1.Case-Finding for Sarcopenia in Community-Dwelling Older Adults: Comparison of Mini Sarcopenia Risk Assessment with SARC-F and SARC-CalF
Shiyun CHUA ; Jia Qian CHIA ; Jun Pei LIM ; Justin CHEW ; Wee Shiong LIM
Annals of Geriatric Medicine and Research 2024;28(1):57-64
		                        		
		                        			 Background:
		                        			We compared the diagnostic performance of the short five-item and full seven-item Mini Sarcopenia Risk Assessment Questionnaire (MSRA-5 and MSRA-7) against the Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F) and SARC-F with calf circumference (SARC-CalF) scales for sarcopenia in healthy community-dwelling older adults.  
		                        		
		                        			Methods:
		                        			We conducted a post-hoc cross-sectional secondary data analysis of a prospective cohort study, using data from 230 older adults (mean age 67.2±7.4 years, 92% Chinese, and 73% female) from the “Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and Osteosarcopenic Obesity in predicting frailty and functional decline in community-dwelling Asian older adults Study” (GeriLABS-2) conducted between December 2017 and March 2019 in Singapore. We performed receiver operating characteristic curve analysis to ascertain the area under the curve (AUC) for sarcopenia diagnosis using the Asian Working Group for Sarcopenia 2019 consensus criteria. We applied the Delong method to compare the AUCs of the four instruments. 
		                        		
		                        			Results:
		                        			The MSRA-5 and MSRA-7 demonstrated poor diagnostic performance (AUC of 0.511, 95% confidence interval [CI] 0.433–0.589 and AUC of 0.526, 95% CI 0.445–0.606, respectively), compared to that in SARC-CalF (AUC of 0.739, 95% CI 0.671–0.808) and SARC-F (AUC of 0.564, 95% CI 0.591–0.636). The SARC-CalF demonstrated significantly superior discriminatory ability compared to that in the SARC-F, MSRA-5, and MSRA-7 (all p<0.01). The MSRA-5 demonstrated lower sensitivity (0.464) and specificity (0.597) than in the SARC-CalF (0.661 and 0.738, respectively), whereas the MSRA-7 had higher specificity (0.887) and lower sensitivity (0.145). 
		                        		
		                        			Conclusions
		                        			The poor diagnostic performances of the MSRA-5 and MSRA-7 in our study suggest limitations of self-reported questionnaires for assessing general and dietary risk factors for sarcopenia in healthy and culturally diverse community-dwelling older adults. Studies in different populations are needed to ascertain the utility of the MSRA for the community detection of sarcopenia. 
		                        		
		                        		
		                        		
		                        	
2.Analysis of risk factors affecting in-hospital mortality in patients with acute mesenteric ischemia
Liang XU ; Ming LI ; Shiyun TAN
Chinese Journal of Digestion 2023;43(6):401-405
		                        		
		                        			
		                        			Objective:To investigate the risk factors affecting in-hospital mortality in patients with acute mesenteric ischemia (AMI).Methods:From January 1, 2014 to June 30, 2022, the clinical data of 67 patients diagnosed with AMI at Renmin Hospital of Wuhan University were retrospectively analyzed, which included basic data (age, gender, past medical history and comorbidities, etc.), laboratory results (white blood cell count (WBC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, prothrombin time (PT), etc.), and imaging manifestations (intestinal pneumatosis, intestinal wall thickening, intestinal dilation, ascites). The clinical data of AMI patients who died during hospitalization were compared with that of AMI patients who survived. Binary logistic regression was used to analyze the independent risk factors of in-hospital mortality in patients with AMI. Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Among the 67 patients with AMI, 17 died and 50 survived. There were significant differences between died and survived patients with AMI in age, the proportion of patients with organ failure, WBC, ALT, AST, creatinine, PT, and the proportion of patients with intestinal dilatation and ascites (76 years old(68 years old, 79 years old) vs. 61 years old (50 years old, 74 years old), 12/17 vs.12.0%(6/50), 15.8×10 9/L(13.5×10 9/L, 23.7×10 9/L) vs. 12.1×10 9/L (9.1×10 9/L, 19.4×10 9/L), 32.0 U/L(19.0 U/L, 88.5 U/L) vs. 20.5 U/L(14.8 U/L, 29.0 U/L), 64.0 U/L(33.8 U/L, 117.0 U/L) vs. 26.0 U/L (18.5 U/L, 36.8 U/L), 135.0 μmol/L(61.5 μmol/L, 198.5 μmol/L) vs. 73.5 μmol/L(60.5 μmol/L, 85.0 μmol/L), 13.7 s(12.9 s, 16.3 s) vs. 12.7 s (11.9 s, 13.6 s), 13/17 vs. 38.0%(19/50), 10/17 vs. 24.0% (12/50); Z=3.06, χ2=22.16, Z=2.01, 2.69, 4.08, 2.45 and 2.78, χ2=7.53 and 6.98; P=0.002, <0.001, =0.044, =0.007, <0.001, =0.014, =0.006, =0.006 and =0.008). The results of binary logistic regression analysis showed that age ( OR=1.224, 95% confidence interval 1.011 to 1.482, P=0.038), organ failure ( OR=113.989, 95% confidence interval 1.353 to 9 604.644, P=0.036), and ascites ( OR=348.289, 95% confidence interval 1.676 to 72 357.934, P=0.032) were independent risk factors of in-hospital mortality in AMI patients. Conclusion:Age, organ failure and ascites are independent risk factors of in-hospital mortality in AMI patients.
		                        		
