1.Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos
Ling SUN ; Jiahui LI ; Simiao ZENG ; Qiangxiang LUO ; Hanpei MIAO ; Yunhao LIANG ; Linling CHENG ; Zhuo SUN ; Hou Wa TAI ; Yibing HAN ; Yun YIN ; Keliang WU ; Kang ZHANG
Chinese Medical Journal 2024;137(16):1939-1949
Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.
2.Preparation and evaluation of immune effect of recombinant S1 protein based on SARS-CoV-2 beta variant
Zechang FAN ; Sheng FENG ; Mingzheng LIANG ; Shanshan MA ; Ningyi JIN ; Zhuo HA ; Huijun LU
Chinese Journal of Veterinary Science 2024;44(6):1133-1139
The codon sequence of the S1 protein of the SARS-CoV-2 Beta variant was optimized ac-cording to the preference of CHO cells and cloned into pSN expression vector to construct the re-combinant plasmid pSN-Beta-sl.Recombinant protein was expressed in CHO cells,identified using SDS-PAGE and Western blot,and purified through affinity chromatography.BALB/c mice were immunized with purified recombinant protein Beta-S1 combined with aluminum hydroxide adju-vant.Specific IgG antibody and its subtypes in serum and the cross-neutralization antibody activity against SARS-CoV-2 variants were evaluated.The results showed that the recombinant plasmid pSN-Beta-S1 was successfully constructed,and the recombinant protein Beta-S1 was produced u-sing the CHO cell expression system.The purified recombinant protein had a single band of about 120 kDa with the purity exceeding 85%and can bind to RBD pAb and strep-tag mAb.The recom-binant S1 protein showed good immunogenicity in BALB/c mice.The titers of specific IgG antibodies against RBD protein and S1 protein reached 1∶66 260 and 1∶133 120 on average 21 d after the third immunization,the antibody subtypes were mainly inclined to IgG1.Serum neutrali-zing antibody titer was 1∶629 for wild type,1∶1 720 for Beta,1∶374 for Delta,1∶77 for Omi-cron BA1 and 1∶101 for Omicron BA2.In this study,S1 recombinant protein of SARS-CoV-2 Beta variant was successfully expressed in CHO cell expression system and produced good immunoge-nicity and cross-neutralizing activity in BALB/c mice.These results provide a reference for the fur-ther development of broad-spectrum SARS-CoV-2 vaccine.
3.Ku80 Inhibition Affects the Chemotherapeutic Sensitivity of T-Acute Lymphoblastic Leukemia Cell Line Jurkat
Journal of Experimental Hematology 2024;32(6):1689-1695
Objective:To investigate the influence of Ku80 inhibition on the chemotherapeutic sensitivity of the T-acute lymphoblastic leukemia (T-ALL) cell line Jurkat,and to explore the potential mechanism.Methods:The transcription and expression level of Ku80 in 6 hematological malignant cell lines were detected by RT-qPCR and Western blot,respectively.The expression of Ku80 in Jurkat cells was detected by Western blot after transfection with the recombinant shKu80 lentiviral vector.The proliferation capacity of Jurkat cells was explored by CCK-8 after Ku80 inhibition.The colony formation ability,apoptosis,and γH2AX(a protein marker of DNA damage)expression in Jurkat cells were investigated after Ku80 silencing and co-treated with etoposide(VP16)for 4 hours through soft agar assay,flow cytometry and Western blot,respectively.Results:The Mrna level and protein expression of Ku80 were both highest in Jurkat among 6 hematological malignant cell lines.Ku80 expression was successfully down regulated in Jurkat cells after relative plasmid transfected.The proliferative ability of cells was significantly decreased after Ku80 inhibition (P<0.05).The colony formation capacity of Jurkat cells was obviously reduced and the cells apoptosis and Γh2ax expression were increased after Ku80 inhibition,with or without VP16 incubation.Conclusion:Targeted silencing of Ku80 could enhance the sensitivity of VP16 in Jurkat cells,which might be associated with the elevated level of DNA damage accumulation.
