Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective·To explore the molecular regulatory mechanism of neural tube defect(NTD)induced by retinoic acid(RA)in mouse embryos,and reveal the gene expression regularity of neural tube closure in mice.Methods·Based on the high-quality brain vesicle transcriptome data of mouse embryo during the critical period of neural tube closure[embryonic day 8.5(E8.5),E9.5 and E10.5],the gene expression trend data of the NTD group and the control group were obtained by using Short Time-series Expression Miner(STEM)software.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for genes with different expression trends between the NTD group and the control group.Some candidate genes were screened for validation.Pregnant mice were divided into the NTD group and control group,with 9 mice in each group.Pregnant mice in the NTD group were treated with RA and those in the control group were treated with sesame oil by gavage at E7.5.Foetal rat brain vesicle tissues were collected at E8.5,E9.5 and E10.5 for experiments.Based on the above animal tissues,the screened candidate genes were validated by quantitative real-time PCR(RT-PCR).Results·A total of 18 255 genes were detected in the transcriptome data of the control group,and the expression patterns of these genes could be summarized into 7 significant profiles.A total of 19 037 gene expression data were detected in the transcriptome data of the NTD group,and gene expression patterns could be summarized into 6 profiles with significant significance.A total of 46 genes in the control group showed an upward trend but a downward trend in the NTD group.They were enriched in the positive and negative regulation of organ development,neuronal apoptosis,oligodendrocyte proliferation,and fibroblast growth factor signaling pathway at the biological process level.At the cellular component level,they were mainly involved in the basic structure of cells and neurons;At the molecular functional level,they were mainly related to the binding of fibroblast growth factor receptor.A total of 61 genes showed a downward trend in the control group but an upward trend in the NTD group.These genes were enriched in functions such as cell lysis and amino acid/ion transport at the biological process level.At the cellular component level,they were enriched in intracellular molecules,particles,extracellular region,intercellular space,etc.At the molecular function level,they were related to the activity of a series of enzymes and transporters.The results of RT-qPCR showed that the transcriptome sequencing data were authentic and reliable.Conclusion·RA intervention causes abnormal cellular activities and stress responses during mouse embryo development,leading to abnormal embryo development,activation of signalling pathways related to organismal self-protection,and suppression of genes that maintain normal embryo development.

Objective To explore the lipid-lowering effect of Qige Decoction before and after compatibility through the combination of pharmacodynamics and liver metabolomics,and to provide new research strategies for exploring the scientific notation of traditional Chinese medicine compatibility.Methods According to the pharmacodynamic strategy,three groups of drug administration were set up as Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group.Four indices of blood lipids,serum biochemical indicators,and liver morphology and pathology were used to evaluate the intervention effect of Qige Decoction on hyperlipidemic rats.Liver metabolomics technology was used to analyze the effects of Qige Decoction on metabolites before and after compatibility,and multivariate statistical analysis was used to evaluate the differences between groups in terms of differential metabolites and metabolic pathways.Results Compared with the model group,the callback abilities of four indices of blood lipid in the Qige Decoction group were higher than those in Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group,among which the total cholesterol(TC)and triglyceride(TG)levels in the Qige Decoction group decreased(P＜0.05).A total of 86 potential biomarkers were identified by liver metabolomics,with 23,13,and 7 metabolites being significantly different in the Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group,respectively(P＜0.05).Metabolic pathway analysis of 29 specific biomarkers with significant callback effects showed that they were related to glycerophospholipid metabolism,linoleic acid metabolism,α-linolenic acid metabolism,sphingolipid metabolism,arachidonic acid metabolism,and unsaturated fatty acid biosynthesis.Qige Decoction mainly regulates glycerophospholipid and linoleic acid metabolism,and uniquely acts on sphingolipid metabolism.Conclusion Qige Decoction has more lipid-lowering targets after compatibility,with better lipid-lowering effects than the Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group.This study provides experimental evidence and research strategies for further revealing the scientific notation of traditional Chinese medicine compatibility.

Objective To explore the classification and changes of macrophage subsets in liver transplant rejection.Methods Rat liver transplantation model were established and divided into immune tolerance group(B-B),where the liver of BN rat donors was transplanted to BN rat recipients,and immune rejection group(L-B),in which the liver of Lewis rat donors was transplanted to BN rat recipients.Single-cell RNA sequencing and high-throughput RNA sequencing were used to distinguish the macrophage subsets of rat liver transplantation,and to find differential gene in rejection reactions.Immunohistochemistry was used to determine the changes and distribu-tion of protein expression and cell subsets.Results CD68 positive macrophages were higher in the rejection group than that in the tolerance group(P<0.05),and macrophages could be divided into 9 subsets.During the rejection reaction,the CXC chemokine ligand 9(CXCL9)in the 8th subsets of macrophages was significantly increased,while the gene for white blood cell differentiation antigen 74(CD74)in the 5th subsets was significantly increased(P<0.05).CD74 ranked first in the differential gene synthesis of macrophages during rejection,followed by CXCL9.Compared with the tolerance group,a large number of CD74 positive macrophages were observed in the hepatic portal area of the rejection group,and the infiltration of CD74 positive macrophages in the hepatic sinuses was also significantly increased(P<0.05),while a large number of CXCL9 positive macrophages were observed in the hepatic portal area and hepatic sinuses of the rejection group,especially in the portal area(P<0.05),and CD14 positive cells were significantly increased(P<0.05).Conclusions The CD74 positive macrophage subsets and CXCL9 positive macrophage subsets may be key subgroups in promoting liver transplant rejection,improving the mechanism of macrophage action in liver transplant rejection.

B-cell lymphoma (BCL) is a highly heterogeneous malignant tumor. In recent years, although the remission rate of BCL patients has been improved with the improvement of diagnosis and treatment methods, some patients still relapse and become refractory. Chimeric antigen receptor T cells (CAR-T) is a novel therapy. At present, CD19 CAR-T has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma. At the 62nd American Society of Hematology Annual Meeting, a number of studies reported the latest progress of CAR-T in the treatment of relapsed/refractory BCL.

Objective To understand the distribution of novel coronaviruses in the external environment of confirmed COVID-19 cases. Methods Environmental surface swab specimens such as bed rails, doorknob, closestool, hand washing sink, table, locker,ward pager, mobile phone, cup, clothes, were collected from the sentinel hospital of COVID-19, and samples were collected for the nucleic acid detection by RT-PCR. Results A total of 150 environmental samples were collected from 30 confirmed COVID-19 cases, 6 samples were determined to be novel coronaviruses postive (positive rate 4.00%). The total 14 mobile phone showed 3 novel coronaviruses positive.Among the 30 confirmed COVID-19 cases, 6 cases (positive rate 20.00%)were found novel coronaviruses in the external environment. Conclusions Novel coronaviruses exists in external environment of confirmed COVID-19 cases, which indicates the potential risk of COVID-19 infection.