Microbial communities are thermally more sensitive in warm-climate lizards compared with their cold-climate counterparts.

Environmental temperature affects the composition, structure, and function of the gut microbial communities in host animals. To elucidate the role of gut microbiota in thermal adaptation, we designed a 2 species × 3 temperatures experiment, whereby we acclimated adult males of two agamid lizard species (warm-climate Leiolepis reevesii and cold-climate Phrynocephalus przewalskii) to 20, 28, and 36°C for 2 weeks and then collected their fecal and small-intestinal samples to analyze and compare the microbiota using 16S rRNA gene amplicon sequencing technology. The fecal microbiota displayed more pronounced interspecific differences in microbial community than the small-intestinal microbiota in the two species occurring in thermally different regions. The response of fecal and small-intestinal microbiota to temperature increase or decrease differed between the two species, with more bacterial taxa affected by acclimation temperature in L. reevesii than in P. przewalskii. Both species, the warm-climate species in particular, could cope with temperature change by adjusting the relative abundance of functional categories associated with metabolism and environmental information processing. Functional genes associated with carbohydrate metabolism were enhanced in P. przewalskii, suggesting the contribution of the fecal microbiota to cold-climate adaptation in P. przewalskii. Taken together, our results validate the two hypotheses tested, of which one suggests that the gut microbiota should help lizards adapt to thermal environments in which they live, and the other suggests that microbial communities should be thermally more sensitive in warm-climate lizards than in cold-climate lizards.

Efficacy and safety of decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) for newly diagnosed acute myeloid leukemia.

The 7 + 3 regimen is the front-line induction chemotherapy in patients with newly diagnosed acute myeloid leukemia, with a response rate of 60-80%. But it's not suitable for all patients especially old/unfit patients because of a higher treatment related toxicity. Therefore, safer and more effective induction therapies are required. In this retrospective study, 50 patients with newly diagnosed acute myeloid leukemia received decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) as induction chemotherapy. Complete remission (CR) rate was 96% (48/50) and overall response rate was 100%. Of note, All 7 patients harboring FLT3-ITD mutation achieved CR. The median overall survival (OS) was 40.0 months (range 2.0, 58.0). The OS at 1, 3, and 5 years were 75.3%, 54.2%, and 49.3%. The median relapse free survival (RFS) was 38.0 months (range 2.0, 58.0). The RFS at 1, 3, and 5 years were 67.3%, 48.9%, and 45.1%. The OS and RFS of patients who received hematopoietic stem cell transplantation (HSCT) were significantly higher than those who did not undergo HSCT (p=0.017; 0.016). The incidence of grade 3-4 neutropenia and thrombocytopenia was 84% and 88%. Meanwhile, the incidence of grade 3-4 infection and bleeding was only 16% and 6%. There was no early death. In conclusion, DAC+HAAG regimen is effective and well-tolerated as induction therapy in patients with newly diagnosed AML.

[Observation of Nutritional Status Changes in Patients with Acute Leukemia During Chemotherapy].

OBJECTIVE: To assess changes of nutritional status by comprehensive nutrition assessment including nutritional risk screening, dietary assessment, blood biochemical index, and body composition in acute leukemia patients who had undergone chemotherapy. METHODS: A total of 169 patients with acute leukemia treated at The First Affiliated Hospital of Soochow University from June 2018 to August 2019 were recruited for this study. Before and after chemotherapy, the NRS-2002 and PG-SGA scales, dietary intake, blood biochemical index and body composition were evaluated to compare the changes of nutritional status. RESULTS: NRS-2002 score and PG-SGA score after chemotherapy were significantly increased than those before chemotherapy (P<0.001). Many patients had insufficient nutritional intake during chemotherapy, and the dietary intake score of patients with induction chemotherapy was significantly lower than that of patients with consolidation chemotherapy (P=0.043). The results of multivariate analysis showed that induction chemotherapy was the independent risk factor for the increase of PG-SGA scores and the decrease of dietary intake (all P<0.05). After chemotherapy, the white blood cell count, hemoglobin, and platelet count were significantly decreased (P<0.001), the prealbumin was significantly increased (P<0.001), and the blood glucose was increased (P=0.04), but albumin was not significantly changed. The weight, body mass index, fat-free mass, skeletal muscle mass and intracellular water were all significantly decreased (P<0.001), and visceral fat area was increased significantly after chemotherapy (P<0.05), especially in newly-diagnosed acute lymphoblastic leukemia patients after the induction of chemotherapy. CONCLUSION: The nutritional status of patients with acute leukemia has undergone significant changes after chemotherapy. A single indicator has limited significance for nutritional status assessment. Comprehensive assessment of nutritional status by multiple tools is worthy of clinical application.

