1.Clinical characteristics of 11 patients with chronic lymphocytic leukemia with t (14;19) (q32;q13).
Cheng Hua CUI ; Ya Nan CHANG ; Ji ZHOU ; Cheng Wen LI ; Hui Jun WANG ; Qi SUN ; Yu Jiao JIA ; Qing Hua LI ; Ting Yu WANG ; Lu Gui QIU ; Shu Hua YI
Chinese Journal of Hematology 2023;44(5):418-423
		                        		
		                        			
		                        			Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Leukemia, Lymphocytic, Chronic, B-Cell/genetics*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Translocation, Genetic
		                        			;
		                        		
		                        			Chromosome Aberrations
		                        			;
		                        		
		                        			Karyotyping
		                        			
		                        		
		                        	
2.Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease.
San Shuai CHANG ; Jia Hui WU ; Jing CUI ; Chang HUA ; Shi Jun XIA ; Liu HE ; Xu LI ; Man NING ; Rong HU ; Xin DU ; Jian Zeng DONG ; Chang Sheng MA
Chinese Journal of Cardiology 2023;51(6):642-647
		                        		
		                        			
		                        			Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Atrial Fibrillation/drug therapy*
		                        			;
		                        		
		                        			Cardiovascular Diseases
		                        			;
		                        		
		                        			Cholesterol, LDL
		                        			;
		                        		
		                        			Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
		                        			;
		                        		
		                        			Atherosclerosis
		                        			;
		                        		
		                        			Dyslipidemias/drug therapy*
		                        			
		                        		
		                        	
3.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
		                        		
		                        			
		                        			Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Natriuretic Peptide, Brain
		                        			;
		                        		
		                        			Simendan/therapeutic use*
		                        			;
		                        		
		                        			Non-ST Elevated Myocardial Infarction
		                        			;
		                        		
		                        			Heart Failure/drug therapy*
		                        			;
		                        		
		                        			Peptide Fragments
		                        			;
		                        		
		                        			Arrhythmias, Cardiac
		                        			;
		                        		
		                        			Biomarkers
		                        			;
		                        		
		                        			Prognosis
		                        			
		                        		
		                        	
4.Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity
Guang-Yue LI ; Shu-Jing ZHANG ; Dong XUE ; Yue-Qi FENG ; Yan LI ; Xun HUANG ; Qiang CUI ; Bo WANG ; Jun FENG ; Tao BAO ; Pei-Jun LIU ; Shao-Ying LU ; Ji-Chang WANG
Journal of Pharmaceutical Analysis 2023;13(3):262-275
		                        		
		                        			
		                        			The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.
		                        		
		                        		
		                        		
		                        	
5.Isolation and identification of chemical constituents from aerial parts of Glycyrrhiza uralensis.
Guan-Hua CHANG ; Lu ZHANG ; Jie CUI ; Wen-Quan WANG ; Jun-Ling HOU
China Journal of Chinese Materia Medica 2023;48(16):4413-4420
		                        		
		                        			
		                        			The present study investigated the chemical constituents from the aerial parts of Glycyrrhiza uralensis. The ethanol extract of the aerial parts of G. uralensis was separated and purified by different column chromatographies such as macroporous resin, silica gel, and Sephadex LH-20, and through preparative HPLC and recrystallization. Thirteen compounds were isolated and identified as(2S)-6-[(Z)-3-hydroxymethyl-2-butenyl]-5,7,3'-trihydroxy-4'-methoxy-dihydroflavanone(1),(2S)-8-[(E)-3-hydroxymethyl-2-butenyl]-5,7,3',5'-tetrahydroxy-dihydroflavanone(2), α,α'-dihydro-5,4'-dihydroxy-3-acetoxy-2-isopentenylstilbene(3), 6-prenylquercetin(4), 6-prenylquercetin-3-methyl ether(5), formononetin(6), 3,3'-dimethylquercetin(7), chrysoeriol(8), diosmetin(9),(10E,12Z,14E)-9,16-dioxooctadec-10,12,14-trienoic acid(10), 5,7,3',4'-tetrahydroxy-6-prenyl-dihydroflavanone(11), naringenin(12), dibutylphthalate(13). Compounds 1-3 are new compounds, and compounds 10 and 13 are isolated from aerial parts of this plant for the first time.
		                        		
		                        		
		                        		
		                        			Glycyrrhiza uralensis/chemistry*
		                        			;
		                        		
		                        			Plant Components, Aerial/chemistry*
		                        			
		                        		
		                        	
6.Factor analysis on serum biomarkers in patients with stage Ⅰ silicosis
ZOU Ji min YUAN Bao jun WANG Dong mei LI Chao GAO Li chang TONG Yan yan CUI Jing jing
China Occupational Medicine 2022;49(06):687-691
		                        		
