1.An experimental study of a novel external fixator based on universal joints for the rapid initial stabilization of mandibular comminuted fractures
Zhi-Qiang HU ; Tai-Qiang DAI ; Lu ZHAO ; Xun LI ; Xu GONG ; Hao JIA ; Hai-Tao KONG ; Bo-Lei CAI ; Shi-Ping CHANG ; Lei TIAN
Chinese Journal of Traumatology 2024;27(5):254-262
		                        		
		                        			
		                        			Purpose::Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. Methods::In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with the novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals’ weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). Results::The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement ( p = 0.496, 0.079) and the slope of load displacement curves ( p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). Conclusion::The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.
		                        		
		                        		
		                        		
		                        	
2.IgA nephropathy with mesangial type Ⅲ collagen deposition:2 cases report
Jie-Bo HUANG ; Xiao-Fan CAI ; Zhong-Hua ZHAO ; Zhi-Gang ZHANG ; Qiang SHEN ; Hao WANG ; Hui-Juan WU
Fudan University Journal of Medical Sciences 2024;51(3):426-430
		                        		
		                        			
		                        			As interstitial collagen,type Ⅲ collagen(Col Ⅲ)does not express in normal glomeruli.However,in Col Ⅲ nephropathy,a large amount of Col Ⅲ deposit in the mesangial and subendothelial area of the glomeruli.IgA nephropathy with Col Ⅲ deposition was extremely rare.In this article,we reported two cases of such disease.After treating with immunosuppressive agents or traditional Chinese medicine decoction,the renal function of the two patients remained stable and the urinary protein levels reduced significantly.
		                        		
		                        		
		                        		
		                        	
3.The Role of NK Cells in Allogeneic Hematopoietic Stem Cell Micro-Transplantation for Acute Myeloid leukemia
Ru-Yu LIU ; Chang-Lin YU ; Jian-Hui QIAO ; Bo CAI ; Qi-Yun SUN ; Yi WANG ; Tie-Qiang LIU ; Shan JIANG ; Tian-Yao ZHANG ; Hui-Sheng AI ; Mei GUO ; Kai-Xun HU
Journal of Experimental Hematology 2024;32(2):546-555
		                        		
		                        			
		                        			Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1%after 1 course and 73.7%after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.
		                        		
		                        		
		                        		
		                        	
4.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
		                        		
		                        			
		                        			Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
		                        		
		                        		
		                        		
		                        	
5.Mechanism of Huangjing Qianshi Decoction in treatment of prediabetic mice based on transcriptome sequencing.
Jia-Luo CAI ; Yi-Lin ZHU ; Xiao-Ping LI ; Xin-Hua XIA ; Gui-Ming DENG ; Qiao-Zhen TONG ; Gang-Qiang YI ; Bo CHENG
China Journal of Chinese Materia Medica 2023;48(4):1032-1042
		                        		
		                        			
		                        			Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Proto-Oncogene Proteins c-akt
		                        			;
		                        		
		                        			Phosphatidylinositol 3-Kinases
		                        			;
		                        		
		                        			Prediabetic State
		                        			;
		                        		
		                        			Vascular Endothelial Growth Factor A
		                        			;
		                        		
		                        			Interleukin-6
		                        			;
		                        		
		                        			Transcriptome
		                        			;
		                        		
		                        			Tumor Suppressor Protein p53
		                        			;
		                        		
		                        			Insulin
		                        			;
		                        		
		                        			Cholesterol
		                        			
		                        		
		                        	
6.Efficacy and Prognostic Factors of Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia.
Yan-Ping SHI ; Bo CAI ; Chang-Lin YU ; Jian-Hui QIAO ; Xin-Rui CHEN ; Yang-Yang LEI ; Yi WANG ; Bo YAO ; Bing-Xia LI ; Tie-Qiang LIU ; Hui-Sheng AI ; Mei GUO
Journal of Experimental Hematology 2023;31(6):1852-1859
		                        		
		                        			OBJECTIVE:
		                        			To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors.
		                        		
		                        			METHODS:
		                        			Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed.
		                        		
		                        			RESULTS:
		                        			The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024).
		                        		
