Abstract Chronic toxicity studies are essential for evaluating potential adverse effects associated with the long-term or repeated administration of pharmaceutical compounds, biologically active substances, herbal products, and emerging materials. These studies aim to identify cumulative and organ-specific toxicities that may not be detected in short-term assessments, thereby supporting dose selection, risk characterization, and regulatory decision-making. This review summarizes current methodologies, key endpoints, regulatory considerations, and recent scientific advances in chronic toxicity evaluation using laboratory animal models.
The review is based on the Organisation for Economic Co-operation and Development (OECD) Test Guidelines 407, 408, and 452, which define standardized approaches for 28-day, 90-day, and long term repeated-dose toxicity studies in rodents. Core evaluation parameters discussed include clinical observations, body weight and food consumption, hematological and biochemical analyses, urinalysis, endocrine assessments, organ weights, necropsy findings, and histopathological examinations, with emphasis on the determination of the no observed adverse effect level (NOAEL).
In addition to conventional endpoints, recent developments such as ophthalmological examinations, molecular and oмics-based technologies, and novel biomarkers are highlighted for their ability to improve mechanistic understanding and early detection of organ injury. The integration of alternative in vitro models, organoids, organ-on-a-chip systems, and in silico approaches in accordance with the 4R principles is also discussed. Despite existing limitations, chronic toxicity studies remain a cornerstone of preclinical safety assessment, and their integration with advanced technologies enhances relevance, ethical compliance, and predictive value.

Background: The first supposition of a possible relationship between occlusion and TMJ (temporomandibular joint) function was suggested by Costen, who hypothesized that changes in dental condition (loss of vertical dimension) can lead to symptoms of temporomandibular disorders (TMD). Symptoms of temporomandibular disorders are more common in women, with a female-to-male ratio ranging from 2:1 to 8:1. Temporomandibular disorders occur in 25-38% of the general population. The reason for conducting this study is that no research has been conducted in Mongolia on the relationship between malocclusion and TMJ. Aim: This study aimed to investigate the association between malocclusion and temporomandibular disorders. Materials and Methods: The study was conducted using a case-control design, and patients requiring orthodontic treat ment who visited the Orthodontics Department of the Center Hospital of the Dentistry, Mongolian National University of Medical Sciences were included in the case group, while relatively healthy individuals with normal occlusion who had not undergone orthodontic treatment were included in the control group. The sample size for each case and control group was calculated to be 20 people, for a total of 40 people aged 20-30. The need for orthodontic treatment was determined by the IOTN index (Index of Orthodontic Treatment Need). Relatively healthy occlusion was defined according to Andrew’s six keys. The condition of the temporomandibular joint was determined using a questionnaire and physical examination. Results: The mean age of the study participants was 24.4±3.7 years in the malocclusion group and 26.0±3.6 years in the control group, 45% (n=8) of the malocclusion group were male and 40% (n=9) of the control group were male. The indicators of malocclusion, such as increased overjet, decreased overjet, increased overbite and mouth breathing were statistically significantly different between the malocclusion group and the control group (p<0.05). Logistic regression analysis showed that CII (OR=11.66, p=0.007) and CIII (OR=16.33, p=0.017) occlusion, increased overbite (OR=6.87, p=0.025) and mouth breathing (OR=4.22, p=0.042) had an impact on the occurrence of TMJ noise in both vertical and horizontal directions. Conclusions 1. Among the study participants, Angle’s Class I accounted for 50% (the highest percentage), while Angle’s Class III accounted for 20% (the lowest percentage). But Angle’s Class II accounted for 30%. 2. Symptoms of temporomandibular joint disorder were statistically significantly higher in the case group (p<0.05). 3. People with Angle’s Class II and Class III were 11-16 times more likely to develop temporomandibular joint (TMJ) noise, a symptom of TMD, compared to people with normal occlusion.

