1.A prospective study of the effect of laparoscopic splenectomy and azygoportal disconnection on liver synthetic function and liver cirrhosis
Kunqing XIAO ; Tianming GAO ; Jinhong CAI ; Zhaobao SHI ; Shengjie JIN ; Chi ZHANG ; Baohuan ZHOU ; Dousheng BAI ; Guoqing JIANG
Chinese Journal of Surgery 2025;63(1):51-57
		                        		
		                        			
		                        			Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.
		                        		
		                        		
		                        		
		                        	
2.A prospective study of the effect of laparoscopic splenectomy and azygoportal disconnection on liver synthetic function and liver cirrhosis
Kunqing XIAO ; Tianming GAO ; Jinhong CAI ; Zhaobao SHI ; Shengjie JIN ; Chi ZHANG ; Baohuan ZHOU ; Dousheng BAI ; Guoqing JIANG
Chinese Journal of Surgery 2025;63(1):51-57
		                        		
		                        			
		                        			Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.
		                        		
		                        		
		                        		
		                        	
3.Synchronous laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration or combined with endoscopic sphincterotomy for gallstones with common bile duct stones
Hongliang TIAN ; Dousheng BAI ; Shengjie JIN ; Baohuan ZHOU ; Tianming GAO ; Guoqing JIANG
Chinese Journal of General Surgery 2024;39(2):105-109
		                        		
		                        			
		                        			Objective:To compare the recurrence of common bile duct stones (CBDS) in patients with gallstones and concurrent CBDS treated by two surgical approaches: synchronous laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct exploration (LCBDE) (LC+LCBDE) and synchronous LC combined with intraoperative endoscopic sphincterotomy (IO-EST) (LC+IO-EST).Methods:From Apr 2013 to Apr 2020, the clinical data of 903 patients with gallstones with CBDS who were admitted to the Clinical Medical College, Yangzhou University were retrospectively analyzed.Results:Based on the chosen surgical method, we categorized 389 cases into group A (LC+LCBDE) and 514 cases into group B (LC+IO-EST). Our findings revealed that group A had a significantly lower rate of CBDS recurrence and re-recurrent CBDS compared to group B (4.4% vs. 8.4%, P=0.024; 0.8% vs. 3.1%, P=0.010). Moreover, Logistic regression analysis after inverse probability of treatment weighting, revealed that the surgical approach implemented in group A was an independent protective factor of recurrent CBDS and second recurrence of CBDS ( OR=0.482, 95% CI: 0.365-0.637, P<0.001; OR=0.118, 95% CI:0.080-0.173, P<0.001). Conclusion:LC+LCBDE is an optimal treatment option to LC+IO-EST for patients with gallstones combined with CBDS and common bile duct ≥8 mm.
		                        		
		                        		
		                        		
		                        	
4.Method for non-invasive prenatal paternity testing based on SNP calculation through high-throughput sequencing
Chinese Journal of Forensic Medicine 2024;39(5):521-529
		                        		
		                        			
		                        			Objective To derive the parentage index(PI)and power of exclusion(PE)formulars for non-invasive prenatal paternity testing(NIPPT),empirically validate the PE formula,and conduct statistical analysis on the PI formula.Methods Firstly,NIPPT was divided into 6 types,including Prenatal parentage testing of Alleged Father with biological mother(PAF),prenatal parentage testing of low fetal concentration Alleged Father with biological mother(PLAF),Prenatal parentage testing of Father-Child(PFC),Prenatal parentage testing of Mother-Child(PMC),Prenatal parentage testing of Alleged Parents(PAP),Prenatal parentage testing of Alleged mother with biological father(PAM).Then the formulas of PI in 6 types of NIPPT both in accordance with genetic laws and in the presence of mutation were derived.The calculation formulas of PE were mathematically derived and applied to the system of 10 SNP loci.And for the same 10 SNP sites,PE was simulated and measured through multiple groups of operation.In principle,the PE formula should be empirically verified using the correlation method for the corresponding values of the formula and simulation.Finally,models of simulated kinship groups and unrelated individual groups were established respectively with 30 to 100 SNP loci.The geometric mean(Π)and 95%confidence interval(CI)of cumulative parentage index(CPI),the percentages of cases where CPI>104 in kinship groups,and the percentages of cases where CPI<10-4 in unrelated individual groups were calculated.Results The formula of PE was all in accord with the simulation experiments.The novel formulas can be used to calculate all kinds of PI in all situations.All types of NIPPT cases in kinship group and unrelated individual group can be correctly identified with 100 SNP loci.In PLAF,75.90%cases in kinship group and 100%cases in unrelated individual group can be correctly identified in 50 SNP loci.Conclusion The formula in this paper can be applied to the calculation of PI and PE of NIPPT and has forensic application value.
		                        		
