1.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.
2.Zinc finger protein A20-targeting siRNA promotes pyroptosis of human rheumatoid arthritis fibroblast-like synoviocytes
Ziqin ZHAO ; Shuhui DONG ; Haibo YIN ; Aidong LIU ; Yong YANG ; Guangyi XIONG
Basic & Clinical Medicine 2024;44(10):1407-1413
Objective To investigate the regulatory effect of small interfering RNA(siRNA)silencing zinc finger protein A20 on pyroptosis of rheumatoid arthritis(RA)fibroblast-like synoviocytes(HFLS-RA).Methods Hu-man FLS-RA cell line MH7A cells were cultivated,A20 siRNA silencing group was synthesized for knocking down the human A20 gene,and then specific A20 gene siRNA and siRNA-NC(negative control)were transfected into MH7A cells using liposome method.RT-qPCR was applied to detect the expression of NLRP3 and Caspase-1 mRNA in cells.The protein expression of NLRP3 and Caspase-1 was detected by Western blot,and IL-1β and IL-18 in cell culture medium were detected by ELISA method.Transmission electron microscopy(TEM)was used to detect pyroptosis.Results After A20 knockdown,the mRNA and expression of NLRP3 and Caspase-1 in MH7A cells in the siRNA-A20 group were significantly increased as compared with the siRNA-NC group(P<0.01).The concentration of IL-1β and IL-18 in the cell culture supernatant of the siRNA-A20 group was sig-nificantly increased compared with the siRNA-NC group(P<0.01).Compared with the siRNA-NC group,some cells in the siRNA-A20 group showed swollen and ruptured.The integrity of the cell membrane was also lost,and a large area of edema was present in the cell.In addition,a blurred depression of the local nuclear membrane was noted,while an increase in heterochromatin pyknosis was accompanied by their uneven distribution as well as their aggregation around the nuclear membrane.Conclusions Silencing of A20 gene with siRNA might promote NLRP3/Caspase-1 mediated pyroptosis in HFLS-RA,which lays an experimental foundation for new clinical treatment meth-ods of RA.
3.Comparative study of endoscopic spine surgery with and without assistance of an electromagnetic navigation surgical robot in the treatment of lumbar disc herniation
Zhichao CONG ; Zhiping YU ; Chengzhen JIN ; Xiaogeng SUN ; Wei XIONG ; Haitao WANG ; Haibo CONG
Chinese Journal of Microsurgery 2023;46(2):139-146
Objective:To compair the clinical effect of endoscopic spine surgery with and without assistance of an electromagnetic navigation surgical robot(ENSR) system in the treatment of lumbar disc herniations(LDH).Methods:From March 2021 to December 2021, 73 patients with LDH underwent endoscopic minimally invasive treatment in the Department of Spine Surgery, Limin Hospital of Weihai High District. Thirty-eight patients were treated with endoscopic spine surgery assisted by domestic ENSR system(ENSR group), and 35 patients were treated with endoscopic spine surgery alone(endoscopic group). The patients received follow up regularly by telephone or Wechat. The intraoperative fluoroscopy times, puncture times, upper facet arthroplasty times, operation time, preoperative and postoperative Visual Analogue Scale(VAS), Japanese Orthopaedic Association Scores(JOA), and the MOS item short from health survey(SF-36)were compared between the 2 groups. The early postoperative efficacy was evaluated by modified MacNab criteria at 1 week after surgery. SPSS 26.0 was used to analyse the data. P<0.05 was considered that the difference was statistically significant. Results:The age, gender, body mass index(BMI) and other general data of the 2 groups were basically the same, and there was no statistically significant difference( P>0.05). There was no significant difference in the excellent and good rate of postoperative treatment between ENSR group(97.37%) and endoscopic group(94.29%)( Z=0.90, P>0.05). In terms of operation time, intraoperative fluoroscopy times, puncture times, and plasty times, ENSR group[(67.00±17.00) min, (4±2) times, 1 time, 1 time, respectively] was compared with the endoscopic group[(82.00±16.00] min, (17±6) times, (9±5) times, (5±2) times], and the difference was statistically significant( t=3.87,12.62, 9.87, respectively, P<0.05). There were significant differences in VAS, JOA and SF-36 scores between the 2 groups between before and after surgery( F=106.42, 112.14, 26.88, respectively, P<0.05). There was no significant difference in VAS, JOA and SF-36 scores before and after surgery between the 2 groups( F=0.95, 3.54, 0.97, respectively, P>0.05). Conclusion:The endoscopic spine surgery assisted by the ENSR can achieve satisfactory clinical results and is a safe and effective surgical assistance system. For the endoscopic surgery, assisted by the ENSR has obvious advantages in reducing the times of fluoroscopy, puncture, and facet arthroplasty, and shortening the operation time.