Successful application of PD-1 knockdown CLL-1 CAR-T therapy in two AML patients with post-transplant relapse and failure of anti-CD38 CAR-T cell treatment.

Patients with relapsed/refractory acute myeloid leukemia (R/R AML) often show resistance to chemotherapy and have dismal outcomes. Therefore, it is urgent to develop new treatment strategies to address this problem. With tremendous achievement of chimeric antigen receptor T cells (CAR-T) therapy against B-cell malignancies, many efforts have been devoted to developing CAR-T therapy for R/R AML but with limited success, in part owing to a lack of specific targets. C-type lectin-like molecule-1 (CLL-1) is highly expressed on AML blasts with no expression on normal hematopoietic stem cells, which makes it an ideal target of immunotherapy for AML. Here, we report 2 R/R AML patients who relapsed after allogeneic stem cell transplantation and failed multiline salvage therapies including anti-CD38 CAR-T therapy, but were successfully treated with PD-1 silenced anti-CLL-1 CAR-T therapy. Both patients achieved molecular complete remission with incomplete hematologic recovery at 28 days of evaluation after CLL-1 CAR-T cell infusion. Cytokine release syndrome in cases 1 and 2 were grade 1 and 2, respectively. At the last follow-up, cases 1 and 2 had maintained continuous remission for 8 and 3 months, respectively. Our results demonstrated that CLL-1 CAR-T cells might be an effective and safe salvage therapy for AML patients with posttransplant relapse.

Haploidentical CD7 CAR T-cells induced remission in a patient with TP53 mutated relapsed and refractory early T-cell precursor lymphoblastic leukemia/lymphoma.

Patients with relapsed/refractory early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) respond poorly to traditional therapy and have dismal prognosis. CD7 is a promising therapeutic targets for chimeric antigen receptor modified T cell therapy (CART) due to its widely expression in almost all T-cell malignancies. Here we present the anti-CD7 CART therapy in a 11-year-old male with TP53 mutated relapsed/refractory ETP-ALL/LBL. The patient suffered second relapse after haploidentical hematopoietic stem cell transplantation, showing resistance to 4 lines salvage therapies including venetoclax. Nanobody derived CD7-CART cells were manufactured by co-transducing CAR-T cells with a CD7 protein expression blocker. 70.5% of blasts (CD7 expression: 92.6%) and extensive extramedullary disease (mediastinal mass, enlarged lymph nodes and spleen) were observed prior to CD7-CART-cell therapy. A total of 5 × 106/kg donor-derived CD7-CART-cells were infused. Hematological and extramedullary remission were both achieved, with persistence of CD7-CART-cells be detected until the last followup at 96th days after the infusion. Reversible adverse effects including grade 3 cytokine release syndrome and macrophage activation syndrome were observed. This case demonstrated that CD7-CART was a potent and safe salvage therapy in relapsed/refractory ETP-ALL/LBL patient with high tumor burden.Trial registration: ClinicalTrials. gov, NCT04785833 , Registered on March 8, 2021, prospectively registered.

The geographical diversification in varanid lizards: the role of mainland versus island in driving species evolution.