		                        		
		                        		
		                        	
3. Correlation of Metabolic Dysfunction-associated Fatty Liver Disease With Colorectal Adenoma and Early Colorectal Cancer
Yaxin LI ; Mengyuan HU ; Ming LI ; Shiyun TAN
Chinese Journal of Gastroenterology 2023;28(3):129-134
		                        		
		                        			
		                        			 Background: The terminology of nonalcoholic fatty liver disease (NAFLD) was changed to metabolic dysfunction ⁃ associated fatty liver disease (MAFLD) in 2020. NAFLD has been confirmed to be a risk factor for colorectal neoplasms, but the association between MAFLD and colorectal neoplasms is conflicting. Aims: To investigate the correlation of MAFLD with colorectal adenoma and early colorectal cancer. Methods: The clinical information of 701 patients who met the criteria and were admitted to Renmin Hospital of Wuhan University from January 2021 to August 2021 was collected retrospectively. Among them, 274 colorectal adenoma patients with low ⁃ grade intraepithelial neoplasia or without intraepithelial neoplasia were classified as adenoma group, 21 patients with high ⁃ grade intraepithelial neoplasia, intramucosal carcinoma, and submucosal carcinoma were classified as early cancer group, and 406 patients with normal colonoscopy or non⁃adenomatous polyps were served as control group. The general information and prevalence of MAFLD between these groups were compared. Furthermore, the correlation of MAFLD with colorectal adenoma and early colorectal cancer, and the gender difference of these correlations were analyzed by Logistic regression models. Subgroup analysis was performed based on the clinicopathological characteristics of colorectal adenoma. Results: When adjusting the confounding variables including gender, age, smoking, alcohol drinking, diabetes, hypertension, and serum creatinine, MAFLD was significantly associated with the prevalence of colorectal adenoma (OR=1.83, 95% CI: 1.04 ⁃ 3.22, P=0.037) and early colorectal cancer (OR=3.91, 95% CI: 1.14⁃13.42, P=0.031). When stratified as gender, the significant association remained in females (OR=4.04, 95% CI: 1.56 ⁃ 10.47, P=0.004), but not in males. In addition, no correlation was found between MAFLD and the location, size, number, and advanced histology of colorectal adenoma (all P>0.05). Conclusions: MAFLD is an independent risk factor for colorectal adenoma and early colorectal cancer. MAFLD is specifically associated with increased risk of colorectal adenoma in females but not in males. 
		                        		
		                        		
		                        		
		                        	
4.Epidemiological characteristics of mpox epidemic in Guangzhou
Ruonan ZHEN ; Wenzhe SU ; Yunjing WEN ; Shiyun LUO ; Xinlong LIAO ; Zhiyong TAN ; Yefei LUO ; Zhigang HAN ; Jianxiong XU ; Biao DI ; Pengzhe QIN
Chinese Journal of Epidemiology 2023;44(9):1421-1425
		                        		
		                        			
		                        			Objective:To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease.Methods:Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform.Results:The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M( Q1, Q3) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type Ⅱb clade, B.1.3 lineage. Conclusions:Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.
		                        		
