Advances in Clinical and Experimental Medicine最新文献

Background: Intravenous ketorolac and metoclopramide are common emergency treatments for adult patients with migraine headaches. The comparison between ketorolac and metoclopramide for migraine treatment is an intriguing issue for research and clinical practice.

Objectives: To provide an updated systematic review and meta-analysis of randomized clinical trials (RCTs) to help determine which treatment has better effects for migraine patients.

Material and methods: Intravenous ketorolac and metoclopramide were compared to evaluate whether intravenous ketorolac is associated with significant benefits for pain intensity, short-term headache relief and sustained headache relief among adult patients with migraines. Adverse effects were also analyzed. Five studies with a total of 674 adult patients were included in the analysis, which focused on the outcomes of pain intensity, short-term headache relief, sustained headache relief, and adverse effects.

Results: The meta-analysis showed that the only modest but statistically significant difference was present in short-term headache relief when comparing intravenous ketorolac with intravenous metoclopramide. There were no significant differences between intravenous ketorolac and metoclopramide in terms of pain intensity, sustained headache relief or adverse effects.

Conclusion: The results suggest that there are no significant differences in most treatment effects (aside from short-term headache relief) and adverse effects when comparing intravenous ketorolac with intravenous metoclopramide. However, the paucity of literature on this topic might have limited the interpretation of the current results. Thus, more relevant studies are warranted.

There are contradictory findings regarding the effects of vitamin D supplementation and cigarette smoking on glucose metabolism in individuals with type 2 diabetes mellitus (T2DM). Consequently, this meta-analysis focused on the association between vitamin D interventions and smoking cessation on glycemic control in T2DM patients. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane Library, EMBASE and PubMed databases were used for a language-inclusive literature search until November 2022. The primary outcomes of this meta-analysis were changes in glycated hemoglobin (HbA1c) level, vitamin D concentration and body mass index (BMI) values. This meta-analysis included 14 randomized controlled trials (RCTs) with a total of 23,289 individuals with T2DM. Nine RCTs were related to vitamin D supplementation interventions, and 5 RCTs were related to smoking cessation interventions. The studies on vitamin D supplementation showed a substantial change in the intervention group, with a risk ratio (RR) of 0.72 (95% confidence interval (95% CI): 0.58, 0.88; p = 0.001) and an odds ratio (OR) of 0.52 (95% CI: 0.34, 0.78; p = 0.002); high heterogeneity was observed (I2 ≥ 95%). Similarly, the smoking cessation studies showed a substantial change in the intervention group, with a RR of 0.92 (95% CI: 0.86, 0.99; p = 0.04) and an OR of 0.86 (95% CI: 0.74, 0.99; p = 0.04); high heterogeneity was observed (I2 = 87%). In conclusion, both vitamin D supplementation and smoking cessation are associated with moderate BMI decline and an improvement of insulin sensitivity in people with T2DM.

Background: Cervical carcinoma and endometrial carcinoma are the most common gynecologic cancers worldwide. Forkhead-box R2 (FOXR2) plays an important role in the progression of various malignant tumors. However, the effects of FOXR2 on the development of uterine lesions remain unclear.

Objectives: This prospective observational study aimed to investigate the diagnostic performance of FOXR2 and transvaginal three-dimensional power Doppler ultrasonography (3D-PDU) for malignant uterine lesions.

Material and methods: This study included 404 uterine lesion patients and 200 healthy individuals who visited the hospital for a physical examination from April 2014 to May 2016. All patients received FOXR2 detection and 3D-PDU examination at admission. The demographic data and clinical data, including age, body mass index (BMI), and the International Federation of Gynecology and Obstetrics (FIGO) stage, were collected. All the patients were followed up for 5 years. The overall survival (OS) was analyzed using Kaplan-Meier (K-M) curve analysis. The diagnostic value of FOXR2 and 3D-PDU was evaluated using receiver operating characteristic (ROC) curves.

