1.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
2.A single-center study on the safety and effectiveness of a novel non-implant interatrial shunt device
San-Shuai CHANG ; Xin-Min LIU ; Zheng-Ming JIANG ; Yu-Tong KE ; Qian ZHANG ; Qiang LÜ ; Xin DU ; Jian-Zeng DONG ; Guang-Yuan SONG
Chinese Journal of Interventional Cardiology 2024;32(8):425-433
Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100%.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80%.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.
3.Evidence-based practice of ankle pump exercises in preventing perioperative lower limb deep vein thrombosis in joint replacement patients
Yu XIE ; Xin LI ; Shizheng DU ; Weiyu PAN ; Junjuan ZHANG ; Jiajia LI
Chinese Journal of Modern Nursing 2024;30(29):3986-3994
Objective:To summarize the best evidence for the use of ankle pump exercises in preventing perioperative lower limb deep vein thrombosis (DVT) in patients undergoing joint replacement surgery and to evaluate its clinical application.Methods:This study utilized an evidence-based continuous quality improvement model. A systematic search was conducted for relevant clinical practice guidelines, expert consensus, systematic reviews, and randomized controlled trials (RCTs) from both domestic and international sources. The best evidence was evaluated and summarized, and audit indicators were developed for baseline assessments. Facilitating and hindering factors were analyzed based on the baseline results. From December 2022 to April 2023, the evidence was applied in the Department of Orthopedics at Henan Provincial People's Hospital. The pre-evidence group for baseline assessments included 36 joint replacement patients and 18 nurses from the orthopedic unit between December 2022 and January 2023, while the post-evidence group included 36 joint replacement patients and the same 18 nurses between March and April 2023. The knowledge level of nurses, the effectiveness of ankle pump exercises, the execution rate, and patient compliance were compared before and after evidence-based practice.Results:A total of 12 articles were included in the study, comprising one clinical practice guideline, five expert consensus papers, one systematic review, and five RCTs. Ten best practices were summarized in terms of applicable populations, exercise assessment, exercise positions, timing, methods, frequency, and patient education. After implementing evidence-based practice, the knowledge scores of nurses on ankle pump exercises significantly improved from (70.56±9.98) to (82.78±8.26) ( P<0.01). The compliance rates of audit items 2, 3, 4, 5, and 6 among nurses increased from 0, 22.2%, 0, 27.8%, and 11.1% respectively, to 94.4%, 94.4%, 83.3%, 100.0%, and 100.0% respectively ( P<0.01). On the patient side, the compliance rates for audit items 7 and 8 increased from 5.6% and 0 to 86.1% and 94.4%, respectively ( P<0.01) . Conclusions:Implementing evidence-based ankle pump exercises to prevent DVT in joint replacement patients can significantly improve nurses' knowledge of evidence-based practice, standardize the practice of ankle pump exercises, and explore balanced educational strategies that enhance patient compliance, ensuring clinical practices are evidence-based.
4.Effects and mechanism of NCTD on proliferation and apoptosis of human leukemic cells by targeting PPP5C
Xin ZHANG ; Bingjie CUI ; Guoxing YU ; Fei WANG ; Liang ZHAO ; Na GAO ; Jing DU
Chinese Journal of Comparative Medicine 2024;34(4):11-19
Objective To study the effects and mechanism of norcantharidin(NCTD)on proliferation and apoptosis of NB4 and K562 human leukemic cells by regulating phosphoprotein phosphatase 5 catalytic(PPP5C).Methods PC3.1 and PPP5C-PC3.1 plasmids were electroporated into NB4 and K562 cells.Stable NB4 and K562 cell lines were selected with geneticin(G418).Protein and mRNA expression levels of PPP5C were measured by Western blot and RT-qPCR,respectively.Proliferation,migration,and apoptosis of NB4 and K562 cells were determined by a CCK-8 assay,transwell assay,and Live & Dead? animal cell viability/toxicity detection kit,respectively.NB4 and K562 cells were divided into 0 μg/mL NCTD group and various NCTD dose groups,and cultured in RPMI 1640 medium containing 0,8,16,or 32 μg/ml NCTD.The Live & Dead? animal cell viability/toxicity detection kit measured the numbers of dead and live cells,and cell morphology was observed under a microscope.Western blot was used to measure protein expression levels of caspase 3,Cleaved caspase 3,JNK,p-JNK,p38,p-p38,and α-Tubulin.Results Proliferation,migration,and apoptosis of NB4 and K562 cells were enhanced by overexpression of PPP5C.Compared with 0 μg/mL NCTD group,NCTD promoted apoptosis in a dose-dependent manner.PPP5C overexpression antagonized the killing effect of NCTD on leukemic cells.Mechanistic investigations showed that PPP5C reduced the protein level of p-JNK by dephosphorylating and regulating the expression of apoptosis-related protein Cleaved caspase 3.Conclusions NCTD promotes apoptosis of NB4 and K562 cells and inhibits their proliferation by inhibiting PPP5C.