		                        		
		                        		
		                        	
5.Factors Influencing Pap Smear Screening Uptake among Women Visiting Outpatient Clinics in Johor
Suzane Shiyun Chin ; Nor Adlina Jamonek@Jamhuri ; Norhayati Hussin ; Nizatul Laili binti Md Zubir ; Jih Ren Tan ; Stanley Chun Wai Chan
Malaysian Family Physician 2022;17(2):46-55
		                        		
		                        			Introduction:
		                        			 Despite the benefits of cervical cancer screening, Pap smear uptake remains variable in Malaysia, with Johor previously reported as the state with the lowest uptake. This study aims to fill the gap in epidemiological knowledge and assess factors affecting the uptake of Pap smear screening among women in Johor.
		                        		
		                        			Methods:
		                        			 A cross-sectional study was conducted in several government and private clinics across Johor, including Pagoh, Muar, Batu Pahat, Kulai, and Johor Bahru districts. Data was collected from 452 women using self-administered questionnaires, and logistic regression was performed to determine factors associated with Pap smear uptake.
		                        		
		                        			Results:
		                        			 Findings showed that 48.5% of the women reported having undergone Pap smear screening in the previous 3 years, and 40.0% and 51.3% of respondents accurately answered questions on symptoms and risk factors of cervical cancer, respectively. Increasing age (ORadj 2.322, 95% CI 1.708–3.158), being married (ORadj 4.860, 95% CI 1.100–21.476), parity of ≥5 (ORadj 8.381, 95% CI 1.326–52.958), young age at first pregnancy (ORadj 0.932, 95% CI 0.877–0.991), knowledge of cervical cancer symptoms (ORadj 1.745, 95% CI 1.065–2.857), support from family (ORadj 3.620, 95% CI 2.081–6.298), and contraception use (ORadj 2.220, 95% CI 1.314–3.750) were significantly associated with increased Pap smear uptake among women visiting outpatient clinics in Johor.
		                        		
		                        			Conclusion
		                        			 Pap smear uptake remains suboptimal in Johor, and broad-based awareness campaigns tailored towards improving knowledge of cervical cancer with family involvement are crucial to improving uptake among women in Johor.
		                        		
		                        		
		                        		
		                        			Papanicolaou Test
		                        			;
		                        		
		                        			 Uterine Cervical Neoplasms
		                        			;
		                        		
		                        			 Knowledge
		                        			;
		                        		
		                        			 Early Detection of Cancer
		                        			
		                        		
		                        	
6.Effects of celastrol on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease
Tian TIAN ; Xingchen LIAO ; Min ZHANG ; Xiaoman WU ; Yitian GUO ; Shiyun TAN
Chinese Journal of Hepatology 2022;30(6):656-662
		                        		
		                        			
		                        			Objective:To investigate the effect of celastrol (CEL) on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease (NAFLD).Methods:Eighteen male C57BL/6J mice were randomly divided into normal control (NC, n=6), high-fat diet (HFD, n=6) and celastrol group (HFD+CEL, n=6). The normal control group was fed with regular diet, and the high-fat diet and celastrol group were fed with high-fat diet for 12 weeks. After successful modeling, celastrol group were injected with 100 μg?kg -1?d -1 celastrol intraperitoneally for 4 weeks, and NC and HFD group were injected intraperitoneally with the same doses of normal saline. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured in mouse after 4-weeks of intervention. HE and Oil Red O staining were used to observe the pathomorphological changes and lipid droplet deposition in mouse liver, and the findings were scored according to NAFLD activity score (NAS). Western blot was used to detect the expression levels of liver microtubule associated protein 1 light chain 3 (LC3), P62, glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), activated transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), cleaved Caspase-3(cleaved caspase-3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 related X protein (Bax).TUNEL staining was used to observe the apoptosis of hepatocytes. One-way analysis of variance was used for the intergroup comparison. Results:Serum levels of ALT (68.71±8.57) U/L, AST (209.63±28.64) U/L, TG (0.97±0.14) mmol/L, TC (4.12±0.64) mmol/L, and LDL -C (0.40±0.06) mmol/L were lower in celastrol group mouse than HFD group [(110.19±10.79) U/L, (399.72±73.47) U/L, (1.44±0.13) mmol/L, (5.65±0.54) mmol /L, (0.61±0.07) mmol/L] ( P<0.05); while the serum HDL-C level (1.29±0.17) mmol/L was higher in celastrol than HFD group (0.72±0.13) mmol/L ( P<0.05). HE and Oil Red O staining showed that lipid deposition and intralobular inflammation were apparent in the liver tissue of HFD group mouse, and the NAS score was significantly increased, while the hepatocyte steatosis and intralobular inflammation were alleviated after celastrol intervention, and the NAS score was decreased significantly ( P<0.05). Compared with HFD group, the ratio of LC3II/I was significantly increased in the liver of celastrol group mouse, and the P62 was significantly decreased ( P<0.05). Meanwhile, the expression level of GRP78, p-PERK/PERK , ATF4, and CHOP was significantly lower in celastrol than HFD group ( P<0.05). In addition, the expressions of cleaved caspase-3 and Bax were significantly lower in celastrol than HFD group, and the expression of Bcl-2 was significantly increased ( P<0.05). At the same time, the apoptosis rate of hepatocytes was also significantly lower in celastrol than HFD group ( P<0.05). Conclusion:Celastrol can effectively alleviate the lipid deposition, protect hepatocytes and delay the progression of non-alcoholic fatty liver disease in mouse liver with non-alcoholic fatty liver disease. In addition, its mechanism of action may be related to the induction of autophagy, inhibition of endoplasmic reticulum stress PERK/ATF4/CHOP pathway and its mediated apoptosis.
		                        		
