Investigación Clínica http://www.produccioncientifica.luz.edu.ve/index.php/investigacion <p>Revista arbitrada dedicada a estudios humanos, animales y de laboratorio relacionados con la investigación clínica y asuntos conexos. Publicada trimestralmente por el Instituto de Investigaciones Clínicas “Dr. Américo Negrette”, de la Facultad de Medicina, de la Universidad del Zulia, Maracaibo, Venezuela.</p> Universidad del Zulia es-ES Investigación Clínica 0535-5133 Tabla de Contenido http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44371 Elena Ryder Copyright (c) 2025-08-31 2025-08-31 66 3 Plagio, similitudes e inteligencia artificial en la evaluación de trabajos científicos. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44372 <p>The reliance on programs that measure percentages of plagiarism (based on the concept of plagiarism), similarities, or AI content—without a thorough analysis of the manuscript’s quality—reflects an editorial approach that prioritizes new technology guidelines over the actual quality of the work. Such measures should not serve as a barrier to the submission of research papers for review by qualified reviewers who can assess the quality of the report.</p> Jesús A. Mosquera Copyright (c) 2025-08-31 2025-08-31 66 3 231 233 10.54817/IC.v66n3a00 A preliminary investigation of the association between KRAS, NRAS, and BRAF mutations and colorectal cancer in Turkish patients. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44373 <p>Somatic mutations in the GTPase RAS protein family and the downstream serine-threonine kinase BRAF are predicted to be key driver muta- tions in colorectal carcinogenesis by disrupting critical control points in cell cycle regulation. In our study, we aimed to investigate the relationship between KRAS, NRAS, and BRAF mutations in colorectal cancer (CRC) samples and corresponding clinicopathological data. This retrospective study included 64 CRC patients who were evaluated for KRAS, NRAS, and BRAF mutations in our department between 2022 and 2024. The findings were evaluated according to the age, gender, tumor localization in the colon, and histopathological subtype of the patients in whom the mutation was detected, and the relationships between these variables were analyzed using the chisquare test. KRAS mutations were detected at 29.6%, NRAS mutations at 3.1% and BRAF mutations at 1.6%. No significant relationship was found between mutation rates and the patients’ age, gender and colon localization. Our study demonstrated that mutations in KRAS, NRAS, and BRAF were not associated with the age, sex, and tumor location of CRC patients. The data presented are preliminary findings, and more research is needed to evaluate the clinical and pathological impact of these mutations on colorectal cancer progression and outcomes.</p> Tuba Devrim Saniye Sevim Tuncer Gamze Erkılınç Copyright (c) 2025-08-31 2025-08-31 66 3 234 240 10.54817/IC.v66n3a01 Analysis of prognostic factors and construction of a risk model for patients with acute cerebral infarction treated with dual antiplatelet therapy after optimal hyper thrombolytic time window. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44374 <p>The objective was to identify potential risk factors for the prognosis of dual antiplatelet therapy in patients with acute cerebral infarction (ACI) treated beyond the optimal time window to prevent thrombolysis, and to construct a nomogram to evaluate such risk. The clinical data of 300 ACI patients treated outside the optimal hyperthrombolytic time window and admitted to our hospital from January 2020 to May 2024 were analyzed retrospectively. The association between potential risk factors for poor prognosis after dual anti- platelet therapy was tested by logistic regression. A nomogram was constructed to evaluate the risk of poor prognosis based on the results. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the ability of the model to differentiate types of prognoses. A calibration curve evaluated the consistency of the model, and the fitting of the model was evaluated by the Hosmer-Lemeshow (HL) test. Of the 300 patients, 52 (17.3%) had a poor prognosis. Old age, hypertension history, elevated homocysteine, elevated fibrinogen level and carotid artery stenosis were risk factors associated with poor prognosis in patients with ACI. A nomogram was built based on these risk factors. The AUC, calibration curve, and HL test demonstrated that the selected model was statistically capable of discriminating between good and poor prognosis. In conclusion, advanced age, a history of hypertension, elevated homocysteine, elevated fibrinogen, and carotid artery stenosis are risk factors associated with a poor prognosis for patients with ACI treated beyond the optimal time window. If validated, the nomogram based on these five risk factors could be used to distinguish between cases with poor prognosis and those with good prognosis among these patients.