4.Efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors of gastric cardia and fundus: a multicenter study
Weifu ZHANG ; Xingyu FENG ; Peng ZHANG ; Wenjun XIONG ; Zaisheng YE ; Tao CHEN ; Haibo QIU ; Yuesheng YANG ; Wei WANG ; Luchuan CHEN ; Jiang YU ; Junjiang WANG ; Deqing WU ; Zhiwei ZHOU ; Kaixiong TAO ; Yong LI
Chinese Journal of Digestive Surgery 2023;22(4):519-525
Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.
5.Primary practice of transcatheter edge-to-edge repair for mitral regurgitation: Early results of MitraClip in multiple centers
Manchen GAO ; Fujian DUAN ; Gejun ZHANG ; Yongquan XIE ; Shouzheng WANG ; Xiaopeng HU ; Haibo HU ; Junyi WAN ; Zhiling LUO ; Jiahua PAN ; Jing ZHANG ; Huijun SONG ; Hui XIONG ; Xiangbin PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(05):547-552
Objective To investigate the early clinical results of MitraClip system in domestic patients. Methods We retrospectively analyzed the clinical data of 36 patients who underwent transcatheter edge-to-edge repair procedure using MitraClip system in Beijing Fuwai Hospital, Shenzhen Fuwai Hospital and Fuwai Yunnan Cardiovascular Hospital between January and June 2021. There were 24 males and 12 females, with a median age of 70 (47-86) years. Ten (27.8%) patients had 3+ mitral regurgitation (MR) and 26 (72.2%) patients had 4+ MR preoperatively. Results All procedures were successfully performed. The reduction in MR was 2+ at least immediately after surgery, and 91.7% of patients had MR≤2+ at 3 days postoperatively. There was no statistical difference in left ventricular ejection fraction change postoperatively. Forward velocity and peak gradient of mitral valve were increased after the procedure. Mean gradient of mitral valve were increased at 3 days postoperatively than immediately after surgery (P<0.001). Two patients had acute pericardial effusion intraoperatively, and received pericardial puncture and drainage immediately. Conclusion MitraClip system has been applied well in domestic patients and can significantly improve MR. This sutdy has a good consistency with foreign studies, and the early results are satisfactory.
6.In-hospital mortality and related risk factors after knee replacement in China: based on national hospital quality monitoring system data
Huizhong LONG ; Chao ZENG ; Hu CHEN ; Yilin XIONG ; Qiao JIANG ; Dongxing XIE ; Yilun WANG ; Jie WEI ; Ying SHI ; Haibo WANG ; Yongcheng HU ; Guanghua LEI
Chinese Journal of Orthopaedics 2022;42(11):730-738
Objective:To estimate in-hospital mortality after knee replacement (KR) and to assess its trend and risk factors in China.Methods:We included patients undergoing KR in the Hospital Quality Monitoring System in China (2013-2019) to estimate in-hospital mortality after KR and assessed relation of patient's and hospital's characteristics (year of surgery, age, gender, marital status, primary indication, Charlson comorbidity index, geographic location, hospital type, hospital volume of KR, and surgery type) to in-hospital mortality using multivariable Poisson regression.Results:The annual amount of KR has increased from 20 307 in 2013 to 35 757 in 2019, and has maintained an upward trend for 7 years. The mean age of patients having KR increased from 64.9 years in 2013 to 66.6 years in 2019. Of the total 218 923 KRs, 63 deaths (0.29‰) occurred within 30 days before discharging. Older age was associated with higher in-hospital mortality ( P for trend <0.001). Male gender had higher incidence of in-hospital mortality compared with female [relative risk (RR), 2.5; 95% CI: 1.5, 4.1]. Single marital status was associated with higher, albeit non-statistically significant, in-hospital mortality than married patients (RR, 2.1; 95% CI: 0.9, 4.6). Higher Charlson comorbidity index was associated with increased risk of in-hospital mortality ( P for trend <0.001). Risk of in-hospital mortality decreased with more hospital-year knee replacement surgeries ( P for trend <0.001). In-hospital mortality varied by geographic regions, with the lowest mortality in East region (0.16‰), followed by South-West (0.31‰), South-Central (0.31‰), North region (0.33‰), North-West (0.54‰) and North-East (0.59‰). Conclusion:In-hospital mortality after KR in China was relatively low. Older age, male gender, higher Charlson comorbidity index and lower hospital-year knee replacement surgeries were risk factors for in-hospital mortality. The mortality varied greatly according to the geographic location of hospital.