Background: Sleep is a complex neuropsychological, biological, and physiological process essential to human health. Obstructive Sleep Apnea (OSA) is a highly prevalent disorder worldwide. In Asian countries, 12–40% of the population, and in the United States, 35.8% of the population are estimated to be at high risk for OSA. In Mongolia, however, there is limited research on the prevalence of OSA, which led to the initiation of this study. Aim: To determine the prevalence and risk level of OSA among the Mongolian population. Materials and Methods: A total of 1,405 individuals aged 18 and older from the clinical Mon-Timeline cohort study were assessed using the Berlin Questionnaire (BQ). The BQ evaluates three categories: snoring and witnessed apneas, daytime sleepiness, and high blood pressure and obesity. Individuals who met criteria in any two of the three categories were classified as being at high risk for OSA. Data on educational attainment and lifestyle behaviors were collected using the Food Frequency Questionnaire and the Global Physical Activity Questionnaire. Statistical analysis was performed using Student’s t-test, Pearson’s chi-square test (χ²), and ANOVA. Results: The mean age of participants was 42 ± 14.3 years, and 42.5% were male. A total of 24.3% (n=341) were found to be at high risk for OSA. The risk increased with age: 6.7% in individuals under 30, 28.3% in those aged 30–50, and 39.4% in those over 50. Participants at high risk for OSA tended to be older and more physically inactive. Additionally, 41.7% of all participants reported snoring, and 39.3% of those stated that their snoring disturbed others. Conclusion A significant portion (24.4%) of the Mongolian population is at high risk for OSA. These individuals are more likely to be older and physically inactive. The high prevalence of snoring and associated disturbances suggests a need for increased awareness, early detection, and age-targeted prevention strategies in Mongolia.

Background: Nasal bone fracture is the most common facial bone injury and remains a significant clinical and forensic concern. Although perceived as minor, management can lead to long-term complications such as external nasal deformity, septal perforation, nasal obstruction, and chronic rhinosinusitis. These sequelae compromise quality of life and frequently give rise to medico-legal disputes regarding the assessment of health damage and work capacity. Aim: To characterize nasal bone fractures and septal deformities and to evaluate their correlation with the severity of health damage and loss of work capacity. Materials and Methods: A cross-sectional study was conducted involving 70 patients individuals with acute nasal bone fractures treated at the Department of Otorhinolaryngology, First Central Hospital of Mongolia, and patients with minor injuries assessed at the National Forensic Agency of Mongolia. Data collection included structured questionnaires, physical examination, nasal endoscopy and computed tomography. Nasal bone fractures were classified according to Hwang (2002) and septal deviations were categorized using Mladina’s classification (1987). Statistical analyses were performed to explore associations between fracture type, septal deviation, nasal obstruction and functional impairment. Results: Septal deviation was identified in 60% of patients without fracture and in 40% of those with concurrent fractures. Among 60 cases of blunt nasal trauma, septal deviation showed a statistically significant association with septal fracture (p=0.001). Hwang type II, III, and IV fractures demonstrated the strongest correlation with unilateral or bilateral nasal obstruction (χ²=29.72). Bilateral nasal bone fractures were more frequently associated with septal deviation, while logistic regression analysis revealed an increased risk of impaired work capacity (coefficient 0.237). Conclusion 1. In 40% of the study participants with nasal trauma, nasal bone fractures were accompanied by septal injury, initially classified as mild. 2. These patients underwent surgical treatment; however, when the recovery period extended beyond four weeks a reassessment of health impairment was required. According to the criterion of prolonged disruption of health, the degree of impairment was subsequently reclassified as moderate.

Background: Implant restoration necessitates meticulous attention to the profile, and texture of gingival soft tissue. The healing abutment plays a critical role as a gingival shaping tool, with its neck design significantly impacting soft tissue profile and crown aesthetics. Aim: This study explores the impact of a modified anatomic healing abutment (MAHA) on morphological changes in gingival soft tissue and patient satisfaction following mandibular first molar implant restoration. Materials and Methods: Thirty patients with a single missing mandibular first molar undergoing implant repair were randomly assigned to either the control group (n=15) or the experimental group (n=15). The experimental group received a MAHA post-dental implantation, while the control group received a standard healing abutment. Both groups underwent crown restoration after 2 months. Peri-implant soft tissue index, Pink Esthetic Score (PES), and patient satisfaction were assessed at postoperative day (T0), 1 month (T1), 3 months (T2), and 6 months (T3). Independent sample t-tests were conducted with a significance level of α=0.05, where P < 0.05 indicated statistical significance Results: No significant differences in peri-implant soft tissue index were observed between the experimental and control groups at T0, T1, T2, and T3 (P>0.05). The mean PES value in the experimental group exceeded that of the control group at T0, T1, and T2 (P < 0.05). VAS scores showed no significant differences between the groups at T0, T1, and T3 (P>0.05), but at T2, the experimental group exhibited higher satisfaction levels than the control group (P < 0.05) Conclusion The modified anatomic healing abutment for a mandibular first molar implant demonstrates superior soft tissue contouring compared to the standard healing abutment, leading to heightened patient satisfaction during prosthesis wear. Clinical Significance: The use of a MAHA in mandibular first molar implant restorations can enhance soft tissue contour and improve early esthetic outcomes without compromising peri-implant health. This approach also contributes to increased patient satisfaction during the prosthetic phase, supporting its clinical application for optimizing both functional and esthetic results in implant dentistry.

