1.Skeleton Binding Protein 1 of Plasmodium berghei Influences Deformability and Cytoskeletal Ultrastructure of Infected Erythrocyte
Xin-Yue GUO ; Huan-Qi ZHAO ; Yan-Xuan ZHONG ; Ru-Meng JIANG ; Yao-Xian LI ; Lei-Ting PAN ; Qian WANG ; Xiao-Yu SHI
Progress in Biochemistry and Biophysics 2026;53(4):1015-1027
ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.
2.Quantitative Chemical Exchange Saturation Transfer MRI for Diagnosing Thyroid-Associated Ophthalmopathy Activity: A Prospective Feasibility Study
YunMeng WANG ; WeiYi ZHOU ; YuanYuan CUI ; JianKun DAI ; YuXin CHENG ; QingQing WEN ; TianYi XING ; HongBiao SUN ; Song JIANG ; MeiLing XU ; ZhenHuan WANG ; Yan SONG ; Tuo LI ; Yi XIAO
Korean Journal of Radiology 2026;27(2):161-173
Objective:
This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO).
Materials and Methods:
A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO.
Results:
Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001).
Conclusion
MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.
3.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
4.Identification and infection rate of densovirus in Culex pipiens pallens in Beijing in 2023
Xiu-yan XU ; Ting YAN ; Si-jie ZHU ; Jing LI ; Mei-de LIU ; Hong-jiang ZHANG ; Ting LIU ; Qiu-hong LI ; Xiao-jie ZHOU ; Ying TONG ; Yong ZHANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):25-30
Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.
5.Investigation of Specific Antibody Levels of Autoimmune Gastritis and Analysis of Influencing Factors in A Community Population in Xinjiang
Huan LIU ; Xiaoling HUANG ; AI HEMAIJIANG KURBANJIANG ; Yan FENG ; Weidong LIU ; Shenglong XUE ; Zequan XIAO ; AINI ABDUREIM ; Xinwen GUO ; Maosen JIANG ; Feng GAO
Medical Journal of Peking Union Medical College Hospital 2026;17(4):1042-1050
To investigate the positivity rates of specific antibodies, including parietal cell antibody (PCA) and anti-inner factor antibody (IFA), in a community population in Xinjiang for autoimmune gastritis (AIG), determine the prevalence of AIG, and analyze the correlations of PCA and IFA with clinical characteristics, pepsinogen (PG), gastrin 17 (G17), and A cross-sectional survey was conducted using stratified random cluster sampling in community populations across 10 regions of Xinjiang from January 2022 to December 2023. General information was collected via a self-designed questionnaire, and fasting venous blood samples were obtained to measure laboratory parameters including PCA, IFA, PG Ⅰ, PG Ⅱ, PG Ⅰ/PG Ⅱ ratio, and G17. The positivity rates of PCA and IFA and the prevalence of AIG were calculated. Spearman correlation analysis was used to assess the relationships of PCA and IFA with PG Ⅰ, PG Ⅱ, PG Ⅰ/PG Ⅱ ratio, and G17. The diagnostic efficacy of PCA and IFA for atrophic gastritis was evaluated using receiver operating characteristic (ROC) curves, and multivariate logistic regression analysis was performed to identify factors influencing PCA and IFA positivity. A total of 2018 community participants were included, comprising 972 males (48.17%) and 1046 females (51.83%), with a mean age of 42±19 years. The predominant ethnic groups were Han (42.22%) and Kazakh (33.10%). Hp-Ab positivity was observed in 1244 cases (61.65%). Serological criteria for atrophic gastritis were met in 56 cases (2.78%). PCA positivity was found in 253 cases (12.54%), IFA positivity in 30 cases (1.49%), and dual positivity in 11 cases (0.55%). A total of 617 participants (30.57%) voluntarily underwent endoscopic examination, among whom 7 cases (1.13%) were histopathologically confirmed as AIG. Positivity rates for PCA and IFA varied among ethnic groups, with the highest rates observed in the Kirgiz population (23.53% and 5.88%, respectively). Spearman correlation analysis revealed that PCA was negatively correlated with the PG Ⅰ/PG Ⅱ ratio ( The positivity rate of PCA is relatively high in the community population in Xinjiang and varies across different ethnic groups, whereas the positivity rate of IFA is lower than that of PCA. Age, history of alcohol consumption, history of allergies, and history of thyroid disease are associated with PCA positivity, while no correlation was found between Hp-Ab and PCA or IFA. The prevalence of histopathologically confirmed AIG among participants undergoing endoscopic examination is 1.13%.