		                        			CONCLUSION
		                        			Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Graft vs Host Disease
		                        			;
		                        		
		                        			Hematopoietic Stem Cell Transplantation/adverse effects*
		                        			;
		                        		
		                        			Leukemia, Myeloid, Acute/complications*
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Recurrence
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
7.Application Progress of High-Throughput Sequencing Technology in Forensic Diatom Detection.
Jie CAI ; Bo WANG ; Jian-Hua CHEN ; Jian-Qiang DENG
Journal of Forensic Medicine 2022;38(1):20-30
		                        		
		                        			
		                        			Diatom detection is an important method for identifying drowning and throwing corpses after death and inferring the drowning sites in forensic examination of corpses in water. In recent years,high-throughput sequencing technology has achieved rapid development and has been widely used in research related to diatom taxonomic investigations. This paper reviews the research status and prospects of high-throughput sequencing technology and its application in forensic diatom detection.
		                        		
		                        		
		                        		
		                        			Cadaver
		                        			;
		                        		
		                        			Diatoms/genetics*
		                        			;
		                        		
		                        			Drowning/diagnosis*
		                        			;
		                        		
		                        			Forensic Pathology/methods*
		                        			;
		                        		
		                        			High-Throughput Nucleotide Sequencing
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Technology
		                        			
		                        		
		                        	
8.Improved Glass Bead-Vortex Oscillation Method for DNA Extraction from Diatom.
Jie CAI ; Bo WANG ; Sun-Lin HU ; Yi-Hong QU ; Tao SONG ; Jian-Hua CHEN ; Jian-Qiang DENG
Journal of Forensic Medicine 2022;38(1):119-126
		                        		
		                        			OBJECTIVES:
		                        			To examine the effect of improving diatom DNA extraction by glass bead - vortex oscillation method.
		                        		
		                        			METHODS:
		                        			The DNeasy PowerSoil Pro kit was used as control, two plant DNA extraction kits with different principles (New Plant genomic DNA extraction kit and Plant DNA Isolation kit) and one whole blood DNA extraction kit (whole blood genomic DNA extraction kit) were selected to extract diatom DNA from lung tissue and water sample of the same drowning case. The combination of mass ratio of glass beads with different sizes and vortex oscillation time was designed, and the optimal DNA extraction conditions were selected with the addition of glass beads oscillation. The extracted products of the conventional group and the modified group were directly electrophoretic and detected by diatom specific PCR. Finally, all the extracts were quantified by qPCR, and the Ct values of different groups were statistically analyzed.
		                        		
		                        			RESULTS:
		                        			When the frequency of vortex oscillation was 3 000 r/min, the optimal combination of DNA extraction was vortex oscillation for 4 min, and the mass ratio of large glass beads to small glass beads was 1∶1. The DNeasy PowerSoil Pro kit was used as a reference, and the Ct value of 10 mL water sample was greater than that of 0.5 g tissue. The Ct values of the other three kits used for plant DNA extraction decreased after the glass beads-vortex oscillation method was used, and the Ct values of the tissues before and after the improvement were statistically significant (P<0.05). The whole blood genomic DNA extraction kit used in this study could successfully extract diatom DNA, the extraction of water samples was close to DNeasy PowerSoil Pro kit, after the modified method was applied to tissue samples, the difference in Ct value was statistically significant (P<0.05). However, when the three kits were used to extract diatom DNA from water samples, Ct values before and after the improvement were only statistically significant in New Plant genomic DNA extraction kit group (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			The improved glass bead-vortex oscillation method can improve the extraction efficiency of diatom DNA from forensic materials, especially from tissue samples, by plant and blood DNA extraction kits.
		                        		
		                        		
		                        		
		                        			DNA, Plant/genetics*
		                        			;
		                        		
		                        			Diatoms/genetics*
		                        			;
		                        		
		                        			Real-Time Polymerase Chain Reaction
		                        			;
		                        		
		                        			Water
		                        			
		                        		
		                        	
9.A retrospective controlled study on the treatment effect of distraction osteogenesis and maxillomandibular advancement for severe obstructive sleep apnea hypopnea syndrome patients.
Yu Fan ZHANG ; Zhi Ru ZHANG ; Zhi Jun TAN ; Bo YU ; Tai Qiang DAI ; Fu Wei LIU ; Liang KONG ; Lei TIAN ; Bo Lei CAI
Chinese Journal of Stomatology 2022;57(9):907-913
		                        		
