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Steroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens. Literature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method. Eight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01-1.32, = 0.04), especially in patients with severe (grade III-IV or grade C-D) aGVHD (RR = 1.26, 95% CI = 1.04-1.52, = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05-1.55, = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy. Adding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487.

The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HD-DNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no statistically significant differences in any other outcomes between HD-DNR and IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse and toxicity.

Background: Niemann-Pick disease type C1 (NP-C1) is a rare, autosomal-recessive neurodegenerative disorder with no United States Food and Drug Administration (FDA)-approved drug. Lithium has been shown to have considerable neuroprotective effects for neurological disorders such as bipolar disorder, Alzheimer’s disease and stroke and has been tested in many clinical trials. However, the pharmacological effect of lithium on NP-C1 neurodegenerative processes has not been investigated. The aim of this study was to provide an initial evaluation of the safety and feasibility of lithium carbonate in patients with NP-C1. Methods: A total of 13 patients diagnosed with NP-C1 who met the inclusion criteria received lithium orally at doses of 300, 600, 900, or 1,200 mg daily. The dose was reduced based on tolerance or safety observations. Plasma 7-ketocholesterol (7-KC), an emerging biomarker of NP-C1, was the primary endpoint. Secondary endpoints included NPC Neurological Severity Scores (NNSS) and safety. Results: Of the 13 patients with NP-C1 (12–33 years) enrolled, three withdrew (discontinuation of follow-up outpatient visits). The last observed post-treatment values of 7-KC concentrations (128 ng/ml, SEM 20) were significantly lower than pretreatment baselines values (185 ng/ml, SEM 29; p = 0.001). The mean NNSS was improved after lithium treatment at 12 months ( p = 0.005). Improvement in swallowing capacity was observed in treated patients ( p = 0.014). No serious adverse events were recorded in the patients receiving lithium. Conclusion: Lithium is a potential therapeutic option for NP-C1 patients. Larger randomized and double-blind clinical trials are needed to further support this finding. Clinical Trial Registration: ClinicalTrials.gov , NCT03201627.

Astrocytomas often recur after surgical resection, but the underlying mechanism remains enigmatic. Elucidation of clonal evolution in primary and relapse tumors may provide important information on tumor progression. Here, we examined genetic factors underlying recurrence in a patient with astrocytoma initially diagnosed with World Health Organization (WHO) grade II astrocytoma, who then relapsed with glioblastoma (WHO grade IV) complicated with local anaplastic astrocytoma (WHO grade III). We performed genomic DNA sequencing and data analysis of paired tumor tissue specimens and a peripheral blood sample (control), and used expands software for subclone analysis. A germline NOTCH1 missense mutation was identified in the peripheral blood sample, the primary tumor and the relapse tumor; in addition, we identified a tumor protein p53 (TP53) heterozygous nonsense mutation in the primary tumor and a TP53 homozygous nonsense mutation and an IDH1 heterozygous missense mutation in the relapse tumor. Clonal evolution trees indicated higher heterogeneity in the relapse tumor. Although germline mutations might contribute to the driving force of the primary tumor, aggressive chemotherapy and radiation may apply selective pressure for tumor clonal evolution; furthermore, a total loss of function of gatekeeping genes (TP53) may result in impaired DNA repair and catastrophic chromosomal aberrations. Astrocytoma often recurs after surgery. In this study, we examined the clonal structures of a primary astrocytoma and its relapse tumor, a malignant glioblastoma. We observed accelerated carcinogenesis in the relapse tumor after intensive radiation and chemotherapy, suggesting that such treatment may contribute to astrocytoma malignant progression.

The objective of this study was to assess the effects of exogenously expressed proinsulin on the biological characters of a hematopoietic stem cell line (HSC) and erythroid myeloid lymphoid (EML) cells and explore new strategies for cell therapy for type I diabetes. EML cells were transduced with lentivirus particles carrying the human proinsulin (proINS) gene. The positive transduced cells were selected based on green fluorescence protein (GFP) positivity and puromycin resistance. Overexpression of proINS was confirmed via real-time PCR and Western blotting. The functional activity of the human proINS secreted by EML cells was elucidated by analyzing the activation of insulin receptor and its downstream signaling. Pro-INS + EML cells were able to prime the phosphorylation of insulin receptor as well as induce the expression of downstream genes of insulin receptor. Furthermore, Wnt3a can significantly promote self-renewal of Pro-INS + EML cells. However, we did not observe significant changes in the proliferation and differentiation of INS + EML cells, compared to the control EML cells. Our results might be useful for developing a new therapy for diabetes mellitus.

Apparel has the potential to influence the external expression of wearer’s emotional state and can even empower them, making patients’ hospital wearing a crucial factor in their emotional experience and medical treatment. This study aims to investigate the emotional factors that drive patients’ behavioral responses to hospital gowns using the pleasure–arousal–dominance (PAD) model. With the survey conduction and data analysis, the results identified that the color and silhouette of hospital gowns lead to the emotional experience of arousal, while the structure leads to the emotional experience of dominance, which in turn brings patients a high sense of pleasure and further affect their acceptance and willingness to continue wearing hospital gowns. Based on the results of the research, new hospital gowns were designed and validated, which further confirmed the relationship between the attributes of hospital gowns and emotions of patients. Thus, by extending the PAD model to the context of patients’ use of hospital gowns, this study provides designers with a basis for creating emotionally driven atmosphere factors in the development of hospital gowns for the Chinese market that improve acceptance and continuation of hospital gowns, making a valuable contribution to knowledge in this field.

To systematically study the quantitative relationship between natural enemies and pests, this paper used grey relational analysis method, angular cosine coefficient method, fuzzy similarity priority ratio method and correlation coefficient method to analyze the closeness of the quantitative relationship between natural enemies and Empoasca onukii Matsuda in \"Anjibaicha\", \"Huangshandayezhong\" and \"Longjing 43\" tea plantations. The conclusions obtained by the grey relational analysis method were used as a criterion to compare the sum of the rankings of the top three natural enemies, Plexippus paykulli, Tetragnatha squamata and Ebrechtella tricuspidata, thus comparing and discussing the similarities and differences between the conclusions obtained by the four research methods. The angular cosine coefficient method and grey relational analysis method yielded no major differences in conclusions, followed by the correlation coefficient method, with the fuzzy similarity priority ratio method yielding more varied results. According to the ranking analysis of the close relationship between the number of E. onukii and its natural enemies, Tetragnatha squamata, Hylyphantes graminicola and Ebrechtella tricuspidata are the first three natural enemies closely related to the number of E. onukii. This paper is an attempt to compare the consistency of research results of various research methods, which provides a reference for selecting research methods in analyzing the quantitative relationship between natural enemies and pests.

The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HD-DNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no statistically significant differences in any other outcomes between HD-DNR and IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse and toxicity.