Results: Serum levels of FOXR2 mRNA were upregulated in patients with malignant uterine lesions. Patients with high expression of FOXR2 showed a higher expression of the cancer biomarkers CA125, CA199, CEA, and SCCA. It was also found that FOXR2 expression was associated with the clinical outcomes of patients with malignant uterine lesions. Moreover, higher expression of FOXR2 predicted a poor prognosis. The combined use of FOXR2 and 3D-PDU showed favorable potential for the diagnosis of malignant uterine lesions, especially for cervical carcinoma and endometrial carcinoma.

Conclusions: The combination of serum FOXR2 and transvaginal 3D-PDU has a potential in the diagnosis of uterine lesions.

Background: Adjuvant therapy after surgery is effective for the treatment of advanced gastric cancer (GC), but the regimens are not uniform, resulting in imbalanced benefits.

Objectives: To compare the overall survival (OS), relapse-free survival (RFS) and disease-free survival (DFS) of patients with local-advanced GC (LAGC) after surgery plus adjuvant therapy and with surgery alone based on meta-analysis.

Material and methods: Literature search was performed among the articles published in the PubMed, Embase and Cochrane Library databases from January 2000 to December 2018. Study selection was conducted based on the following criteria: randomized clinical trials (RCTs) on surgery plus adjuvant therapy compared to surgery alone; studies compared OS and/or RFS/DFS; and cases medically confirmed with LAGC. Only articles in English were included.

Results: A total of 12 datasets from 11 randomized controlled trials (RCTs) involving 4606 patients were included in the meta-analysis. There was a significant improvement in OS of patients who underwent postoperative adjuvant therapy (HR 0.78; 95% CI: 0.72-0.84; p < 0.001). In the subgroup analysis, it showed a higher improvement in OS patients who received adjuvant chemotherapy plus immunotherapy or radiotherapy (HR 0.72; 95% CI: 0.61-0.85; p < 0.001).

Conclusion: Adjuvant therapy led to survival benefits in patients with LAGC.

Background: Minimally invasive endodontics is recommended for young, immature teeth to preserve healthy pulp and dentin tissue.

Objectives: The aim of the study was to examine the cold sensitivity of immature teeth that received photobiomodulation (PBM) after vital pulp therapy (VPT).

Material and methods: The study followed the STROBE guidelines and included 123 healthy patients aged 8-13. The immature teeth (incisors, premolars and molars) that qualified for VPT received the bioceramic material - Biodentine. In this experiment, teeth were treated immediately and at 24 h post-VPT with a 635-nm diode laser using a power of 100 mW, a power density of 200 mW/cm2 and a total energy of 4 J (PBM group, n = 43), while those not treated were the control group (n = 43). The tooth sensitivity to cold was measured using a visual analogue scale (VAS) before and at 6 h, 1 day, 7, 30, and 90 days after treatment. The predictor variable was PBM skills regarding the ability to decrease cold sensitivity after VPT. The primary endpoint was the time to reverse hypersensitivity to cold, and the secondary endpoint was the occurrence of possible side effects. The Mann-Whitney U test, Friedman test along with Dunn's post hoc test, and the χ2 test were used to investigate tooth sensitivity.

Results: Eighty-six immature permanent teeth of 86 children were included in the study. It was shown that the difference was significant for sensitivity to a cold stimulus between the groups at 6 h, 24 h, 7 days, and 30 days, but no difference was found preoperatively and at 90 days (6 h, 24 h, 7 days, and 30 days, p < 0.001, and 90 days, p = 0.079). However, patients in both groups reported a decrease in discomfort provoked by cold stimuli throughout the follow-up period.

Conclusions: Photobiomodulation decreased postoperative sensitivity and was more acceptable for patients. Further randomized clinical studies with placebo-controlled groups are needed.

Background: Coronavirus disease 19 (COVID-19) is a viral infection mediated by coronavirus-2 that causes severe acute respiratory syndrome (SARS-CoV-2). The disease may affect biochemical parameters and electrolytes. C-terminal cross-linking telopeptide (CTX-I) is released during mature bone resorption and is a biomarker for predicting bone resorption.

