipes. (2) The active bearing mode of exerting its bearing capacity in advance by prepressing the foot steel pipe can effectively reduce the settlement of the vault. The settlement rate of the vault can be reduced by about 70% in 1–2 days and more than 50% in 1–3 days. (3) At the initial stage of surrounding rock deformation, this technology can provide a large bearing capacity, thereby reducing the overall deformation of the surrounding rock, slowing down the release of the surrounding rock pressure, and playing a positive role in the settlement control of the vault

Petroleum systems and resource potential in Sverdrup Basin, Arctic

The Sverdrup Basin is one of the important petroliferous basins in the Arctic. It has abundant oil and gas resources, but the exploration degree is relatively low. Based on the IHS database and literatures in the public domain, this paper documented the geological characteristics and distribution of oil and gas in the Sverdrup Basin, and classified the petroleum systems and hydrocarbon plays in the basin. The undiscovered hydrocarbons were eventually assessed by Monte Carlo simulation and the favorable exploration areas were predicted. The investigation results show that the discovered oil and gas accumulations are mainly distributed in the western area of the basin, which consists of Sabin and Edinburgh sub-basins. Oil and gas are mainly reserved in the Jurassic and Triassic clastic reservoirs. Two petroleum systems, which are the Paleozoic and Mesozoic systems, were identified in the basin. The Mesozoic petroleum system has a far greater exploration potential. Undiscovered recoverable reserves (mean value) in the Mesozoic petroleum system are 474.81 MMbbl (1 MMbbl=1×106 bbl, 1 bbl=0.137 t) of oil, 13 620.82 Bcf (1 Bcf=1×109 ft3, 1 ft3=0.028 3 m3) of natural gas and 63.66 MMbbl of condensate, amounting to 2 808.61 MMboe (3.85×108 t), of which the natural gas accounts for 80.82%. The Lower Jurassic structural hydrocarbon play in the western area of the basin, the Upper Triassic-Lower Jurassic structural hydrocarbon play in the Edinburgh sub-basin and the Upper Jurassic structural hydrocarbon play in the Sabine sub-basin are the most promising exploration areas