1.Association of Age, Sex and Education With Access to the Intravenous Thrombolysis for Acute Ischemic Stroke
Yoona KO ; Beom Joon KIM ; Youngran KIM ; Jong-Moo PARK ; Kyusik KANG ; Jae Guk KIM ; Jae-Kwan CHA ; Tai Hwan PARK ; Kyungbok LEE ; Jun LEE ; Keun-Sik HONG ; Byung-Chul LEE ; Kyung-Ho YU ; Dong-Eog KIM ; Joon-Tae KIM ; Jay Chol CHOI ; Jee Hyun KWON ; Wook-Joo KIM ; Kyu Sun YUM ; Sung-Il SOHN ; Hyungjong PARK ; Sang-Hwa LEE ; Kwang-Yeol PARK ; Chi Kyung KIM ; Sung Hyuk HEO ; Moon-Ku HAN ; Anjail Z. SHARRIEF ; Sunil A. SHETH ; Hee-Joon BAE ;
Journal of Korean Medical Science 2025;40(13):e49-
		                        		
		                        			 Background:
		                        			Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. 
		                        		
		                        			Methods:
		                        			We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. 
		                        		
		                        			Results:
		                        			Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). 
		                        		
		                        			Conclusion
		                        			Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization. 
		                        		
		                        		
		                        		
		                        	
2.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
		                        		
		                        			 Background:
		                        			and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. 
		                        		
		                        			Methods:
		                        			We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. 
		                        		
		                        			Results:
		                        			Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. 
		                        		
		                        			Conclusion
		                        			Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke. 
		                        		
		                        		
		                        		
		                        	
3.Performance of Noninvasive Indices for Discrimination of Metabolic Dysfunction-Associated Steatotic Liver Disease in Young Adults
Jaejun LEE ; Chang In HAN ; Dong Yeup LEE ; Pil Soo SUNG ; Si Hyun BAE ; Hyun YANG
Gut and Liver 2025;19(1):116-125
		                        		
		                        			 Background/Aims:
		                        			Although numerous noninvasive steatosis indices have been developed to assess hepatic steatosis, whether they can be applied to young adults in the evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain. 
		                        		
		                        			Methods:
		                        			Data from patients under 35 years of age who visited the Liver Health Clinic at the Armed Forces Goyang Hospital between July 2022 and January 2024 were retrospectively collected. Steatosis was diagnosed on the basis of a controlled attenuation parameter score ≥250dB/m. MASLD was defined as the presence of steatosis in patients with at least one cardiometabolic risk factor. 
		                        		
		                        			Results:
		                        			Among the 1,382 study participants, 901 were diagnosed with MASLD. All eight indices for diagnosing steatosis differed significantly between the MASLD and non-MASLD groups (p<0.001). Regarding the predictive performance, the hepatic steatosis index (HSI), fatty liver index (FLI), Framingham steatosis index, Dallas steatosis index, Zhejiang University index, lipid accumulation product, visceral adiposity index, and triglyceride glucose-body mass index exhibited an area under the curve of 0.898, 0.907, 0.899, 0.893, 0.915, 0.869, 0.791, and 0.898, respectively. The cutoff values for the FLI and HSI were re-examined, indicating a need for alternative cutoff values for the HSI, with a rule-in value of 42 and a rule-out value of 36 in this population. 
		                        		
		                        			Conclusions
		                        			This study presents novel findings regarding the predictive performance of established steatosis markers in young adults. Alternative cutoff values for the HSI in this population have been proposed and warrant further validation. 
		                        		
		                        		
		                        		
		                        	
4.Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice
Seung Sik YOO ; Yuri KIM ; Dong Won LEE ; Hyeon Joo HAM ; Jung Ho PARK ; In Jun YEO ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2025;33(3):417-428
		                        		
		                        			
		                        			 To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation. 
		                        		
		                        		
		                        		
		                        	
5.Association of Age, Sex and Education With Access to the Intravenous Thrombolysis for Acute Ischemic Stroke
Yoona KO ; Beom Joon KIM ; Youngran KIM ; Jong-Moo PARK ; Kyusik KANG ; Jae Guk KIM ; Jae-Kwan CHA ; Tai Hwan PARK ; Kyungbok LEE ; Jun LEE ; Keun-Sik HONG ; Byung-Chul LEE ; Kyung-Ho YU ; Dong-Eog KIM ; Joon-Tae KIM ; Jay Chol CHOI ; Jee Hyun KWON ; Wook-Joo KIM ; Kyu Sun YUM ; Sung-Il SOHN ; Hyungjong PARK ; Sang-Hwa LEE ; Kwang-Yeol PARK ; Chi Kyung KIM ; Sung Hyuk HEO ; Moon-Ku HAN ; Anjail Z. SHARRIEF ; Sunil A. SHETH ; Hee-Joon BAE ;
Journal of Korean Medical Science 2025;40(13):e49-
		                        		
		                        			 Background:
		                        			Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. 
		                        		