		                        		
		                        		
		                        	
5.Analysis and reference of research hotspots on physician remuneration abroad based on bibliometrics
Mian XIA ; Zhiling CHEN ; Yining GAO ; Shengjie YIN ; Ming′ou WANG ; Zheng WANG
Chinese Journal of Hospital Administration 2023;39(9):710-716
		                        		
		                        			
		                        			Objective:To provide reference for solving relevant problems in China and conducting in-depth research in this field by learning the research hotspots, ideas, and methods regarding physician remuneration abroad.Methods:Themes of " Physician" and " Remuneration" were used, to retrieve English literature from the Web of Science core set database collected from 2012 to 2022. After a descriptive analysis of the journals distribution of valid literature, the researchers made a co-word analysis and chose high-frequency keywords, followed by a cluster analysis of the keywords to summarize hot topics in the field of physician remuneration research abroad.Results:From 2012 to 2022, 379 representative and relevant papers were included, and a total of 91 papers were published in the top 10 journals, then top 30 keywords of 8-41 times frequency were intercepted. The research summarized 4 main research directions in the field by cluster analysis, namely macro healthcare policies and physicians′ remuneration, as well as the presentation, cause and impact of wage gap, the remuneration design and physicians′ attitude and behavior, the industry payment and information disclosure.Conclusions:How to better evaluate the value of physicians′ work and pay them scientifically and reasonably is key to the study. Chinese researchers are expected to further explore physician remuneration in terms of macro policy level, payment technology design and remuneration management level, as well as individual behavior and attitude level.
		                        		
		                        		
		                        		
		                        	
6.Effects of TRIM59 gene silencing on proliferation and cell cycle of colorectal cancer cells
Xiaobin Gao ; Xueliang Wu ; Shengjie Wang ; Guangyuan Sun ; Wenjing Wang ; Feng Liang ; Yifeng Zhao ; Zhenxian Liu
Acta Universitatis Medicinalis Anhui 2022;57(5):796-801
		                        		
		                        			Objective:
		                        			To investigate the effect of tripartite motif containing 59(TRIM59) on the biological function of human colorectal cancer HCT116 cells and its possible mechanism. 
		                        		
		                        			Methods:
		                        			The recombinant TRIM59 interference plasmid(si-TRIM59) was constructed and transfected into colorectal cancer cell line HCT116 by liposome transfection. The transfection efficiency was verified by RT-qPCR and Western blot. The effects of TRIM59 gene silencing on the proliferation, colony-formation ability and cell cycle of colorectal cancer cells were detected by CCK-8 method, colony formation assays and flow cytometry respectively. Western blot was used to detect the expression level of CDK4 and cyclinD1.
		                        		
		                        			Results:
		                        			The expression levels ofTRIM59mRNA and protein in colorectal cancer cells were significantly higher than those in normal colorectal mucosa cells(P<0. 05). After knockdown of TRIM59expression, the proliferation activity and colony forming ability of HCT116 cells were significantly inhibited(P<0. 05), and the cell cycle was arrested in G0/G1 phase. At the same time, the expression levels of CDK4and CyclinD1 significantly decreased(P<0. 05).
		                        		
		                        			Conclusion
		                        			TRIM59was highly expressed in colorectal cancer cells. Down regulation ofTRIM59expression can inhibit the proliferation and clone formation of colorectal cancer cells, suggesting thatTRIM59may become a new target for gene therapy of colorectal cancer.
		                        		
