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Lung cancer (LC) is a highly invasive malignancy and the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) as its most prevalent histological subtype. Despite all breakthroughs achieved in drug development, the prognosis of NSCLC remains poor. The mitogen-activated protein kinase signaling cascade (MAPKC) is a complex network of interacting molecules that can drive oncogenesis, cancer progression, and drug resistance when dysregulated. Over the past decades, MAPKC components have been used to design MAPKC inhibitors (MAPKCIs), which have shown varying efficacy in treating NSCLC. Thus, recent studies support the potential clinical use of MAPKCIs, especially in combination with other therapeutic approaches. This article provides an overview of the MAPKC and its inhibitors in the clinical management of NSCLC. It addresses the gaps in the current literature on different combinations of selective inhibitors while suggesting two particular therapy approaches to be researched in NSCLC: parallel and aggregate targeting of the MAPKC. This work also provides suggestions that could serve as a potential guideline to aid future research in MAPKCIs to optimize clinical outcomes in NSCLC.

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Chlorogenic acids are plant secondary metabolites, chemically-polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. Both chlorogenic acids and plant extracts containing significant amounts of the compounds show promising in vitro activity against colorectal cancer. With coffee being the most popular drink in the world, and colorectal cancer at an unfortunate peak in incidence and mortality, the mechanisms through which the anti-tumorigenic effect of chlorogenic acids could be functionalized for CRC prevention seem appealing to study. Therefore, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK signal transduction pathways, alongside the reduction in the number of inflammatory cytokines and chemokines and the counterintuitive beneficial elevation of oxidative stress.

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Background: Colorectal cancer, 3rd in incidence and 2nd in mortality among cancers worldwide, represents the most common malignant tumor of the digestive tract. In Romania, it is the most frequently diagnosed type of cancer (approximately 0.06% of the population/year). During the COVID-19 pandemic the legislation preventing the SARS-CoV-2 viral transmission impairing access to outpatient healthcare services combined with patients fear of SARS-CoV-2 infection had consequences on the diagnosis and treatment of all other pathologies. Methods: A 5-year retrospective cohort study was conducted in a tertiary hospital in Arad, Romania, and included 1329 newly diagnosed colorectal cancer patients. For statistical analysis, Fisher's exact test was used for categorical data and the unpaired test with Welch's correction for continuous data. Results: The age on diagnosis decreased during the early COVID-19 pandemic to 68.50 (95% CI [67.90 69.11]) years, with the highest percentage (7.41%) of early onset colorectal cancer patients, a steady post-pandemic increase in the percentage of male (52.71% in 2019 to 62.20% in 2022) and urban (54.18% in 2018 to 70.10% in 2022) patients, admitted to the hospital due to an emergency presentation (peaking at 83.95% in 2020) and requiring a longer hospitalization period (10.03 [95% CI (8.76-11.30)] days in 2020 to 8.37 [95% CI (7.44-9.30)] days in 2022). The most common colo-rectal cancer diagnosis of patients in our reference population was malignant neoplasm of the rectum (ICD-10 code C20.0), while the most common complications were peritumoral adherence-related disorder, occlusion, and perforation, encountered in patients with comorbidities such as arterial hypertension, ischemic cardiomyopathy, diabetes mellitus, obesity, and non-alcoholic steatohepatitis. Conclusions: Regional particularities should be analyzed to better target the population at risk and to better direct the necessary healthcare resources towards the reference population, especially during crisis periods similar to the COVID-19 pandemic.

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Glioblastoma remains one of the most aggressive cancers of the brain, warranting new methods for early diagnosis and more efficient treatment options. Circular RNAs (circRNAs) are rather new entities with increased stability compared to their linear counterparts that interact with proteins and act as microRNA sponges, among other functions. Herein, we provide a critical overview of the recently described glioblastoma-related circRNAs in the literature, focusing on their roles on glioblastoma cancer cell proliferation, survival, migration, invasion and metastasis, metabolic reprogramming, and therapeutic resistance. The main roles of circRNAs in regulating cancer processes are due to their regulatory roles in essential oncogenic pathways, including MAPK, PI3K/AKT/mTOR, and Wnt, which are influenced by various circRNAs. The present work pictures the wide implication of circRNAs in glioblastoma, thus highlighting their potential as future biomarkers and therapeutic targets/agents.