		                        		
		                        		
		                        	
7.Efficacy and safety of rifaximin in the prevention of spontaneous bacterial peritonitis: A Meta-analysis
Shuping CHENG ; Ming LI ; Qingyu ZHANG ; Shiyun TAN
Journal of Clinical Hepatology 2021;37(2):318-325
		                        		
		                        			
		                        			 ObjectiveTo evaluate the efficacy and safety of rifaximin in the prevention of spontaneous bacterial peritonitis (SBP). MethodsCNKI, Wanfang Data, CBM, PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) and cohort studies on rifaximin in the prevention of SBP published up to July 5, 2020. The articles were screened according to the inclusion and exclusion criteria, and data extraction and quality assessment were performed. RevMan 5.3 software was used to conduct the meta-analysis. Results  A total of 13 studies (with 2207 patients in total) were included, among which there were 6 RCTs and 7 cohort studies. The results of the meta-analysis showed that compared with the non-prevention group, the rifaximin group had significantly lower incidence rate of SBP (odds ratio [OR]=0.36, 95% confidence interval [CI]: 0.14-0.96, P=0.04) and mortality rate (OR=0.59, 95% CI: 037-0.95, P=0.03); compared with the norfloxacin group, the rifaximin group had significantly lower incidence rate of SBP (OR=039, 95% CI: 025-0.62, P<0.001), mortality rate (OR=0.55, 95% CI: 0.34-0.92, P=0.02), and adverse reactions (OR=0.36, 95% CI: 0.22-059, P<0.001). The subgroup analysis based on the type of prevention showed that there was no significant difference in primary prevention between the two groups (OR=0.56, 95% CI: 0.23-1.35, P=0.20), and in secondary prevention, the rifaximin group had a significantly lower incidence rate of SBP (OR=0.18, 95% CI: 0.08-0.43, P<0.001). In addition, it was also found that rifaximin significantly reduced the incidence rate of hepatorenal syndrome (OR=0.34, 95% CI: 0.15-0.77, P=0.01) and hepatic encephalopathy (OR=0.55, 95% CI: 0.32-0.95, P=0.03). ConclusionRifaximin is safe and effective for the primary and secondary prevention of SBP. Rifaximin is superior to norfloxacin in secondary prevention, which still needs to be confirmed by high-quality multicenter RCTs. 
		                        		
		                        		
		                        		
		                        	
8. Effect of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease
Pengbo WU ; Qi SONG ; Yuanjie YU ; Honggang YU ; Hesheng LUO ; Shiyun TAN
Chinese Journal of Hepatology 2020;28(1):64-68
		                        		
		                        			 Objective:
		                        			To investigate the effects of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease.
		                        		
		                        			Methods:
		                        			An in vitro cell model of nonalcoholic fatty liver disease was established using 0.6 mmol/L oleic acid to induce lipid accumulation in HepG2 cells. HepG2 cells were divided into control (Con) group, oleic acid (OA) group, and metformin-low (1mmol/L) and high (10mmol/L) dose group. Oil Red O stain was used to detect intracellular lipid droplet distribution. The levels of alanine aminotransferase and aspartate aminotransferase in the culture supernatant were detected by assay kits. DCFH-DA method was used to detect the reactive oxygen species of HepG2 cells. Double staining flow cytometry was used to detect the apoptosis rate of HepG2 cells. Western blot was used to detect caspase-3, B-lymphocyte lymphoma-related protein, B-cell lymphoma 2, and cytochrome c protein. One-way analysis of variance was used to compare the data between groups.
		                        		
