BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Formate is an important solar fuel, with large application potential in bioconversion. Especially, the win-win collaboration is achieved when formate is applied to the cultivation of microalgae, which combines the advantages from both artificial and natural photosynthesis. However, the inhibition of formate on the photosynthetic electron transport hinders the application of formate at high concentrations. The engineering or directed evolution of the regulation pathway is a case-by-case and time-consuming strategy. Here, we developed a new strategy by introducing a Stenotrophomonas sp. strain which was isolated and identified from the long-term self-evolution process of Chlamydomonas reinhardtii for adapting to high concentrations of formate. The co-culture with the strain or the fermentation broth relieved the inhibition of formate (50 mmol/L) on C. reinhardtii and promoted the growth of the microalga. Especially, the protein content increased significantly to nearly 50% of the dried weight. In addition, the co-culture also benefited the growth of both Chlorella pyrenoidesa and Synechocystis sp. PCC 6803 exposed to formate, which indicated broader applicability of this strategy. This strategy provides the opportunity to overcome the bottleneck in the formate-mediated artificial-natural hybrid photosynthesis and to aid the development of technologies for solar energy-driven production of bulk biomass, including proteins, by carbon dioxide reduction.
Photosynthesis/physiology* ; Formates/pharmacology* ; Stenotrophomonas/growth & development* ; Microalgae/metabolism* ; Chlamydomonas reinhardtii/growth & development*

This review introduces the concept,design and implementation of longitudinal mixed methods research.It summarizes its common applications,including the in-depth exploration of potential causes and association among variables of the complex phenomenon over time,the comprehensive evaluation of intervention effectiveness,the identification of facilitators and challenges for implementation,as well as the exploration of changes in behavior and underlying mechanisms.Moreover,this review analyzes existing challenges and future insights of this method.In conclusion,this review aimed to strengthen the nursing researchers'understanding of longitudinal mixed methods research and provide insights for future related studies.

ObjectiveTo investigate the relative content changes of differential metabolites and reducing sugars during the processing process of Rehmanniae Radix Praeparata （RRP） processed with Amomi Fructus （AF） and Citri Reticulatae Pericarpium （CRP）， and to lay the foundation for revealing the processing principle of this characteristic variety. MethodThe samples of the 0-54 h processing process of RRP processed with AF and CRP were taken as the research object， and their secondary metabolites were detected by ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. The 0.1% formic acid aqueous solution （A）-acetonitrile （B） was used as the mobile phase for gradient elution （0-1 min， 1%-3%B； 1-10 min， 3%-9%B； 10-15 min， 9%-12%B； 15-22 min， 12%-18%B； 22-31 min， 18%-24%B； 31-35 min， 24%-100%B； 35-36 min， 100%-5%B； 36-40 min， 5%-1%B； 40-45 min， 1%B）， column temperature was 40 ℃， injection volume was 3 μL， flow rate was 0.3 mL·min^-1. Electrospray ionization （ESI） was used to scan and collect MS data in the negative ion mode， the scanning range was m/z 50-1 250. Data analysis was carried out using PeakView 1.2 software， and the chemical composition of RRP processed with AF and CRP was identified by combining the literature information and chemical composition databases. The MS data were normalized by MarkerView 1.2， and then the multivariate statistical analysis was applied to screen the differential metabolites， and the changes of the relative contents of the differential metabolites with different processing times was analyzed， finally， correlation analysis was performed between the differential metabolites， the change of the reducing sugar content was combined to determine the most suitable processing time of RRP processed with AF and CRP. ResultA total of 121 compounds were identified from RRP processed with AF and CRP at different processing times， and 12 differential metabolites were screened out by multivariate statistical analysis， including catalpol， hesperidin， isoacteoside， acteoside， narirutin， echinacoside， isomartynoside， decaffeoylacteoside， 6-O-E-feruloylajugol， dihydroxy-7-O-neohesperidin， jionoside D， and rehmapicroside. With the prolongation of processing time， the relative contents of these 12 differential metabolites and reducing sugars changed slightly at 52-54 h. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents of RRP processed with AF and CRP at different processing times， and the suitable processing time of 52-54 h is determined according to the content changes of different metabolites and reducing sugars， which provides a basis for revealing the scientific connotation of the processing principle of this variety.

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

Objective:To explore the causes and influencing factors of financial toxicity in young breast cancer survivors, and to provide evidence for intervention program development to improve financial toxicity in young breast cancer survivors.Methods:Using descriptive qualitative research methods, 29 young breast cancer patients from September to December 2021 in Breast Surgery Follow-up Clinic of Fudan University Shanghai Cancer Center were interviewed. The Nvivo 12.0 qualitative data analysis software was used to analyze the data.Results:Four themes were extracted as following, direct cost of cancer treatment was the primary cause of financial toxicity, indirect costs related to cancer and treatment cannot be ignored, long-term effects of cancer and treatment further exacerbated financial toxicity, and cancer-related financial toxicity was also influenced by a variety of other factors.Conclusions:Multiple causes affected the experience of financial toxicity in young breast cancer survivors. The occurrence and risks of financial toxicity in young breast cancer survivors should be assessed. Intervention and support should be provided to meet the needs of young breast cancer survivors.