</p> Jing Chen Yuxiu Han Meng Liu Copyright (c) 2025-08-31 2025-08-31 66 3 241 251 10.54817/IC.v66n3a02 Novedosos agentes dopaminérgicos y serotoninérgicos derivados del quinolinmetiladamantano y amino-metiladamantano. Síntesis y perfil farmacológico. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44375 <p>Serotonin (5-HT) and dopamine (DA) are key neurotransmitters in the central nervous system (CNS) that are involved in the regulation of behavior. Dysfunction of dopaminergic and serotonergic neurotransmitter pathways, which are responsible for the regulation of mood, cognition, and movement, can lead to a wide range of brain disorders, both neurological and psychiatric. DA is implicated in various neurodegenerative and neuropsychiatric diseases, and dopaminergic systems in the brain are known to receive serotonergic innervation. In the present study, we present the synthesis and preliminary pharmacological evaluation of the compounds N-[(2-chloro-quinolin-3-yl) methyl]-methyladamantane (7) and amino-methyladamantane (10), which were found to have dopaminergic and serotonergic activities in the central nervous system.<br>The strategy used in the design of hybrid compound 7 led to the development of a novel agent with antipsychotic and/or anxiolytic activity. Compound 10 only showed antiparkinsonian activity. These compounds contribute to the pharmacological arsenal for the treatment of pathologies related to neurodegenerative and neuropsychiatric disorders.</p> María M. Ramírez José D. García Marienmy del V. Velásquez Alexander E. Albarracín Ligia B. Ángel Biagina del C. Migliore Ana B. Cáceres Jaime E. Charris Miguel A. Rodríguez María R. Garrido Anita Israel Simón E. López Jorge E. Ángel Copyright (c) 2025-08-31 2025-08-31 66 3 252 268 10.54817/IC.v66n3a03 Experimental study on the regulatory effect of Qinggan Dongyin on T lymphocyte homeostasis in MRL/lpr mice. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44376 <p>Systemic lupus erythematosus (SLE) is an autoimmune disease marked by autoantibody overproduction and increased infection risk, even with current treatments. Dysregulated T lymphocyte homeostasis contributes &nbsp;to SLE progression, prompting exploration of immunomodulatory therapies. This study evaluated the effects of Qinggan Dongyin (QGDY), a compound of traditional Chinese medicine, in a murine SLE model. Twelve female MRL/lpr mice were randomly divided into model and QGDY treatment groups (n=6 each), with age-matched C57BL/6 mice as controls. QGDY (5 mL/kg/day) was administered via gavage for two weeks; controls received saline. Flow cytometry analyzed T cell subsets (CD4+, CD8+, Treg, Th1, Th2, Th17), ELISA measured plasma cytokines (IFN-γ, IL -6, TNF-α, IL -17A, TGF-β), HE staining assessed lung and kidney pathology, and qPCR evaluated cGAS and STING expression. Compared to the model group, QGDY significantly restored T cell balance by increasing CD4+, CD8+, and Treg cells and reducing Th1, Th2, and Th17 cells (p&lt;0.01). QGDY also lowered pro-inflammatory cytokine levels (p&lt;0.05), improved organ histopathology, and normalized elevated cGAS and STING expression (p&lt;0.01). These findings indicate that QGDY exerts immunomodulatory effects in SLE, suggesting therapeutic potential through the regulation of T cell function and inflammatory signalling pathways.</p> Nan Jiang Xiangqing Che Haiyan Han Haoyang Xin Shuo Wang Jingpeng Li Shuo Zhang Copyright (c) 2025-08-31 2025-08-31 66 3 269 281 10.54817/IC.v66n3a04 MiR-451 ameliorates red blood cell storage damage and macrophage polarizationmediated transfusion immunity by regulating the AMPK/mTOR signalling pathway. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44377 <p>Red blood cells (RBCs) undergo a series of structural and function- al changes during storage, and miR-451 is crucial for maintaining homeostasis of RBCs. Inflammatory factors and miR-451 expression in whole blood at different storage times were detected by ELISA and qRT-PCR. THP-1 cells were induced into M0 macrophages. Subsequently, miR-451 mimics, miR-451 inhibitor, and activat- ing transcription factor 2 (ATF2) were transfected into the cells, followed by the application of compound C. Macrophages were then polarized to the M1 pheno- type. Macrophage markers were discovered through flow cytometry and Western blot. The adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway protein levels were detected using Western blot. Finally, a mouse model of traumatic hemorrhagic shock was constructed, and blood transfusion and tail vein injection of agomir-451 were performed. The levels of M1 macrophage markers and inflammatory factors were detected by flow cytom- etry and ELISA, respectively. When the human whole blood storage time was 21 d and 35 d, the expression of miR-451 decreased, and the proinflammatory factor contents increased. When miR-451 was overexpressed, proinflammatory cytokines and M1 macrophage markers’ expression in THP-1 cells were reduced, p-AMPK level was increased, and p-mTOR level was decreased. After overexpression of ATF2 or compound C, proinflammatory factors and M1 macrophage markers in THP-1 cells increased, and p-AMPK and p-mTOR expression reversed. Overexpression of miR- 451 also inhibited macrophage M1 polarization and inflammation in shock mice. miR-451 inhibits ATF2-regulated AMPK/mTOR pathway, inhibits macrophage M1 polarization and inflammation, and improves RBC storage damage.</p> Xuechun Wang Xingxing Chen Hong Zhou Lingzhi Chen Hongyun Wang Hongmei Qiu Copyright (c) 2025-08-31 2025-08-31 66 3 282 300 10.54817/IC.v66n3a05 Vitamin D attenuates epithelial-mesenchymal transition of renal tubular epithelial cells in infant rats with hypothyroidism via the Traf6/TAK1 signalling pathway. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44379 <p>In the hypothyroidism(HT) state, renal hemodynamics is &nbsp;disor- dered, oxidative stress is intensified, and inflammatory factors are activated. Vi- tamin D (VD) not only regulates calcium and phosphorus metabolism, but its active form (1,25-dihydroxyvitamin D) could also exert anti-inflammatory and an- ti-fibrotic effects by binding with the vitamin D receptor (VDR) widely distributed in the kidney. This study aimed to elucidate the impact of VD on the epithelial- mesenchymal transition (EMT) of renal tubular epithelial cells in HT-induced re- nal injury in young rats, as well as its regulatory mechanism involving the tumor necrosis factor receptor-associated factor 6 (Traf6)/transforming growth factor-β activated kinase 1 (TAK1) pathway. An HT model in young rats was established via propylthiouracil (PTU) gavage, and a functional rescue experiment was con- ducted by overexpressing TAK1 (pcDNA3.1-TAK1). The animals were divided into five groups: normal, HT, low-dose VD (HT+VD-L), high-dose VD (HT+VD-H), and HT+VD-H+pcDNA3.1-TAK1 (HT+VD-H+pc). Each group consisted of 10 rats. Serum creatinine (Scr) and blood urea nitrogen &nbsp;(BUN) &nbsp;levels &nbsp;were &nbsp;measured using an automatic biochemical analyzer. Renal apoptosis (TUNEL), TGF-β1/α- SMA/E-cadherin (immunohistochemistry), and Bcl-2/Bax/Traf6/TAK1/p-TAK1 (Western blot) expressions were assessed in renal tissue. VD significantly reduced Scr and BUN levels in the serum of HT young rats, downregulated renal tissue apoptosis, decreased TGF-β1 and α-SMA expressions, and upregulated E-cadherin expression. Additionally, VD inhibited Traf6, p-TAK1, and Bax expressions while increasing Bcl-2 expression. All differences were statistically significant.</p> Aiyuan Cai Qingpeng Hu Haixia Wu Zilong Li Yuanhong Lin Jiaohua Yu Hailong Huang Ruizhong Zhang Jing Xiao Ping Liu Copyright (c) 2025-09-01 2025-09-01 66 3 301 312 10.54817/IC.v66n3a06 Clinical effect of laparoscopic surgery on patients with colon cancer complicated with intestinal obstruction. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44380 <p>Colon cancer is a malignant tumor of the digestive tract, often complicated by intestinal obstruction. Laparoscopic surgery is widely used and has the advantages of a small postoperative wound, less intraoperative blood loss, and fewer postoperative complications. To measure the clinical effect of laparoscopic surgery on patients with colon cancer complicated with intestinal obstruction, the clinical data of 100 patients with this condition, who under- went surgical treatment in the Baoji High-tech Hospital between January 2020 and December 2022, were retrospectively analyzed. Based on different surgical methods, the patients were separated into a control group (CG, traditional lap- arotomy) and an observation group (OG, laparoscopic surgery). The total clini- cal effect of OG was superior to that of CG, as evidenced by shorter operation times, reduced intraoperative blood loss, faster recovery times for intestinal function, earlier discharge from bed, and shorter hospital stays. After surgery, the NRS score declined in both groups, with a lower score in the OG. TNF-α, IL -6, and CRP levels were elevated in both groups, but those in OG were lower. The occurrence of complications in the OG was reduced compared to the CG. Quality-of-life scores, including physical function, psychological state, social communication, and self-care ability in the OG, were higher than those in the CG. Laparoscopic surgery is effective for treating colon cancer complicated with intestinal obstruction in patients, which can effectively lessen their pain, reduce their inflammatory indicators, reduce the postoperative complications of patients, and improve their quality of life.