4.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
5.Correlation of plasma levels of 3 markers with risk stratification and poor prognosis in elderly patients with acute pulmonary embolism
Yuanming WANG ; Huicai ZHENG ; Yue ZHUO ; Liang CHEN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(10):1147-1151
Objective To investigate the plasma levels of signal peptide-CUB epidermal growth fac-tor domain inclusion protein-1(SCUBE-1),asymmetric dimethylarginine(ADMA)and insulin-like growth factor binding protein-2(IGFBP-2)in elderly patients with acute pulmonary embol-ism(PE)and their relationship with risk stratification and poor prognosis.Methods A total of 117 elderly patients with acute PE admitted to our hospital from January 2022 to December 2023 were retrospectively enrolled in this study.With risk stratification,there were 41 patients of high-risk,46 of medium-risk and 30 of low-risk.According to their clinical outcomes,they were divided into good prognosis group(85 cases)and bad prognosis group(32 cases).The plasma levels of SCUBE-1,ADMA,and IGFBP-2 were measured using ELISA.Multivariate logistic regression analysis was applied to identify the risk factors for poor prognosis,and ROC curves were drawn to analyze the predictive value of plasma levels of SCUBE-1,ADM A and IGFBP-2 for poor prognosis of these patients.Results The levels of cTnI,BNP,D-dimer,SCUBE-1,ADMA and IGFBP-2 were significantly higher in the poor prognosis group than the good prognosis group(0.95±0.28μg/L vs 0.30±0.08 μg/L,2017.62±308.15 μg/L vs 538.14±102.73 μg/L,5.24±1.13 μg/L vs 1.63±0.27 μg/L,22.50±10.14 μg/L vs 9.25±4.36 μg/L,2.01±0.72 μmol/L vs 0.61±0.17μmol/L,468.16±90.51 μg/L vs 155.27±30.74 μg/L,P<0.01).The high-risk patients had high-er plasma levels of SCUBE-1,ADMA and IGFBP-2 than the medium-and low-risk patients in or-der(all P<0.01).Multivariate logistic regression analysis showed that elevated levels of cTnI,BNP,D-dimer,SCUBE-1,ADMA and IGFBP-2 were risk factors for death in acute PE patients(P<0.05).ROC curve analysis indicated that the AUC value of SCUBE-1,ADMA and IGFBP-2 combined together in predicting death for acute PE patients was the highest(0.927,95%CI:0.864-0.993),with an accuracy of 93.1%.The plasma levels of SCUBE-1,ADMA and IGFBP-2 were positively correlated with the levels of cTnI,BNP and D-dimer in the elderly patients(P<0.01).Conclusion For the elderly patients with acute PE,elevated plasma levels of SCUBE-1,ADMA and IGFBP-2 are associated with risk stratification and poor prognosis.Combination of these three indicators has certain predictive value for poor prognosis in the patients.
6.Effects of Moluodan Dami Pills on chronic atrophic gastritis rats
Meng-Lei WANG ; Yi-Feng WU ; Jian-Liang SUI ; Miao-Miao YIN ; Hui-Yun LIU ; Qi-Chao LIU ; Zhuo-Chen WU ; Zhen WANG
Chinese Traditional Patent Medicine 2024;46(5):1476-1482
AIM To investigate the effects of Moluodan Dami Pills on chronic atrophic gastritis(CAG)rats and their mechanism.METHODS The rat models were randomly divided into the model group,the low-dose group and high-dose Moluodan Dami Pills groups(2.43 g/kg and 4.86 g/kg),and vitamin A group(0.32 g/kg),following the 16 weeks successful induction of CAG by five-factor modeling method,in contrast to another 10 normal rats of the control group.After 8 weeks corresponding administration,the rats of each group had their general physiological status and pH value of gastric juice assessed;their pathological changes of gastric mucosa observed by naked eyes combined with HE staining;their changes of gastrin-secreting cells(G cells)and somatostatin-secreting cells(D cells)in gastric mucosa observed by immunohistochemistry;and their serum levels of pepsinogen Ⅰ/pepsinogen Ⅱ(PG Ⅰ/PG Ⅱ)ratio,TNF-α and IL-6 detected by ELISA.RESULTS Compared with the model group,the groups intervened with Moluodan Damei Pills and vitamin A displayed lower pH values of gastric juice(P<0.05),improved pathological changes of gastric mucosa,increased G and D cells counts(P<0.05,P<0.01),increased ratio of serum PGⅠ/PGⅡ,and decreased levels of IL-6 and TNF-α(P<0.05,P<0.01).CONCLUSION Moluodan Dami Pills can effectively improve the symptoms of CAG rats through its influence on the number and secretion abilityof G and D cells,the levels of serum PG Ⅰ/PG Ⅱ ratio and inflammatory factors.
