1.Expert consensus on strategies to correct proximal contact loss between implant prostheses and the adjacent natural teeth
Guangbao SONG ; Xinquan JIANG ; Qianbing WAN ; Cui HUANG ; Yan LI ; Xinhua GU ; Zhe WU ; Zhenhua WANG ; Hongbo LI ; Longquan SHAO ; Hongchen LIU
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(7):485-493
		                        		
		                        			
		                        			The problems caused by proximal contact loss(PCL)of dental implants have been a mainstream research topic in recent years,and scholars are unanimously committed to analyzing their causes and related factors,aiming to identify solutions to the problems related to PCL.The effects of the anterior component of force(ACF),the lifelong re-molding of the adult craniofacial jaw and alveolar socket,and the osseointegration characteristics of dental implants are the main causes of PCL.On the one hand,the closing movement of the mandible causes the ACF of the tooth to move through the posterior molar cusp.Moreover,drifting between the upper and lower posterior teeth and mandibular anteri-or teeth can cause the anterior teeth of the upper and lower jaws to be displaced labially.On the other hand,reconstruc-tion of the jaw,alveolar socket and tooth root,the forward horizontal force of the masticatory muscles,the dynamic com-ponent of the jaw and the forward force generated by the oblique plane of the tooth cusp can cause the natural tooth to experience near-middle drift.Additionally,natural teeth can shift horizontally and vertically and rotate to accommodate remodeling of the stomatognathic system and maintain oral function.Nevertheless,the lack of a natural periodontal mem-brane during implant osseointegration,the lack of a physiological basis for near-medium drift,the small average degree of vertical motion and the integrated silence of dental implants without the overall drift characteristics of natural teeth increases the probability of PCL.The high incidence of PCL is clearly associated with the duration of prosthesis delivery and the mesial position;but it is also affected by the magnitude of the bite force,occlusion,the adjacent teeth,restora-tion design,implant location,jaw,and patient age and sex.PCL has shown a significant correlation with food impaction,but not a one-to-one correspondence,and did not meet the necessary and sufficient conditions.PCL is also associated with peri-implant lesions as well as dental caries.PCL prevention included informed consent,regular examinations,se-lection of retention options,point of contact enhancement,occlusal splints,and the application of multipurpose digital crowns.Management of the PCL includes adjacent contact point additions,orthodontic traction,and occlusal adjust-ment.Existing methods can solve the problem of food impaction in the short term with comprehensive intervention to seek stable,long-term effects.Symmetric and balanced considerations will expand the treatment of issues caused by PCL.
		                        		
		                        		
		                        		
		                        	
2.Effectiveness of three electronic fetal monitoring systems in identifying neonatal acidosis during labor
Lili QIU ; Huilian HU ; Ling YANG ; Ning GU ; Zhenhua ZHU ; Jing FANG ; Yan ZHOU ; Yimin DAI
Chinese Journal of Perinatal Medicine 2024;27(5):362-370
		                        		