		                        		
		                        		
		                        	
7.Effects of different hemodialysis methods on insulin resistance, inflammatory factors and coronary artery calcification in patients with non-diabetic end-stage renal disease
Liping WU ; Jie CHENG ; Jian LI ; Yun GAO ; Xianjun SHI
Chinese Journal of Blood Transfusion 2021;34(10):1101-1105
		                        		
		                        			
		                        			【Objective】 To compare the effects of low flux and high flux hemodialysis on insulin resistance (IR), inflammatory factors and coronary artery calcification(CAC) in patients with non-diabetic end-stage renal disease (ESRD), and analyze the related factors affecting the prognosis survival of patients. 【Methods】 A total of 217 patients with non-diabetic ESRD treated in our hospital from February 2015 to April 2017 were selected and randomly divided into control group (n=108) and observation group (n=109) according to the random number table. Low flux and high flux hemodialysis were adopted respectively. Baseline data, renal function, lipid metabolism, inflammatory factors, IR, CAC, complications, outcomes and health and economic benefits of the two groups were compared. The patients were followed up for 3 years and divided into survival group (n=130) and death group (n=75). The clinical data of the two groups were compared and related factors affecting the prognosis and survival were analyzed. 【Results】 Scr, BUN, UAER, TC, TG and LDL-C in the two groups were significantly lower than those before treatment [control group: Scr (μmol/L)349.62±37.16 vs 201.73±24.58, BUN (mmol/L) 28.43±5.39 vs20.81±3.47, UAER(μg /min)60.14±11.52 vs 55.73±9.86, TC (mmol/L)5.46±0.93 vs 4.75±0.69, TG (mmol/L)2.58±0.64 vs 2.13±0.57, LDL-C(mmol/L)3.69±0.73 vs 2.45±0.60; observation group: Scr (μmol/L) 352.14±38.29 vs 136.85±16.47, BUN (mmol/L) 27.96±5.25 vs17.56±3.68, UAER(μg /min) 60.32±12.07 vs 49.85±7.42, TC (mmol/L)5.48±0.97 vs 4.27±0.56, TG (mmol/L) 2.55±0.62 vs 1.49±0.35, LDL-C(mmol/L) 3.72±0.74 vs1.91±0.48), and eGFR and HDL-C were significantly higher than those before treatment [control group: eGFR(mL/min/1.73m)29.32±3.25 vs 72.54±7.86, HDL-C(mmol/L)1.13±0.24 vs1.28±0.31, observation group: eGFR(mL/min/1.73m)30.05±3.29 vs 121.63±13.34, HDL-C(mmol/L)1.09±0.22 vs 1.57±0.46), differences between groups were statistically significant (P<0.05); FBG, FINS, HOMA-IR, IL-6, IL-8, TNF-α and hs-CRP in the two groups were significantly lower than those before treatment [control group: FBG(mmol/L)4.99±0.95 vs 4.52±0.63, FINS(mU/L)12.93±2.54 vs10.15±2.21, HOMA-IR 2.87±0.54 vs 2.04±0.43, IL-6(pg/mL)120.16±13.54 vs 75.94±9.28, IL-8(mg/L)56.83±6.15 vs 41.52±5.38, TNF-α(ng/L)50.03±5.42 vs 45.62±4.81, hs-CRP(mg/L)26.75±2.79 vs 14.37±2.19; observation group: FBG(mmol/L)5.01±0.97 vs 4.11±0.56, FINS(mU/L)13.07±2.62 vs 8.86±1.79, HOMA-IR 2.91±0.55 vs 1.62±0.31, IL-6(pg/mL)119.85±12.91 vs 31.07±4.46, IL-8(mg/L)57.04±6.09 vs 32.65±4.27, TNF-α(ng/L)49.78±5.36 vs 40.15±4.27, hs-CRP(mg/L)23.04±2.82 vs 7.56±1.03], and the CACS score was significantly higher than that before treatment(control group: 26.75±2.79 vs 53.68±26.93, observation group: 27.04±2.82 vs 75.49±7.66), differences between groups are statistically significant (all P<0.05). Compared with the control group, the total incidence of complications during dialysis was significantly lower in the observation group (P<0.05), and has more economic advantages.Venerable age(OR=1.893, P<0.05), low HDL-C level(OR=0.575, P<0.05), high CACS score(OR=2.384, P<0.05), and high hs-CRP level(OR=3.526, P<0.05) were independent risk factors affecting the survival rate of non-diabetic ESRD patients after dialysis treatment (P<0.05). 【Conclusion】 Compared with low-flux hemodialysis, high-flux hemodialysis has significant effects in improving renal function, lipid metabolism, IR, micro-inflammatory state, and reducing CAC progression and complications, with more prominent cost-effectiveness advantages. HDL-C and Hs-CRP levels and CACS scores of patients should be closely monitored during clinical application, and active preventive measures should be taken to improve the survival rate of patients.
		                        		