Abstract: Liver fibrosis is a key process in the progression of chronic liver diseases. It occurs when liver cells experience repeated damage and regeneration, leading to an excessive build-up and abnormal distribution of extracellular matrix components, such as collagen, glycoproteins, and proteoglycans, in the liver.
In vivo models of hepatic fibrosis are crucial for studying the development of liver fibrosis and evaluating potential antifibrotic therapies. These models aim to replicate the progressive scarring of liver tissue that occurs in chronic liver diseases. In vivo hepatic fibrosis models can be classified based on their underlying causes, including chemical, dietary, surgical, transgenic, and immune-mediated models. For instance, carbon tetrachloride (CCI4) is known to induce significant fibrosis, while models of non-alcoholic steatohepatitis (NASH) are used to investigate advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). Among various models, the carbon tetrachloride (CCI4) induced liver fibrosis model is one of the most widely used experimental approaches. Its popularity stems from its reliability, reproducibility, cost-effectiveness, ease of implementation, and resemblance to human fibrotic liver injury. While this model is considered the gold standard in fibrosis research, it has several limitations that researchers must carefully consider. For instance, an overdose of CCI4 can lead to substantial hepatocellular necrosis, particularly in the centrilobular area. This can cause acute liver failure, which may result in rapid death rather than fibrosis. This review aims to outline the optimal experimental parameters for the CCI4-induced liver fibrosis model. It covers aspects such as the appropriate doses of CCI4, routes of administration, duration, frequency, and the choice of vehicle needed to establish a pathologically relevant model of liver fibrosis in experimental animals. The review also seeks to investigate therapeutic effects and contribute to the development of new medications.

Introduction : Intravascular ultrasound (IVUS) is an advanced technology used to guide percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD). Goal: This study aims to describe the first successful implementation of IVUS in patients with stable CAD in Mongolia. Materials and Methods : Patients with CAD who underwent either CAG or IVUS-guided PCI were prospectively selected. All patients provided informed consent, which was approved by the Ethical Committee of the Ministry of Health of Mongolia (March 17, 2023, №23/014). For patients who underwent CAG-guided PCI, stent deployment was performed under conventional CAG guidance, while stent implantation was performed under IVUS guidance in patients who underwent IVUS-guided PCI. Stent restenosis at 1-year follow-up was selected as the primary endpoint. The differences between the CAG-guided PCI and IVUS-guided PCI groups were compared using independent sample t-tests and chi-square tests. The association between treatment strategy (CAG-guided PCI vs. IVUS-guided PCI) and all cause restenosis (the study endpoint) was analyzed. Results: A total of 51 patients with stable coronary artery disease (CAD) who underwent coronary angiography CAG guided PCI and intravascular ultrasound (IVUS)-guided PCI were included in the present study. The mean age was 63±9.44 years, with 88.2% male (n=45). In the IVUS-guided PCI group, the minimal lumen area (mm²) was 4.46±1.1, and after stenting, the minimal stent area was 8.59±0.5, showing a statistically significant difference (p<0.001). The stent restenosis rate at 1-year follow-up in the CAG-guided PCI group and the IVUS-guided PCI group were 16% and 3.84%, respectively. The restenosis rate in the IVUS-guided PCI group was lower than in the CAG-guided PCI group. Conclusion Complete expansion of the stent on the coronary artery wall is effective in improving long term outcomes of PCI, and IVUS guided coronary artery intervention has better long-term results compared to angiography-guided PCI group (96.1% vs 84%).

Surgical result of velopharyngeal insufficiency Background: The main purpose of primary cleft palate (CP) repair is to reconstruct anatomical structure with minimal impairment of maxillary growth and normalize velopharyngeal function and feeding process. One of the most common complications after the primary CP repair is velopharyngeal insufficiency (VPI), which leads to the subsequent surgery. The velopharyngeal function assessment characterizes speech development in children. Researches noted that VPI causes in 5-86% after primary CP repair. Early diagnosis of VPI and prompt surgical treatment are essential to prevent the development of speech disorders in children. Methods and Material: A retrospective longitudinal study was completed. The patients who diagnosed VPI after primary CP repair in the Department of Maxillo-facial surgery of the National Center for Maternal and Child Healt and had velopharyngeal function assessment were recruited to the study. The results were compared with pre and postoperative nasopharyngoscopy ratio. Results: A total of 133 patients with VPI were included: 75.9% had Furlow Z plasty, 24.1% had pharyngeal flap surgery. The patients ranged in age from 3 years 6 months to 17 years. VPI ratio was 17.3% - severe, 19.5% - moderate. Postoperative VPI ratio were 97.0% normal in the Furlow group and 84.4% in the pharyngeal surgery group (p=0.02). Nasal emission was 94.0% before surgery and 31.6% after surgery, a statistically significant difference (t = -14.2, p <0.0001). Conclusions: The Furlow Z plasty and pharyngeal flap surgeries were superior for maintaining velopharyngeal function.