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Atonic wounds represent a major health problem, being frequently encountered in medical practice with consequences that have a negative impact on the patient's daily life as well as their general condition. In this study, a brand laser with a 12-watt probe was used to stimulate patients' wounds. We involved in this study a group of 65 patients, which was compared with a group of 30 patients, the latter not receiving this laser therapy. The data were accumulated from the questionnaire of subjective assessment of the laser impact on patients' condition as well as from the local evolution. We noticed the improvement of the local symptomatology which was found to be more effective in the patients from the study group compared to the reference group. The beneficial and positive effects, mainly on the symptoms but also on the local evolution of atonic wounds, can be observed in our study. We consider that this therapy is of major importance considering the lower costs both from the shortening of hospitalization and the long-term use of various substances. The early reintegration of patients into daily life is an important benefit for them.

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(1) Background: Patients suffering from chronic wounds report physical, mental, and social consequences due to their existence and care. There is a global need for tissue repair strategies and, in our case, for chronic wound healing. PRP therapy is based on the fact that platelet-derived growth factors (PGF) support the three phases of the wound healing and repair cascade (inflammation, proliferation, and remodeling); (2) Methods: A comparative study was carried out on two groups of patients with atonic wounds totaling a total of 80 cases as follows: a study group in which the PRP procedure was applied and a control group in which the biological product was not injected. The study was carried out in the surgery clinic of the Clinical Hospital C.F. Oradea City; (3) Results: A much faster healing was achieved in the case of patients who benefited from the platelet-rich plasma injection therapy compared to the group of patients in whom this therapy was not used. Three weeks after the plasma injection, a considerable reduction of the wound was evident, with some of the patients presenting with a closed wound; (4) Conclusions: The effect of PRP on the healing of chronic wounds is promising in most cases. A positive effect was also highlighted in terms of reducing treatment costs by considerably reducing the materials used as well as the number of hospitalizations for the same pathology.

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In the last decades total hip arthroplasty (THA) has become a standard procedure with many benefits but also a few still unsolved complications, which can lead to surgical revision in 19-23% of cases. Thus, aseptic loosening and metal hypersensitivity remain challenges. The phenomenon of wear debris causes chronic inflammation, which produces osteolysis and aseptic loosening. Wear debris promotes osteoclast production and inhibits osteoblasts by secretion of pro-inflammatory cytokines. Micro-abrasions can be induced by abrasive, adhesive and fatigue wear and cause a liberation of metal ions, which lead to another immune response elicited mostly by macrophages. Another reaction in the neocapsule can be a type IV hypersensitivity reaction to various alloys, containing metals such as nickel, cobalt and chromium. Patch testing and the lymphocyte transformation test (LTT) are not the best diagnostic possibilities to exclude a postoperative hypersensitivity reaction, because of the different alignment of the epicutaneous cells compared to the periprosthetic deep tissue. This hypersensitivity reaction is mostly induced by cytokines, which are secreted by macrophages rather than lymphocytes. In cell cultures and in animal studies, multipotent mesenchymal stem cells (MSC) have been shown to play a role in improving initial implant integration, to limit periprosthetic osteolysis and also to reconstitute peri-implant bone stock during implant revision. Thus, MSC might be used in the future to prolong the durability of THA. A better understanding of the interactions between primary chronic inflammation, corrosion, osteolysis and hypersensitivity is mandatory to develop new therapeutic strategies, aiming at the reduction of the incidence of implant failures. In this article the underlying immunological mechanisms to aseptic loosening are presented.

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Epidermoid cysts are most often benign cystic lesions, with uterine cervical localisation being very unusual. We present the case of a 52-year-old female patient diagnosed with an epidermoid cyst at the level of the uterine cervix. A bioptic and haemostatic uterine curettage was performed, followed by total hysterectomy with bilateral adnexectomy. The histopathologic analysis and immunohistochemical essay of the resection specimens confirmed the cervical epidermoid cyst. The presence of high-risk HPV (human papillomavirus) was only seen in the cervical mucosa. The exact etiopathogenesis is unknown, but postpartum cell implantation of reminiscent embryonic tissue can be involved in the development of these lesions.