		                        		
		                        		
		                        	
8.Comparison of prefabricated path with an awl for guiding pin and traditional screw placement in anterior odontoid screw fixation
Kun GAO ; Zhenghong YU ; Jia SHAO ; Shengjie WANG ; Yanzheng GAO
Chinese Journal of Trauma 2020;36(4):309-314
		                        		
		                        			
		                        			Objective:To compare the application value of prefabricated path with an awl for guiding pin and traditional screw placement during anterior odontoid screw fixation.Methods:A retrospective case-control study was conducted to analyze 35 patients with fresh odontoid fractures treated from January 2010 to August 2017 in Henan Provincial People's Hospital, including 25 males and 10 females with age range of 19-55 years (mean, 36.9 years). The preoperative odontoid fractures were classified into type IIA in 15 patients, type IIB in 20 patients according to Anderson and D'Alonzo classification. Among them, 16 patients in Group A were treated with prefabricated path by an awl for guiding pin during anterior odontoid screw fixation, and 19 patients in Group B were implanted screws according to traditional experience in anterior odontoid screw fixation. Operation time, intraoperative fluoroscopy time, success rate of first-time guiding pin implantation, intraoperative blood loss, fracture healing outcomes and American Spinal Injury Association (ASIA) grade at the latest follow-up were collected and compared between the two groups.Results:All patients were followed up for 13-20 months [(16.8±1.5)months]. Two groups had significant differences in operation time [Group A: (73.5±12.9)minutes; Group B: (82.6±13.6)minutes], intraoperative fluoroscopy time [Group A: (3.1±0.6)minutes, Group B: (7.0±0.9)minutes], and success rate of first-time guiding pin implantation (Group A: 94%, Group B: 58%) ( P<0.05), but not in intraoperative blood loss [Group A: (129.4±40.6)ml; Group B: (135.8±38.4)ml] and fracture healing rate (Group A: 94%, Group B: 95%) and ASIA grade at the latest follow-up (Group A: grade C in 1 patient, grade D in 3, grade E in 12; Group B: grade C in 2 patients, grade D in 2, grade E in 15) ( P>0.05). All patients were successfully operated without occurrence of cerebrospinal fluid leakage, neurovascular injury or incision infection. Conclusions:Prefabricated path with an awl for guiding pin during anterior odontoid screw fixation is superior to traditional experience, which can reduce operation time, intraoperative fluoroscopy time and improve the success rate of first-time guiding pin implantation. Meanwhile, there is no effect on intraoperative blood loss or fracture healing outcomes.
		                        		
