Objective To review the implications for diagnosis,pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia (CNL).Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1993 to 2013 and highly regarded older publications were also included.The terms "chronic neutrophilic leukemia" and "diagnosis" were used for the literature search.Study selection We identified,retrieved and reviewed the information on the clinical and laboratory features,the new genetic findings,prognosis and disease evolution and management of CNL.Results The discovery of high-frequency granulocyte-colony stimulating factor receptor (CSF3R) mutations in CNL identifies a new major diagnostic criterion,and lends more specificity to the World Health Organization (WHO) diagnostic criteria for CNL,which are variably applied in routine clinical practice.Conclusions In patients for whom the cause of neutrophilia is not easily discerned,the incorporation of CSF3R mutation testing can be a useful point-of-care diagnostic to evaluate the presence of a clonal myeloid disorder,as well as providing the potential for genetically informed therapy.The oncogenic CSF3R mutations are molecular markers of sensitivity to inhibitors of the SRC family-TNK2 and JAK kinases and may provide a new avenue for therapy.

Background:Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN), since the first description of CNL in 1920, more than 150 cases have reported in the literature. The World Health Organization (WHO) recognizes CNL, as a MPN and, for the frst time, provides recognized criteria to permit the operational classifcation of this poorly defned disease. Until recently, the molecular pathogenesis of CNL was unknown and the diagnosis was based on morphological aspects, clinical criteria and exclusion of known genetic entities like the Philadelphia translocation indicative of CML, or JAK2 mutations indicative of MPNs. Recent discovery of highfrequency granulocyte-colony stimulating factor receptor (CSF3R) mutations in CNL identifes a new major diagnostic criterion, and lend more specificity to the WHO diagnostic criteria for CNL, which are variably applied in routine clinical practice. In 2013 Maxson et al., and Pardanani and colleagues identified granulocyte-colony stimulating factor 3 receptor (CSF3R) mutations in 8 of 9 (89%), and in 13 of 13 (100%) patients with CNL, respectively. CSF3R mutations fall into 2 classes: nonsense or frameshift mutations that lead to premature truncation of the cytoplasmic tail of the receptor (truncation mutations) and point mutations in the extracellular domain of CSF3R (membrane proximal mutations). These nonsense or frameshift mutations truncate the cytoplasmic tail of CSF3R, impair its internalization,and alter its interactions with proteins such as SHP-1/2 and SOCS family members. These structural and functional alterations are thought to perturb the capacity of CSF3R to regulate granulocyte differentiation and to increase granulocytic proliferative capacity. Thetwo types of CSF3R mutations may have differential susceptibility to classes of tyrosine kinase inhibitors,with CSF3R truncation mutations showing activation of SRC family–TNK2 kinase signaling and sensitivity to dasatinib, and CSF3Rmembrane proximal mutations strongly activate the JAK/signal transducer and activator of transcription pathway and are sensitive to JAK kinase inhibitors such as ruxolitinib.The most common CSF3R mutation in CNL is themembrane proximal mutation: T618I. On September 2012 we got a case (a 67-years-old Chinese man), which had fulflled the WHO diagnostic criteria for CNL with a novel mutation site of colony stimulation factor 3 receptor (CSF3R). In our case was identifed a membrane proximal mutations CSF3RT618I and also a unreported novel mutation site of CSF3R-H54A in the CD34+ and CD15+ cell fractionsby sorting bone marrow samples (BD FACSAria™ III; BD Biosciences) using a PCR-based DNA pyrosequencing method. Thus, we sought to determine CSF3R-FL, CSF3R-T618I, CSF3R-H54A mutations have some correlation with molecular pathogenesis of CNL.Objective:To determine CSF3R-FL, CSF3R-T618I, CSF3RH54A mutations that have some signifcance on the molecular pathogenesis of CNL.Materials/Methods:1. Plasmid construction. Plasmids were constructed by PCR amplifcation of the insert, restriction digestion and ligation using standard molecular biology methods, briefly: the host vectors pLV-EF1α-EYFP-N, pLP-2, pVSV-G, pLP-1 gag pol were purifed with Omegabiotek maxi prep kit and digested by restriction enzymes (ECO RI, NOTI). The linearized vectors were purified from agarose gel using a AxyPrep TM DNA Gel Extraction