5.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
6.Preparation and Recognition Features of Molecularly Imprinted Polymer Membrane for Lamotrigine in Plasma
Dong-Yu LU ; Yu-Xin YOU ; Yan-Lin ZHAO ; Han JIANG ; Ying ZHANG ; Yan DU ; Dao-Quan TANG
Chinese Journal of Analytical Chemistry 2024;52(1):80-92
The molecularly imprinted polymers membranes(MIPMs)were prepared for selective adsorption of lamotrigine(LTG)in plasma by surface molecular imprinting technology with polyvinylidenefluoride(PVDF)membranes as supporter,lamotrigine as template molecule,methyl methacrylate as functional monomer,ethylene glycol dimethacrylate as cross-linking agent,azodiisobutyronitrile as initiator and acetonitrile-dimethylformamide(1∶1.5,V/V)as pore-forming agent.The prepared MIPMs were characterized by scanning electron microscope,Fourier transform infrared spectroscopy,Brunaner-emmet-teller measurements,X-ray photoelectron spectroscopy,and thermogravimetric analysis.The adsorption properties of the materials were investigated by kinetic adsorption,isothermal adsorption,selective adsorption,adsorption-desorption and reusability experiments.The results showed that the imprinted layer of LTG was successfully coated on the surface of PVDF,and the materials had uniform particle size.The adsorption capacity and imprinting factor of the MIPMs towards LTG were 3.77 mg/g and 8.97,respectively.The nanomaterials showed fast mass transfer rate(30 min)and good reusability(the adsorption efficiency was 86.66%after 6 cycles),and could be used for the adsorption of LTG in plasma with low matrix interference,recoveries of 86.54%-90.48%and RSD of 1.51%-3.15%(n=5).The proposed LTG MIPMs were demonstrated to be simple and environment friendly,and had high selectivity in rapid separation and extraction of LTG in plasma.
7.Current status of neonatal skin disinfectant use in 71 medical institutions in China
Jing-Wen MENG ; Qian-Nan ZHANG ; Shu-Hui YU ; Bian LI ; Xue-Yan DU ; Xin ZHANG ; Xi YAO
Chinese Journal of Infection Control 2024;23(2):169-174
Objective To understand the application of skin disinfectant in neonatal intensive care units(NICUs)nationwide.Methods From April to May 2023,application of skin disinfectant in 93 NICUs nationwide was sur-veyed with convenience sampling method by a self-designed questionnaire.Questionnaire contents included types of disinfectant,disinfection tools,cleaning and disinfection frequency,disinfectant drying status,removal of disinfec-tant,and adverse reactions caused by disinfectant.Results A total of 93 nursing units in 71 medical institutions from 25 provinces/municipalities were included in this study.In NICUs,three most commonly used disinfectants were ethanol(79.57%),iodophor(74.19%),and anerdian(62.37%).In nursing units for neonates<2 months of age,chlorhexidine was prohibited in 28 units(30.11%),used with caution in 23 units(24.73%),allowed in 9 units(9.68%),and there was no unified requirement in 33 units(35.48%).When using ethanol,staff only wiped once in 13(17.57%)nursing units.In some nursing units,there was no unified requirements on the wiping fre-quency of disinfectant.As for the removal of residual iodine,saline was used in 29(42.03%)nursing units,ethanol in 8(11.59%),and 19(27.54%)did not have unified requirements.The adverse reactions of disinfectant mainly included rash and contact dermatitis.Disinfectants that caused adverse reactions included ethanol,iodophor,aner-dian,and chlorhexidine.Conclusion In clinical practice,unified standards for the use of neonatal skin disinfectant remain absent.Selection and use of neonatal skin disinfectant vary considerably.Neonatal skin disinfectants have common adverse reactions.It is necessary to strengthen the training of health care workers on the standardized use of disinfectant,as well as carry out large-scale and rigorous randomized controlled trial designs to provide scientific basis for the correct selection of disinfectant.