		                        			
		                        			Objective:To analyze the effectiveness and interobserver agreement of the Parer five-tier, the National Institute of Child Health and Human Development (NICHD) three-tier, and the International Federation of Gynecology and Obstetrics (FIGO) three-tier electronic fetal monitoring (EFM) systems in identification of neonatal acidosis during labor.Methods:This retrospective study was conducted on full-term singleton cephalic deliveries with neonatal acidosis (umbilical artery blood gas pH≤7.1) and normal newborns (umbilical artery blood gas pH≥7.2) in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January to December 2020. EFM tracings during the last 30-60 min before delivery were collected. Four obstetricians independently described the features of randomly sorted and coded EFM tracings. Another obstetrician categorized these tracings using the NICHD three-tier, FIGO three-tier, and Parer five-tier evaluation systems based on the features. All researchers were masked to the clinical characteristics and maternal and neonatal outcomes. The sensitivity and specificity for identifying neonatal acidosis, as well as the interobserver agreement, were analyzed for all three systems. Independent sample t-test, Chi-square (or Fisher's exact test) and Mann-Whitney U tests were used for statistical analysis. Inter-group comparisons of sensitivity and specificity between the three evaluation systems were assessed using McNemar's test. The Kappa statistic was used to analyze interobserver agreement. Results:This study included a total of 3 558 cases. After propensity score matching, there were 44 cases of neonatal acidosis and 78 control cases. There were no significant differences in parity, gestational weeks, modes of delivery, placental abruption, or analgesia rates between the two groups. The rates of instrumental vaginal delivery and neonatal intensive care unit (NICU) admission in the acidosis group were significantly higher than those in the control group [15.8% (7/44) vs. 2.6% (2/78), χ2=8.45, P=0.003; 31.8% (14/44) vs. 12.8% (10/78), χ2=8.45, P=0.004], while the umbilical artery blood pH and mean base excess were lower in the acidosis group than in the control group [7.04±0.07 vs. 7.30±0.05, t=4.98; (-12.40±3.32) vs. (-5.64±1.95) mmol/L, t=13.61; both P<0.001]. (2) Using the NICHD three-tier system, 95.5% (42/44) of the acidosis cases and 89.7% (70/78) of the control cases were classified as having category Ⅱ EFM tracings, indicating potential fetal acid-base imbalance; category Ⅲ EFM tracings were only observed in 4.5% (2/44) of the cases in the acidosis group. With the FIGO three-tier system, 81.8% (36/44) of the acidosis cases were categorized as having "pathological" tracings, and with the Parer five-tier system, 86.4% (38/44) of the acidosis cases were correctly classified into the "orange or red" risk zones that indicated acid-base imbalance. Among the control cases, there were 28.2% (22/78) with EFM tracings of "normal patterns" categorized by the FIGO three-tier system, and 41.0% (32/78) classified into the "green or blue" risk zones by the Parer five-tier system, which indicated good fetal conditions. None of the acidosis cases were misdiagnosed as being normal by the Parer five-tier system. (3) Compared with the NICHD three-tier system, both the FIGO three-tier and the Parer five-tier systems showed increased diagnostic sensitivity [4.5% (1.2%- 14.5%) vs. 81.8% (66.8%-89.4%) and 86.4% (71.8%-92.4%)], but decreased specificity [100.0% (95.3%- 100.0%) vs. 87.2% (78.0%-92.9%) and 84.6% (75.0%-91.0%)]. There was no statistically significant difference in the sensitivity or specificity between the FIGO three-tier and Parer five-tier systems for identifying neonatal acidosis ( P=0.727 and 0.791). (4) When reading the tracings of control cases, the total agreement rate for the NICHD three-tier system by different observers was as high as 94.2%, while the total agreement rates for the FIGO three-tier and Parer five-tier systems were 69.7% and 67.7%, respectively. In the interpretation of EFHR tracings for acidosis cases, the interobserver agreement for the Parer five-tier system was excellent [Kappa (95% CI): 0.87 (0.79-0.95)], while both the NICHD three-tier and FIGO three-tier systems showed good agreement [Kappa (95% CI): 0.77 (0.66-0.88) and 0.72 (0.60-0.84)]. Conclusions:The Parer five-tier and the FIGO three-tier systems have higher sensitivity in identifying neonatal acidosis than the NICHD three-tier system, and the Parer five-tier system achieves a higher negative predictive value and a greater agreement in the interpretation of pathological EFM patterns.
		                        		
		                        		
		                        		
		                        	
3.Effect of matrine on proliferation, apoptosis and radiotherapy sensitivity of uveal melanoma cells
Zhenhua WANG ; Xiaoqi GUO ; Lijun CHEN ; Runan ZHANG ; Liuqin YANG ; Liping WU ; Xiaohua GU
Chinese Journal of Ocular Fundus Diseases 2023;39(10):828-835
		                        		