Objectives: As the pandemic progressed, understanding the effects of COVID-19 disease remained critical. Inflammatory responses triggered by the virus can result in a bone metabolism regulation imbalance. As such, this study aimed to analyze serum levels of CTX-I, calcium (CA), phosphorus (P), magnesium (Mg), C-reactive protein (CRP), and alkaline phosphatase (ALP) in COVID-19 patients to investigate the relationship between bone resorption and the disease.

Material and methods: The study included 56 individuals with COVID-19 (divided into mild, moderate and severe subgroups depending on disease severity) and 25 healthy adults as a control group. Serum CTX-I concentrations were measured with enzyme-linked immunosorbent assay (ELISA). In addition, CRP, Ca, Mg, P, and ALP levels were measured using an automated clinical chemistry analyzer.

Results: Serum CTX-I levels were significantly higher in COVID-19 patients than in the control group (p < 0.05). Furthermore, a positive weak relationship was detected between CRP and CTX-I (r = 0.303, p < 0.05).

Conclusions: Increased serum CTX-I levels in the patient group caused COVID-19-driven bone degradation, though serum CTX-I levels did not differ according to disease severity.

Background: Sepsis is a life-threatening organ dysfunction without effective therapeutic options. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce sepsis. It is associated with oxidative stress, inflammation and multiple organ failure. Gedunin (GN) is a tetranortriterpenoid isolated from the Meliaceae family. Gedunin possesses numerous pharmacological properties, including antibacterial, anti-inflammatory, antiallergic, and anticancer activities. However, the molecular anti-inflammatory mechanism of GN in sepsis has not been established.

Objectives: The aim of the study was to explore the antioxidant and anti-inflammatory molecular actions underlying the antiseptic activity of GN in an LPS-induced rat model.

Material and methods: Rats were randomized into 4 sets: group 1 (control) was given 1 mL of dimethyl sulfoxide (DMSO) by gavage, group 2 rats were treated with LPS (100 μg/kg body weight (BW), intraperitoneally (ip.)), group 3 rats were given LPS (100 μg/kg BW, ip.)+GN (50 mg/kg BW in DMSO), and rats in the group 4 were given GN (50 mg/kg BW in DMSO) alone. We studied hepatic markers, inflammatory cytokines and antioxidants using specific biochemical kits and analyzed their statistical significance. Histopathology of liver, lungs and kidney tissues was also explored. The mRNA levels and conducted protein investigations were performed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, respectively.

Results: Our findings revealed that GN significantly (p < 0.05) inhibited oxidative stress, lipid peroxides, toxic markers, pro-inflammatory cytokines, and histological changes, thereby preventing multi-organ impairment. Additionally, GN attenuated the HMGβ1/NLRP3/NF-κB signaling pathway and prevented the degradation of Iκβα.

Conclusions: Gedunin is a promising natural antiseptic agent for LPS-induced sepsis in rats.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, and while advancements in diagnosis, surgery, radiotherapy, and molecular therapy have improved clinical prognosis, the long-term survival rate and quality of life of patients remain unsatisfactory. Therefore, identifying new prognostic biomarkers and potential therapeutic targets is crucial.

Objectives: This study aimed to analyze the role of anoikis-related gene characteristics in LUAD.

Material and methods: The anoikis-related genes were obtained from the GeneCards database. Genetic expression data and clinical characteristic information were collected from The Cancer Genome Atlas (TCGA)-LUAD, and the Gene Expression Omnibus (GEO) GSE31210, GSE37745, and GSE68465 datasets. Random survival forest and least absolute shrinkage and selection operator (LASSO) models were applied to construct the risk model. An analysis of immune cell infiltration and function was performed with the scores.

Results: Four prognosis-related genes (TLE1, GLI2, PLK1, and BAK1) were obtained and used to construct the anoikis score. We found that the patient survival rate was higher in the low-anoikis score (LAS) group. Moreover, both the stromal and immune scores were negatively correlated with the anoikis score. With the increase of the anoikis score, the levels of natural killer cells, regulatory T cells, CD4+ T cells, CD8+ T cells, B cells, and macrophages decreased. The anoikis score had a negative regulatory relationship with the immune response, natural killer cell activation and T cell activation. The TP53 mutation was significant in LUAD patients and was present in 56% of the high-anoikis score (HAS) group and in 40% of the LAS group.