Monitor lizards (Varanidae) inhabit both the mainland and islands of all geological types and have diversified into an exceptionally wide range of body sizes, thus providing an ideal model for examining the role of mainland versus island in driving species evolution. Here we use phylogenetic comparative methods to examine whether a link exists between body size-driven diversification and body size-frequency distributions in varanid lizards and to test the hypothesis that island lizards differ from mainland species in evolutionary processes, body size, and life-history traits (offspring number and size). We predict that: 1) since body size drives rapid diversification in groups, a link exists between body size-driven diversification and body size-frequency distributions; 2) because of various environments on island, island species will have higher speciation, extinction, and dispersal rates, compared with mainland species; 3) as a response to stronger intraspecific competition, island species will maximize individual ability associated with body size to outcompete closely-related species, and island species will produce smaller clutches of larger eggs to increase offspring quality. Our results confirm that the joint effect of differential macroevolutionary rates shapes the species richness pattern of varanid lizards. There is a link between body size-driven diversification and body size-frequency distributions, and the speciation rate is maximized at medium body sizes. Island species will have higher speciation, equal extinction, and higher dispersal rates compared with mainland species. Smaller clutch size and larger hatchling in the island than in mainland species indicate that offspring quality is more valuable than offspring quantity for island varanids.

Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion.

Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in ~10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a member of the ABL/Src-tyrosine kinase family. Somatic LYN rearrangements are found in 5 cases of hematopoietic malignancies so far, although none of them were treated with tyrosine kinase inhibitors. Case presentation: A 6-year-old boy with relapsed B-ALL had no response to reinduction chemotherapy. He was then treated with the ABL1 tyrosine kinase inhibitor dasatinib and achieved complete remission within 2 weeks. Haploidentical allogenic stem cell transplantation (allo-HSCT) was subsequently performed and maintenance therapy with dasatinib initiated 8 weeks post-transplantation. He has been in minimal residual disease negative remission for 10 months after allo-HSCT. Result: His bone marrow karyotype showed a balanced translocation between chromosomes 8 and 17, leading to a NCOR1-LYN fusion gene confirmed with sequencing. Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion.

Global, regional, and cladistic patterns of variation in climatic niche breadths in terrestrial elapid snakes.

We obtained geo-referenced occurrence and climatic data from individual localities for 59 species of terrestrial elapid snakes, used phylogenetic generalized least squares regression to investigate spatial and cladistic patterns of variation in climatic niche breadths, and compared patterns within and across regions and clades to see if they parallel or differ from each other. Specifically, we test (1) whether a species' climatic niche breadth on a given niche axis relates to its position along that axis, and to its climatic niche breadth on another niche axis, and (2) whether variation in niche breadths among species is explained by within-locality variation in climatic conditions or by among-locality variation. We found that: (1) there is an overall global pattern, and patterns in individual regions or clades generally parallel each other and global patterns; (2) species in warmer environments have narrower temperature niche breadths (TNBs); (3) precipitation niche breadth (PNB) and position are positively related; (4) TNB and PNB are not related; and (5) within-locality variation in climatic conditions explains most variation in TNBs, whereas among-locality variation explains most variation in PNBs. Our results are consistent with those reported for lizards of the families Phrynosomatidae and Varanidae, confirm the importance of within-locality niche breadth to species niche breadth, and show a more important role of among-locality niche breadth in affecting species niche breadth in terrestrial elapids than in lizards.

Effects of preemptive interferon-α monotherapy in acute leukemia patients with relapse tendency after allogeneic hematopoietic stem cell transplantation: a case-control study.

Interferon-α (IFN-α) inhibits tumor growth and mimics graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the current case-control study, we compared treatment responses in acute leukemia patients with relapse tendency post-allo-HSCT receiving preemptive IFN-α after withdrawal of immunosuppressants (n = 31) vs. receiving no IFN-α (n = 67). In the IFN-α group, 25 patients responded to the treatment without progressing to hematological relapse. In the non-IFN-α group, only 22 patients responded to the treatment. The response rate differed significantly (80.6 vs. 32.8%, P < 0.001). The 2-year cumulative incidence of relapse was 31.6 and 61.2% in the IFN-α and the non-IFN groups, respectively (P = 0.006). The 2-year leukemia-free survival and overall survival rate was 57.4 vs. 28.4% (P < 0.001) and 67.6 vs. 32.9% (P = 0.001), respectively. Among the 31 patients in the IFN-α group, 18 patients (58.1%) developed graft-versus-host disease (GVHD): 6 acute and 12 limited chronic GVHD. Patients who developed GVHD had higher treatment response rate than patients without GVHD (88.9 vs. 53.8%, P = 0.022). In conclusion, preemptive IFN-α therapy is a safe and effective treatment to prevent disease progression in high-risk patients with relapse tendency post-allo-HSCT.