7.Risk factors for premature proximal femur physeal closure after femoral neck fractures in children treated surgically
Wentao WANG ; Yiqiang LI ; Yueming GUO ; Ming LI ; Haibo MEI ; Zhu XIONG ; Jingfan SHAO ; Jin LI ; Shunyou CHEN ; Canavese FEDERICO
Chinese Journal of Orthopaedics 2021;41(2):76-83
Objective:To identify the risk factors for premature proximal femur physeal closure (PPC) in children treated surgically for femoral neck fractures.Methods:Data of 106 children with an open triradiate cartilage who were treated surgically for a femoral neck fracture were retrospectively analyzed. Age, gender, laterality, mechanism of injury, the type of fracture, initial displacement, time to reduction, fixation method, whether the implant crossed the physeal plate, reduction method, reduction quality and development of femoral head avascular necrosis (AVN) were collected. PPC of the proximal femur was assessed through postoperative 6-12 months radiographs.Results:A total of 106 patients with an open triradiate cartilage were followed up, with an average duration of 20.4±13.3 months (range, 6-86 months). The overall rate of PPC following paediatric femoral neck fractures treated surgically was 36.8% (39/106). Among the 39 patients with PPC, 25 were males and 14 were females; the average age at the time of injury was 9.7±3.6 years (range, 3-15 years); 23 patients were involved in left hips and 16 were in right; the mechanisms of injury included motor vehicle accident in 5 fractures, falling injury in 21, sports-related injury in 12 and other causes in 1 fracture; two hips were Delbet type I, and 26 hips and 11 hips were Delbet type II and III, separately; type II and III of initial displacement were involved in 26 and 13 patients, separately; the mean duration from injury to surgery was 3.3±2.8 d (range, 1-14 d); 2 hips were treated with Kirschner wires, 35 hips with screw fixation, and the remaining 2 hips underwent screw and plate fixation; 2 hips had the hardware crossing the proximal femoral growth plate, and the remaining 37 hips didn’t; 15 hips were treated by closed reduction and internal fixation, and the other 24 hips underwent open reduction and internal fixation; anatomical reduction was achieved in 14 patients, acceptable reduction in 24 hips and unacceptable reduction in 1 hip; 24 hips developed AVN at the latest follow-up and the remaining 15 hips didn’t. Statistical analysis indicated that age ( t=3.875, P< 0.001), the severity of initial displacement ( Z=-2.118, P=0.034) and the rate of AVN ( χ2=42.280, P< 0.001) in patients with PPC were significantly higher than those in patients without; Logistic regression analysis confirmed age ( OR=1.288, P=0.011) and AVN ( OR=40.336, P< 0.001) as risk factors for PPC. ROC curve analysis indicated 10 years was the cut off age to significantly increase the rate of PPC. The rate of PPC in patients aged over 10 years (63.6%, 21/33) was significantly higher than that (24.7%, 18/73) in those aged less than 10 years ( χ2=14.848, P< 0.001). Conclusion:Age over 10 years and AVN are risk factors for PPC in children with femoral neck fractures treated surgically.
