Journal of Biomedical Research最新文献

{"title":"Washed microbiota transplantation for ribotype 027 <i>Clostridioides difficile</i> infection in a pregnant woman with a two-year follow-up: A case report.","authors":"Xinyi He, Sibusiso Luthuli, Quan Wen, Chuan Wang, Jinli Ding, Bota Cui, Faming Zhang","doi":"10.7555/JBR.39.20250063","DOIUrl":"10.7555/JBR.39.20250063","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> ( <i>C. difficile</i>) is one of the major causes of nosocomial infections. Pregnant women, who are generally considered at low risk for <i>C. difficile</i> infection (CDI), have attracted attention because of an increasing number of reports. Oral vancomycin, the only first-line treatment for pregnant women infected with <i>C. difficile</i>, has been associated with increasing strain resistance, leading to decreased efficacy. Fecal microbiota transplantation (FMT) is recommended for severe, fulminant, and recurrent CDI; however, it is generally avoided in pregnant women because of safety concerns. We report a case of a pregnant woman with a primary ribotype 027 CDI who experienced a successful outcome with washed microbiota transplantation (WMT), an improved form of FMT, <i>via</i> enema. The specific strain of ribotype 027 is related to severe outcomes but has not previously been reported in pregnant women. The follow-up lasted for two years, during which the patient's diarrhea was fully alleviated without recurrence. The baby showed normal growth and development, and no adverse events were recorded for either. This case provides evidence for the efficacy and safety of WMT in pregnant women infected with <i>C. difficile</i>, indicating that WMT <i>via</i> enema may be a viable therapeutic strategy for this population for treating CDI.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"99-102"},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype and genotype analyses of 21 Chinese patients with Dent disease.","authors":"Ruochen Che, Yuwen Cai, Wei Zhou, Sanlong Zhao, Songming Huang","doi":"10.7555/JBR.38.20240183","DOIUrl":"10.7555/JBR.38.20240183","url":null,"abstract":"<p><p>Dent disease is a rare X-linked recessively inherited renal tubulopathy, caused by variants in the <i>CLCN5</i> (Dent disease type 1, DD1) and <i>OCRL</i> (Dent disease type 2, DD2) genes, and characterized by low molecular weight proteinuria, hypercalciuria, microscopic hematuria, or nephrocalcinosis. In the current study, we collected and analyzed clinical data and genetic testing results of 21 children diagnosed with Dent disease, who were hospitalized at the Department of Nephrology, Children's Hospital of Nanjing Medical University between January 2014 and August 2023, aiming to assist in the early diagnosis and treatment of these patients. Among the 21 patients, 16 (76.19%) had <i>CLCN5</i> variants, and five (23.81%) had <i>OCRL</i> variants, and four of the variants were novel. All patients presented with low molecular weight proteinuria, 14 (66.67%) of whom had nephrotic-range proteinuria. Eight patients underwent renal biopsies because of diagnostic uncertainty. We transfected the novel <i>CLCN5</i> missense variant (p.G222R) and <i>OCRL</i> missense variant (p.I371T) plasmids into both HEK293 and HK-2 cells and found a significantly lower expression of the OCRL1 protein in the transfected cells than in the wild-type cells ( <i>P</i> < 0.05). Moreover, we observed an extremely skewed X-chromosome inactivation pattern in a female patient carrying the same novel <i>CLCN5</i> variant, as assessed by the human androgen receptor gene assay. These findings provide insight into the clinical characteristics of Dent disease in Chinese patients and may shed light on its pathogenesis.