</p> Peihua Wu Zhengquan Ta Copyright (c) 2025-09-01 2025-09-01 66 3 313 321 10.54817/IC.v66n3a07 Condiciones comórbidas del síndrome de West y autismo: Reporte de 5 casos. http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44381 <p>West syndrome (WS) is an epileptic encephalopathy characterized by infantile spasms (IS), psychomotor delay or regression, and a typical EEG pattern called Hypsarrhythmia. IS are tonic seizures of sudden onset, in flexion, extension, or mixed, of short duration, and in series, which usually occur in the first year of life. It is estimated that at least 20 percent of children with WS develop autism. Both WS and autism spectrum disorders (ASD) share genetic, structural, and metabolic alterations, as well as immune dysfunction, which in- teract with environmental factors, suggesting potential common mechanisms linking both disorders. We performed a retrospective and descriptive analysis of clinical records of five children between the ages of three and seven years, all presenting with IS and clinical signs of ASD. Comprehensive neurological and psychological assessments were conducted, along with EEGs. The average age was 4.4 years, with a predominance of males. The onset of symptoms occurred between four and seven months, and signs of autism were identified between one and 2.5 years. All patients exhibited hypsarrhythmia on their EEGs. Three of the five children had a diagnosis of neurocutaneous syndrome. All were treated with ACTHH or nitrazepam, with a satisfactory response. We highlight the relationship with neurocutaneous syndromes, particularly tuberous sclerosis, where cellular, molecular, and pathophysiological mechanisms may impact neuronal connectivity, thus influencing the epileptogenic process and developmental delay. Early identification of these clinical signs by the pediatrician will allow for timely interventions.</p> Raiza Portillo Pérez Nelly Petit-Molero Enoe Medrano-Toledo Gustavo Morales-Rincón Joaquín Peña Copyright (c) 2025-09-01 2025-09-01 66 3 322 331 10.54817/IC.v66n3a08 Long-term effects of antenatal administration of corticosteroids. Where are we? http://www.produccioncientifica.luz.edu.ve/index.php/investigacion/article/view/44382 <p>There is increasing concern about the long-term effects of antenatal administration of corticosteroids, as some complications have been reported in neonates, adolescents and adults, which could be transmitted to subsequent generations, as it has been shown in animal and observational studies in humans. In this review, we summarize the current understanding of the long-term effects of antenatal corticosteroid administration and provide data to inform the preparation of guidelines. A literature search was performed in the PubMed database. A mechanism has been proposed as to how antenatal administration of corticosteroids could produce morbidity in neonatal neuro-development and lead to future diseases in adulthood. However, this hypothesis has not been proven in large randomized controlled trials. We summarize here the current data supporting and opposing the long-term effects of antenatal corticosteroid administration. Follow-up studies from randomized controlled trials have found no increased risk of neurologic impairment in children after exposure to a single course of antenatal corticosteroids. Observational and clinical trials of maternally administered antenatal corticosteroids show no evidence of increased disability on follow-up and describe associations rather than a proximate cause. Before 34 weeks of gestation, antenatal administration of corticosteroids in women at high risk for preterm birth appears to improve most neurodevelopmental outcomes. It is still recommended to administer a single course of corticosteroid treatment before preterm delivery.</p> Carlos Briceño-Pérez Liliana Briceño-Sanabria Eduardo Reyna-Villasmil Paulino Vigil-De Gracia Copyright (c) 2025-09-01 2025-09-01 66 3 332 346 10.54817/IC.v66n3a09