• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.548-555
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• 2018

Objective: This experiment was conducted to investigate whether asparagine (Asn) could improve liver energy status in weaning pigs when challenged with lipopolysaccharide. Methods: Forty-eight weaned pigs ($Duroc{\times}Large\;White{\times}Landrace$, $8.12{\pm}0.56kg$) were assigned to four treatments: i) CTRL, piglets received a control diet and injected with sterile 0.9% NaCl solution; ii) lipopolysaccharide challenged control (LPSCC), piglets received the same control diet and injected with Escherichia coli LPS; iii) lipopolysaccharide (LPS)+0.5% Asn, piglets received a 0.5% Asn diet and injected with LPS; and iv) LPS+1.0% Asn, piglets received a 1.0% Asn diet and injected with LPS. All piglets were fed the experimental diets for 19 d. On d 20, the pigs were injected intraperitoneally with Escherichia coli LPS at $100{\mu}g/kg$ body weights or the same volume of 0.9% NaCl solution based on the assigned treatments. Then the pigs were slaughtered at 4 h and 24 h after LPS or saline injection, and the liver samples were collected. Results: At 24 h after LPS challenge, dietary supplementation with 0.5% Asn increased ATP concentration (quadratic, p<0.05), and had a tendency to increase adenylate energy charges and reduce AMP/ATP ratio (quadratic, p<0.1) in liver. In addition, Asn increased the liver mRNA expression of pyruvate kinase, pyruvate dehydrogenase, citrate synthase, and isocitrate dehydrogenase ${\beta}$ (linear, p<0.05; quadratic, p<0.05), and had a tendency to increase the mRNA expression of hexokinase 2 (linear, p<0.1). Moreover, Asn increased liver phosphorylated AMP-activated protein kinase (pAMPK)/total AMP-activated protein kinase (tAMPK) ratio (linear, p<0.05; quadratic, p<0.05). However, at 4 h after LPS challenge, Asn supplementation had no effect on these parameters. Conclusion: The present study indicated that Asn could improve the energy metabolism in injured liver at the late stage of LPS challenge.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.233-241
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• 2007

Purpose: We examined the effect of the dual EGFR/HER2 tyrosine kinase inhibitor, GW572016, on EGFR/HER2 receptor phosphorylation, inhibition of downstream signaling and radiosensitization in either an EGFR or HER2 overexpressing human breast cancer xenograft. Materials and Methods: We established SCID mice xenografts from 4 human breast cancer cell line that overexpressed EGFR or HER 2 (SUM 102, SUM 149, SUM 185, SUM 225). Two series of xenografts were established. One series was established for determining inhibition of the EGFR/HER2 receptor and downstream signaling activities by GW572016. The other series was established for determining the radiosensitization effect of GW572016. Inhibition of the receptor and downstream signaling proteins were measured by the use of immunoprecipitation and Western blotting. For determining the in vivo radiosensitization effect of GW572016, we compared tumor growth delay curves in the following four treatment arms: a) control; b) GW572016 alone; c) radiotherapy (RT) alone; d) GW572016 and RT. Results: GW572016 inhibited EGFR, HER2 receptor phosphorylation in SUM 149 and SUM 185 xenografts. In addition, the p44/42 MAPK (ERK 1/2) downstream signaling pathway was inactivated by GW572016 in the SUM 185 xenograft. In the SUM 225 xenograft, we could not observe inhibition of HER2 receptor phosphorylation by GW572016; both p44/42 MAPK (Erk1/2) and Akt downstream signal protein phosphorylation were inhibited by GW572016. GW572016 inhibited growth of the tumor xenograft of SUM 149 and SUM 185. The combination of GW572016 and RT enhanced growth inhibition greater than that with GW572016 alone or with RT alone in the SUM 149 xenograft. GW572016 appears to act as an in vivo radiosensitizer. Conclusion: GW572016 inhibited EGFR/HER2 receptor phosphorylation and downstream signaling pathway proteins. GW572016 modestly inhibited the growth of tumor in the SUM 185 xenograft and showed radiosensitization in the SUM 149 xenograft. Our results suggest that a better predictor of radiation response would be inhibition of a crucial signaling pathway than inhibition of a receptor.

