Background: Identifying pathogenic variants in the F8, F9 gene in patients with hemophilia A (HA) and Hemophilia B (HB) is crucial for improving genetic counseling, understanding genotype–phenotype correlations, assessing inhibitor risk, and establishing family-specific mutation profiles. Aim: To detect mutations in the F8 and F9 genes among people with hemophilia A and B diagnosed in Mongolia. Materials and Methods: Long-distance PCR were used to detect intron-22 and intron-1 inversions. Sanger sequencing identified nucleotide substitutions, deletion, and insertion in F8 and F9 gene. Result: Thirty-two male patients with HA (30 severe, one moderate, and one mild) from 27 unrelated families, eight patients with Hemophilia B were analyzed. Among 25 families with severe HA, pathogenic variants were found in 24 families (95.6%). Large structural rearrangements were detected in 22 patients from 19 families, including intron-22 inversion in 16 cases of 14 families, intron-1 inversion in four cases from three families, and two large deletions found in two unrelated families. In one severe case, no pathogenic variant was identified in the entire F8 gene. Small scale changes were identified in the remaining patients, including missense in three families and two frameshift variants, all associated with severe phenotype. We found novel c.2240del variant and classified as pathogenic. A known polymorphism (c.3864A>C) was identified in one patient with moderate HA, while a novel intronic deletion (c.1010-106delA) was detected in a patient with mild disease. Two families had a history of HB. A total of five different variants (c.223C>T; c.344A>G; c.464G>C; c.187_188del; and c.1314_1314delA) were identified in six patients with severe HB. Of these, two (c.187_188del and c.1314_1314delA) were novel. No variant in the entire F9 was found in two patients with mild HB. Nonsense c.223C>T (p.Arg75*) mutation was detected in two unrelated patients. Conclusion Intron-22 (56%) and intron-1 (12%) inversions were detected in families with severe HA. A novel c.2240del variant was also identified in association with a severe phenotype. The novel variants c.187_188del and c.1314_1314delA of F9 can cause severe Hemophilia B.

Background: Hemophilia A (HA) and hemophilia B (HB) are monogenic bleeding disorders caused by pathogenic variants in the F8 and F9 genes, respectively, which are located on the X chromosome and result in deficiencies of coagulation factor VIII (FVIII) and factor IX (FIX). The diseases predominantly affect males, while females are usually asymptomatic heterozygous carriers. Identification of female carriers among relatives of affected males is important for preventing bleeding complications associated with surgery and childbirth. Aim: The main aim of this study was to detect carrier and non-carrier women and compare some phenotypes. Materials and Methods: The study included 50 female relatives of 32 male patients diagnosed with hemophilia A and 13 female relatives of 8 male patients diagnosed with hemophilia B, giving a total of 63 female relatives. Molecular genetic testing was performed to identify the pathogenic variants previously detected in the probands and to determine the carrier status of female relatives. Among them, 33 confirmed carriers and 18 non-carriers completed a 28-item questionnaire comprising three sections to assess bleeding-related symptoms. The questionnaire evaluated easy bruising, duration of menstruation, postpartum bleeding, and bleeding following injuries, surgical procedures, and dental procedures. Questionnaire findings were compared between molecularly confirmed carriers and non-carriers. Continuous variables were compared using the Mann–Whitney U test, while categorical variables were analyzed using Fisher’s exact test in R software. In female relatives of patients with hemophilia A, plasma FVIII activity was also measured. Result: Molecular genetic testing was performed in 52 female relatives. Eleven women were excluded from carrier-status analysis because no pathogenic variant was identified in the F8 or F9 gene of their respective probands. Among 43 female relatives of patients with hemophilia A who underwent carrier testing, 26 (60.4%) were identified as carriers and 17 (39.5%) as non-carriers. Among eight male patients with hemophilia B, pathogenic F9 variants were identified in six; among their seven female relatives, six were confirmed carriers and one was a non-carrier. The mean FVIII activity among heterozygous HA carriers was 58.5±20.6 IU/dL (n=17), which was significantly lower than that of non-carriers (101±28.8 IU/dL; p<0.001). Of the nine bleeding-related symptoms assessed, only easy bruising of the skin was significantly more common among carriers (OR=6.8; p=0.0069). Although prolonged menstrual bleeding and bleeding after childbirth, surgery, or dental procedures were reported among some carriers, no statistically significant differences were observed between carriers and non-carriers. Conclusion Among female relatives of males diagnosed with Hemophilia A or B in Mongolia, 32 (64%) of 50 women were identified as carriers and 18 (36%) as non-carriers. Plasma FVIII activity was significantly lower in HA carriers than in non-carriers (58.5±20.6 IU/dL vs. 101±28.8 IU/dL; p<0.001). Easy bruising was significantly more frequent among carriers (OR=6.8; p=0.0069). These findings support the importance of molecular genetic testing for identifying female carriers and recognizing women who may be at increased risk of bleeding, particularly in the context of surgery and childbirth.