		                        			
		                        			Objective:To investigate the effects of matrine on proliferation, apoptosis and radiotherapy sensitivity of uveal melanoma cells.Methods:An animal experiment study. In vitro experiment: MuM2B cells of human choroidal melanoma were randomly divided into control group and matrine 0.25, 0.50, 1.00, 2.00 g/L groups. The cell morphology was observed by transmission electron microscope. Cell proliferation was detected by thiazole blue colorimetry. The mRNA and relative expression levels of CyclinD D (CyclinD), B lymphoblastoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) were detected by real-time polymerase chain reaction and Western blot. In vivo experiment: BALB/C mice were injected with MuM2B cell suspension subcutaneously on the back of forelimb to prepare transplanted tumor model. After successful modeling, they were randomly divided into blank group and matrine treatment group with different concentrations. Mice in blank group were injected with phosphate buffer subcutaneously. Mice in different matrine treatment groups were injected with 15, 25, 50, 100 mg/kg matrine subcutaneously, respectively, for 7 consecutive days. The tumor was weighed and its volume was measured after the last administration. Single factor analysis of variance was used to compare different groups. The t test was used for pairwise comparison between groups. Results:In the control group, the cell structure was normal, the distribution was uniform, and no or rare nuclear pyknosis was seen. With the increase of matrine dosage, the nuclear pyretosis increased gradually and cell morphology changed obviously. Compared with the control group, the cell survival rate in 0.50, 1.00 and 2.00 g/L groups gradually decreased with matrine concentration increasing and treatment time prolongating, the relative expression levels of CyclinD and Bcl-2 mRNA and protein gradually decreased, and the relative expression levels of Bax mRNA and protein gradually increased. Under the same radiation dose X-ray irradiation, the cell survival rate of 0.50, 1.00 and 2.00 g/L groups gradually decreased, and the differences were statistically significant ( P<0.05). Compared with blank group, the tumor weight and volume of mice in different doses of matrine group were significantly decreased, and the differences were statistically significant ( P<0.05). Conclusion:Matrine can down-regulate the expression of CyclinD and Bcl-2, up-regulate the expression of Bax, promote the apoptosis of MuM2B human melanoma cells, inhibit cell proliferation, and enhance cell radiosensitivity.
		                        		
		                        		
		                        		
		                        	
4.Effect comparison of lateral-rectus approach and ilioinguinal approach in the treatment of toddlers with Torode-Zieg type IV pelvic fracture
Yujin TANG ; Chengliang YANG ; Cheng GU ; Xiaodong YANG ; Qiguang MAI ; Tao LI ; Yuhui CHEN ; Zhenhua ZHU ; Jianwen LIAO ; Shicai FAN
Chinese Journal of Trauma 2022;38(1):40-46
		                        		
		                        			
		                        			Objective:To compare the clinical efficacy of lateral-rectus approach and ilioinguinal approach in the treatment of Torode-Zieg type IV pelvic fracture in toddlers.Methods:A retrospective cohort study was used to analyze the clinical data of 12 toddlers with Torode-Zieg type IV pelvic fracture admitted to Affiliated Hospital of Youjiang Medical College for Nationalities and Third Affiliated Hospital of Southern Medical University from June 2012 to June 2019. There were 6 males and 6 females, aged 13-36 months [(23.9±7.4)months]. Treatment via ilioinguinal approach was performed for 5 patients (ilioinguinal group), and via lateral-rectus approach for 7 patients (lateral-rectus group). Operation duration, intraoperative blood loss and postoperative complications were compared between the two groups. At the last follow-up, pelvic function was evaluated by Majeed function score, and fracture reduction was evaluated according to Mears-Velyvis radiological evaluation criterion.Results:All patients were followed for 24-72 months [(46.0±18.5)months]. In ilioinguinal group and lateral-rectus group, the operation time was (295.0±95.3)minutes and (165.1±52.2)minutes, respectively ( P<0.05), and the intraoperative blood loss was (190.0±65.2)ml and (225.7±92.0)ml, respectively ( P>0.05). In ilioinguinal group, the development of bilateral iliac wings was asymmetric in 3 patients. In lateral-rectus group, fracture-dislocation of epiphyseal plate together with abnormal development of iliac wing occurred in 1 patient, but had no effects on the function of lower limbs. According to Majeed function score at the last follow-up, the pelvic function in ilioinguinal approach group was rated as excellent in 1 patient, good in 2, fair in 1 and poor in 1, with the excellent and good rate of 60%, while the pelvic function in lateral-rectus group was excellent in 4 patients, good in 1, fair in 2 and poor in none, with the excellent and good rate of 71% ( P>0.05). According to Mears-Velyvis radiological evaluation criterion at the last follow-up, the fracture reduction in ilioinguinal group was rated as satisfied in 3 patients and dissatisfied in 2 patients, with the satisfaction rate of 60%, while the fracture reduction in lateral-rectus group was satisfied in 7 patients and dissatisfied in none, with the satisfaction rate of 100% ( P>0.05). Conclusions:For Torode-Zieg type IV pelvic fracture in toddles, both surgical approaches can complete the reduction and fixation. However, the lateral-rectus approach has shorter operation time and less damage to the epiphyseal structure around the pelvis than the ilioinguinal approach.
		                        		