• Korean Journal of Pharmacognosy
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• v.43 no.4
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• pp.328-337
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• 2012

In order to investigate anti-inflammatory, anti-allergic and anti-obesity activities of Samchulkunbi-tang (SCT; Shen zhu jian pi-tang) water and 70% ethanol (EtOH) extracts, in vitro inhibitory activities against nitric oxide (NO), prostaglandin $E_2$ $PGE_2$), interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ production in lipopolysaccharide-stimulated RAW 264.7 cells, and macrophage-derived chemokine (MDC/CCL22) and regulated on activation of normal T-cell-expressed and -secreted (RANTES/CCL5) production in TNF-${\alpha}$/interferon-${\gamma}$-stimulated HaCaT and BEAS-2B cells as well as glycerol-3-phosphate dehydrogenase (GPDH) activity and leptin production in 3T3-L1 cells were determined. A HPLC was used for quantification of the seven marker components (albiflorin, paeoniflorin, liquiritin, naringin, hesperidin, poncirin and glycyrrhizin) of SCT water and 70% EtOH extracts. SCT showed inhibitory effects against MDC and RANTES production in HaCaT cells, as well as RANTES production in BEAS-2B cells. In addition, SCT reduced not only NO, $PGE_2$, IL-6 and TNF-${\alpha}$ production in RAW 264.7 cells, but also GPDH activity and leptin production in 3T3-L1 cells. Furthermore, the biological activities and the contents of six compounds (except paeoniflorin) were higher in 70% EtOH extract than water extract. These results suggest that SCT has anti-inflammatory, anti-allergic and anti-obesity activities. These efficacies of 70% EtOH extract are relatively higher than that of water extract.

• The Journal of Korean Medical History
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• v.14 no.2
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• pp.109-152
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• 2001