Conclusions: The anoikis score was associated with poor prognosis in LUAD patients. Anoikis-related genes were associated with tumor immune dysregulation and TP53 mutation in LUAD. This study opens a new perspective for LUAD therapy.

Background: Short regulatory RNAs, called microRNAs (miRNAs), have been found to possess regulatory functions in cancer and, as such, have recently been evaluated for their therapeutic role against various human malignancies.

Objectives: The present work aimed to investigate whether miR-520a can play a therapeutic role in the treatment of human acute myeloid leukemia.

Material and methods: Human myeloid leukemia cell lines (Kasumi-1, Kasumi-3, Kasumi-6, BDCM, and K562) and a normal myeloid cell line (NCI-H5N6) were used for the study. Cell lines were subjected to real-time quantitative polymerase chain reaction (RT-qPCR), evaluation of cell viability and proliferation by MTT assay and colony formation assays. Dual acridine orange (AO)/ethidium bromide (EB) staining was applied for transfected K562 cells with miR-negative control (NC) or miR-520a mimics, and annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) dual staining and flow cytometry were performed to analyze cancer cell apoptosis followed by western blot.

Results: Cancerous cell lines exhibited lower gene expression of miR-520a, and its overexpression significantly reduced (p < 0.05) the proliferation and viability of cancer cells. Cancer cells demonstrated the induction of Bax/Bcl-2-mediated apoptosis following miR-520a overexpression. The miR-520a was shown to target the PI3K/AKT signaling pathway in human acute myeloid leukemia to exercise its regulatory role in cancer.

Conclusions: The study showed that miR-520a actively regulated cell proliferation in acute myeloid leukemia and illustrated the mechanism by which it exerts its regulatory role, emphasizing the possibility of targeting miR-520a as an efficient therapeutic strategy against human acute myeloid leukemia.

Background: Dendritic cells (DCs) are a key class of immune cells that migrate to the draining lymph nodes and present processed antigenic peptides to lymphocytes after being activated by external stimuli, thereby establishing adaptive immunity. Moreover, DCs play an important role in tumor immunity.

Objectives: The aim of the study was to investigate whether MCT1 gene silencing in DCs affects their ability to mount an immune response against cervical cancer cells.

Material and methods: We silenced the expression of MCT1 in DCs from mouse bone marrow (BM) by infection with adenovirus. The surface antigen profile of DCs was analyzed by flow cytometry and cytokine secretion was evaluated using enzyme-linked immunosorbent assay (ELISA) following sodium lactate (sLA) exposure and lipopolysaccharide (LPS) stimulation. Then, various groups of DC-induced cytotoxic T lymphocytes (CTLs) were prepared and their cytotoxicity against U14 was tested.

Results: Without sLA exposure, silencing MCT1 did not affect the expression of CD1a, CD80, CD83, CD86, and major histocompatibility complex class II (MHCII) in DCs after LPS challenge. Similar results were found for interleukin (IL)-6, IL-12 p70 and tumor necrosis factor alpha (TNF-α). After sLA exposure, silencing MCT1 significantly decreased the expression of CD1a, CD80, CD83, CD86, and MHCII in DCs after the LPS challenge, as well as the secretion of IL-6, IL-12 p70 and TNF-α. In addition, sLA exposure significantly reduced the toxicity and inhibited the proliferation of DC-induced CTLs compared to U14 cells in vitro and in vivo. However, silencing MCT1 significantly attenuated the changes caused by sLA exposure. At the same time, in the absence of sLA, silencing MCT1 did not affect the toxicity nor inhibit the proliferation of DC-induced CTLs on U14 cells.

Conclusions: Lactate exposure reduces the immune effect of DCs on cervical cancer cells, but MCT1 gene silencing attenuates these alterations.