Advances in Clinical and Experimental Medicine最新文献

Background: Individuals with metastatic gastric cancer (MGC) are incurable and have a poor prognosis. To date, surgical resection with curative intent is the only treatment providing hope for a cure, but the role of surgical resection is still controversial.

Objectives: To assess the effects of gastrectomy compared to non-resection on MGC patient survival.

Material and methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to October 10, 2023. Primary outcomes were 1-, 2-, 3-, and 5-year overall survival (OS), OS, and OS time.

Results: Forty-six studies with 7,152 MGC patients were included. Compared to MGC patients receiving no resection, MGC patients with gastrectomy had significantly improved 1-year OS (pooled relative risk (RR):1.90, 95% confidence intervals (95% CIs): 1.50, 2.41), 2-year OS (pooled RR: 2.23, 95% CI: 1.40, 3.53), 3-year OS (pooled RR: 6.09, 95% CI: 3.12, 11.87), 5-year OS (pooled RR: 4.30, 95% CI: 1.35, 13.74), and reduced risk of death (pooled hazard ratio (HR): 0.49, 95% CI: 0.37, 0.65). Gastrectomy combined with metastasectomy or not also revealed similar results regarding OS and risk of death. Additionally, OS time was significantly longer in patients receiving gastrectomy than patients not receiving resection (pooled weighted mean difference (WMD): 6.06, 95% CI: 1.36, 10.760). No significant difference in postoperative morbidity was detected between the patients receiving gastrectomy and patients not receiving resection (pooled RR: 2.54, 95% CI: 0.13, 51.39).

Conclusion: Gastrectomy, with or metastasectomy, may provide MGC patients with survival benefits.

This review examines recent progress in developing nanoscale drug delivery systems for biomedical applications. Key nanocarriers, including inorganic nanoparticles, dendrimers, protein nanoparticles, polymeric micelles, liposomes, carbon nanotubes (CNTs), quantum dots (QDs), and biopolymeric nanoparticles, were summarized. Compared with free drugs, the tunable physicochemical properties of these materials allow for the encapsulation of therapeutics and improved pharmacokinetics. However, limitations such as toxicity, poor biodegradability, lack of controlled release, and low encapsulation efficiency remain. Inorganic nanoparticles exhibit issues with accumulation and toxicity. Dendrimers require complex syntheses and demonstrations of long-term safety. Protein nanoparticles suffer from low drug loading and stability. Polymeric micelles have stability and tumor penetration limitations. Liposomes exhibit low encapsulation efficiency and rapid clearance. Carbon nanotubes demonstrate toxicity and poor aqueous solubility. Quantum dots contain heavy metals, leading to toxicity. Biopolymeric nanoparticles have low stability and control over release kinetics. Strategies such as surface engineering with polymers and ligands aim to enhance nanoparticle targeting and biocompatibility. The combination of nanostructures in hybrid systems aims to synergize benefits while mitigating individual limitations. Stimulus-responsive and multifunctional nanoparticles enable triggered release and imaging capabilities. Overall, continued research into novel bioinspired designs, smart responsiveness and hybrid approaches is critical to fully realize the clinical potential of engineered nanomedicines for advanced drug delivery applications.

Background: The impact of cysteine-rich angiogenic inducer 61 (Cyr61, also called CCN1) on endothelial progenitor cells (EPCs) from diabetic-rat-derived whole peripheral and bone marrow remains poorly understood. Therefore, the expression levels of CCN1, CCN1-induced C-X-C chemokine receptor type 4 (CXCR4), and stromal-cell-derived factor-1 (SDF-1) were explored under high glucose (HG) conditions.

Objectives: The aim of the study was to explore the effects of high CCN1 levels on EPC activity in diabetic rats through mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway modulation.