		                        		
		                        		
		                        	
9.Comparison between non-fusion and fusion internal fixation with posterior pedicle screw for odontoid fracture
Shengjie WANG ; Jiwei TIAN ; Zhenghong YU ; Kun GAO ; Jia SHAO ; Jiantao LIU ; Dongbo LYU ; Yanzheng GAO
Chinese Journal of Trauma 2019;35(8):723-729
		                        		
		                        			
		                        			Objective To investigate the clinical efficacy of non-fusion and fusion internal fixation with posterior pedicle screw for odontoid fractures. Methods A retrospective case control study was conducted to analyze the clinical data of 46 patients with odontoid fractures admitted to Henan Provincial People's Hospital from January 2013 to June 2015. There were 35 males and 11 females, aged 19-62 years [(36. 9 ± 1. 6)years]. The preoperative odontoid fractures were classified as type IIA in five patients, type IIB in eight, type IIC in 22, shallow type III in six according to Anderson and D'Alonzo typing. The fractures of five patients were not classified. According to the ASIA grading, the preoperative spinal cord function was graded as D or E in the 46 patients. Among the patients, 15 underwent posterior pedicle screw non-fusion internal fixation ( Group A) , with 60 pedicle screws removed 12-29 months after operation. A total of 31 patients were treated with fusion internal fixation with posterior pedicle screw ( Group B) , with 124 pedicle screws free from removal after operation. The follow-up time, operation time, intraoperative fluoroscopy time, intraoperative blood loss as well as visual analog scale (VAS), cervical rotation degree, and neck disability index ( NDI) before operation, 1 year after surgery ( when no internal fixation was removed ) and at the last follow-up were compared between the two groups. Results There were no significant differences between the two groups in the follow-up time, operation time, intraoperative fluoroscopy time, intraoperative blood loss, VAS score, neck rotation degree, NDI score before operation and at 1 year after operation (P >0. 05). There were significant differences between two groups in VAS scores, neck rotation degree, NDI scores indicating driving and walking and recreational activities at the last follow-up ( P <0. 05 ) . There were no significant differences between two groups in other NDI scores items, including neck discomfort, personal care, lifting heavy objects, reading & watching TV, headache situation, attention, working status, and sleep disorder at the last follow-up ( P> 0. 05 ) . Conclusions Posterior pedicle screw internal fixation for odontoid process fracture has good curative effect. Non-fusion internal fixation with posterior pedicle screw is more conducive to the recovery of cervical spine rotation function, the relief of neck and back pain, and the improvement of patients' driving, walking and entertainment activities.
		                        		
		                        		
		                        		
		                        	
10.Vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection
Guoqing JIANG ; Dousheng BAI ; Ping CHEN ; Jianjun QIAN ; Jie YAO ; Shengjie JIN ; Xiaodong WANG ; Zhihui GAO
Chinese Journal of General Surgery 2018;33(7):548-551
		                        		
		                        			
		                        			Objective To investigate the clinical safety and value of vagus nerve-preserving versus conventional laparoscopic splenectomy and azygoportal disconnection.Methods A total of 60 cirrhotic patients with bleeding portal hypertension undergoing modified laparoscopic splenectomy and azygoportal disconnection between Apr 2015 and Sep 2016 were retrospectively analyzed.Patients were divided into nonvagus nerve-preserving (n =37) and vagus nerve-preserving group (n =23).Results Operative time (169 ± 42) min,and incidences of postoperative complications (102/370),delayed gastric emptying (35/37),epigastric fullness (22/37),diarrhea (26/37) in non-vagus nerve-preserving group were all more than those in vagus nerve-preserving group [(147 ± 21) min,(21/230),(2/23),(2/23),(2/23)] (t =2.684,x2 =29.583,44.272,15.229,21.606,all P < 0.05).There was no significant between-group difference in body weight at admission and on postoperative day 7 (POD 7) between the two groups.However,body weight in vagus nerve-preserving group was significantly higher on postoperative 6 month (POM) compared with that in non-vagus nerve-preserving group [(63 ± 10) kg vs.(70 ± 12) kg,t =2.546,P < 0.05].There was no significant between-group difference in ALB levels at admission and on POD 7 between the two groups.However,ALB levels in vagus nerve-preserving group at POM 6 were significantly higher than those in non-vagus nerve-preserving group [(42 ±6) g/L vs.(46 ±5) g/L,t =-2.607,P < 0.05].Conclusion Vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection for cirrhotic portal hypertension is safe,feasible and with good therapeutic effect.
		                        		
		                        		
		                        		
		                        	
            

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