Introduction: Cases of gastric cancer have been declining worldwide in recent years. However, gastric cancer incidence increased in the last decade in Mongolia. In Mongolia, over 80% of gastric cancer cases are diagnosed during the late stage. Several studies have revealed that serum pepsinogens (PGs) level reflects, indirectly, histological and functional characteristics of the gastric mucosa. Goal: We aimed to evaluate the risk of gastric cancer and its precancerous condition based on serum PGI, PGI/II biomarkers. Materials and Methods: This case-control study enrolled 114 subjects, including patients with gastric cancer (n=36), atrophic gastritis (n=40) and healthy controls (n=138). The questionnaires were obtained to determine risk factors. Serum PGI, PGII, and H. pylori IgG levels were measured by ELISA (Pepsinogen I ELISA; Pepsinogen II ELISA; H.Pylori IgG ELISA; BIOHIT Plc, Helsinki, Finland). PGI to PGII ratio was calculated. Patients were classified into the ABC(D) group according to Miki K approach. Also, we developed new scoring system based on some risk factors and serum PGI, PGI/II ratio. Logistic regressions were performed to evaluate risk and expressed by odds ratio (OR) and 95% confidence intervals (95%CI). Results: Mean age of the subjects was 60±10.9 years. H.Pylori was positive in 67 subjects. The serum PGI and PGI/II ratio levels were significantly decreased in gastric cancer and atrophic gastritis groups compared to the healthy control. According to classification ABC(D), group D (OR 5.04, 95% CI 1.13-22.50) had higher proportion of atrophic gastritis cases, group C (OR 6.19, 95% CI 1.04-36.78) had higher proportion of gastric cancer cases than others. Additionally, we created a risk prediction scoring system with a score ranging from 0 to 7, based on variables age, family history of gastric cancer, prior disease history, PGI and PGI/II ratio levels. For the atrophic gastritis patients, 17 (42.5%) were classified into medium-risk category (OR 4.49, 95% CI 1.38-14.58) and 17 (42.5%) were classified into high-risk category (OR 7.69, 95% CI 2.16-27.43). Whereas, 11 (30.6%) patients with gastric cancer were classified into medium-risk category (OR 4.35, 95% CI 1.13-16.85), 21 (58.3%) were classified into high-risk category (OR 14.25, 95% CI 3.60-56.43). Conclusion The methods based on serum PGI and PGI/II may identify a high risk population of gastric cancer and atrophic gastritis.

Background and Aims: Hepatocellular carcinoma (HCC) is a common cause of cancer related death in Mongolia. Early diagnosis is the very important management to increase successful treatment and survival rate. Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue and in serum of HCC patients. Recent studies have been conducted and suggested as a diagnostic biomarker for detecting HCC in the early stage. Therefore, we investigated the diagnostic value of the serum GPC3 level and compared it to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. Methods: We enrolled a total of 90 participants and divided into 3 groups with HCC (30), with liver cirrhosis (LC/30) and healthy (30) as the control group (30). GPC3 and AFP serum (sGPC-3, sAFP) levels were measured using commercially available enzyme-linked immunosorbent assay kits. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve and estimated sensitivity and specificity of each biomarker. Results: sGPC3 was significantly elevated in the HCC group as compared to liver cirrhosis and healthy subjects (658±138.2 pg/ml, 378±25.5 pg/ml, 356.3±29 pg/ml) respectively. sGPC-3 sensitivity was 96.6% and specificity was 100%. The area under the ROC curve (AUC) for GPC3 was 0.999 (0.996- 1.0).
In comparison, the mean of AFP was significantly higher in HCC (16.9±11.7 ng/ml) than in LC (6.7±7.6 ng/ml) and in healthy subject (3.3±2.1 ng/ml) and AFP sensitivity was 43,3 %, specificity was 95 % with an AUC of 0.808 (0.696- 0.921).
The combination of GPC-3 with AFP achieved the highest sensitivity (97.1%) and specificity (97%). Conclusion Serum GPC3 has a higher sensitivity than AFP for the early diagnosis of HCC. Combination of two markers showed greatest diagnostic accuracy.

