DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

CRISPR/Cas system, an adaptive immune system with clustered regularly interspaced short palindromic repeats, may interfere with exogenous nucleic acids and protect prokaryotes from external damages, is an effective gene editing and nucleic acid detection tools. The CRISPR/Cas system has been widely applied in virology and bacteriology; however, there is relatively less knowledge about the application of the CRISPR/Cas system in parasitic diseases. The review summarizes the mechanisms of action of the CRISPR/Cas system and provides a comprehensive overview of their application in gene editing and nucleic acid detection of parasitic diseases, so as to provide insights into future studies on parasitic diseases.

The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.

Objective: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Methods: Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves. Results: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Conclusion Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Objective: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Methods: Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves. Results: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Conclusion Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Objective: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Methods: Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves. Results: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Conclusion Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Objective:To investigate the clinical characteristics, diagnosis, treatment and prognosis of acute leukemia (AL) with NUP98-DDX10 fusion gene-positive.Methods:The clinical data of 2 AL patients with NUP98-DDX10 fusion gene-positive who admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences in April 2020 and February 2021, respectively were retrospectively analyzed. Transcriptome gene sequencing was used to detect fusion gene, and the fusion gene fragment was amplified by using reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing was used to clarify sequences. The clinical and experimental indicators characteristics were analyzed and the relevant literatures were reviewed.Results:According to the clinical diagnosis, 1 patient was diagnosed as acute myeloid leukemia M 5 (AML-M 5) and 1 patient was diagnosed as acute leukemia of ambiguous lineage, not otherwise specified (ALAL-NOS). The AML-M 5 patient presented with severe coagulation abnormalities, and fulfilled the diagnostic criteria for diffuse intravascular coagulation (DIC) at the initial visit. Transcriptome sequencing of 2 patients showed NUP98-DDX10 fusion gene- positive. RT-PCR confirmed that sequencing results identified 2 different splice fusion modes: one was NUP98 exon 14 fused with DDX10 exon 7(usually called "type Ⅱ"), the other was NUP98 exon 14 fused with DDX10 exon 13, which was never reported and named as "type Ⅳ". From 1997 to 2018, a total of 16 cases with NUP98-DDX10 related hematologic neoplasms were reported in the literature. A summary analysis of 16 cases added with 2 patients in our center included 13 males and 5 females with median age 31.5 years (0.08-61 years). The median overall survival was 12 months (1-46 months). Conclusions:A novel fusion gene NUP98-DDX10 transcriptome is identified in ALAL-NOS patient. Hematological malignancies with NUP98-DDX10 are very rare. They respond poorly to conventional treatment and require allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve the prognosis.

Objective:This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients. Methods:This prospective, single-arm, and open clinical study enrolled 30 adult Ph + ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results:All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS ( P=0.004) , HRFS ( P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS ( P=0.030) and EFS ( P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions:The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph + ALL patients. Clinical trial registration:ClinicalTrials.gov, NCT02523976.

Objective:To analyze the influence of CD19 isoforms to the efficacy of CD19/CD3 Bispecific T-cell Engager (BiTE) antibody, and explore the resistance mechanism of BiTE immunotherapy.Methods:Semi-quantitative RT-PCR (qRT-PCR) was used to detect the expression of CD19 mRNA isoforms before and after BiTE treatment in a patient with CD19 + B cell acute lymphoblastic leukemia (ALL) . CD19 isoforms were analyzed by Sanger sequencing. Flow cytometry and transcriptome sequencing were performed to analyze the expression of cell lineage specific molecules before and after BiTE treatment. Results:The expression of CD19 isoform with exon 2 deletion was identified at diagnosis. After relapsed and treatment of BiTE antibody, the patient did not achieve remission and CD19 antigen on leukemic cells turned negative detected by flow cytometry after BiTE treatment. However the expression ratio of CD19 isoform with exon 2 deletion was not increased. Flow cytometry phenotype and transcriptome sequencing confirmed that no linage switching developed, which suggested the expression of CD19 isoform caused by exon alternative splicing and lineage switching was not related to CD19 epitope loss in this patient. This patient achieved complete remission by sequential administration of self-developed CD22 CAR-T and CD19 CAR-T after disease progression.Conclusion:Targeting or combining an alternative antigen specific CAR-T may be a promising treatment option after losing CD19 expression in relapsed ALL.

Objective:This study aimed to explore the efficacy and safety of rituximab combined with short-course and intensive regimens in the treatment of adult patients with Burkitt leukemia.Methods:The clinical data of 11 Burkitt leukemia patients in our hospital from January 30, 2006, to September 12, 2018, were collected. The clinical details, complete remission (CR) rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were evaluated.Results:The median age of 11 patients was 34 (15-54) years, of which six were males and five were females (M∶F, 1.2∶1) . The median white blood cell (WBC) count was 12.28 (2.21-48.46) ×10 9/L, and the median blast percent of peripheral blood and bone marrow were 40% (3%-76%) and 84.0% (29.5%-94.5%) , respectively. Ten patients were administered with rituximab combined with a short-course and intensive regimens, and two patients underwent autologous hematopoietic stem cell transplantation following consolidation chemotherapy. The CR rate after one cycle of induction therapy was 100%, the four-year OS was 90%, and RFS was 90%. Out of the ten treated patients, only one patient suffered from tumor lysis syndrome during the induction chemotherapy. Consequently, renal function recovered after hemodialysis and other treatments. The regimen is safe with no treatment-related deaths. Conclusions:Rituximab combined with short-course and intensive chemotherapy regimens is effective and well-tolerated in adult Burkitt leukemia.