8.Study on Prevention Effect and Mechanism of Miao Medicine Liangjiang Weiyang Capsule on Gastric Ulcer Model Rats
Lianli DENG ; Jinjuan ZHANG ; Bing LIANG ; Ying XIONG ; Shanggao LIAO ; Haibo WANG ; Xun HE
China Pharmacy 2019;30(7):946-950
OBJECTIVE: To study the protective effect and mechanism of Miao medicine Liangjiang weiyang capsule on gastric ulcer model rats. METHODS: Rats were randomly divided into normal group (normal saline), model group (normal saline), positive control group (omeprazole, 0.02 g/kg) and Liangjiang weiyang capsule low-dose, medium-dose and high-dose groups (0.3, 0.6, 1.2 g/kg), with 12 rats in each group. All rats were intragastrically administered once a day for consecutive one week. 1 h after last administration, all rats except those in normal group were given the absolute ethanol to induce gastric ulcer model. 1 h after modeling, gastric juice volume, gastric juice pH, pepsin activity, gastric ulcer area and inhibitory rate of gastric ulcer were recorded in each group. Histopathological changes of gastric mucosa in rats of each group were observed by HE staining. The serum levels of TNF-α and IL-6 were determined by ELISA. The expression of nuclear factor-κB pathway related protein (p-NF-κB p65, p-IκBα) in gastric tissue of rats were determined by Western blot. RESULTS: Compared with normal group, gastric juice volume, pepsin activity, gastric ulcer area, TNF-α and IL-6 levels in serum, p-NF-κB p65 and p-IκBα levels in the gastric tissue were significantly increased/rised (P<0.05), while gastric juice pH was significantly decreased (P<0.01); there were gastric mucosal hyperemia and redness, obvious defect of mucosal epithelial cells, destruction of gland structure and incomplete cell structure. Compared with model group, gastric juice volume, pepsin activity, gastric ulcer area and the levels of TNF-α and IL-6 were reduced/decreased significantly in positive control group, Liangjiang weiyang capsule medium-dose and high-dose groups (P<0.05 or P<0.01), while pH value of gastric juice was increased significantly (P<0.05); gastric mucosa was normal, gland destruction was alleviated and cell structure was intact. The levels of p-NF-κB p65 and p-IκBα in gastric tissue were significantly decreased in Liangjiang weiyang capsule high-dose groups (P<0.05). CONCLUSIONS: Liangjiang weiyang capsule play a role to protect gastric ulcer by increasing gastric juice pH, inhibiting pepsin activity, reducing the release of inflammatory factors as TNF-α, IL-6 and inhibiting the expression of NF-κB pathway related protein.
9.Qualitative study on care needs in parents of children with congenital pseudarthrosis of the tibia during Ilizarov fixation
Fengliang DENG ; Jianhui XIE ; Haibo MEI ; Jiong TAN ; Yinzhi YI ; Xin LIU ; Hua XIONG
Chinese Journal of Modern Nursing 2019;25(10):1271-1274
?? [Abstract]? Objective? To deeply explore the care needs in parents of children with congenital pseudarthrosis of the tibia (CPT) during Ilizarov fixation. Methods? Totally 10 parents of CPT children during Ilizarov fixation hospitalized in the Department of Orthopedics, Hu'nan Children's Hospital between March and December 2017 were selected using purposive sampling and received semi-structural interview. Colaizzi phenomenological methods were used to analyze the data. Results? Totally 4 themes were refined, including informational support needs (needle way care, functional exercise and feeding), psychological support needs, economic support needs, and children's educational support needs. Conclusions? The parents of CPT children during Ilizarov fixation have many care needs. Nursing workers should pay attention to their needs and take targeted measures to accelerate the postoperative recovery of children.
10.Effects of aripiprazole on clinical symptoms and serum neurotrophic factor levels in patients with schizophrenia
Qigen WAN ; Jinqiong ZHAN ; Yuanjian YANG ; Yonghui FU ; Jianwen XIONG ; Zhipeng LIU ; Kun YAN ; Haibo CHEN ; Yating TU ; Bo WEI
Chinese Journal of Nervous and Mental Diseases 2018;44(4):217-221
Objective To explore the effects of aripiprazole on clinical symptoms and neurotrophic factor levels in patients with schizophrenia. Methods Forty patients with schizophrenia and 40 normal controls were included in the study. The clinical symptoms of patients receiving aripiprazole only for 12 weeks were evaluated by using the Positive and Negative Syndrome Scale (PANSS). Stroop Color-Word Test (SCWT), Continuous Performance Test, Digit-Symbol Coding Test and Trail Making Test-A were used to evaluate the cognitive function both in patients and controls. Serum levels of Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin 3 (NT-3) were measured using enzyme linked immunosorbent assay. Results The clinical scores, cognitive function and levels of neurotrophic factors were different before and after treatment (P<0.01). And those were significantly lower in patients than in control group (P<0.05). Before treatment, BDNF was negatively correlated with PANSS negative symptom score (r=-0.362, P=0.022);NGF was related to the total score of PANSS (r=0.332, P=0.037) and positive symptoms (r=0.401, P=0.010); NT-3 was associated with negative symptom scores (r=-0.376, P=0.017) and SCWT-color words (r=0.332, P=0.037) in patient group. After treatment, the increase in BDNF was correlated with the reduction in PANSS total score (r=0.371, P=0.018), negative symptom score (r=0.345, P=0.029) and general pathology score (r=0.342, P=0.031). There was a correlation of the increase of NGF with the decrease of PANSS total scores (r=0.437, P=0.005) and with positive symptom scores (r=0.357, P=0.024). Conclusion Treatment with Aripiprazole can improve the clinical symptoms and cognitive functiona impairments in patients with schizophrenia, which may be related to the increase in serum levels of BDNF, NGF and NT-3.

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