Kit and the concentration of the samples was estimated on an agarose gel stained with ethidium bromide.The inserts (CSF3R-FL, CSF3R-T618I, CSF3R- H54A) were generated by PCR, the sequences of the primer-pairs used and the conditions of the PCR reactions. The amplifed DNA fragments were purifed from agarose gels using AxyPrep TM DNA Gel Extraction kits and digested by ECO RI, NOTI was used to linearize the acceptor vector. Enzymatic reactions in the case of the i) insert: 100–3000 ng purifed PCR product was digested by appropriate amount of enzyme and 4 µl of 10x reaction buffer in 40 µl of fnal volume for overnight at the appropriate temperature; ii) vector: 2000–4000 ng plasmid DNA was digested by appropriate amount of enzyme and 2 µl of 10x reaction buffer in 20 µl of fnal volume for 4 hours at the appropriate temperature. When necessary Research on the Influence of new oncogenic CSF3R mutations in Chronic Neutrophilic Leukemia Otgonbat Altangerel1, Ming Feng Zhao2, Wu Ri Mao21Department of Internal Medicine, Division of Hematology, Mongolian National University of Medical Sciences, Mongolia 2Department of Hematology, Tianjin First Central Hospital, First Central Clinical College of Tianjin Medical University,P.R. China11 the digested fragments were purifed again and the concentrations of the inserts were estimated on agarose gels, as described above. A 1:3 vector: insert molar ratio was used for the ligation reactions. Chemically competent DH5α Escherichia coli bacteria were transformed with the products of the ligation reactions and were grown on Luria Bertrani (LB) agar plates containing the required antibiotic, such as ampicillin (Sigma). A day later single colonies were picked from the plate, inoculated into and grown overnight in LB medium containing with ampicillin. Plasmids were purifed from the overnight cultures as above and tested by restriction mapping for the presence of the insert. Selected clones were sequenced by Sanger sequencing.2. Lentiviral packaging system we used 3 main components, such as the lentiviral expression vector(Plasmid DNA of CSF3R-FL, CSF3R-T618I), the lentiviral packaging plasmids (pLP-1, pLP-2 plasmids that encode for gag, pol, and rev from the HIV or FIV genome and pVSV-G), 293TNN producer cells. We seed 1X105 293TNN cells per 10 cm2 culture plate in 2-3 ml of culture medium containing DMEM medium supplemented with 4 mM L-glutamine, 4.5 g/l glucose, and fetal bovine serum (10%) without antibiotics. Grow for 18-24 hours at 37 °C with 5% CO 2 so that the cell density reaches ~60 - 80% confluency at the time of transfection. We used a GFP as a positive control, to confrm transfection experiment was successful. Then we collected the cell culture supernatant, which is containing infectious pseudoviral particles.3. Transduction of Pseudotyped Viral Particles into the primary cell of mouse. In the fnal step we have used the Mouse Colony Forming Unit Assay using MethoCultTM to assess the effects of CNL-associated oncogenes on the morphology and number of primary murine cells derived bone marrow. For this purpose cells are transduced with either control, which is without viral construct or a construct expressing the oncogene of interest (CSF3R-FL, CSF3R-T618I).Results:1. On the Plasmid construction step we successfully extracted and purifcated of recombinant plasmids ofCSF3R-FL and CSF3R-T618I cloning, but we still didexperiment to obtain the recombinant plasmid CSF3R- H54A cloning.2. After 24 hours of transfection 293TNN Cells with Packaging Plasmids and the Expression Construct, cells we visualized with green fluorescence protein under the fluorescence microscope.3. The both two of CSF3Rcloning were capable of transforming murine colony forming cells. After transforming, CFU-GM colonies were counted manually by light microscopy seven days after plating. We found that the membrane proximal mutation (T618I) transformed CFU-GM colonies number was more than the full length non-mutants (CSF3RFL), which indicates that T618 mutation of CSF3R conferred the clonal advantage of CNL leukemia cells.Conclusions:1. The establishment of the plasmid reconstruction, lentiviral packaging system and Mouse Colony Forming Unit Assay were done successfully.2. We confrmed the transformation capacity of the CSF3R mutations, especially CSF3R-T618I was higher than CSF3R-FL. This result demonstrates that T618 mutation of CSF3R conferred the clonal advantage of CNL leukemia cells.3. Further studies will be continued and are needed to prove the effects of the novel mutation site CSF3RH54A on the transduced murine bone marrow progenitor cells by using CFC assay