		                        		
		                        		
		                        	
5.Investigation of treatment and analysis of prognostic risk on intra-abdominal fistula in China: a multicenter prospective study
Haohao XIE ; Tao ZHENG ; Wei ZHOU ; Feng WANG ; Zhenhua YANG ; Qiang CHI ; Gefei WANG ; Guosheng GU ; Xiuwen WU ; Jian′an REN
Journal of Chinese Physician 2020;22(6):805-809
		                        		
		                        			
		                        			Objective:To investigate the diagnosis and treatment for intra-abdominal fistula in China, and to explore the prognostic factors.Methods:A multi-center cross-sectional study was conducted based on the Registration System of Chinese Gastrointestinal Fistula and Intra-Abdominal Infections to collect the clinical data of patients with intra-abdominal fistula from 18 medical centers from January 1, 2018 to December 31, 2018, including basic information, medical records and prognosis.Results:A total of 106 patients were enrolled in this study, including 57 males and 49 females, with an average age of (48.0±17.8)years. The most common type of intra-abdominal fistula was entero-vesical fistula (34.0%), followed by entero-vaginal fistula (31.1%), entero-enteric fistula (26.4%) and multiple fistula (8.5%). The direct causes of intra-abdominal fistula were mainly surgical operation (66.0%), followed by spontaneous fistula due to Crohn′s disease (18.9%), radiation intestinal injury (11.3%), and 4 cases (3.8%) of unknown reasons. During the whole treatment, 95 patients received nutritional support therapy, mainly EN+ PN (75.8%). Finally, 86 patients (81.1%) received surgical treatment, with a healing rate of 95.3%. After surgery, 8.1% of patients developed surgical site infections (SSI), and 10.5% had a relapse of fistula. 20 patients (18.9%) were treated conservatively, with a self-healing rate of 80.0%. The overall mortality rate was 8.5%, and the highest mortality (15.2%) was found in entero-enteric fistula. Statistical analysis showed that the age ( t=-4.664, P<0.001), leucocyte level ( U=663.000, P=0.010), sepsis ( P=0.002) and multiple organ dysfunction syndrome (MODS) ( P=0.019) were higher in the death group than those in the healing group. Multivariate analysis suggested that advanced age ( OR=1.073, 95% CI: 1.008-1.141, P=0.026) and complications of sepsis ( OR=11.806, 95% CI: 1.064-131.048, P=0.044) were independent risk factors of the death for patients with intra-abdominal fistula. Conclusions:The overall mortality rate of intra-abdominal fistula is still high, and malignant tumor is the most common primary disease. Advanced age and sepsis are independent risk factors for death in patients with intra-abdominal fistula.
		                        		
		                        		
		                        		
		                        	
6. Investigation of treatment and analysis of prognostic risk on enterocutaneous fistula in China: a multicenter prospective study
Tao ZHENG ; Haohao XIE ; Xiuwen WU ; Qiang CHI ; Feng WANG ; Zhenhua YANG ; Chaowu CHEN ; Wei MAI ; Suming LUO ; Xiaofei SONG ; Shimin YANG ; Wei ZHOU ; Haiyan LIU ; Xinjian XU ; Zheng ZHOU ; Chuanyuan LIU ; Lian′an DING ; Kai XIE ; Gang HAN ; Hongbin LIU ; Jianzhong WANG ; Shichen WANG ; Peige WANG ; Gefei WANG ; Guosheng GU ; Jian′an REN
Chinese Journal of Gastrointestinal Surgery 2019;22(11):1041-1050
		                        		
		                        			 Objective:
		                        			To investigate the diagnosis and treatment for enterocutaneous fistula (ECF) in China, and to explore the prognostic factors of ECF.
		                        		