		                        			
		                        			Objective ,
To investigate the role of serum chemokines and oxidative and antioxidant biomarkers in occupational
( silicosis) Methods
silicosis hereinafter referred to as . A total of 58 patients with stage Ⅰ silicosis were selected as the
- ( ),
research subjects using convenient sampling method. The serum levels of nuclear factor erythroid 2 related factor 2 Nrf2
-( - ) - ( - - ) -
heme oxygenase 1 HO 1 and 8 isoprstaglandin F2α 8 iso PGF2α were determined by enzyme linked immunesorbent assay.
( ) ( - )
The serum levels of lipid peroxide LPO and total antioxidant capacity TAOC were determined by chemistry colorimetric method.
- - ( - ),
Luminex flow fluorescence technology was used to detect the serum levels of interferon γ inducible protein10 IP10 macrophage
( )- , - - ( )
inflammatory protein MIP 1α MIP1β and macrophagederived chemokine MDC . The above indicators were analyzed by factor
Results -
analysis. The information extraction rate of the original indicators of the nine biomarkers was 58.5%96.5%. Four common
, , ( ) ,
factors were extracted including Nrf2 antioxidant signaling pathway helper T cell Th 1 dominant chemotaxis the total
, , , , ,
oxidation/antioxidant balance and Th2 dominant chemotaxis whose variance contribution rates were 32.2% 19.1% 16.4%
, , Conclusion -
and 11.8% respectively and the cumulative variance contribution rate was 79.5%. Both the oxidant antioxidant
,
disturbance and the dominance chemotaxis are involved in the occurrence and development of silicosis and the Nrf2 antioxidant
signaling pathway plays the most critical role.
		                        		
		                        		
		                        		
		                        	
7.Implications for risk management of foodborne pathogens in China from the outbreak of monophasic salmonella enterica serovar Typhimurium contaminated chocolate products.
Li BAI ; Jun WANG ; Li Sha LIU ; Sheng Hui CUI ; Yun Chang GUO ; Ning LI ; Zhao Ping LIU
Chinese Journal of Preventive Medicine 2022;56(11):1648-1656
		                        		
		                        			
		                        			Outbreaks caused by highly industrialized food companies are characterized by cross-border, trans-regional, rapid and unpredictable, related to serious disease and economic burden. A cluster of cases with monophasic salmonella enterica serovar Typhimurium ST34 infection suspected to be associated with consumption of contaminated chocolate products have been reported in several Europe countries since December 2021. After retrospective investigations, the buttermilk circuit in the Belgian factory was suspected to be the point of origin of the contamination. This outbreak could provide a reference for the risk management of foodborne pathogens contamination in China. The objective of this paper was to summarize the process and characteristics of the outbreak of monophasic S. Typhimurium caused by contaminated chocolate products, analyze the characteristics of ST34 monophasic S. Typhimurium and the microbial management measures in the process of chocolate products, and systematically discuss the suggestions for the risk management of foodborne pathogens contamination and countermeasures for the rapid development of industrialization of food enterprises in China, in order to provide scientific and technological support for the prevention and control, prediction and early warning of sudden cases in China.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Salmonella typhimurium
		                        			;
		                        		
		                        			Serogroup
		                        			;
		                        		
		                        			Salmonella Infections/prevention & control*
		                        			;
		                        		
		                        			Chocolate
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Salmonella enterica
		                        			;
		                        		
		                        			Disease Outbreaks/prevention & control*
		                        			;
		                        		
		                        			Risk Management
		                        			
		                        		
		                        	
8.Outcomes at discharge of preterm infants born <34 weeks' gestation.
Ning Xin LUO ; Si Yuan JIANG ; Yun CAO ; Shu Jun LI ; Jun Yan HAN ; Qi ZHOU ; Meng Meng LI ; Jin Zhen GUO ; Hong Yan LIU ; Zu Ming YANG ; Yong JI ; Bao Quan ZHANG ; Zhi Feng HUANG ; Jing YUAN ; Dan Dan PAN ; Jing Yun SHI ; Xue Feng HU ; Su LIN ; Qian ZHAO ; Chang Hong YAN ; Le WANG ; Qiu Fen WEI ; Qing KAN ; Jin Zhi GAO ; Cui Qing LIU ; Shan Yu JIANG ; Xiang Hong LIU ; Hui Qing SUN ; Juan DU ; Li HE
Chinese Journal of Pediatrics 2022;60(8):774-780
		                        		
		                        			
		                        			Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
		                        		
		                        		
		                        		
		                        			Bronchopulmonary Dysplasia/epidemiology*
		                        			;
		                        		
		                        			Gestational Age
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant Mortality/trends*
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Infant, Premature
		                        			;
		                        		
		                        			Infant, Premature, Diseases/epidemiology*
		                        			;
		                        		
		                        			Patient Discharge
		                        			;
		                        		
		                        			Retinopathy of Prematurity/epidemiology*
		                        			;
		                        		
		                        			Sepsis/epidemiology*
		                        			
		                        		
		                        	
9.Myocardial hypertrophy in a patient with eosinophilic dermatitis.
Li Li XU ; Jie CUI ; Qing LI ; Hong Yi WU ; Shu Fu CHANG ; Xue Ying CHEN ; Ju Ying QIAN ; Jun Bo GE
Chinese Journal of Cardiology 2022;50(4):401-403
10.Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis.
Li Na CUI ; Xiu Fang WANG ; Rui Qing SUN ; Juan DENG ; Zheng Jun GAO ; Xin Min ZHOU ; Chang Cun GUO ; Gui JIA ; Yu Long SHANG ; Chun Mei YANG ; Ying HAN
Chinese Journal of Hepatology 2022;30(3):279-284
		                        		
		                        			
		                        			Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
		                        		
		                        		
		                        		
		                        			End Stage Liver Disease
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Liver Cirrhosis/drug therapy*
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Peripheral Blood Stem Cells
		                        			;
		                        		
		                        			Severity of Illness Index
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
            
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