		                        			Methods:
		                        			We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. 
		                        		
		                        			Results:
		                        			Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). 
		                        		
		                        			Conclusion
		                        			Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization. 
		                        		
		                        		
		                        		
		                        	
6.Impact of RNF213 Polymorphism in Isolated Intracranial Arterial Steno-Occlusive Disease
Dong Young JEONG ; Bum Joon KIM ; Jae Han BAE ; Chulhong KIM ; Sun U KWON
Journal of Clinical Neurology 2025;21(3):173-181
		                        		
		                        			 Background:
		                        			and Purpose To determine whether the RNF213 p.R4810K mutation modifies the number of moyamoya disease manifestations and recurrent strokes in isolated intracranial arterial steno-occlusive disease (ICAD). 
		                        		
		                        			Methods:
		                        			This retrospective case–control study analyzed patients who visited the Asan Medical Center with steno-occlusive lesions in the M1 segment of the middle cerebral artery and terminal internal carotid artery, and underwent RNF213 genetic testing for screening moyamoya disease between January 2010 and November 2022. Patients with supportive findings of moyamoya disease or moderate-to-severe stenosis in the extracranial arteries were excluded.After matching antiplatelet drugs, the presentation of moyamoya disease and stroke recurrence were analyzed using chi-squared analysis and Kaplan–Meier survival curve analysis. 
		                        		
		                        			Results:
		                        			The 1,567 patients who underwent evaluations of RNF213 polymorphisms included 753 with ICAD, among whom females predominated (n=452, 60.0%) and 289 (38.4%) had an RNF213 mutation. The follow-up period was 2.47±3.51 years (mean±standard deviation; median=1.00 year, interquartile range=0–4 years). The risk of progression to moyamoya disease was higher in the RNF213-related-vasculopathy group than the RNF213-negative stenosis group (n=27 [9.3%] versus n=6 [1.3%], p<0.01), as were the risks of ischemic stroke (n=13 [4.5%] versus n=7 [1.5%], p=0.01) and hemorrhagic stroke (n=5 [1.7%] versus n=1 [0.2%], p=0.02, respectively). Furthermore, the presence of an RNF213 mutation was significantly associated with the risk of stroke recurrence (odds ratio=2.34, 95% confidence interval=1.44–3.80, p< 0.01). 
		                        		
		                        			Conclusions
		                        			Evaluations of RNF213 polymorphisms may help to identify patients with isolated ICAD at a high risk of progression to moyamoya disease and stroke. 
		                        		
		                        		
		                        		
		                        	
7.Erratum: Korean Gastric Cancer Association-Led Nationwide Survey on Surgically Treated Gastric Cancers in 2023
Dong Jin KIM ; Jeong Ho SONG ; Ji-Hyeon PARK ; Sojung KIM ; Sin Hye PARK ; Cheol Min SHIN ; Yoonjin KWAK ; Kyunghye BANG ; Chung-sik GONG ; Sung Eun OH ; Yoo Min KIM ; Young Suk PARK ; Jeesun KIM ; Ji Eun JUNG ; Mi Ran JUNG ; Bang Wool EOM ; Ki Bum PARK ; Jae Hun CHUNG ; Sang-Il LEE ; Young-Gil SON ; Dae Hoon KIM ; Sang Hyuk SEO ; Sejin LEE ; Won Jun SEO ; Dong Jin PARK ; Yoonhong KIM ; Jin-Jo KIM ; Ki Bum PARK ; In CHO ; Hye Seong AHN ; Sung Jin OH ; Ju-Hee LEE ; Hayemin LEE ; Seong Chan GONG ; Changin CHOI ; Ji-Ho PARK ; Eun Young KIM ; Chang Min LEE ; Jong Hyuk YUN ; Seung Jong OH ; Eunju LEE ; Seong-A JEONG ; Jung-Min BAE ; Jae-Seok MIN ; Hyun-dong CHAE ; Sung Gon KIM ; Daegeun PARK ; Dong Baek KANG ; Hogoon KIM ; Seung Soo LEE ; Sung Il CHOI ; Seong Ho HWANG ; Su-Mi KIM ; Moon Soo LEE ; Sang Hyun KIM ; Sang-Ho JEONG ; Yusung YANG ; Yonghae BAIK ; Sang Soo EOM ; Inho JEONG ; Yoon Ju JUNG ; Jong-Min PARK ; Jin Won LEE ; Jungjai PARK ; Ki Han KIM ; Kyung-Goo LEE ; Jeongyeon LEE ; Seongil OH ; Ji Hun PARK ; Jong Won KIM ;
Journal of Gastric Cancer 2025;25(2):400-402
		                        		