		                        			Methods:
		                        			A multi-center cross-sectional study was conducted based on the Registration System of Chinese Gastrointestinal Fistula and Intra-Abdominal Infections to collect the clinical data of ECF patients from 54 medical centers in 22 provinces/municipalities from January 1, 2018 to December 31, 2018. The clinical data included patient gender, age, length of hospital stay, intensive care unit (ICU) admission, underlying diseases, primary diseases, direct causes of ECF, location and type of ECF, complications, treatment and outcomes. All medical records were carefully filled in by the attending physicians, and then re-examined by more than two specialists. The diagnosis of ECF was based on the clinical manifestations, laboratory/imaging findings and intraoperative exploration.
		                        		
		                        			Results:
		                        			A total of 1521 patients with ECF were enrolled, including 1099 males and 422 females, with a median age of 55 years. The top three primary diseases of ECF were malignant tumors in 626 cases (41.2%, including 540 gastrointestinal tumors, accounting for 86.3% of malignant tumors), gastrointestinal ulcers and perforations in 202 cases (13.3%), and trauma in 157 cases (10.3%). The direct causes of ECF were mainly surgical operation in 1194 cases (78.5%), followed by trauma in 156 (10.3%), spontaneous fistula due to Crohn
		                        		
		                        	
7.The Changes and clinical significance of platelet parameters in children with dengue fever
Xiaoyun LIANG ; Daowen WANG ; Pengcheng XIE ; Lanlan ZENG ; Zhenhua HUANG ; Meigan HUANG ; Xiaoqiong GU
International Journal of Laboratory Medicine 2018;39(5):562-565
		                        		
		                        			
		                        			Objective To investigate the variation characteristics of peripheral platelet parameters in children with dengue fever and to assess their use and value in diagnosis,prognosis and treatment for dengue fever.Methods Platelet parameters of 69 pediatric patients with dengue fever in acute febrile phase and remission period and 103 healthy controls were compared.The difference of platelet parameters between the liver function injury group and the normal liver function group,the coagulation dysfunction group and the coagulation function normal group,the severe group and the mild group with dengue fever was compared,the causes of thrombocytopenia in children with dengue was investigated so as to better understand the situation of bone marrow producing platelets.Results P-LCR,PDW,MPV were significantly higher in patients in acute febrile phase of dengue fever,compared with the healthy subjects(P<0.01),while PCT,PLT were significantly lower in patients in acute febrile phase of dengue fever,compared with the healthy subjects(P<0.01).MPV was significantly lower in patients with abnormal hepatic function when compared with patients with normal hepatic function(P<0.05),while other platelet parameters did not show significant differences(P>0.05).PLT and PCT were significantly lower in the severe patients than those in the mild patients(P<0.05),while other platelet parameters did not show significant differences(P>0.05).Peripheral platelet parameters did not show significant differences between patients with or without abnormal coagulation function (P>0.05).Conclusion Peripheral platelet parameters may play a role in the diagnosis,treatment and prognosis of dengue fever in children.
		                        		
		                        		
		                        		
		                        	
8.Clostridium difficile carriage in infants and the characteristics of isolates
Tianxiang ZHOU ; Zhenhua SHU ; Kelin XIAO ; Zhongxing WANG ; Guangxing MAI ; Yong XIA ; Zhen HUANG ; Huisheng FAN ; Conghui GU
International Journal of Laboratory Medicine 2017;38(13):1735-1737
		                        		
		                        			
		                        			Objective To investigate the carrying status and characteristics of Clostridium difficile isolated from infants.Methods Two hundred and thirty-eight stool specimens were collected from infant younger than 1 year old,that were hospitalized or outpatient from August to November 2015.Immunochromatography targeted GDH and toxin A&B of C.difficile was used for C.difficile screening,and those positive specimens were inoculated in CDIF and anaerobic culture.C.difficile isolates were genotyped by using slpA sequence typing (slpA ST),and tcdA,tcdB,cdtA and cdtB of C.difficile isolates were detected by PCR.Results Fifty C.difficile strains were isolated from 238 stool samples,and the isolated rates of C.difficile from <3 months,3 months to <6 months,and 6 months to 1 years old groups were 9.3%,17.6% and 27.3%(χ2=6.940,P=0.031<0.05),respectively.52.0%(26/50) of the C.difficile isolates were toxigenic,and 69.2% (18/26) toxigenic isolates harbored tcdA+tcdB+cdtA-cdtB-.Fifty C.difficile isolates were genotyped as 11 slpA STs,slpA ST fr-02 and kr-02 were the commonest genotypes in toxigenic C.difficile isolates;however,that was slpA ST xr-03 in non-toxigenic isolates.Conclusion High C.difficile carriage is found in infants younger than 1 year old,and more than half of C.difficile isolates are toxigenic.Most of toxigenic isolates harbored toxin A and B.The genotype of C.difficile isolates is different between toxigenic isolates and non-toxigenic isolates.
		                        		