Throughout this paper, I adjusted the study of 'Qian Yi'(錢乙)'s Medical Thought, and the following is the summary. 1. 'Qian Yi' wrote 'Xiao Er Yao Zheng Zhi Jue'("小兒藥證直訣", edited by 誾季忠), and there were 'Shang Han Lun Zhi Wei'("傷寒論指微"), 'Ying Ru Lun', however those are loss of the record. 2. Qian Yi's 'Zhi Jue'("直訣") was influenced by 'Lu Xin Jing', yet if we compare the quality of 'Sheng Li, Byeng Li, Bang Jae'(生理, 病理, 方劑), 'Lu Xin Jing' cannot be the foundation of 'Zhi Jue'. He took over 'Nei Jing, Shang Han Lun, Jin Gui Yao Lue, Shen Long Ben Cao Jing, Tai Ping Sheng Hui Fang'("內經", "傷寒論", "金?要略", "神膿本草經", "太平聖惠方") and put them together to the direct clinical experiences of pediatrics. 3. There is no reference regarding the difficulties of pediatric diagnosis and diseases in 'Huang Di Nei Jing'("黃帝內經") Before 'Bei Song'(北宋), regardless of the lack of data related to pediatric diseases, 'Qian Yi' established the pediatric system in 'Xiao Er Yao Zheng Zhi Jue' for the first time. 4. In his diagnosis of the pediatric diseases, he 'Si Zhen He Can'(四診合參), also considered in the eye exam seriously. In addition, he closely combined 'Wu Zang Bian Zheng'(五臟辨證), and diagnosis the pediatric diseases. 5. 'Wu Zang Bian Zheng', what Qian established method was based on 'Zheng Ti Guan'(整體觀) in 'Huang Di Nei Jing'. It was based on clinical experiences and established the perspectives of 'Tian Ren Xiang Ying'(天人相應). First of all, he pinpointed 'Zhu Zheng'(主證) clearly. Secondly, he pinpointed the relationships to symptoms and then, he distinguished a generic character of 'Xu, Shi, Han, Re'(虛, 實, 寒, 熱). Finally, he made an induction from genealogical pediatric physiology. 6. 'Qian Yi' took a serious view of 'Ban Zhen'(斑疹), the inadequate field in those days. At that time, he criticized on the habituation of the misuse of medication. He treated separately which 'Ji Jing'(急驚) as 'Liang Xie'(凉瀉) and 'Man Jing'(慢驚) as 'Wen Bu'(溫補). He proposed 'Cong Gan Zhu Feng, Xin Zhu Jing'(從肝主風, 心主驚) theory and formulated 'Jing Feng'(驚風) theory as well. 7. As an opponent of a tendency to misusage of medicine, 'Qian Yi' made out a prescription with pliant medicine. He emphasized on the treatment to 'Gong Bu Shang Zheng, Bu Bu Zhi Xie, Xiao Bu Jian Shi'(攻不傷正, 補不滯邪, 消補兼施) because he had so lucid demonstration to 'Xu Shi Han Re'(虛實寒熱) of the five viscera in the field of 'Bang Yak'(方藥). 8. There were no pediatrics schools at that time, however, the pediatrics was being made up gradually by 'Jin Yuan Si Da Jia'(金元四大家) who was influenced by 'Qian Yi'. He raised an objection to medical treatment using pliant medicine. 'Qian Yi' applied 'Qu Xia'(驅下) treatment using 'Han Liang'(寒凉) medicine. 'Han Liang Pai'(寒凉派) is greatly influenced by Qian. 'Chen Wen Zhong'(陳文中) had a great impact on 'Han Liang Pai' who used a 'Zao Shu Wen Bu'(燥熟溫補) medicine for treatment. Since 'Song Jin'(宋金), he had a tremendous influence on pediatrics treating patients in both 'Han Wen'(寒溫) ways. 9. 'Qian Yi' had an influence on his medical thoughts on future generations, especially to 'Wan Quan'(萬全) of 'Ming Dai', 'Wu Tang'(吳塘) of 'Qing Dai'(淸代) and 'Yun Shu Jie'(?樹珏) of 'Min Guo'(民國). 'Wan Quan' is an advocate of 'You Yu, Bu Zu Zhi Shuo'(有餘, 不足之說)of 'Xiao Er Wu Zang'(小兒五臟) that he revealed Qian's 'Wu Zang Bian Zheng'(五臟辨證). 'Wu Tang' disclosed Qian's 'Xiao Er Ti Zhi Shuo'(小兒體質說) and 'Xiao Er Ke'(小兒科)'s 'Yong Yao Lun'(用藥論), therefore, he uncovered pediatric physiological characteristics through the advocate of Qian's 'Zang Fu Rou Ruo, Ji Gu Nen Qie, Yi Xu Yi Shi, Yi Han Yi Re' (臟腑柔弱, 肌骨嫩怯, 易虛易實, 易寒易熱). 'Yun Shu Jie' developed intrinsic relationships among time, symptom and 'Tian Ren Xiang Ying Guan'(天人相應觀), What 'Qian Yi' stated about them. And also, he developed Qian's 'Di Huang Wan'(地黃丸), 'Xie Qing Wan'(瀉靑丸), 'Yi Huang San'(益黃散) clinical usages as well. 10. Regarding Qian's 'Wu Zang Xu Shi'(五臟虛實), it has an influence on 'Zhang Yuan Su'(張元素)'s 'Zang Fu Bing Ji Bian Zheng'(臟腑病機辨證). 'Di Huang Wan', 'Xie Qing Wan', 'Xie Xin Tang'(瀉心湯), 'Yi Huang San', 'Xie Huang San'(瀉黃散) are the standard prescription of 'Wu Zang Bu Xie'(五臟補瀉). It is under the influence of Qian's treatment. Besides, 'Qian Yi' took a serious view of 'Xiao Er'(小兒)'s 'Pi Wei'(脾胃). 'Qian Yi' had an impact on 'Li Dong Yuan'(李東垣) one of the member of 'Bu Tu Pai'(補土派). 'Di Huang Wan', which placed great importance on 'Bu Yi Shen Yin'(補益腎陰), had a great impact on 'Da Bu Yin Wan'(大補陰丸) and 'Jin Yuan Si Da Jia' as well. 11. In a theory of Qian's 'Wu Zang Bian Zheng', though it had been stated clearly in 'Wu Zang Bian Zheng', but he neglected in 'Liu Fu Bian Zheng'(六腑辨證). In prescription field, The problem with the medicine is that it is either toxic or mineral, therefore, we are not able to use those medicine in a clinical testing at the present time.

