Effects of Patient-Controlled Transcutaneous Electrical Acupoint Stimulation on Cancer Induced Bone Pain Relief in Patients with Non-Small Cell Lung Cancer: Study Protocol for a Randomized Controlled Trial.

Background: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC). Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight. Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP. Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.

Meta-Analysis of Metformin on Recurrence Risk and Long-Term Survival in Patients with Diabetes and Renal Cell Carcinoma.

Objective: To evaluate the effect of metformin on the survival of patients with diabetes mellitus complicated with renal cell carcinoma by Meta-analysis. Methods: To collect the required data, we looked through the databases of the Cochrane Library, PubMed, and EMBASE, as well as the network for querying registration data from clinical trials (https://clinicaltrials.gov). Retrieve relevant ongoing or closed clinical trials. To avoid publication bias, the search process is limited to randomized controlled trials, and the search results are not limited to language, publication time, or other restrictions. All included studies need to be evaluated according to the quality evaluation standard of the Cochran system evaluation manual. The relevant data were statistically analyzed by Revman 5.3 software. In the evaluation of overall survival (OS) and progression-free survival (PFS), the index of hazard risk (HR) was selected in this paper. Results: Eight cohort studies were included in the analysis. Partial and metastatic subgroup analysis of renal cell carcinoma demonstrated no significant effect of metformin on PFS, CSS, or OS. There was no evidence of publication bias, according to the findings. Conclusion: This systematic review and meta-analysis found that metformin did not improve survival rates for diabetic patients with renal cell carcinoma.

Effects of Music Intervention on Anxiety, Depression Symptoms and Quality of Life in Breast Cancer Patients: A Meta-Analysis.

BACKGROUND: Music therapy is often used to relieve anxiety and depression in breast cancer patients, but the clinical effect of music therapy on breast cancer patients is still controversial. This study was a systematic review to investigate the effects of music intervention on anxiety, depression, pain, and quality of life in breast cancer patients. METHOD: A computer search of PubMed, Embase, Web of Science, and The Cochrane Library repositories was conducted. We searched for randomized controlled trials (RCTs), published in English until October 2023, on the effects of music interventions on anxiety, depressive symptoms, pain levels, and quality of life in breast cancer patients. The Cochrane Manual of Systematic Review 5.3 was used to evaluate the quality of the included references, and Stata15.0 software was selected for meta-analysis of the study indicators. RESULTS: A total of 10 articles were included in this study, including 593 patients. Meta-analysis showed that music intervention could effectively alleviate anxiety symptoms [standardized mean difference (SMD) = -2.12, 95% confidence interval (CI): -3.17~-1.07], depression symptoms (SMD: -0.77, 95% CI: -1.47~-0.07), and pain degree (SMD: -3.47, 95% CI: -6.45~-0.48). There was no significant difference in the improvement of patients' quality of life (SMD: -0.07, 95% CI: -0.48~0.34). CONCLUSION: Music intervention can effectively relieve anxiety and depression symptoms in patients with breast cancer, and reduce the degree of pain, but demonstration of its ability to improve the quality of life of patients requires additional research.

Effects of Music Intervention on Anxiety, Depression Symptoms and Quality of Life in Breast Cancer Patients: A Meta-Analysis

Background: Music therapy is often used to relieveanxiety and depression in breast cancer patients, but theclinical effect of music therapy on breast cancer patientsis still controversial. This study was a systematic review toinvestigate the effects of music intervention on anxiety, de-pression, pain, and quality of life in breast cancer patients. Method: A computer search of PubMed, Embase,Web of Science, and The Cochrane Library repositories wasconducted. We searched for randomized controlled trials(RCTs), published in English until October 2023, on the ef-fects of music interventions on anxiety, depressive symp-toms, pain levels, and quality of life in breast cancer pa-tients. The Cochrane Manual of Systematic Review 5.3was used to evaluate the quality of the included references,and Stata15.0 software was selected for meta-analysis of thestudy indicators. Results: A total of 10 articles were included inthis study, including 593 patients. Meta-analysis showedthat music intervention could effectively alleviate anxietysymptoms [standardized mean difference (SMD) = –2.12,95% confidence interval (CI): –3.17~–1.07], depressionsymptoms (SMD: –0.77, 95% CI: –1.47~–0.07), and paindegree (SMD: –3.47, 95% CI: –6.45~–0.48). There was nosignificant difference in the improvement of patients’ qual-ity of life (SMD: –0.07, 95% CI: –0.48~0.34). Conclusion: Music intervention can effectively re-lieve anxiety and depression symptoms in patients withbreast cancer, and reduce the degree of pain, but demonstra-tion of its ability to improve the quality of life of patientsrequires additional research.(AU)

Solanine Inhibits Immune Escape Mediated by Hepatoma Treg Cells via the TGFß/Smad Signaling Pathway.

OBJECTIVE: To observe the inhibitory effect of solanine on regulatory T cells (Treg) in transplanted hepatoma mice and to study the mechanism of solanine inhibiting tumor growth. METHODS: The levels of Treg cells and IL-2, IL-10, and TGFß in the blood of patients with liver cancer were detected by flow cytometry and ELISA, respectively. A mouse hepatocellular carcinoma (HCC) graft model was established and randomly divided into four groups: control group, solanine group, TGFß inhibitor group (SB-431542), and solanine +TGFß inhibitor combined group. Tumor volume of each group was recorded, tumor inhibition rate was calculated, and tumor metastasis was counted. The proportion of CD4+CD25+Foxp3+ Treg in transplanted tumor tissues was detected by flow cytometry. The expression levels of Foxp3 and TGFß in transplanted tumor tissues were detected by quantitative fluorescence PCR. RESULTS: Compared with healthy people, Treg cells and IL-2, IL-10, and TGFß contents in peripheral blood of liver cancer patients were increased. The results of the transplanted tumor model in mice showed that the tumor volume of the transplanted mice in the solanine group and the TGFß inhibitor mice was reduced compared with the control group. The combined group had the smallest tumor volume. The proportion of CD4+CD25+Foxp3+ Treg in the transplanted tumor tissues of mice in the solanine treatment group was significantly lower than that in the control group. The expressions of Foxp3 and TGFß in the transplanted tumor tissues of mice in the solanine group were significantly lower than those in the control group. CONCLUSION: Solanine may enhance the antitumor immune response by downregulating the proportion of CD4+CD25+ Treg and the expression of Foxp3 and TGFß in tumor tissues.