		                        		
		                        		
		                        	
9.Changes of serum inflammatory mediators in secondary septic shock after chemotherapy for acute leukemia
Feiyan YU ; Zhenhua WANG ; Xiaolin GU
Chinese Journal of Biochemical Pharmaceutics 2017;37(3):288-290
		                        		
		                        			
		                        			Objective To observe and analyze the change state of serum inflammatory mediators of patients with secondary septic shock after chemotherapy for acute leukemia .Methods 56 patients with secondary septic shock after chemotherapy for acute leukemiawere were selected as the group A,56 patients without secondary septic shock after chemotherapy for acute leukemia were selected as the group B ,56 healthy persons of the same age were selected as the group C,then the serum inflammatory mediators levels of three groups were detected and compared,and the serum indexes of group A with different severity degree of shock were compared, then the detection results of group A and group B with different types ( lymphocytic leukemia and nonlymphocytic leukemia)were compared.Results The serum inflammatory mediators levels, including TNF-α, IL-4, IL-6, IL-10 and other inflammatory factors, including PGE2 , sICAM-1, sVCAM-1 and sCD44, there were group A >group B >group C, severe shock >moderate shock>mild shock ( all P<0.05 ) .The above serum inflammatory mediators and other inflammatory factors levels of different types in group A were higher than those in group B, and the above mediators in lymphocytic leukemia of group A and group B were higher than those in nonlymphocytic leukemia (all P<0.05).Conclusion The serum inflammatory mediators of patients with secondary septic shock after chemotherapy for acute leukemia show higher expression state,and the influence of shock degree and leukemia types for the expression are great.
		                        		
		                        		
		                        		
		                        	
10.Effects of keyhole hematoma evacuation and internal medicine conservative treatment on 30-40 mL hypertensive intracerebral hemorrhage
Yusheng WANG ; Yiquan KE ; Yingbiao HONG ; Shaoming CAI ; Zhenhua HUANG ; Gu HUANG ; Lehui XIE
Chinese Journal of Neuromedicine 2016;15(6):629-632
		                        		
		                        			
		                        			Objective To compare the differences of hospital stays,hospitalization costs and effectiveness via keyhole hematoma debridement (KHED) and internal medicine conservative treatment (IMCT) in treating 30-40 mL hypertensive intracerebral hemorrhage.Methods Fifty-eight patients with hypertensive intracerebral hemorrhage whose bleeding was 30-40 mL,admitted to our hospital from January 2014 to September 2015,were chosen in our study;according to the will of the patients and their family members,the patients were divided into KHED group (n=31) and IMCT group (n=27).The differences of hospital stays,hospitalization costs,neurological dysfunction rate at hospital and three months after discharge,and recovery results were compared between the two groups.Results The average hospital stays of KHED group were (7.4±2.3) d and those of IMCT group were (14.5±5.1) d,with significant difference (P=0.012);the hospitalization costs for the two groups were (36 296.28±5292.12)yuan,and (41 769.48±6342.83) yuan,with significant difference (P=0.027).Glasgow outcome scale of KHED group at discharge indicated 29 patients with good recovery and 2 with poor recovery;that of IMCT group indicated 20 with good recovery and 7 with poor recovery,including two with cerebral edema accepted craniotomy operation in second time.Follow-up for three months showed that the KHED group had basic activities of daily living in 16 patients,mild hemiplegia in 11 and severe hemiplegia in 4,and IMCT group had basic activities of daily living in 9 patietns,mild hemiplegia in 13 and severe hemiplegia in 5;significant differences were noted between the two groups (Z=2.499,P=0.001).Conclusion KHED in treatment of 30-40 mL hypertensive intracerebral hemorrhage can shorten hospitalization time,reduce cost,have better prognosis and better short-term and long-term effectiveness than IMCT.
		                        		
		                        		
		                        		
		                        	
            

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