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INTRODUCTION: Squamous cell carcinoma (SCC) is the most common skin cancer with a high rate of death. Different lymphocyte populations play an important role in modulating the immune response in the tumor microenvironment. The increase in the proportion of cluster of differentiation (CD)4+ CD25+ regulatory T-cell (Treg) lymphocytes is associated, in different studies, with the increase of the cell multiplication rate. AIM: To analyze the Treg lymphocyte subpopulations and to correlate the results with the presence of the CD8+ cytotoxic T-cell (Tc) lymphocyte population. MATERIALS AND METHODS: Sixty primary skin SCC specimens were incubated with anti-CD8 (clone SP57) rabbit monoclonal antibody and anti-CD25 (clone 4C9) mouse monoclonal antibody. RESULTS: The ratio of the intratumoral∕peritumoral CD4+ CD25+ forkhead box protein p3 (Foxp3) lymphocytes was 0.46, emphasizing that at tumor margins, where tumor aggressiveness is higher, these lymphocytes subpopulations facilitate tumor progression. The comparative analysis of the tumor microenvironment profile revealed that in the case of intratumoral immune response, the number of Tc-type lymphocytes (CD8+) was 3.34 times higher compared to Treg lymphocytes (p<0001). In the peritumoral area, the number of Tc lymphocytes was 5.05 times higher compared to Treg lymphocytes (p<0001). CONCLUSIONS: Treg lymphocytes inhibition may cause the suppression of the antitumoral cell immune response in the tumor environment. We believe that Treg lymphocytes should represent a focus of interest for a new personalized therapy. New studies are needed to better understand the immune response in the tumor microenvironment.

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Malignant melanoma is one of the common skin cancers but as a primary cancer localized in urinary bladder is a very rare clinical entity, 0.2% of all melanomas. We report the very rare case of primary malignant melanoma of the bladder in an 80-year-old man. According with our knowledge is the first case of primary malignant melanoma reported in Romania. Only a few percent of malignant melanoma have origin outside the skin. Less than 30 cases of primary bladder melanoma have been reported in the literature. The most common metastasis in urinary bladder comes from breast carcinoma and skin melanoma The tissue examination presents the same futures does not matter if is a primary or secondary malignant melanoma. The ancillary tests like immunohistochemistry help us to do an accurate diagnostic but to discriminate primary vs. metastatic tumor remain an important issue. Usually, the bladder melanoma has an aggressive lethal behavior. Histopathological examination, immunohistochemistry, clinical history, and endoscopic evaluation can provide certain diagnostic features.

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Lower respiratory infections are an important cause of morbidity and mortality in children, especially in newborns, infants and young children. We conducted a retrospective study and we analyzed the causes of death in newborns, infants and young children, in the necropsy protocols from two Departments of Pathology (Mures County Hospital and Emergency County Hospital of Târgu Mures, Romania), between 2016-2018. We performed descriptive statistics: number of necropsies per year, distribution by gender (male∕female), by place of origin (rural∕urban), by age and leading causes of death in our study. To establish the pattern of lung injuries, we performed a morphological, histopathological and immunohistochemical study [cluster of differentiation (CD) 3, CD14, CD20, CD31, CD34, CD68]. Our study is showing the most frequent and typical aspects of pulmonary pathologies in fetuses, newborns, infants and young children. In this way, we are highlighting the microscopic aspects of the immature lung, amniotic fluid and meconium aspiration, pulmonary distress syndrome in children, pneumonia, bronchopneumonia and vascular pulmonary disease developed in patients with congenital cardiac defects. Most deaths were recorded in the first 30 days or in the first year of life. Primary respiratory diseases were the leading causes of death in these patients. Secondary respiratory diseases were associated with the major causes of death in these patients as an aggravating or precipitating factor.