8.Wumeiwan regulate Keap-1-Nrf2/HO-1 signaling pathway to inhibit oxidative stress injury in mice with ulcerative colitis
Li-Dong DU ; Ying WANG ; Rui-Hua XIN ; Zheng-Ying QIU ; Guan-Yu ZHAO ; Neng-Lian LI ; Jin SHAO ; Guo-Tai WU
The Chinese Journal of Clinical Pharmacology 2024;40(14):2088-2092
Objective To investigate the inhibitory effects of Wumeiwan on oxidative stress injury of ulcerative colitis mice induced by dextran sulfate sodium(DSS)by regulating Kelch-like ECH related protein 1(Keap-1)-nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathwayand.Methods Forty C57BL/6 mice were randomly divided into five groups:normal group,model group,positive control group,experimental-L,-H groups.UC mice model were induced by free access to 2%DSS water.Mice in normal and model group were orally administered with 0.9%NaCl,mice in positive control group were orally treated with Mesalazine solution(0.005 g·10 g-1·d-1),while mice in experimental groups were orally administered with Wumeiwan decoction at the dose of 0.13 and 0.26 g·10 g-1·d-1,respectively.All the drugs were administered for consecutive 7 days,1 times a day.The levels of disease activity index(DAI)and the colon length were scored.The levels of superoxide dismutase(SOD),catalase(CAT),cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)in colon tissue of mice were determined by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)method.The level of Keap-1,Nrf2,HO-1 proteins in colon tissue were determined by Western blot method.Results The levels of DAI of seventh day in normal group,positive control group,experimental-L,-H groups were 0、(2.62±0.33),(1.87±0.35),(1.87±0.35)and(1.58±0.35);the colon lengths were(8.16±0.47)、(5.98±0.24),(7.58±0.38),(7.33±0.24)and(7.48±0.51)cm;the SOD mRNA were 1.01±0.16、0.40±0.01,1.43±0.45,0.65±0.01 and 0.83±0.02;the CAT mRNA were 1.01±0.20、0.45±0.01,0.84±0.02,0.68±0.07 and 0.87±0.05;the COX-2 mRNA were 1.03±0.33、16.65±0.60,4.78±0.25,14.07±0.60 and 7.39±0.15;the iNOS mRNA were 1.04±0.40、20.71±0.66,8.09±0.93,15.44±0.68 and 11.66±0.06;the levels of Keap-1 were 1.22±0.16、1.10±0.05,1.18±0.05,1.94±0.08 and 1.17±0.08;the levels of Nrf2 were 1.12±0.16、0.76±0.15,0.65±0.13,0.70±0.16 and 0.82±0.18;the levels of HO-1 were 1.34±0.15、1.00±0.12,0.89±0.10,1.50±0.18 and 1.40±0.13,respectively.Significant difference was found between normal group and model group(P<0.01,P<0.05);significant difference was also found between the experimental-L,-H groups and model group(P<0.01,P<0.05).Conclusion Wumeiwan can inhibit oxidative stress in mice with UC,the mechanisms may be related to adjusted the expression of Keap-1-Nrf2/HO-1 signaling pathway protein in colon.