• Korean Journal of Ecology and Environment
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• v.48 no.4
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• pp.253-262
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• 2015

The sustainability of Cypripedium japonicum, a rare plant designated by the Korea Forest Service, is threatened due to artificial factors such as habitat loss and climate change etc. and internal factors such as changes in biological properties of the habitat etc. but conservation research has not been performed in South Korea. The objective of this study is to establish the species conservation strategies by analyzing the characteristics of their habitats, including: 1) Population characteristics, and 2) habitat analysis of the vegetation and abiotic environments. From April to September, 2014, population characteristics [density (stems $m^{-2}$), flowering rate (%), and leaf area ($cm^2$)] in Cypripedium japonicum habitats such as Chuncheon (CC), Hwacheon (HC), Muju (MJ), and Gwangyang (GY) and vegetation characteristics (plant sociological research and ordination analysis), and abiotic environments [temperature ($^{\circ}C$), relative humidity (%), transmitted light ($mol{\cdot}m^{-2}{\cdot}d^{-1}$) and canopy openness (%)] were measured. Cypripedium japonicum was mainly distributed at elevation 450 to 990 m and 5 to $30^{\circ}$ slope. Slope direction was shown as 0 to $110^{\circ}$. Habitats temperature (mean $18.94^{\circ}C$) was well matched to seasonal changes. Differences among sites showed greater level according to latitude difference. It showed the highest in habitat, GY located in the South. On the other hand, relative humidity (77.38%) didn't show much difference among sites. The average degree of canopy openness was 18.17%. It showed the highest at HC (22.1%) and the lowest at MJ (16.1%). The average degree of transmitted light was $9.1mol{\cdot}m^{-2}{\cdot}d^{-1}$. It showed the highest at CC ($10.6mol{\cdot}m^{-2}{\cdot}d^{-1}$) and the lowest at GY ($6.87mol{\cdot}m^{-2}{\cdot}d^{-1}$). Chlorophyll content showed average 26.12 SPAD. It showed the highest at MJ (30.64 SPAD value) and the lowest at HC (23.69 SPAD value). Leaf area was average $253.35cm^2$. It showed the highest at CC ($281.51cm^2$) and the lowest at HC ($238.23cm^2$).

• Journal of Korean Society of Transportation
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• v.24 no.2 s.88
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• pp.65-78
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• 2006