		                        		
		                        		
		                        	
8.Korean Gastric Cancer AssociationLed Nationwide Survey on Surgically Treated Gastric Cancers in 2023
Dong Jin KIM ; Jeong Ho SONG ; Ji-Hyeon PARK ; Sojung KIM ; Sin Hye PARK ; Cheol Min SHIN ; Yoonjin KWAK ; Kyunghye BANG ; Chung-sik GONG ; Sung Eun OH ; Yoo Min KIM ; Young Suk PARK ; Jeesun KIM ; Ji Eun JUNG ; Mi Ran JUNG ; Bang Wool EOM ; Ki Bum PARK ; Jae Hun CHUNG ; Sang-Il LEE ; Young-Gil SON ; Dae Hoon KIM ; Sang Hyuk SEO ; Sejin LEE ; Won Jun SEO ; Dong Jin PARK ; Yoonhong KIM ; Jin-Jo KIM ; Ki Bum PARK ; In CHO ; Hye Seong AHN ; Sung Jin OH ; Ju-Hee LEE ; Hayemin LEE ; Seong Chan GONG ; Changin CHOI ; Ji-Ho PARK ; Eun Young KIM ; Chang Min LEE ; Jong Hyuk YUN ; Seung Jong OH ; Eunju LEE ; Seong-A JEONG ; Jung-Min BAE ; Jae-Seok MIN ; Hyun-dong CHAE ; Sung Gon KIM ; Daegeun PARK ; Dong Baek KANG ; Hogoon KIM ; Seung Soo LEE ; Sung Il CHOI ; Seong Ho HWANG ; Su-Mi KIM ; Moon Soo LEE ; Sang Hyun KIM ; Sang-Ho JEONG ; Yusung YANG ; Yonghae BAIK ; Sang Soo EOM ; Inho JEONG ; Yoon Ju JUNG ; Jong-Min PARK ; Jin Won LEE ; Jungjai PARK ; Ki Han KIM ; Kyung-Goo LEE ; Jeongyeon LEE ; Seongil OH ; Ji Hun PARK ; Jong Won KIM ; The Information Committee of the Korean Gastric Cancer Association
Journal of Gastric Cancer 2025;25(1):115-132
		                        		
		                        			 Purpose:
		                        			Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. 
		                        		
		                        			Materials and Methods:
		                        			The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. 
		                        		
		                        			Results:
		                        			Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. 
		                        		
		                        			Conclusions
		                        			The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research. 
		                        		
		                        		
		                        		
		                        	
9.Performance of Noninvasive Indices for Discrimination of Metabolic Dysfunction-Associated Steatotic Liver Disease in Young Adults
Jaejun LEE ; Chang In HAN ; Dong Yeup LEE ; Pil Soo SUNG ; Si Hyun BAE ; Hyun YANG
Gut and Liver 2025;19(1):116-125
		                        		
		                        			 Background/Aims:
		                        			Although numerous noninvasive steatosis indices have been developed to assess hepatic steatosis, whether they can be applied to young adults in the evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain. 
		                        		
		                        			Methods:
		                        			Data from patients under 35 years of age who visited the Liver Health Clinic at the Armed Forces Goyang Hospital between July 2022 and January 2024 were retrospectively collected. Steatosis was diagnosed on the basis of a controlled attenuation parameter score ≥250dB/m. MASLD was defined as the presence of steatosis in patients with at least one cardiometabolic risk factor. 
		                        		
		                        			Results:
		                        			Among the 1,382 study participants, 901 were diagnosed with MASLD. All eight indices for diagnosing steatosis differed significantly between the MASLD and non-MASLD groups (p<0.001). Regarding the predictive performance, the hepatic steatosis index (HSI), fatty liver index (FLI), Framingham steatosis index, Dallas steatosis index, Zhejiang University index, lipid accumulation product, visceral adiposity index, and triglyceride glucose-body mass index exhibited an area under the curve of 0.898, 0.907, 0.899, 0.893, 0.915, 0.869, 0.791, and 0.898, respectively. The cutoff values for the FLI and HSI were re-examined, indicating a need for alternative cutoff values for the HSI, with a rule-in value of 42 and a rule-out value of 36 in this population. 
		                        		
		                        			Conclusions
		                        			This study presents novel findings regarding the predictive performance of established steatosis markers in young adults. Alternative cutoff values for the HSI in this population have been proposed and warrant further validation. 
		                        		
		                        		
		                        		
		                        	
10.Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice
Seung Sik YOO ; Yuri KIM ; Dong Won LEE ; Hyeon Joo HAM ; Jung Ho PARK ; In Jun YEO ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2025;33(3):417-428
		                        		
		                        			
		                        			 To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation. 
		                        		
		                        		
		                        		
		                        	
            
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