Guilu Erxian Glue () Inhibits Chemotherapy-Induced Bone Marrow Hematopoietic Stem Cell Senescence in Mice May via p16INK4a-Rb Signaling Pathway.

OBJECTIVE: To evaluate the effect of Guilu Erxian Glue (, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism. METHODS: The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally (i.p.) with 5 × 106/mL H22 cells per mouse. Fifty tumor-bearing mice were divided into the control, model, pifithrin-α, GEG, and GEG+pifithrin-α groups using a random number table, 10 mice in each group. CTX (100 mg/kg i.p.) was administrated to mice from day 1 to day 3 (d1-d3) continuously except for the control group. The mice in the pifithrin-α, GEG and GEG+pifithrin-α groups were treated with pifithrin-α (2.2 mg/(kg·d) i.p.) for 6 consecutive days (d4-d9), GEG (9.5 g/(kg·d) i.p.) for 9 consecutive days (d1-d9), and GEG plus pifithrin-α, respectively. HSCs were collected after 9-d drug treatment. The anti-aging effect of GEG was studied by cell viability, cell cycle, and ß -galactosidase (ß -gal) assays. The mRNA and protein expressions of cyclin-dependent kinase 2 (CDK2), CDK4, inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16 (p16INK4a), p21Cip1/Waf1, p53, and phosphorylated retinoblastoma (pRb) were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot, respectively. RESULTS: Compared with the model group, GEG increased cell viability as well as proliferation (P<0.05 or P<0.01) and reduced ß -gal expression. Furthermore, GEG significantly decreased the expressions of p16INK4a, p53 and p21Cip1/Waf1 proteins, and increased the expressions of CDK2, CDK4 and pRb proteins compared with the model group (P<0.05 or P<0.01). CONCLUSION: GEG can alleviate CTX-induced HSCs senescence in mice, and the p16INK4a-Rb signaling pathway might be the underlying mechanism.

Certain interleukin polymorphisms might influence predisposition to lung cancer: A meta-analysis of 35 published studies.

Interleukin polymorphisms might influence predisposition to lung cancer (LC), but the results of already published studies regarding the relationship between interleukin polymorphisms and LC were still controversial and ambiguous. So the authors designed this meta-analysis to more precisely estimate relationship between interleukin polymorphisms and LC by pooling the results of already published related studies. The authors searched Pubmed, Embase, Web of Science, and CNKI for already published studies. Thirty-five already published studies were pooled and analyzed in this meta-analysis. The pooled meta-analyses results showed that distributions of IL-4 rs2243250 polymorphism among patients and controls from Asian countries differed significantly (dominant comparison: OR = 1.29, 95% CI 1.07-1.55; overdominant comparison: OR = 0.83, 95% CI 0.73-0.95; allele comparison: OR = 1.26, 95% CI 1.03-1.54), and distributions of IL-10 rs1800872 polymorphism among patients and controls from Caucasian countries also differed significantly (recessive comparison: OR = 0.54, 95% CI 0.35-0.83; overdominant comparison: OR = 1.26, 95% CI 1.05.1.51). No genotypic distribution differences were observed for IL-4 rs2070874, IL-6 rs1800795, IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, and IL-10 rs1800896 polymorphisms in pooled meta-analyses. This meta-analysis suggested that IL-4 rs2243250 might influence predisposition to LC in Asians, whereas IL-10 rs1800872 polymorphism might influence predisposition to LC in Caucasians.

Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and chemotherapy resistance in non-small cell lung cancer.

BACKGROUND: NIPBL, the sister chromatid cohesion 2 (SCC2) human homolog, is a cohesin loading factor which is essential for deposition of cohesin onto the sister chromatid. Recent studies have shown that NIPBL contribute to sister chromatid cohesion and plays a critical role in development, DNA repair, and gene regulation. In this study, we measured the expression of NIPBL in clinical non-small cell lung cancer specimens, and determined its effects on cellular processes and chemosensitivity in vitro. METHODS: NIPBL immunohistochemistry was performed on 123 lung adenocarcinoma samples. Through knockdown of NIPBL protein expression, non-small cell lung cancer cell lines were used to test the potential involvement of NIPBL silencing on cell proliferation, migration, invasion, and apoptosis. Chemosensitivity was assessed with clonogenic assays, and chromatin immunoprecipitation assays were performed to analyze the relationship between NIPBL and signal transducers and activators of transcription 3 (STAT3). RESULTS: Immunohistochemical analysis showed that high expression of NIPBL was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis further indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer. Knockdown of NIPBL in non-small cell lung cancer cell lines significantly reduced cellular proliferation, migration, and invasion, and enhanced cellular apoptosis and sensitivity to cisplatin, paclitaxel, and gemcitabine hydrochloride. NIPBL bound to the promoter region of the STAT3 gene, directly regulating the expression of STAT3. CONCLUSIONS: These data suggested that NIPBL played a significant role in lung carcinogenesis. NIPBL expression conferred poor prognosis and resistance to chemotherapy in non-small cell lung cancer, suggesting that NIPBL may be a novel therapeutic target.