7.Expression levels of miR-934 and miR-1307 in serum of patients with esophageal squamous cell carcinoma and their relationship with clinicopathological features and prognosis
Zhuo LIU ; Zheng ZHAO ; Liang-Liang ZHANG ; Zhao JIN
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(2):158-162
Objective To clarify the expression levels of miR-934 and miR-1307 in serum of patients with esophageal squamous cell carcinoma(ESCC),and analyze the relationship between their expression and clinicopathological features and prognosis.Methods A total of 125 ESCC patients(ESCC group)who were admitted to our hospital from January 2018 to December 2019 were selected,and 100 healthy subjects(control group)were selected during the same period,the expression of miR-934 and miR-1307 in serum were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction(qRT-PCR).After 3 years of follow-up,the patients were divided into miR-934 low expression group(<2.53)and miR-934 high expression group(≥2.53),miR-1307 low expression group(<2.10)and miR-1307 high expression group(≥2.10),based on their mean values,the prognosis of patients with different expression of miR-934 and miR-1307 in serum was compared,and the related factors affecting the survival and prognosis of patients were analyzed by univariate and multivariate COX regression analysis.Results The relative expression levels of serum miR-934 and miR-1307 in ESCC group were 2.53±0.72 and 2.10±0.68 respectively,significantly higher than those in control group's 1.32±0.39 and 1.12±0.33(all P<0.05).Serum miR-934 and miR-1307 were closely related to TNM stage,lymph node metastasis,tumor differentiation and distant metastasis in ESCC patients(all P<0.05).The 3-year progression-free survival(PFS)in serum miR-934 and miR-1307 high expression group was lower than that in miR-934 and miR-1307 low expression group.Multivariate Cox regression analysis showed that,TNM stage Ⅲ~Ⅳ,high expression of miR-934 and high expression of miR-1307,low differentiation degree and distant metastasis were independent risk factors for PFS in ESCC patients(all P<0.05).Conclusion Serum miR-934 and miR-1307 are abnormally highly express in ESCC patients,and their high expression is an independent risk factor for poor prognosis of ESCC patients,which is expected to be a marker for prognosis evaluation of ESCC.
8.Evaluation of Mechanical Properties of a Novel Sacroiliac Lag Screw
Cheng LIANG ; Chuanchuan ZHUO ; Guan WANG ; Wen LI ; Ke DUAN ; Zhong LI ; Xiaobo LU ; Naiqiang ZHUO
Journal of Medical Biomechanics 2024;39(2):265-271
Objective To investigate the biomechanical properties of a novel sacroiliac lag screw with a spiral blade.Methods Percutaneous sacroiliac lag screws were used as the controls.Polyurethane material was used to simulate the trabecular bone,and the pullout resistance performance was tested on an Instron mechanical testing machine.Subsequently,pelvic specimens were utilized to analyze the static stiffness and dynamic stability of the novel sacroiliac lag screw in repairing sacroiliac joint injuries under normal standing conditions,with normal pelvis,single-sided sacroiliac joint injury pelvis,percutaneous sacroiliac lag screw-single screw repair,and percutaneous sacroiliac lag screw-double screw repair as controls.Results The damage to the polyurethane material after screw extraction was smaller in the novel sacroiliac lag screw group.The average effective holding displacement of the novel sacroiliac lag screw was significantly greater than that of the percutaneous sacroiliac lag screw(P<0.05).However,the maximum resistance to the pullout force for the percutaneous sacroiliac lag screw was significantly higher than that for the novel sacroiliac lag screw(P<0.05).The stiffness after repair of sacroiliac joint injuries was significantly higher when using a single sacroiliac lag screw than when using two percutaneous sacroiliac lag screws(P<0.05).The displacement amplitude was the highest in the sacroiliac joint injury group,followed by that in the normal group.The displacement amplitudes in the other groups were similar;however,the differences were statistically significant(P<0.05).The dynamic stability of the sacroiliac lag screw repair group was the best,slightly better than that of the percutaneous sacroiliac lag screw-double screw repair group,and the dynamic stability of the sacroiliac joint injury group was the worst.The novel sacroiliac lag screw effectively repaired the sacroiliac joint injuries.Conclusions The novel sacroiliac lag screw can effectively hold the trabecular bone and has practical clinical utility.