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"356-366"},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1-year outcomes of single bolus r-SAK before primary PCI for STEMI: The follow-up of OPTIMA-5.","authors":"Chen Li, Jie Yu, Tian Wu, Qingxia Lin, Rui Hua, Zihang Zhong, Yule Li, Kun Liu, Li Zhu, Naiquan Yang, Xin Chen, Xiaoyan Wang, Xin Zhao, Jun Jiang, Bo Zhao, Xiwen Zhang, Pengsheng Chen, Tong Wang, Yi Xu, Gaoyong Liao, Liang Yuan, Bo Chen, Zhihui Xu, Xiaoxuan Gong, Wenhao Zhang, Chunyue Tan, Lei Xu, Qiang Huang, Jianling Bai, John W Eikelboom, Chunjian Li","doi":"10.7555/JBR.39.20250043","DOIUrl":"10.7555/JBR.39.20250043","url":null,"abstract":"<p><p>The OPTIMA-5 study demonstrated that a single bolus of half-dose recombinant staphylokinase (r-SAK) before primary percutaneous coronary intervention (PCI) significantly improved the patency of infarct related artery in patients with ST-elevation myocardial infarction (STEMI) expected to undergo PCI within 120 minutes. This study aimed to investigate the 1-year clinical outcome and the effect of the r-SAK antibody on a second r-SAK thrombolysis in OPTIMA-5 patients. The clinical outcome was major adverse cardiovascular events (MACE) within 360 days. Patients' r-SAK antibodies were determined on days 90 ± 7, 180 ± 7, and 360 ± 14 after thrombolysis, and <i>in-vitro</i> r-SAK antibody neutralization experiments were performed to explore an optimal interval for a second r-SAK thrombolysis. Results showed that the MACE incidence was numerically lower in r-SAK group compared with normal saline (NS) group (14.0% <i>vs</i>. 20.0%, HR 0.67, 95% CI: 0.34-1.32; log-rank <i>P</i>=0.245). The r-SAK antibody levels in r-SAK group decreased by time, but kept significantly higher than those in NS group on days 90 ± 7 (2.96 ± 0.68 <i>vs</i>. 0.22 ± 0.53, <i>P</i><0.001), 180 ± 7 (2.19 ± 0.74 <i>vs</i>. 0.44 ± 0.65, <i>P</i><0.001) and 360 ± 14 (1.73 ± 0.97 <i>vs</i>. 0.37 ± 0.71, <i>P</i><0.001). The <i>in-vitro</i> r-SAK antibody neutralization experiments illustrated that the thrombolysis rate decreased exponentially as the antibody titer increased from 1.90 to 2.20 (67.80 ± 14.19% <i>vs</i>. 44.32 ± 21.54%, <i>P</i>< 0.0001). Therefore, for STEMI patients expected to undergo PCI within 120 minutes, a single bolus of half-dose r-SAK before primary PCI may reduce 1-year MACE risk. The r-SAK antibody lasts over 1 year, and a second r-SAK thrombolysis may not be indicated until 1 year after the first r-SAK thrombolysis if necessary.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-10"},"PeriodicalIF":3.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using higher cut-off values to diagnose acute myocardial infarction in patients with elevated hs-cTnT.","authors":"Tian Wu, Jiaqi Chai, Chunyue Tan, Zhiwen Tao, Hui Yong, Zhenyu Lin, Xiaoxuan Gong, Kun Liu, Lei Xu, Qin Wang, Shenqi Jing, Jiani Xu, Hui Zhou, Tao Li, Liang Yuan, Bo Chen, Fang Wang, Ruxing Wang, Yun Liu, Chunjian Li","doi":"10.7555/JBR.38.20240364","DOIUrl":"10.7555/JBR.38.20240364","url":null,"abstract":"<p><p>It is often challenging to diagnose acute myocardial infarction (AMI) in patients with elevated high-sensitivity cardiac troponin T (hs-cTnT) before a significant rise and/or fall of hs-cTnT can be observed. This study aimed to find an optimal cut-off to rule in AMI. A total of 76411 patients with elevated hs-cTnT were included. The predictive cut-off values for diagnosing ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) were assessed by the area under the receiver operating characteristic curves (AUC). Among the patients, 50466 (66.0%) had non-cardiac diseases, 25945 (34.0%) had cardiac diseases, and 15502 (20.3%) had AMI, including 816 (1.1%) with STEMI and 14686 (19.2%) with NSTEMI. The median hs-cTnT level was 3788.0 ng/L in STEMI patients and 67.2 ng/L in NSTEMI patients. The optimal cut-off for diagnosing STEMI was 251.9 ng/L, with a sensitivity of 90.7%, specificity of 86.5%, and an AUC of 0.942; the optimal cut-off for diagnosing NSTEMI was 130.5 ng/L, with a sensitivity of 40.9%, specificity of 83.8%, and an AUC of 0.638. In patients with elevated hs-cTnT, optimizing the cut-off values for diagnosing STEMI and NSTEMI to 251.9 ng/L and 130.5 ng/L, respectively, demonstrated high accuracy in a large cohort of Chinese patients.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-10"},"PeriodicalIF":3.