Background: One of the main goals of pharmaceutical care is the developing proper drug use and high lighted “The Government of Mongolia is aiming to provide health organizations and veterinary clinic by highly effective, safe, quality assured and selectable drugs with continuous, uniform and accessible”.
World Health Organization (WHO) recommended that there are 5 standard to assess pharmaceutical care services. In Mongolia, people unused drugs with prescription and doctor direction. Background of this survey is to define appropriate use of drug in Ulaanbaatar citizen according to the WHO criteria and to determine the necessary parameters for the proper use of drugs in the future. Discussion: The survey was based on the WHO recommendation and selection of pharmacies nearby the hospitals which we selected each 50 and 50 citizen’s prescription from total 12 hospital of Ulaanbaatar city, a total of 600 recipes and questionnaire on specific drug information and knowledge of clients. Result: Average counseling was 1.02 minutes, duration of dispense was 35.3 seconds, 85% of drug % from written on prescription and 61.6% of customers knowledge about drug. Conclusion
1. It doesn’t meet the requirements of pharmaceutical assistance because of the citizen’s drug knowledge is insufficient and pharmacist’s counseling time is not enough.
2. Customer’s knowledge about drug name, dose, and method of usage is 62% and it is insufficient.

Background: Reference values for a complete blood count (CBC) can vary due to multiple factors, including geographical location, environmental influences, nutrition, genetic characteristics, lifestyle, and the physical-chemical properties of the blood. Mongolia’s high-altitude geography (an average of 1,580 meters above sea level) reduces oxygen supply and activates hematopoiesis through the body’s physiological adaptation mechanisms. As a result, the number of red blood cells, hemoglobin, and hematocrit levels tend to increase, as studied by researchers Ch. Sharav and A. Ulziikhutag. Considering the unique geographical regions of Mongolia (urban, rural, steppe, desert, and high mountain areas), studying the physiological blood parameters of the population and identifying regional differences are crucial for improving diagnostic accuracy and the reliability of clinical assessments, which form the basis for conducting this study. Aim: Select a healthy group from the population that participated in the ‘National Preventive Screening and Early Diagnosis Program’ for preventing and early detecting infectious and non-infectious diseases based on age, gender, and health risks. Establish reference values for comprehensive blood test indicators by geographical location. Materials and Methods: In Mongolia, from 2022 to May 2023, a comprehensive blood analysis was conducted on 7,301 individuals aged 18 and above who participated in the ‘National Preventive Screening and Early Diagnosis Program’ aimed at preventing and early detecting infectious and non-infectious diseases based on age, gender, and health risks. The analysis included red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count (WBC), and platelet count (PLT) in relation to their geographical location. The study results were calculated using IBM SPSS (20) software. Statistical significance was considered at p<0.05. Results: In our study, 7,301 people aged 18-87 participated, of whom 36.4% (2,644) were male and 63.6% (4,657) were female. The average age was 30.2±0.2 years for men and 35.1±0.1 years for women. Among them, there were 1,764 males and 1,774 females aged 18-30, 603 males and 2,069 females aged 31-45, 199 males and 670 females aged 46-60, and 78 males and 144 females over 61 years old. A total of 26.6% (1,944) of the study participants were from Ulaanbaatar, 12.75% (931) from the western region, 10.12% (739) from the eastern region, 33.18% (2,423) from the Khangai region, and 17.31% (1,264) from the central region. In the Ulaanbaatar region, HGB, HCT, MCV, MCH, and WBC increased with age, while PLT showed a tendency to decrease. Differences in HGB, HCT, MCV, MCH, MCHC, WBC, and PLT indicators were observed between the western, eastern, Khangai, and central regions depending on the area (p<0.05). Conclusion Statistically significant differences in blood parameters were observed across different regions of Mongolia, indicating the necessity of establishing reference values for blood tests that reflect the influences of geographical location, lifestyle, and environmental factors (p<0.05).

