Combining Traditional Chinese Herbs and csDMARDs for the Treatment of Rheumatoid Arthritis Involves Tapering and Discontinuing Glucocorticoids: Protocol for a Two-Stage Non-Randomized Controlled Trial.

Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).

Effect of evidence-based nursing management of protocol compliance in anticancer drug clinical trial.

Objective: This study aimed to construct evidence-based anticancer drug clinical trial nursing management norms to ensure the safety and quality of clinical trial nursing. Methods: This before-after study was carried out to complete the evidence implementation in a cancer hospital in Shanghai, China. Seven review indicators were developed and reviewed in one phase I clinical trial center and two oncology wards. The corresponding evidence-based intervention program was formulated, and the completion rate of good clinical practice certification, protocol training, delegation of duties, qualification rate of administration, sampling and document recording in anticancer drug clinical trials before and after implementation were compared. Results: After implementation, the completion rate of protocol training, delegation of duties, and the qualification rate of document recording were significantly higher than those of the baseline review, whereas the completion rate of good clinical practice certification and the qualification rate of sampling did not significantly differ from those observed at the baseline review. There was no administration or infusion device-related protocol deviation during the baseline and post reviews. Conclusions: Anticancer drug clinical trial nursing management norms and relevant standard operating procedures were constructed. The results showed that the implementation of this intervention improved the standardization of nurse qualification procedures and the nursing original document recording in anticancer drug clinical trials, and nursing-related protocol deviation could be reduced to a certain extent.

Clinical Characteristics and Prognostic Factors in Primary Breast Diffuse Large B-Cell Lymphoma.

Background: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on the clinical features and prognostic factors. Patients and Methods: A consecutive cohort of patients with PB-DLBCL was retrospectively analyzed in our hospital from February 1997 through July 2018. The primary endpoint is overall survival (OS) contributing to any cause. Results: A total of 76 patients were diagnosed with PB-DLBCL. The median age at diagnosis was 51 years (range: 25-80 years), with female prevalence (98.7%). Forty (52.6%) patients had right-sided breast involvement but no bilateral breast involvement at diagnosis. Overall, disease stages IE and IIE were seen in 55 (72.4%) and 21 (27.6%) patients, respectively. According to the stage-modified International Prognostic Index (IPI), 37 (48.7%) patients were classified in the very good risk group (IPI 0). Of the 72 patients available, the non-germinal center B-cell (non-GCB) subtype of DLBCL was observed in 66 (91.6%) patients. All patients received anthracycline-based chemotherapy, 56 (73.7%) with rituximab, 31 (40.8%) also with additional radiation therapy, and 14 (18.4%) patients received a prophylactic intrathecal injection. Seven (9.2%) patients had refractory disease. With a median follow-up of 6.8 years (range 0.4-25.0 years), 10 (13.2%) patients had a relapse in the central nervous system (CNS) site. The 5-year and 10-year OS of all the patients was 97.2% (95% CI: 99.3-89.5) and 84.8% (95% CI: 70.0-93.5), respectively. The median OS was not reached. The median progression-free survival (PFS) was 10.3 years for patients with PB-DLBCL. The 5-year PFS of all the patients was 76.3% (95% CI: 64.6-84.6). Univariate analysis revealed several prognostic factors, including stage-modified IPI, breast surgery, refractory disease, and CNS relapse. Multivariate analyses produced two independent prognostic factors for patients with PB-DLBCL, including stage-modified IPI score (2-3 versus 0) (hazard ratio: 19.114, 95% CI 1.841 to 198.451, p=0.013) and CNS relapse (hazard ratio: 5.522, 95% CI 1.059 to 28.788, p=0.043). Conclusion: In our cohort, PB-DLBCL clinical features are similar to prior literature reports. Stage-modified IPI score and CNS relapse were associated with overall survival.

Silencing of LIMD1 promotes proliferation and reverses cell adhesion-mediated drug resistance in non-Hodgkin's lymphoma.