9.Effects of pirfenidone on chronic nonbacterial prostatitis in rats
Yu-Feng DU ; Ying-Xin WANG ; Huang-Hui CHEN ; Hui YU
The Chinese Journal of Clinical Pharmacology 2024;40(19):2858-2863
Objective To investigate the effects of pirfenidone(PFD)on inflammatory response and apoptosis in chronic nonbacterial prostatitis(CNP)and its mechanism.Methods Wistar rats were randomly divided into sham group(injected with the same amount of normal saline),model group(injected with carrageenan),positive group(35 mg·kg-1 celecxib),compound C group(150 mg·kg-1 pirfenidone+0.2 mg·kg-1 compound C),experimental-L group(50 mg·kg-1 PFD),experimental-H group(150 mg·kg-1 PFD),10 mice per group.Mechanical pain threshold was determined by Von Frey fibrograph;tissue related protein expression was detected by Western blot assay;inflammatory factor expression was detected by enzyme-linked immunosorbent assay(ELISA);apoptosis was detected by TdT mediated dUDP nick end labeling(Tunel)assay.Raw264.7 was randomly divided into control group(normal culture),lipopolysaccharide(LPS)group(1 μg·mL-1 LPS),PFD group(1 μg·mL-1 LPS+4 mmol·L-1 PFD)and combined group(1 μg·mL-1 LPS+4 mmol·L-1 PFD+10 μmol·L-1compound C).The expression of inflammatory factors was detected by ELISA.Results The pain thresholds of sham operation group,model group,positive group,experimental-H group and compound C group were(45.33±5.09),(23.13±3.20),(35.27±4.65),(33.96±2.65)and(30.30±4.77)g,respectively;phosphorylated adenylate activated protein kinase(p-AMPK)protein expression levels were 0.84±0.11,0.33±0.07,0.31±0.05,0.65±0.09 and 0.20±0.04,respectively;the contents of interleukin-6(IL-6)were(80.10±3.33),(237.82±15.68),(91.30±5.57),(139.79±16.93)and(207.92±13.22)pg·mL-1,respectively;Tunel apoptosis rates were(3.57±0.18)%,(26.29±1.84)%,(12.16±0.76)%,(11.78±1.45)%and(15.76±1.05)%,respectively.The above indexes in the model group were compared with those in the sham group,the experimental-H group was compared with those in the model group,and the above indexes in the compound C group were compared with those in the experimental-H group,and the differences were significant(all P<0.05).IL-6 content in control group,LPS group,PFD group and combined group were(72.06±4.03),(328.03±27.80),(169.84±19.38)and(204.53±18.39)pg·mL-1,respectively.The above indexes were significantly different in LPS group compared with control group,PFD group compared with LPS group,and combined group compared with PFD group(all P<0.05).Conclusion Pirfenidone can reduce inflammation and apoptosis by inhibiting the polarization of macrophages towards M1 type,improvemen t of CNP pelvic pain.
10.Epidemiological characteristics of pulmonary tuberculosis in Shaanxi Province from 2016 to 2021
ZHANG Lin ; DU Xin ; MA Yu ; LIU Yini
Journal of Preventive Medicine 2024;36(8):706-709
Objective:
To understand the epidemiological characteristics of pulmonary tuberculosis (PTB) in Shaanxi Province from 2016 to 2021, so as to provide the basis for improving PTB prevention and control strategies.
Methods:
The incidence data of PTB cases in Shaanxi Province were collected from the Tuberculosis Information Management System of the Chinese Disease Prevention and Control Information System from 2016 to 2021. The temporal, geographical, and demographic distribution characteristics of PTB were described.
Results:
A total of 121 280 PTB cases were reported in Shaanxi Province from 2016 to 2021, with the reported incidence rate decreasing from 56.30/105 in 2016 to 40.98/105 in 2021 (P<0.05). The etiological positivity rate increased from 16.61% in 2016 to 54.37% in 2021 (P<0.05). The average annual number of reported cases peaked in March (1 984.67 cases, accounting for 9.81%), followed by January (1 885.50 cases, accounting for 9.33%), and hit its lowest in October (1 458.50 cases, accounting for 7.22%). The incidence of PTB was relatively high in northern Shaanxi and southern Shaanxi, at 67.99/105 and 64.05/105, respectively, while it was relatively low in Guanzhong Region, at 44.83/105. The incidence rates of Ankang City (85.81/105), Fugu County (73.92/105), and Yulin City (72.20/105) ranked the top three. There were 80 111 male cases and 41 169 female cases of PTB, with a male-to-female ratio of 1.95︰1. The reported incidence rate of males (67.38/105) was significantly higher than that of females (36.61/105), and the difference was statistically significant (P<0.05). Among males, the highest average reported incidence rate was found in the 80 to <85 age group (179.46/105), while among females, the highest was in the 75 to <80 age group (104.38/105). The main occupations were farmers, accounting for 68.87% (83 526 cases).
Conclusions
The reported incidence rate of PTB in Shaanxi Province showed an overall downward trend from 2016 to 2021, with a high incidence in winter and spring. The epidemic in southern Shaanxi and northern Shaanxi is more severe than in Guanzhong Region of Shaanxi Province. The incidence of PTB is predominantly found among males, the elderly, and farmers.


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