9.Drug resistance characteristics and treatment strategies of TB patients in three age groups in Guangdong Province from 2014 to 2020
Wenji ZHUO ; Ran WEI ; Yanmei CHEN ; Xunxun CHEN ; Meiling YU ; Huixin GUO ; Hongdi LIANG ; Jing LIANG ; Xiaoyu LAI
The Journal of Practical Medicine 2024;40(5):702-707
Objective To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.
10.Finite element and biomechanical analysis of different implants in repair for unilateral unstable pelvic posterior ring injury
Cheng LIANG ; Linqi ZHANG ; Guan WANG ; Wen LI ; Ke DUAN ; Zhong LI ; Xiaobo LU ; Naiqiang ZHUO
Chinese Journal of Tissue Engineering Research 2024;28(9):1336-1341
BACKGROUND:The stability of the pelvis is mainly determined by the posterior pelvic ring and the sacroiliac joint.The posterior pelvic ring injury and the dislocation of the sacroiliac joint caused by high energy impacts such as car accidents increase year by year.Surgical treatment is the best method,and there are many kinds of endophytorepair methods in clinical practice,but which treatment method has the best biomechanical properties is still controversial. OBJECTIVE:To compare the biomechanical properties of three kinds of internal implants:anterior double plates,posterior bridging plate and tension nail in the repair of unilateral unstable pelvic posterior ring injury,to provide a reference for the clinical treatment and development of a new pelvic tension screw. METHODS:(1)Finite element simulation:Mimics,Wrap and SolidWorks were used to establish normal pelvic model,unilateral injured pelvis model,and three kinds of internal implant repaired models(anterior double plates,posterior bridging plate and tension nail).Ansys was used to analyze the stress and deformation of the models.(2)Biomechanical test:A total of 15 intact pelvic specimens were randomly grouped into five groups,normal pelvic model,unilateral injured pelvis model,anterior double plates,posterior bridging plate and tension nail groups.The mechanical test was performed using an Instron E10000 testing machine. RESULTS AND CONCLUSION:(1)Simulation:In the normal pelvic model,the average displacement of the sacrum was 0.174 mm,and the maximum stress of the sacral iliac bone was 10.51 MPa,and the stress distribution was uniform.The mean sacral displacement of the unilateral injured pelvis model was 0.267 mm,and the stress concentration of the model was obvious.The mean displacement of the sacrum in the three repaired models was close to that in the normal pelvic model,and the stress distribution of the sacral iliac bone in the tension nail repaired model was uniform.(2)Mechanical test:The stiffness of the normal pelvic model was(226.38±4.18)N/mm,and that of the unilateral unstable pelvic model was the smallest(130.02±2.19)N/mm.The deviation of the normal pelvic model stiffness and the three repaired models'stiffness were all within(±10%),and the repair effect was obvious.(3)The simulation results were in agreement with the experimental results.(4)The biomechanics of the tension nail repaired model was the most similar to that of the normal pelvis,and this method was the best.The repairing stiffness of the anterior double plate was too large,and the stress shielding effect was more significant.The posterior bridging plate repair could not solve the compensatory effect of the normal side soft tissue and had defects.This study provides an optimal basis for clinical surgery.(5)The new type of pelvic tension nail should be improved from the point of view of the tension nail to retain the good biomechanical properties of the tension nail,while adding other advantages,such as being used for the osteoporotic pelvis.

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