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Ethylene glycol is a toxic alcohol that is mainly introduced into an organism through the digestive pathway. Its priority toxic metabolites are glycolic acid and oxalic acid. We present the case of a young person, of the male persuasion, without any personal pathological history, found unconscious and presenting signs of violence. The patient is emergency hospitalized presenting coma, convulsive syndrome, severe metabolic acidosis and a positive result for alcoholism. Anamnestic data is extremely poor. The results of the clinical and paraclinical examinations suggest a possible poisoning with toxic alcohols. Despite the drug treatment and the hemodialysis, the evolution is unfavorable, resulting in death one week after admission. Through the forensic examination, the followings were found: cerebral and leptomeningeal edema, focal cerebral microhemorrhages, bronchopneumonia, septic spleen, shock kidney, hepatic fatty dystrophy, excoriated plaques in the head area. The histopathological (HP) examination confirms the macroscopic diagnosis and identifies the presence of calcium oxalate crystals in the kidney tubules. Subsequently, the toxicological examination of the biological samples taken from the corpse at the forensic examination, confirms the presence of the glycolic acid. Postmortem, the investigation conducted by the criminal investigation authorities confirms the oral ingestion of antifreeze. The absence of a positive history, along with alcohol consumption, nonspecific clinical symptomatology and the absence of calcium oxalate in urine are trap elements in the diagnosis of acute ethylene glycol poisoning. The presence of calcium oxalate in tissues, identified through the HP examination, is an extremely important factor when establishing the cause of death.

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Dandy-Walker complex (DWC) is a malformative association of the central nervous system. DWC includes four different types: Dandy-Walker malformation (vermis agenesis or hypoplasia, cystic dilatation of the fourth ventricle and a large posterior fossa); Dandy-Walker variant (vermis hypoplasia, cystic dilatation of the fourth ventricle, normal posterior fossa); mega cysterna magna (large posterior fossa, normal vermis and fourth ventricle) and posterior fossa arachnoid cyst. We present and discuss four cases with different morphological and clinical forms of the Dandy-Walker complex. In all four cases, diagnosis was reached by incorporation of clinical (macrocephaly, seizures) and imaging [X-ray, computed tomography (CT), magnetic resonance imaging (MRI)] data. Two patients were diagnosed with Dandy-Walker complex, one patient was diagnosed with Dandy-Walker variant in a rare association with neurofibromatosis and one patient was diagnosed with a posterior fossa arachnoid cyst associated with left-sided Claude Bernard-Horner syndrome, congenital heart disease (coarctation of the aorta, mitral stenosis) and gastroesophageal reflux. In all forms of DWC, the clinical, radiological and functional manifestations are variable and require adequate diagnostic and therapeutic measures.

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The main objective of this study is to draw the attention that repeated induced abortions in the women's physiological history are very dangerous and could lead to developing uterine cancer. The legislation regarding this practice is variable in different countries. Relevant information in the field concerning the numerous risk factors that appear with abortions must be taught in schools before girls start their sexual life and can help avoiding the complications that may follow. Also, the abortion should be an extreme measure that must be used only in extreme cases that threaten the mother's life or imply the health of the future child. The study comprised 258 women diagnosed with endometrial carcinoma, without any risks factors for this type of cancer, which were questioned regarding the abortions in previous history. The results show that the age when the uterine carcinoma appears is even lower as the number of abortions is higher and the number of this type of cancer cases is directly proportional with the number of abortions suffered. In order to avoid this fact we have to pay more attention to the legislation and education of the patients. Also, we followed the expression of both estrogen and progesterone hormone receptors, in the case of uterine cancer that occurred in women who had abortions in history compared to the expression of hormone receptors in the case of patients who did not have abortions.

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BACKGROUND: Monitoring the effects of treatment in malignant diseases is very important in study of the influence on the cell metabolism. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics. The purpose of the present study is to evaluation and analysis of the colon cancer cells under anti-angiogenic treatment, to establish the changes in the cellular energy metabolism and apoptotic potential. Anti-angiogenic drugs block the vascular endothelial growth factors, preventing the formation of new vessels. MATERIALS AND METHODS: We use immunohistochemical analysis of cytochrome c release and histoenzymatic analysis of adenosine triphosphatase (ATP-ase), succinate dehydrogenase (SDH), lactate dehydrogenase (LDH) enzymes. Colorectal tumor tissue samples were obtained by biopsy following the surgical procedures at the County Clinical Hospital of Oradea (Romania). RESULTS: The obtained results show that the apoptotic potential of malignant cells increases during the anti-angiogenic treatment, in the same time the rate of glycolysis increases, due to installed hypoxia and reduced ATP synthesis. Our results have been confirmed by international studies too. CONCLUSIONS: It was been demonstrated that the apoptotic potential of malignant cells increases significantly during anti-angiogenic treatment. There is growing evidence that cancer's "Achilles' heel" is tumor cell metabolism.

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