LIM domains-containing protein 1 (LIMD1) is a tumor suppressor protein downregulated in numerous solid malignancies. However, the functional role of LIMD1 in non-Hodgkin's lymphoma (NHL) remains unclear. In the present study, it was demonstrated that LIMD1 is associated with the proliferation of NHL and cell adhesion mediated-drug resistance (CAM-DR). It was indicated by western blot analysis that LIMD1expression is lower in progressive lymphoma compared with indolent lymphoma. Furthermore, it was indicated that the role of LIMD1 in cell viability and proliferation remains unclear. Finally, the present study demonstrated that LIMD1 serves an important role in CAM-DR by regulating cell cycle progression. Silencing of LIMD1 may reverse CAM-DR in NHL. Therefore, the findings of the present study suggested that LIMD1 may be a potential therapeutic target for patients with NHL.

Expression of TRIM28 correlates with proliferation and Bortezomib-induced apoptosis in B-cell non-Hodgkin lymphoma.

Tripartite motif containing 28 (TRIM28) as a transcriptional co-repressor has been reported playing a role in regulating DNA damage response (DDR), cell differentiation, immune response, and tumorigenesis. The present study was performed to explore the biological function and clinical significance of TRIM28 in B-cell non-Hodgkin lymphoma (B-NHL). Results of the study displayed that high expression of TRIM28 was positively associated with the poorer survival of B-NHL patients as an independent prognostic factor. In addition, TRIM28 could promote the B-NHL cells proliferation through modulating cell cycle progression. The change of cyclinA, P21, and PCNA expression after TRIM28 expression modified further illustrated the mechanism in which TRIM28 participated in cell proliferation progression. Moreover, inhibition TRIM28 expression in B-NHL cells enhanced the sensibility to Bortezomib by regulating p53-mediated apoptosis pathway. Taken together, the present study showed that TRIM28 functions as a tumor promoter in B-NHL and may be a novel target for drug resistance to Bortezomib.

The assessment and management of chemotherapy-induced nausea and vomiting among cancer patients in a chemotherapy ward: a best practice implementation project.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are considered to be two of the most distressing side-effects of chemotherapy. They have a negative impact on a patient's quality of life and can influence the continuance of treatment. Owing to the lack of effective management of CINV, regular assessment and management of CINV is recommended for patients undergoing chemotherapy. AIMS/OBJECTIVES: The aim of this project was to integrate the available evidence on the assessment and management of CINV into practice, and implement strategies to improve compliance with evidence-based practice. METHODS: The project carried out a pre- and post-implementation audit procedure using the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice programs. Five audit criteria were established according to the best available evidence on the assessment and management of CINV. The program was divided into three phases and conducted over four months in the chemotherapy ward, Fudan University Shanghai Cancer Center, Shanghai, China. RESULTS: Sixty patients and 14 oncology nurses were involved in this project. The results of the follow-up cycle showed that the compliance rates regarding patient education, risk factors evaluation and non-pharmacologic managements were 100%, 100% and 80%, respectively. The rate of validated tools being used by patients and nurses improved by 93% and 97%, respectively. CONCLUSION: This project demonstrated that the use of pre- and post-best practice audits is an effective method for incorporating evidence into practice in a chemotherapy ward. The practice of assessing and managing CINV was significantly improved. The next step is to develop strategies for sustaining the new procedures of CINV assessment and management.

Genome shuffling of Aspergillus niger for improving transglycosylation activity.

Isomaltooligosaccharides (IMO), the glucosylsaccharides used as food additives, are made from saccharified starch by enzymes or microbial cells with transglycosylation activity. This study aimed to generate shuffled futants of Aspergillus niger with enhanced transglycosylation activity for industrial IMO production. The starting mutant population was generated by (60)Co-γ radiation; mutants with higher transglycosylation activity were selected and subjected to recursive protoplast fusion. The resulting fusants were screened by a novel high-throughput method based on detecting non-fermentable reducing sugar. After three rounds of genome shuffling, the best performing strain GS3-3 was obtained, its transglycosylation activity (14.91 U/mL) was increased by 194.1 % compared to that of original strain C-6181. In fermentor test, transglycosylation activity of GS3-3 was obtained at 16.61 U/mL. The mycelia of GS3-3 were reused ten times to produce IMO syrup from liquefied cassava starch containing about 280 g/L total sugar within 4 days. The conversion of liquefied cassava starch to IMO was at 71.3-72.1 %, which was higher than the best conversion (68 %) ever reported. GS3-3 shows a great potential for industrial IMO production.