Material and methods: Primary EPCs were isolated from bone marrow and whole peripheral blood of streptozocin (STZ)-induced diabetic Sprague-Dawley rats and controls. Cell migration, tube formation ability and viability were determined using transwell, Cell Counting Kit-8 (CCK-8), and Matrigel®-based capillary-like tube formation assays. Protein and gene expression levels were measured by western blot and real-time quantitative polymerase chain reaction (RT-qPCR).

Results: The study findings showed that EPC migration, viability and tube formation ability were significantly lower under HG conditions. High CCN1 expression levels restored EPC function by inducing SDF-1 and CXCR4 in EPCs under HG conditions. Furthermore, HG suppressed MEK/ERK phosphorylation, while an ERK1/2 agonist rescued EPC CCN1-SDF-1/CXCR4 expression under HG conditions through the activation of the MEK/ERK pathway.

Conclusions: This study demonstrates that high CCN1 expression levels restored EPC functions, partly by modulating MEK/ERK signaling. These findings provide a basis for developing novel therapeutic methods for diabetic vascular neogenesis and vascular injury repair.

Background: The number and diversity of published peer-reviewed studies in the discipline of laser dentistry have grown considerably during the past 10 years.

Objectives: Within primary research, the development of protocols to guide and formulate clinical practice demands precision and ease of reproducibility. Errors in data acquisition and management may become amplified as the applied randomized clinical trials (RCTs) forge new levels of clinical diversity and predictability in the use of laser photonic energy in both ablative (surgical) and sub-ablative (photobiomodulation (PBM) or photodynamic therapy (PDT)) applications.

Material and methods: A comprehensive range of empirical and computational operating parameters must be included in published studies to facilitate the uniformity of powerand time-related values of laser irradiation.

Results: Choosing the correct "tissue irradiation parameters" is difficult and depends on the pathology and symptoms, the surface area to be treated, laser wavelength, the thermal relaxation time of each targeted tissue, and controlling penetration depth of the light into tissues. Therefore, to allow the reproducibility of the results, it is recommended that authors mention with the greatest care and clarity the irradiation parameters used in their study.

Conclusion: This paper outlines the concerns felt regarding the general shortfalls and proposes a minimum range of laser operating parameters that should be represented in future peer-reviewed publications.

Background: Nowadays, there are a variety of viewpoints on problem-based learning (PBL) and mind mapping teaching outcomes in nursing education, but there are not many thorough assessments that are pertinent.

Objectives: We performed a meta-analysis to evaluate the effect of the PBL method combined with mind mapping on nursing instruction.

Material and methods: A systematic literature search up to July 2022 was performed, and 1765 related studies were evaluated. The chosen studies comprised 1473 nursing teaching participants as the trial's baseline, with 770 of them using the PBL model with mind mapping and 703 enrolled as controls. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (95% CIs) were calculated to assess the effect of the PBL method combined with mind mapping on nursing instructions using dichotomous and continuous methods with a random or fixed effect model. The study protocol was registered in PROSPERO (registration No. CRD 42022432130).

Results: The PBL model with mind mapping reached a significantly higher results of nursing knowledge test (MD: 7.29, 95% CI: 6.88-7.71, p < 0.001) and pediatric practice test (MD: 9.89, 95% CI: 9.04-10.74, p < 0.001), as well as higher students' ability of independent learning (OR: 3.49, 95% CI: 2.11-5.76, p < 0.001) compared to the controls in nursing teaching.

Conclusion: The PBL model with mind mapping resulted in a significantly higher results of nursing knowledge test, pediatric practice test and students' ability of independent learning compared to controls in nursing teaching.

Background: Glioblastoma multiforme (GBM) is a lethal brain tumor with high mortality and morbidity. Nerolidol (NRD) is a sesquiterpene alcohol sequestered from the essential oils of aromatic florae with potent antioxidant, antiviral, anticancer, cardioprotective, and neuroprotective activity.

Objectives: The aim of the study was to investigate the underlying cell-cycle mechanisms of NRD-mediated antiproliferative and apoptosis activities in GBM using human U-251 cells.