Objective:To explore the epidemiological characteristics, risk factors, preventions and treatments of recent human parvovirus B19 (HPV-B19) infections in recipients of renal transplantation (RT).Methods:From May 2020 to June 2021, retrospective review was conducted for epidemiological characteristics, treatment protocols, preventions and outcomes of HPV-B19 infected recipients after RT.Risk factors were analyzed using uninfected recipients after RT in the same period as controls.And 78 recipients who were not infected after RT with similar operation time were used as a control group for risk factor analysis.The infection rates of the four liver transplant recipients infected with HPV-B19 during the same period were calculated and compared with those of the kidney transplant recipients.Chi-square test and Fisher's exact test were used for statistical analysis.Results:During the observation period, HPV-B19 infection occurred in 39/368 recipients after RT with an overall infection rate of 10.60%(39/368). In terms of clinical symptoms, all 39 recipients presented with pure red cell aplasia (PRCA). In terms of season of infection, HPV-B19 infections occurred predominantly in autumn and winter [74.3% (29/39) of infections in autumn and winter, including 48.7% (19/39) in autumn]. Comparing the infection rates of different transplant recipients, 4 out of 123 liver transplant recipients were infected with HPV-B19 during the same period.The rate of infection was lower in liver transplant recipients than in RT counterparts (3.25% vs.10.60%, χ2=6.225, P=0.013). Analysis of OR values showed that transfusion of blood products was a risk factor for recent postoperative infection ( χ2=4.806, P=0.028, OR=2.418, 95% CI=1.088-5.373). Conclusions:HPV-B19 infection in renal transplant patients is mainly manifested as PRCA and is more likely than in liver transplant patients.Autumn and winter may be susceptible seasons for HPV-B19 and protection should be increased to prevent infection.Transfusion of blood products is a risk factor for recent HPV-B19 infection after RT, therefore donors should be routinely examined and it is imperative to test the safety of blood products in patients after RT.Thus HPV-B19 infection is well-controlled so that further spread may be prevented to avoid an epidemic outbreak.

Objective:To retrieve, evaluate, and integrate the best evidence for the prevention of central venous catheter-associated thrombosis in children, so as to provide a basis for clinical nursing programs for children with catheter-associated thrombosis.Methods:UpToDate, British Medical Journal Best Practice, Joanna Briggs Institute Evidence Synthesis, the Cochrane Library, CINAHL, Guideline International Network, National Guideline Clearinghouse, ACP Journal Club, PubMed, China Medlive Guidelines Network, China Biomedical Database, WanFang Data, China National Knowledge Infrastructure were retrieved by computer. The retrieval time limit was from June 30, 2011 to June 30, 2021. Four researchers independently screened the article, and extracted and summarized the article that met the quality standards.Results:A total of 10 articles were included, including four guidelines, three expert consensus articles, two evidence summaries, and one systematic review. A total of 24 pieces of evidence were summarized in five aspects of children's central venous catheter training, risk factor assessment, central venous catheter placement, catheter maintenance and thrombosis prevention.Conclusions:The best evidence for the prevention of central venous catheter-associated thrombosis in children is comprehensive and extensive, instructive and actionable, and can provide a basis for the clinical nursing program of catheter-associated thrombosis prevention in children. Medical and nursing staff can further refine evidence-based nursing practice programs according to the characteristics of children of different ages from the above five aspects, standardize the process of central venous catheter placement and maintenance, and provide children with drug or non-drug prevention.

Objective:To evaluate the effect of evidence-based nursing practice for functional rehabilitation of post-stroke neurogenic bladder (PSNB) .Methods:From October 2020 to July 2021, 136 PSNB patients admitted to the Department of Neurology, Jiangyin People's Hospital were selected by convenience sampling as the research object. According to the random number table method, the patients were divided into the study group and the control group, with 68 cases in each group. The control group received routine rehabilitation nursing, while the study group was given evidence-based rehabilitation nursing based on the control group. The urodynamics, rates of bladder balance, urinary incontinence and urinary retention after intervention were compared between the two groups.Results:After three months of intervention, bladder compliance and bladder balance rate in the study group were higher than those in the control group, and the residual urine volume was less than that in the control group, with statistical differences ( P<0.05) . After three months of intervention, urinary retention rate in the study group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Evidence-based rehabilitation nursing can help to promote the rapid recovery of bladder balance in PSNB patients and improve the prognosis of patients.

Objective:To observe the safety and efficacy of early conversion into a simplified once-daily immunosuppressive regimen of sirolimus plus low-dose extended-release tacrolimus in kidney transplant recipients.Methods:From April 2019 to August 2020, clinical data were collected from 44 recipients (22 pairs) of kidney transplantation. Two kidneys from the same donor were randomly divided into observed and control groups. The immunosuppressive regimen of two groups was the same within 1 month post-transplantation, i. e. tacrolimus plus mycophenolatemofetil (or mycophenolate sodium) and prednisone. Then the immunosuppressive regimen of observed group was switched into a simplified once-daily regimen of sirolimus plus low-dose extended-release tacrolimus and prednisone while control group remained unchanged. The changes of graft function, proteinuria and the incidence of related adverse events were recorded.Results:No inter-group difference existed in serum level of creatinine at Month 1 post-transplantation (163.40±51.57 vs 166.10±49.48 μmol/L). After regimen conversion, serum level of creatinine was slightly lower in observed group than that in control group at Months 3 and 6 post-transplantation (130.10±30.10 vs 134.90±28.97, 121.50±24.96 vs 136.30±27.06). However, there was no statistic difference. The 24-hour urinary total trace protein was slightly higher in observed group than that in control group (331.20±84.21 vs 279.50±80.91 and 209.60±66.02 vs 179.50±37.60 mg/24 h) at Months 3 and 6 post-transplantation. However, there was no statistic difference. No inter-group difference existed in the incidence of drug side effects or other adverse events.Conclusions:In kidney transplant recipients at Month 1 post-transplantation, a conversion of immunosuppressive regimen into a simplified once-daily of sirolimus plus low-dose extended-release tacrolimus can significantly boost patient compliance without an elevated risk of drug side effects or adverse events and offer an advantage of reducing nephrotoxicity.