Background/Aims: Ledipasvir/sofosbuvir (LDV/SOF) shows high efficacy and safety in patients with genotype 1-hepatitis C virus (HCV). We aimed to investigate the efficacy and safety of LDV/SOF in real-world Mongolian patients. Methods: Between 2015 to 2019, 23 (0.5%) and 5,005 patients (99.5%) with genotype 1a and 1b HCV, respectively, were treated with a fixed-dose tablet containing 90 mg ledipasvir and 400 mg sofosbuvir for 12 weeks, and 81 patients (1.6%) with previous experience of interferon (IFN)-based treatment received additional 1,000 mg ribavirin. HCV RNA was measured at 4, 12, and 24 weeks after the first dose to determine rapid virologic response, end of treatment response (ETR), and sustained virologic response at 12 weeks after end of treatment (SVR12). Results: Most patients (n=5,008; 99.6%) achieved ETR and SVR12 without virologic relapse. Patients with genotype 1a showed low rates of ETR and SVR12 in only 16 patients (69.6%). There was no significant difference in SVR12 rate between patients regardless of IFN experience (n=81; 1.6%), cirrhosis (n=1,151; 22.9%), HCV RNA >6×106 IU/mL (n=866; 17.2%), or liver stiffness >9.6 kPa (n=1,721; 34.2%) (100.0%, 99.3%, 99.4%, and 99.4%, respectively). No severe adverse events (AEs) were reported, and there was no dose reduction or interruption due to AE. The most common AEs were headache (n=472; 9.4%), fatigue (n=306; 6.2%), abdominal discomfort (n=295; 5.9%), and skin rash (n=141; 2.8%). Conclusions LDV/SOF showed high efficacy and safety for patients with genotype 1, especially 1b HCV, in Mongolia. The real-world data might be applicable to patients in other Asian-Pacific countries.

Background: The main purpose of primary cleft palate repair is to reconstruct anatomical structure with minimal impairment of maxillary growth and normalize velopharyngeal function and feeding process. One of the most common complications after the primary cleft palate repair is velopharyngeal insufficiency, which leads to the subsequent surgery. The velopharyngeal function assessment characterizes speech development in children. Researches noted that velopharyngeal insufficiency causes in 5-86% after primary cleft palate repair. Therefore, it is essential to choose an adequate primary surgical method for each particular type of cleft palate. Objective: To compare velopharyngeal function using nasopharyngoscopy after primary CP repair Materials and Methods: The patients who with congenital cleft palate and, underwent primary cleft palate repair in the Department of Maxillo-facial surgery of the National Centre for Maternal and Child Health and had velopharyngeal function assessment were recruited to the study. Patients with wound dehiscence and oronasal fistula postoperatively were excluded from the study.
Cleft palate was classified according to the Veau system and Golding-Kushner scale of nasopharyngoscopy was used to assess patient’s velopharyngeal function in order to associate with cleft types and the primary palatoplasty techniques. Pearson’s chi-squared analysis and Fisher exact test were used for statistical analysis. Results: A total of 335 patients were included in the study. The mean age at primary palate repair was 22.9±13.6 months. There were 56, 42, 177, and 60 patients with Veau-I type, Veau-II type, Veau-III type and Veau- IV type respectively, whereas for primary palatoplasty 65 patients underwent Furlow technique, 148 patients – Mongolian technique, 108 patients – Two flap technique, 34 patients – Von Langenbeck technique.
Nasopharyngoscopy assessment of adequate velopharyngeal function was as followed as by “Furlow” technique in 89.4% cases, ”Mongolian” technique in 62.2% cases but by “Two flap” technique only in 48.1% and Von Langenbeck technique in 47.1% cases. Conclusion The Furlow and Mongolian techniques were superior for maintaining velopharyngeal function after primary palatoplasty.