		                        			Results:
		                        			Oleic acid-induced HepG2 cells were significantly increased with lipid droplets. Low and high-dose metformin had reduced intracellular lipid droplets accumulation. The effect of metformin in the high-dose group was more significant than that in the low-dose group. Aspartate aminotransferase and alanine aminotransferase in HepG2 cells of OA group were significantly increased, which were (43.41 ± 7.11) U/L and (29.56 ± 4.11) U/L, respectively. The intracellular aspartate aminotransferase and alanine aminotransferase were decreased significantly after the treatment with low and high-dose metformin, which were (32.44 ± 4.08)U/L, (19.31 ± 3.03) U/L, (26.00 ± 3.11) U/L and (15.11 ± 4.11) U/L, respectively and the differences were statistically significant (
		                        		
		                        	
9. Treatment of postprandial discomfort syndrome in the elderly: a multi-centered prospective randomized controlled clinical study
Gangshi WANG ; Le XU ; Hongtan CHEN ; Liping SHI ; Minjing HUANG ; Ling XI ; Lishu XU ; Fen WANG ; Hongyi LI ; Shu LI ; Yijun ZHANG ; Shiyun TAN ; Rutao HONG ; Nonghua LYU ; Mei YE ; Huatian GAN ; Miao LIU ; Benyan WU
Chinese Journal of Internal Medicine 2020;59(2):117-123
		                        		
		                        			 Objective:
		                        			To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym®) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs.
		                        		
		                        			Methods:
		                        			A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym® group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated.
		                        		
		                        			Results:
		                        			A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym® group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (
		                        		
		                        	
10.Verification of accuracy of warfarin stable dose prediction models in Shandong population.
Yiping GE ; Fengxia QU ; Songtao WANG ; Xiao GUO ; Cuicui WANG ; Shiyun LIU ; Aiqing MA ; Xianyan JIANG ; Kai TAN
Chinese Journal of Medical Genetics 2020;37(4):401-404
		                        		
		                        			OBJECTIVE:
		                        			To compare the accuracy of five warfarin-dosing algorithms and warfarin stable dose model (2.5 mg/day) for Shandong population.
		                        		
		                        			METHODS:
		                        			One hundred and twenty five patients who achieved stable warfarin dose were enrolled. Clinical and genetic data were used to evaluate the value of each algorithm by calculating the percentage of patients whose predicted warfarin dose was within 20% of the actual stable therapeutic dose and mean absolute error (MAE).
		                        		
		                        			RESULTS:
		                        			The frequency of patients with CYP2C9*1/*1, CYP2C9*1/*3 and CYP2C9*1/*2 genotype was 92.00%, 7.20%, 0.80%, respectively. That of VKORC1-1639 AA, AG and GG genotype was 82.40%, 15.20%, 2.40%, respectively. CYP4F2*1/*1, *1/*3, *3/*3 genotype was 50.40%, 39.20%, 10.40%, respectively. With the same genotypes for other loci, patients who carried at least one VKORC1-16398G mutant allele had increased warfarin stable daily dose compared with VKORC1-1639AA. Compared with CYP4F2*1/*1, those carrying at least one CYP4F2*3 mutant allele had warfarin stable daily dose increased by 5.9%-13.00%. The percentage of ideal prediction calculated from IWPC model (59.20%), Huang model (57.60%) and Ohno model (52.80%) were higher than others. The MAE were 0.35 (95%CI: 0.11-0.49), 0.15 (95%CI: 0.10-0.32), 0.39 (95%CI: 0.12-0.51), respectively.
		                        		
		                        			CONCLUSION
		                        			The polymorphisms of CYP2C9, VKORC1 and CYP4F2 genes can influence the stable dose of warfarin in Shandong population. IWPC algorithm is suitable for guiding the use of warfarin in this population.
		                        		
		                        		
		                        		
		                        			Anticoagulants
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Aryl Hydrocarbon Hydroxylases
		                        			;
		                        		
		                        			Cytochrome P-450 CYP2C9
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Cytochrome P450 Family 4
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Dose-Response Relationship, Drug
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Models, Theoretical
		                        			;
		                        		
		                        			Polymorphism, Genetic
		                        			;
		                        		
		                        			Vitamin K Epoxide Reductases
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Warfarin
		                        			;
		                        		
		                        			administration & dosage
		                        			
		                        		
		                        	
            

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