Material and methods: The current research investigated the antiproliferative and apoptotic activities of NRD on U-251 cells. The effects of NRD were measured using a Cell Counting Kit-8 (CCK-8) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, messenger ribonucleic acid (mRNA) level assessment, and western blot assay.

Results: Nerolidol decreased U-251 viability in a dose-dependent manner, as well as induced apoptotic activity, reduced B-cell lymphoma-2 (BCL-2) levels, and increased mRNA expression of BCL-2-associated X (Bax), caspase-3 and caspase-9. The attenuation of the cyclin-D1, cyclin-dependent kinase 4 (CDK4) and CDK6 mRNA expression confirmed cell cycle regulation. Western blot analysis of CDK1 indicated reductions in cyclin-B1 and p21. Furthermore, NRD prompted apoptosis through p38 amelioration and increased phosphorylated extracellular signal-related kinase 1 (p-ERK1) and phosphorylated c-Jun N-terminal protein kinase 1 (p-JNK1) levels.

Conclusions: Nerolidol inhibited GBM cell viability and induced apoptosis through the regulation of cell-cycle proteins via p38 mitogen-activated protein kinase (MAPK) signaling pathways. Thus, NRD could be developed as a potential natural therapeutic agent for GBM.

Background: Myostatin (Mstn) plays an important role in adipocyte growth, differentiation and metabolism, leading to the development of obesity.

Objectives: We aimed to explore the effect of Mstn on white fat browning in a mouse model of type 2 diabetes mellitus (T2DM).

Material and methods: Twelve wild-type (WT), 12 heterozygous (Mstn(+/-)) and 12 homozygous (Mstn(-/-)) male mice were randomly divided into 6 groups: WT, Mstn(+/-), Mstn(-/-), WT+DM, Mstn(+/-)+DM, and Mstn(-/-)+DM. The first 3 groups were fed normal chow, while the last 3 were fed high-fat diet and administered streptozotocin to generate T2DM. Subsequently, body mass, length, and white and brown fat masses were measured, after which Lee's index, white-brown ratio and fat index were calculated. The serum free fatty acid (FFA) levels were detected using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was used to analyze white and brown fat cell morphology. The relative expression levels of peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), uncoupling protein 1 (UCP1), and cluster of differentiation 137 (CD137) protein were determined with western blotting.

Results: The Mstn(-/-) group displayed higher levels of PPARγ, PGC-1α and CD137 proteins in white and brown fat compared to the WT and Mstn(+/-) groups, while the expression level of UCP1 protein in the Mstn(-/-) group was higher than in the WT group. The expression levels of PPARγ, PGC-1α, UCP1, and CD137 proteins in the WT+DM group were lower than in the WT group. Moreover, PPARγ, PGC-1α, UCP1, and CD137 proteins were more highly expressed in the Mstn(-/-)+DM group compared to the WT+DM and Mstn(+/-)+DM groups.

Conclusions: The Mstn gene inhibition antagonizes obesity phenotypes, such as white fat accumulation and lipid metabolism derangement caused by T2DM, thus promoting white fat browning.

Background: Non-standardized insulin injection has an impact on the efficacy of glucose control.

Objectives: The aim of the study was to explore the effectiveness of a nursing project in improving the insulin self-injection accuracy of diabetes mellitus patients.

Material and methods: A total of 200 type 2 diabetes patients who received insulin therapy with an insulin pen were recruited at the First Affiliated Hospital of Army Medical University (Chongqing, China). Patients were randomly assigned to a control (n = 100) or intervention (n = 100) group. Conventional health education was conducted in the control group, while a nursing project and conventional health education were undertaken in the intervention group. The following parameters were analyzed between the 2 groups: standardized insulin pen use at admission and discharge, glycosylated hemoglobin (HbA1c), time in range (TIR), and adipose hyperplasia incidence rate 6 months after discharge.