		                        			
		                        			Objective: To compare the treatment effect of distraction osteogenesis (DO) and maxillomandibular advancement (MMA) for severe obstructive sleep apnea hypopnea syndrome (OSAHS) patients and to guide clinical decisions about treatment of OSAHS. Methods: Thirty-seven OSAHS patients which accepted maxillomandibular advancement (MMA) or distraction osteogenesis (DO) in Stomatological Hospital of the Department of Maxillofacial Trauma and Orthognathic Surgery, School of Stomatology, The Forth Military Medical University from June 2017 to June 2019 were collected. Their preoperative and postoperative data of cephalometry, polysomnography (PSG), Pittsburgh sleep quality index (PSQI) and Epworth sleepiness scale (ESS) scores were collected and analyzed. With propensity score matching method, the treatment effect of MMA and DO was analyzed and compared. Results: According to the statistics of MMA group, only AHI was correlated with operative successful rate and cure rate. With the increase of AHI, the treatment effect of MMA on OSAHS patients gradually decreased. The cut-off point of AHI as a predictor of MMA treatment failure was 78.2 n/h. All the matched cases were severe OSAHS patients. Statistical analysis showed that the mandibular elongation of DO patients[(24.00±4.39) mm] was significantly more than that of MMA group [(11.20±1.37) mm] (t=-6.11, P<0.001), the improvement of PSG index [including lowest oxygen saturation (LSpO2), longest apnea (LA) and longest hypopnea (LH)] in DO group [LSpO2=(93.40±1.82)%; LA=(18.28±8.32) s; LH=(61.84±32.94) s] was significantly higher than that in the MMA group [LSpO2=(86.00±4.06)%, LA=(64.08±21.78) s, LH=(172.40±30.70) s](t=-3.72, P=0.005; t=4.39, P=0.003; t=5.49, P=0.004). The PSQI and the ESS scores of DO group (PSQI=4.20±0.83; ESS=3.40±1.52) were also significantly better than that of MMA group (PSQI=8.80±2.39, ESS=9.40±2.88)(t=4.07, P=0.001; t=4.12, P=0.002). Conclusions: For severe OSAHS patients, the objective and subjective indicators of DO treatment group showed a better therapeutic effect than that of MMA.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Mandibular Advancement
		                        			;
		                        		
		                        			Osteogenesis, Distraction
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Sleep Apnea, Obstructive/surgery*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
10.The comparison of survival between active surveillance or watchful waiting and focal laser ablation in patients with low-risk prostate cancer.
Jia-Kun LI ; Chi-Chen ZHANG ; Shi QIU ; Kun JIN ; Bo-Yu CAI ; Qi-Ming YUAN ; Xing-Yu XIONG ; Lian-Sha TANG ; Di JIN ; Xiang-Hong ZHOU ; Yi-Ge BAO ; Lu YANG ; Qiang WEI
Asian Journal of Andrology 2022;24(5):494-499
		                        		
		                        			
		                        			Prostate cancer (PCa) is the second-most common cancer among men. Both active surveillance or watchful waiting (AS/WW) and focal laser ablation (FLA) can avoid the complications caused by radical treatment. How to make the choice between these options in clinical practice needs further study. Therefore, this study aims to compare and analyze their effects based on overall survival (OS) and cancer-specific survival (CSS) to obtain better long-term benefits. We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010-2016. Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups. To eliminate bias, this study applied a series of sensitivity analyses. Moreover, Kaplan-Meier curves were plotted to obtain survival status. A total of 18 841 patients with low-risk PCa were included, with a median of 36-month follow-up. According to the multivariate Cox proportional hazard regression, the FLA group presented inferior survival benefits in OS than the AS/WW group (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.37-3.33, P < 0.05). After adjusting for confounders, the result persisted (HR: 1.69, 95% CI: 1.02-2.81, P < 0.05). According to the results of the sensitivity analysis, the inverse probability of the treatment weighing model indicated the same result in OS. In conclusion, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment. Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa. More relevant researches and data will be needed for further clarity.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Laser Therapy
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Proportional Hazards Models
		                        			;
		                        		
		                        			Prostatectomy
		                        			;
		                        		
		                        			Prostatic Neoplasms
		                        			;
		                        		
		                        			Risk
		                        			;
		                        		
		                        			Watchful Waiting
		                        			
		                        		
		                        	
            
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