Background: A Complete Blood Count (CBC) is essential for early disease detection, diagnosis, treatment, monitoring therapeutic progress, and evaluating a patient’s overall health status. Therefore, establishing reference values for blood tests tailored to the demographic characteristics of a specific population plays a crucial role in improving diagnostic accuracy and treatment outcomes. In our country, there is a lack of studies determining reference values for blood test parameters based on age, gender, body weight, and quality of life, which serves as the basis for conducting this research. Aim: To select a healthy population from those participating in the ‘preventive screening, early detection, and diagnosis of infectious and non-communicable diseases based on age, sex, and health risk factors,’ and to establish the reference range for red blood cells and their additional parameters in relation to body mass index, gender, and age groups. Materials and Methods: A total of 7,301 individuals aged 18 and above who participated in the ‘preventive screening, early detection, and diagnosis of infectious and non-communicable diseases based on age, sex, and health risk factors’ conducted from 2022 to May 2023 in Mongolia were included in the study. The study involved complete blood count (CBC) analysis, including red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). The data were analyzed in relation to age and sex. The statistical analysis was performed using IBM SPSS (version 20), and results with P<0.05 were considered statistically significant. Results: Our study included 7,301 individuals aged 18 to 87, of whom 36.3% (2,644) were male and 63.7% (4,657) were female. The average age was 30.23±0.22 years for males and 35.11±0.15 years for females. Specifically, there were 1,764 males and 1,774 females in the 18-30 age group, 603 males and 2,069 females in the 31-45 age group, 199 males and 670 females in the 46-60 age group, and 78 males and 144 females in the >61 age group. In the 18-30 age group, RBC, HGB, MCV, MCHC, and HCT levels showed statistically significant differences between males and females. In the 31-45 age group, RBC, HGB, MCH, MCHC, and HCT levels also showed statistically significant differences. In the 46-60 age group, RBC, HGB, and HCT showed statistically significant differences, while in the >61 age group, only RBC levels showed statistically significant differences between males and females. When analyzing red blood cells and their associated parameters in relation to BMI, no statistically significant differences were observed between the groups (p>0.05). Conclusion By including the general population in early screening programs, it has become possible to establish reference values for red blood cells and their additional parameters specific to the Mongolian people. Future studies should focus on examining these parameters in relation to geographical location, genetic characteristics, and environmental influences.

OBJECTIVETo review the implications for diagnosis, pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia (CNL).

DATA SOURCESData cited in this review were obtained mainly from PubMed and Medline from 1993 to 2013 and highly regarded older publications were also included. The terms "chronic neutrophilic leukemia" and "diagnosis" were used for the literature search.

STUDY SELECTIONWe identified, retrieved and reviewed the information on the clinical and laboratory features, the new genetic findings, prognosis and disease evolution and management of CNL.

RESULTSThe discovery of high-frequency granulocyte-colony stimulating factor receptor (CSF3R) mutations in CNL identifies a new major diagnostic criterion, and lends more specificity to the World Health Organization (WHO) diagnostic criteria for CNL, which are variably applied in routine clinical practice.

CONCLUSIONSIn patients for whom the cause of neutrophilia is not easily discerned, the incorporation of CSF3R mutation testing can be a useful point-of-care diagnostic to evaluate the presence of a clonal myeloid disorder, as well as providing the potential for genetically informed therapy. The oncogenic CSF3R mutations are molecular markers of sensitivity to inhibitors of the SRC family-TNK2 and JAK kinases and may provide a new avenue for therapy.

Carrier Proteins ; genetics ; Female ; Humans ; Leukemia, Neutrophilic, Chronic ; diagnosis ; genetics ; Male ; Mutation ; Nuclear Proteins ; genetics ; Receptors, Colony-Stimulating Factor ; genetics