Improvement of Constipation in Leukemia Patients Undergoing Chemotherapy Using Sweet Potato.

BACKGROUND: Leukemia patients undergoing chemotherapy commonly develop constipation, which is difficult to treat using routine methods. OBJECTIVE: The aim of this study was to determine whether sweet potato can alleviate constipation in leukemia patients undergoing chemotherapy. METHODS: Leukemia patients receiving their first chemotherapy were randomized to an intervention group (n = 57) or a control group (n = 63). The control and intervention groups were managed by using routine nursing methods and routine methods plus dietary sweet potato consumption (eating sweet potato 200 g/d, from admission to discharge), respectively. Related data regarding patients' defecation were collected on the second and fifth days after chemotherapy initiation, which included rates of constipation, frequency and duration of purgative usage, constipation status assessed by Rome III criteria, and scores on defecation satisfaction. RESULTS: On the second day, the rate of constipation and the rate of having first defecation within 24 hours after chemotherapy initiation were significantly improved in the intervention group, but the difference of the defecation satisfaction and "almost no loose stools without purgative use" in Rome III criteria were not significantly changed. On the fifth day, except for "the sensation of anorectal obstruction" and "requirement of manual assistance" in Rome III criteria, other items regarding defecation were significantly improved. CONCLUSION: This study demonstrates that sweet potato had a positive impact on the prevention of constipation and the defecation satisfaction in leukemia patients receiving their first chemotherapy. IMPLICATIONS FOR PRACTICE: As sweet potato is inexpensive, abundant, tasty, and easy to prepare, it can be widely used in leukemia patients undergoing chemotherapy.

[Efficacy and safety study of subcutaneous injection of bortezomib in the treatment of de novo patients with multiple myeloma].

OBJECTIVE: To explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo multiple myeloma (MM) patients. METHODS: A total of 36 MM patients treated with bortezomib, adriamycin and dexamethasone (PAD) from January 2012 to April 2013 were analyzed. Among them, 18 received improved PAD (improved PAD group) with the subcutaneous injection of bortezomib, another 18 received conventional PAD (PAD group). The efficacy and safety of two groups were analyzed. RESULTS: Except 4 cases can not be assessed, 32 patients were evaluated. Of 32 cases, 19(59.4%) achieved complete remission (CR) or very good partial remission (VGPR) after induction therapy, which were 61.1% and 57.1% for PAD group and improved PAD group, respectively (P=1.000). No significant difference between the time to achieve maximum effectiveness in two groups was detected. In the PAD group, one patient (5.6%) died of serious lung infection and eight (44.4%) experienced grade 3 or higher adverse events, while only one (5.6%) discontinued treatment in improved PAD group due to similar toxicity. Compared to PAD group, grade 3 or worse adverse events was significantly reduced in improved PAD group, the most common symptoms were leucopenia (33.3% vs 61.1%, P=0.086), thrombocytopenia (50.0% vs 61.1%), anaemia (27.8% vs 16.7%), infection (16.7% vs 50.0%, P=0.075), diarrhea (5.6% vs 33.3%, P=0.088), peripheral neuropathy(0 vs 27.8%, P=0.045). CONCLUSION: The improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had great progress.

[Pulmonary disease caused by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation--a case report and literature review].

OBJECTIVE: To report a case with pulmonary disease caused by nontuberculous mycobacteria (NTM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a literature review. METHODS: Case report and literature review. RESULTS: A patient with acute non-lymphocytic leukemia was treated by allo-HSCT. Her NTM lung disease developed after HSCT was successfully treated with a 3 antimicrobials combination of clarithromycin, levofloxacin and capreomycin for 10 months. CONCLUSION: NTM infections are infrequent in allo-HSCT recipients and have a good clinical prognosis if correctly treated.