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the plasma antioxidant activity in women with early pregnancy losses.","authors":"Olga Gennadievna Tishkova, Lydmila Vasilievna Dikareva, Nadezhda Titovna Berberova, Maria Alexandrovna Polovinkina, Victoria Pavlovna Osipova","doi":"10.7555/JBR.38.20240396","DOIUrl":"10.7555/JBR.38.20240396","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-4"},"PeriodicalIF":2.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homoharringtonine exerts anti-silicosis potential by inhibiting the CCR1 and PI3K/AKT signaling pathways in lung fibroblasts.","authors":"Xinying Jia, Ziwei Li, Xiyue Hu, Ting Wang, Wenxiu Lian, Wenqing Sun, Yi Liu, Chunhui Ni","doi":"10.7555/JBR.39.20250074","DOIUrl":"10.7555/JBR.39.20250074","url":null,"abstract":"<p><p>Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace. It has a complex pathogenesis and currently lacks effective treatments. Homoharringtonine(HHT), a natural compound approved for the treatment of acute myeloid leukemia, but its effects on silicosis are unclear. In the present study, we constructed a mouse model of silica (SiO ₂)-induced pulmonary fibrosis and evaluated the preventive and therapeutic capacity of HHT. The results showed that HHT attenuated the progression of SiO ₂-induced pulmonary fibrosis in mice. We then used MRC-5, a human lung fibroblast cell line to explore the mechanisms underlying HHT's inhibitory effects <i>in vitro</i> and found that HHT significantly inhibited the activation and migratory capacity of MRC-5 cells. Mechanistically, the effects were mediated by enhanced ubiquitination and degradation of the CCR1 protein. Furthermore, HHT exhibited favorable biocompatibility <i>in vivo</i>, and its preventive and therapeutic effects were validated in SiO ₂-treated mice. This study demonstrates that HHT holds significant potential as a therapeutic agent for silicosis by targeting CCR1 and the PI3K/AKT/mTOR signaling pathway, highlighting it as a promising candidate for clinical development in silicosis treatment.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-16"},"PeriodicalIF":2.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OSBPL2 deficiency inhibits Rho/ROCK2/p-ERM signaling and impairs actin cytoskeletal regulation in auditory cells.","authors":"Cheng Zhang, Qian Yang, Yajie Lu, Qinjun Wei, Rong Zhou, Guangqian Xing, Xin Cao, Zhibin Chen, Jun Yao","doi":"10.7555/JBR.38.20240389","DOIUrl":"10.7555/JBR.38.20240389","url":null,"abstract":"<p><p>Mutation in oxysterol-binding protein-like 2 ( <i>OSBPL2</i>) has been identified as the genetic cause of autosomal dominant nonsyndromic hearing loss (DFNA67, OMIM No. 616340). However, the pathogenesis of the <i>OSBPL2</i> mutation in DFNA remains unclear. Our previous work showed that OSBPL2 deficiency impaired cell adhesion in auditory HEI-OC1 cells. In addition, loss of hair cells (HCs) and morphological abnormalities of HC stereocilia were detected in <i>OSBPL2</i>-disrupted pigs, suggesting that OSBPL2 plays an important role in the regulation of the actin cytoskeleton in auditory cells. In the present study, we found that OSBPL2 deficiency inhibited the Rho/ROCK2 signaling pathway and downregulated phosphorylated Ezrin-Radixin-Moesin (p-ERM), resulting in abnormal F-actin morphology in HEI-OC1 cells and stereociliary defects in mouse HCs. The present study demonstrates the underlying mechanism of OSBPL2 in the regulation of the actin cytoskeleton in HCs, which contributes to a deeper understanding of the pathogenesis of <i>OSBPL2</i> mutations in DFNA.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal depression during pregnancy and children's physical development.","authors":"Di Pi, Shuifang Lei, Wenjing Chang, Cong Liu, Yangqian Jiang, Yuanyan Dou, Jinghan Wang, Chang Wang, Haowen Zhang, Xin Xu, Hong Lyu, Bo Xu, Xiumei Han, Xiaoyu Liu, Kun Zhou, Tao Jiang, Jiangbo Du, Guangfu Jin, Hongxia Ma, Hongbing Shen, Zhibin Hu, Kan Ye, Yuan Lin","doi":"10.7555/JBR.39.20250164","DOIUrl":"10.7555/JBR.39.20250164","url":null,"abstract":"<p><p>Prenatal maternal psychological distress, particularly depression, has been increasingly recognized as a factor that influences fetal growth; however, its impact on early childhood