Introduction: Air pollution has become one of the major problems in socio-economic and health issues in Mongolia. Among the various hazards of particulate matter (PM) pollutants, microorganisms in PM2.5 and PM10 are thought to be responsible for various allergies and for the spread of respiratory diseases. Recent studies have shown that PM2.5 particles can cause chronic heart failure, heart arrhythmias, and strokes, as well as lung damage, cirrhosis, inflammation, cancer, cardiovascular disease, and metabolic disorders. Furthermore, some studies have concluded that PM2.5 particles in the environment are a risk factor for gastrointestinal, liver, colon, and lung cancer as well as it affects the growth and metastasis of various cancer cells caused by other factors. In our country, the health effects of air pollution and the relationship between the pathogenesis of cancer research are scarce. Therefore, the study of the effects of PM2.5 particles on cancer cell proliferation, migration (metastasis) can provide a significant role for cancer treatment, diagnosis, and prevention. Purpose: Determining the effects of PM2.5 particles on cancer cell proliferation, migration (metastasis) in in-vitro Material and Methods: A human liver cancer cell line (HepG2), human gastric cancer cell line (AGS) were obtained from the central scientific research laboratory in the Institute of medical sciences. HepG2, AGS cells were seeded at a concentration of 1*105 cells/mL in a culture flask and cultured in RPMI-1640 medium supplemented with 10% FBS, 1% antibiotic mix (penicillin, streptomycin) in a humidified atmosphere of 5% CO2 at 37 °C. The cytotoxic effect of PM 2.5 in AGS, HepG2 cells were evaluated by MTT, CCK8 assays. AGS, HepG2 cells were incubated in 96 well plates for 24h then treated with different concentrations (0, 5, 10, 25, 50 and 100 μg ) of Bayankhoshuu, Buhiin urguu, and Zaisan samples for 24h, respectively. Results: Concentrations of 10, 25, and 50 μg/ml of samples collected from the Bukhiin urguu and Zaisan in March increased HepG2 cell growth, while doses of 25, 50 μg/ml of samples collected from Bayankhoshuu in March and December increased HepG2 cell growth. Therefore, concentrations of 25 and 50 μg/ml of samples collected from Bayankhoshuu in March increased AGS cell growth, while concentrations of 25, 100 and μg/ml of samples collected in December increased AGS cell growth. However, no cytotoxic effect was observed in the sample collected from Zaisan in March, whereas the PM2.5 sample enhanced AGS cell growth in dose dependent manner in December.(p <0.05) Conclusion High levels of heavy metals were detected in samples collected in December from Bayankhoshuu, Bukhiin urguu and Zaisan of Ulaanbaatar. Concentration of 25 μg/ml of samples collected from the Bukhiin urguu and Zaisan in March increased HepG2 cell growth. Concentrations of 25 μg/ml of PM2.5 collected from three regions around Ulaanbaatar increased HepG2 and AGS cell migration.

Gastric cancer is the second leading cause of death worldwide. About half of the incidence of stomach cancer has been reported in East Asian countries. In Mongolia, gastric cancer is the second most common cancer in males and the third most common in females. The age-standardized mortality rate for gastric cancer was 29.3 per 100,000 in 2016, ranking second after liver cancer. Pepsinogen (PG) is a proenzyme of pepsin, by chief and mucous neck cells in the gastric mucosa. On the basis of the source of secretion, PGs are subdivided into 2 types: PG I and II. PG I is only secreted from the fundic glands in the corpus of the stomach, whereas PG II is secreted from the corpus, as well as the pyloric glands in the antrum and proximal duodenum. PG is excreted mainly into the stomach lumen, but approximately 1% diffuses into the blood stream. Atrophic gastritis and intestinal metaplasia are well-known risk factors for gastric neoplasms including dysplasia. To identify these premalignant gastric conditions, histological biopsy or image-enhanced endoscopy is performed. Gastric cancer is usually preceded by a decades-long precancerous process driven by Helicobacter pylori infection and environmental conditions with well-defined successive lesions. In the advanced stages, they are characterized by glandular atrophy and intestinal metaplasia. These changes involve loss of the original glands and result in decrease of the mass of chief cells of the gastric corpus, where PGI is produced. Loss of chief cells leads to lower PGI levels and PGI/PGII ratio in the peripheral blood. Serum PG levels are therefore a key tool to be used in screening programs. Serum PG measurements could provide a simple and noninvasive method for screening gastric neoplasms.

The double and triple test is a prenatal screening used to identify those pregnant women who shouldbe offered a diagnostic test to identify whether their fetus has an aneuploidy. It was first described in1988, but has largely been superseded by newer tests either conducted earlier in the first trimester(ie, the combined test, using ultrasound measurement of nuchal translucency, pregnancy-associatedplasma protein A, and human chorionic gonadotrophin [hCG]) or in the second trimester (ie, thetriple and quadruple test, using α-fetoprotein, hCG, uE3, and inhibin).These newer tests have been introduced because they offer greater detection and lower screenpositive results thereby enhancing diagnosis rates, while decreasing the risk of iatrogenic harmcaused by the invasive testing required when collecting suitable sample tissue. Both first andsecond trimester screening programs have been expanded to include risk assignment for trisomy18. Targeted screening algorithms have not been developed for chromosomal abnormalities otherthan Down syndrome and trisomy 18, although it has been suggested that a trisomy13 risk might becalculated. The construction of such algorithms would require recognition of a characteristic patternfor each condition using the appropriate combination of markers. It is likely, therefore, that the doubleand triple test will continue to be used in routine antenatal care for the foreseeable future.