: BACKGROUND: The Mongolian National drug policy states, “The rational drug rehabilitation is one of the main goals of pharmaceutical care”. Recruitment and prescription medications are important issues for improving rational use of medicines. According to the recommendations of the World Health Organization (WHO), the status of rational use of medicines is assessed through the recipe by 10 criteria. The needs to study on rational drug use in hospitals of Ulaanbaatar and determining standard criteria for the proper use of drugs by recommendation of World Health Organization is the main justified issue of the study. METHODS: In order to study the rational use of medicines, a single moment /descriptive/ research type was used. Recipes for 50 and 50 people who received prescription from pharmacy within 12 hospitals TFCHM, TSCHM, TTCHM, NCCD, NTaORC, NCMH, HCSKhD, HCChD, HCSBD, HCKhUD, HCBZD, HCBGD June 2017 in Ulaanbaatar, it was based on the WHO recommended methodology, a total of 600 clients, 600 recipes and 1249 medicines were selected and submitted to the conclusions. RESULTS: The average number of medicines per minute was 2.08 ± 0.25, 45.2% in International Health Prescription were 42.6% antibiotics. According to a study on a contingency test, 85% did not have prescription signs, 38.8% without diagnostic prescription, 25% did not have physicians, and 48% did not have any medical information. The knowledge about the dose was 68.5% . CONCLUSION The results of the study were compared with the recommendations of the World Health Organization and the proportion of medicines included in the ICS list was lower than the recommendations of the World Health Organization list and the proportion of antibiotic drugs. The study found that 11 different incidents were encountered. Knowledge about medicines dose was 68.5%, compared to World Health Organization recommendations

Background: Complete blood count (CBC) is one of the most widely used clinical tests, offering a high-quality, inexpensive, and routine diagnostic tool for various diseases and for monitoring treatment outcomes. Due to modern technological advancements, blood cells are now measured in greater detail, with 36 parameters being evaluated. The prevalence of diabetes mellitus (DM) is rapidly increasing, not only globally but also in our country. This rise in prevalence leads to numerous adverse consequences, including delayed diagnosis, poor control, an increase in chronic complications, and treatment failure. Hyperglycemia is a predisposing factor for chronic inflammation, and a relatively new inflammatory marker, the neutrophil-to-lymphocyte ratio (NLR), may be useful for assessing diabetes control. In recent years, NLR has been studied as a composite biomarker that more effectively reflects systemic inflammation and is easier to detect compared to other inflammatory markers. An increase in neutrophil count and percentage indicates chronic, low-grade, toxic, and non-specific inflammation, while a decrease in lymphocyte count suggests insufficient immune regulation. Thus, an elevated NLR not only reflects the immune system’s functional state in chronic inflammation, but it is also studied as a reliable and selective marker of systemic inflammation in chronic diseases. NLR is considered more stable than the total leukocyte count, is less affected by physiological and pathological factors, is inexpensive, and can be incorporated into daily clinical practice. Aim: To study the relationship between the neutrophil-to-lymphocyte ratio in a complete blood count and diabetes control and complications Materials and Methods: A cross-sectional study was conducted involving 145 patients with type 2 diabetes mellitus, who were treated at the Endocrine Clinic of the Mongolian-Japanese Hospital, Mongolian National University of Medical Sciences. Data on the neutrophil-to-lymphocyte ratio (NLR), glycated hemoglobin (HbA1c), and diabetic complications, including retinopathy, neuropathy, and foot complications, were collected from the Carte-Hospital Management System. Based on the frequency distribution of the NLR parameter, the values were classified into three groups: low, medium, and high. These groups were subsequently compared with glycemic control and complications using correlation and linear regression analyses, with statistical significance set at p<0.05. Results: The mean age of the study participants (n=145) was 57.3±12.9 years, with 46.8% (n=131) being male. The mean duration of diabetes was 9.6 years (range: 1-31 years), and the mean HbA1c level was 8.6±2.47%. Among the participants, 59.3% (n=86) exhibited poor glycemic control. Regarding complications, 52.3% of participants experienced at least one diabetes-related complication. Of these, 25.2% had one complication, 13.3% had two, and 7.1% had three or more. The most common complications were retinopathy (25.7%), nephropathy (18.6%), and macrovascular complications (11.9%). A statistically significant increase in the mean HbA1c level was observed across groups stratified by NLR levels (p=0.003). Linear correlation analysis revealed a statistically significant positive correlation between HbA1c levels (r=0.194, p=0.001) and the number of chronic diabetes complications (r=0.162, p=0.002). Conclusion The NLR level is positively correlated with both diabetes control and the occurrence of chronic complications. As an inexpensive and easily accessible test, it can be used for daily monitoring and early detection of complications.