development remains less well understood. The present study investigated the association between prenatal depression and children's growth trajectories, as well as the odds of overweight and obesity from 1 to 36 months, while also accounting for maternal anxiety and stress. We analyzed data from 4710 mother-child dyads in the Jiangsu Birth Cohort, assessing maternal psychological distress across trimesters and categorizing participants into groups with mild, moderate, and severe depressive symptomatology. Children's weight-for-length z-scores (WLZ) were used to assess overweight/obesity prevalence, and growth patterns were identified through trajectory models. The results from the generalized estimating equations analysis showed that greater depressive symptomatology during pregnancy was associated with a 28% to 41% increase in the odds of childhood overweight/obesity across all three trimesters, compared with mild depressive symptomatology. We identified five distinct WLZ growth trajectory patterns, and found that mothers with greater depressive symptomatology were 39%-47% more likely to have children who followed a very-high-stable growth trajectory, compared with mothers with mild depressive symptomatology. These findings highlight the significant impact of prenatal depression on adverse growth patterns and childhood overweight/obesity, underscoring the need for early intervention.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of biomarkers of male infertility through the circRNA expression profiling of seminal plasma.","authors":"Zhaode Liu, Xinrui Li, Xiaoyu Yang, Bohang Zhang, Dingdong Chen, Yan Yuan, Yiqiang Cui","doi":"10.7555/JBR.38.20240192","DOIUrl":"10.7555/JBR.38.20240192","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are key regulators of reproductive biology. However, limited information is available regarding circRNA expression profiles in seminal plasma samples from individuals with male infertility. The present study aimed to identify circRNAs associated with infertility in seminal plasma samples and to clarify their potential as biomarkers, as well as the possible molecular mechanisms underlying their functions. Next-generation RNA sequencing was conducted to analyze circRNA profiles in seminal plasma from healthy controls, oligoasthenospermia (OAZ) patients, and non-obstructive azoospermia (NOA) patients. Bioinformatics analysis revealed that 637 circRNAs were differentially expressed between OAZ and control subjects, and 272 circRNAs were differentially expressed between NOA and control subjects. The expression of key circRNAs ( <i>hsa-SAP130_0002</i>, <i>hsa-TRPC1_0001</i>, <i>hsa-FBRS_0001</i>, <i>hsa-ACACA_0025</i>, <i>hsa-UTRN_0042</i>, and <i>hsa-ZNF532_0023</i>) was then validated by qPCR, and their diagnostic accuracy for infertility was confirmed through receiver operating characteristic curve analysis. Additionally, a possible circRNA-miRNA-mRNA regulatory network was constructed for these candidate biomarkers. Collectively, this study identifies a novel set of circRNAs with potential as diagnostic biomarkers for male infertility and provides molecular insights that may facilitate both diagnostic and therapeutic efforts.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"367-381"},"PeriodicalIF":2.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Washed microbiota transplantation effectively treats a case of acute severe ulcerative colitis combined with viral myocarditis.","authors":"Rujun Ai, Yan Jin, Faming Zhang, Bota Cui, Guozhong Ji","doi":"10.7555/JBR.39.20250036","DOIUrl":"10.7555/JBR.39.20250036","url":null,"abstract":"<p><p>Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis. Management of myocarditis is primarily supportive, because there are currently no established targeted therapies. Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis. Here, we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis. The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation, suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"430-434"},"PeriodicalIF":2.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}