This paper investigates the cost structure ot the Korea and Japan railroad industry with respect to density, scale and scope economies as well as productivity growth rate using a generalized trans)og multiproduct cost function model. The paper then assumes that the Korea and Japan railway companies pi·educe three outputs (incumbent railway passenger-kilometers. Shinkansen passenger-kilometers, ton-kilometers of freight) using four input factors (labor, fuel, maintenance, rolling stock and capital). The specified cost function includes foul other independent variables: track lengths to reflect network effects, two dummies to reflect nation and ownership effects, and time trend as a proxy for technical change. The simultaneous equation system consisting of a cost function and three input share equations is estimated with the Zellner's iterative seemingly unrelated regression. The unbalanced panel data used in the paper, a total of 154 observations. are collected from the annual records of the Korea National Railroad (KNR) for the yews $1977{\sim}2003$, Japan National Railways (JNR) for the years $1977{\sim}1984$. seven Japan Railways (JR's) for the years $1987{\sim}2003$. The findings show that the Korean and Japanese railways exhibit product-specific and overall economies of density but product-specific diseconomies of scale with respect to incumbent railway passenger-kilometers, Shinkansen-kilometers and ton-kilometers. However, the railways experience mild overall economies of scale which result from economies of scope associated with the joint production of incumbent railway/Shinkansen and feight, freight/incumbent railway and Shinkansen except Shinkansen/incumbent railway and freight. In addition, the economies of density and scale in the KNR, JR east, JR central, and JR west companies at the point of the years $1990{\sim}2003$ average is generally analogous to the above results at the point of sample average. There also appear to be economies of ssope associated with the joint Production of the incumbent railway and Shinkansen in JR central but diseconomies of scope in JR East and JR West. The findings also indicate that the productivity growth rate of the privately-owned JR's is larger than that of the government-owned KNR.

• Toxicological Research
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• v.33 no.2
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• pp.107-118
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• 2017

Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

• Neonatal Medicine
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• v.16 no.2
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• pp.213-220
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• 2009

Purpose: Hearing loss is one of the common birth defects in humans, with a reported prevalence of 1-3 per 1000 newborns. We investigated the incidence of hearing loss and evaluated the use of neonatal hearing screening test in neonatal intensive care unit (NICU) graduates who are at greater risk for hearing loss than normal newborns. Methods: The neonates admitted to the NICU of Asan Medical Center from 1 March, 2003 to 30 March, 2008 who were available for follow-up were included. Those who failed the first auditory brainstem response prior to discharge were retested with the stapedial reflex test, auditory brainstem response and tympanometry in the Otolaryngology department. Results: Of 2,137 neonates, 2,000 (93.5%) neonates were tested prior to discharge. Sixty-seven neonates (3.4%) failed the first newborn hearing screening test. Of 67 infants, 52 infants were retested for a second hearing test. Excluding 10 infants (19.2%) who were lost during follow-up, 16 infants were confirmed to have hearing impairment of which 12 and 4 infants had unilateral and bilateral hearing loss, respectively. Of 16 infants, 5 did not meet the criteria set by the Korean National Health Insurance Corporation. Conclusion: The prevalence of hearing impairment in NICU graduates is about 0.8%, excluding those who were lost for follow up, necessitating a systemic and effective hearing assessment program among these high risk infants and more generous national insurance coverage.

• Neonatal Medicine
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• v.16 no.2
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• pp.154-162
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• 2009

Purpose: Death is an important problem for physicians and parents in neonatal intensive care unit. This study was intended to evaluate the mortality rate, causes of death, and the change of mortality rate by year for infants admitted to the neonatal intensive care unit. Methods: We retrospectively surveyed the medical records of the infants who were admitted to the neonatal intensive care unit at Asan Medical Center and who died before discharge between 1998 and 2007. Gestational age, birth weight, gender, time to death and the underlying diseases related to the causes of infant deaths and obtained from the medical records and analyzed according to year. Results: A total of 6,289 infants were admitted and 264 infants died during the study period. The overall mortality rate was 4.2%. For very low and extremely low birth weight infants, the mortality rate was 10.6% and 21.4%, respectively. There was no significant change in the mortality rate during the study period. Prematurity related complications and congenital anomalies were the conditions most frequently associated with death in the neonatal intensive care unit. of the infant deaths 37.1% occurred within the first week of life. Conclusion: Even though a remarkable improvement in neonatal intensive care has been achieved in recent years, the overall mortality rate has not changed. To reduce the mortality rate, it is important to control sepsis and prevent premature births. The first postnatal week is a critical period for deaths in the neonatal intensive care unit.