Results: Concerning standardized insulin self-injection, the intervention group was superior to the control group, and the difference between the 2 groups was statistically significant (p < 0.05). The HbA1c levels (p = 0.000), TIR (p = 0.005) and adipose hyperplasia incidence rate 6 months after discharge (p = 0.000) all improved in the intervention group compared to the control group.

Conclusions: The application of the nursing project effectively improved the efficacy of glucose control in diabetes mellitus patients.

Background: Tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) can be cleaved from the cell surface and circulate alone or in combination with tumor necrosis factor alpha (TNF-α). These soluble receptors may play a key role in regulating the inflammatory response.

Objectives: The study aimed to evaluate the role of TNFRs in regulating the inflammatory response in immunoglobulin A nephropathy (IgAN).

Material and methods: The study included 26 patients with newly diagnosed and biopsy-confirmed IgAN and 20 healthy controls. Study material included blood and fresh urine collected the morning before kidney biopsy and therapy. The serum concentrations of TNFR1 (STNFR1) and TNFR2 (STNFR2) and urinary excretion of TNFR1 (UTNFR1) and TNFR2 (UTNFR2) were determined with immunoassay. Subsequently, the data were evaluated statistically.

Results: The STNFR1 and STNFR2 levels were higher in IgAN patients than in healthy subjects (4747.87 pg/mL and 2817.62 pg/mL compared to 2755.68 pg/mL (95% CI: from -2948.41 to -1035.97; p = 0.001) and 1437.83 pg/mL (95% CI: from -1958.50 to -419.60; p = 0.001). The power of the test was 98.5% for STNFR1 and 96% for STNFR2. Urinary concentrations only increased for TNFR1 (3551.29 compared to 2338.95 pg/mg of creatinine (Cr) (95% CI: from -2247.03 to -177.66; p = 0.023). The STNFR1 marker was characterized by a sensitivity of 73.08% and a specificity of 90.00% (p < 0.001).

Conclusions: Our results suggest that TNFR1 and TNFR2 are good markers of TNF-α pathway activation in IgAN patients.

Background: The development of malocclusion is related to various factor, many of which are still not fully explained. The steroid hormone, 1,25-dihydroxyvitamin D3, has pleiotropic effects. It plays a key role in skeletal metabolism and the control of cell repair by attaching to the nuclear vitamin D steroid receptor (VDR). This vitamin affects bone turnover through the processes of bone tissue formation and resorption via its action on cells of the osteoblastic and osteoclastic lineage, exerts a modulating effect on the immune system, and is involved in the regulation of cell proliferation and differentiation. The role of vitamin D3 (VD3) and its receptor polymorphisms is a rarely studied topic in dentistry. Due to the proven influence on bone turnover processes and immune responses, the main research topic is its relation to periodontal diseases, but so far, its role in the formation and development of malocclusions has not been assessed.

Objectives: This study aimed to assess the association of selected VDR polymorphisms: Cdx2 (rs11658820), TaqI (rs7975232), BsmI (rs1544410), ApaI (rs7975232), and FokI (rs2228570) with the development of malocclusions.

Material and methods: A prospective observational study was performed. The examination consisted of a medical interview, intraand extraoral orthodontic diagnosis, alginate impression, cone beam computed tomography (CBCT), and venous blood sample to obtain genomic DNA and assess VDR polymorphisms.

Results: The rs11658820 polymorphism causes an almost 4-fold increase in the probability of the presence of a malocclusion. GT and TT genotypes of rs7975232 are also associated with a similar risk - almost 6 and almost 5 times higher, respectively. In turn, the effect of the rs2228570-AG and GG genotype polymorphisms on the occurrence of transversal anomalies was demonstrated (odds ratio (OR) = 8.46 and OR = 6.92, respectively).

Conclusions: The association of individual polymorphisms with specific malocclusions should be carefully assessed, especially since some trends have been indicated.