6.Activation of α7nAChR optimises thermogenesis in brown adipose tissue of obese mice
Wencheng TIAN ; Sutong WANG ; Hesong FAN ; Yan LI ; Ping JIANG ; Xiao LI
Acta Universitatis Medicinalis Anhui 2026;61(7):1191-1199
ObjectiveTo investigate the mechanism by which activation of α7nicotinic acetylcholine receptors (α7nAChR) optimizes brown adipose tissue (BAT) thermogenesis in obese mice. MethodsObesity was induced in C57BL/6J mice via a high-fat diet. Fifty 8-week-old mice were randomly assigned to five groups: low-fat diet (Control), high-fat diet (HFD), high-fat diet plus a β3-adrenergic receptor agonist (HFD+β3), high-fat diet plus a β3-adrenergic receptor agonist and an α7nAChR selective agonist (HFD+β3+GTS-21), and high-fat diet plus a β3-adrenergic receptor agonist and an α7nAChR selective antagonist (HFD+β3+α-BGT). Haematoxylin and eosin (HE) staining was used to evaluate BAT morphology. Transmission electron microscopy was performed to assess mitochondrial number and lipid droplet morphology in adipocytes. ELISA was used to measure levels of tumour necrosis factor-α (TNF-α), interleukin(IL)-1β,IL-10, transforming growth factor-β (TGF-β), cyclic adenosine monophosphate (cAMP), and norepinephrine (NE). RT-qPCR was conducted to determine mRNA expression levels of vascular endothelial growth factor A (VEGF-A), nitric oxide synthase 2 (NOS2), arginase 1 (Arg1), uncoupling protein 1 (UCP1), PR domain-containing protein 16 (PRDM16), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in BAT. Immunohistochemistry was used to detect macrophage markers (CD31, CD86, and CD206). Protein expression levels of UCP1, α7nAChR, nuclear factor-κB p65(NF-κB p65), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were analyzed by Western blot. ResultsCompared with the Control group, the HFD group showed enlarged lipid droplets and reduced mitochondrial numbers in adipocytes, accompanied by increased TNF-α and IL-1β and decreased IL-10, TGF-β, Arg1, and VEGF-A (all P<0.01). Compared with the HFD+β3 group, the HFD+β3+GTS-21 group showed a smaller lipid droplet area and a higher mitochondrial number, along with reduced levels of pro-inflammatory factors, NOS2, and NF-κB p65, and increased levels of anti-inflammatory factors, Arg1, and phosphorylation of JAK2 and STAT3 (all P<0.01). ConclusionActivation of α7nAChR in combination with a β3-adrenergic receptor agonist effectively enhances thermogenesis, alleviates local adipose tissue hypoxia, and shifts the local inflammatory phenotype toward an M2-like state, thereby reducing inflammation in brown adipose tissue and improving its thermogenic capacity.
7.A Latent Class Trajectory Model Based Analysis of KCCQ Symptom Score Trajectories and Readmission Risk in Heart Failure Patients during the Vulnerable Period
Yuan XU ; Yan JIANG ; Yanan ZHANG ; Hui HU ; Dan XIAO
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(5):899-912
ObjectiveThis study examined KCCQ symptom score trajectories during the vulnerable phase of heart failure and their association with readmission within 6 months. MethodsThis prospective cohort study included 1 109 patients hospitalized for chronic heart failure at a tertiary hospital in Nanchang, China, between August 2020 and July 2025. KCCQ scores were assessed at six time points: day 3 after admission, discharge, and 1, 2, 3, and 6 months after discharge. Group-based trajectory modeling was used to identify patterns of change in KCCQ scores. Multiple logistic regression was used to assess the association between trajectory membership and readmission risk. ResultsDuring follow-up, 229 patients were readmitted, accounting for 20.6% of the cohort. Four KCCQ trajectories were identified: persistently declining scores (n=228, 20.6%), persistently improving scores (n=110, 9.9%), stable intermediate scores (n=545, 49.1%), and stable high scores (n=226, 20.4%). Compared with the stable intermediate group, the persistently declining group had a higher risk of readmission in the fully adjusted model (OR=2.099, 95% CI: 1.027–4.315, P=0.043), whereas the stable high-score group had a lower risk (OR=0.260, 95% CI: 0.127–0.494, P<0.001). The association between the persistently improving trajectory and readmission was not statistically significant (OR=0.614, 95% CI: 0.306–1.154, P=0.147). ConclusionsKCCQ symptom score trajectories during the vulnerable phase of heart failure show marked heterogeneity and are associated with readmission within 6 months. A persistently declining trajectory is associated with higher readmission risk, whereas a stable high-score trajectory is associated with lower risk. Longitudinal monitoring of KCCQ score changes may help inform post-discharge risk stratification and follow-up management in patients with heart failure.
8.A Latent Class Trajectory Model Based Analysis of KCCQ Symptom Score Trajectories and Readmission Risk in Heart Failure Patients during the Vulnerable Period
Yuan XU ; Yan JIANG ; Yanan ZHANG ; Hui HU ; Dan XIAO
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(5):899-912
ObjectiveThis study examined KCCQ symptom score trajectories during the vulnerable phase of heart failure and their association with readmission within 6 months. MethodsThis prospective cohort study included 1 109 patients hospitalized for chronic heart failure at a tertiary hospital in Nanchang, China, between August 2020 and July 2025. KCCQ scores were assessed at six time points: day 3 after admission, discharge, and 1, 2, 3, and 6 months after discharge. Group-based trajectory modeling was used to identify patterns of change in KCCQ scores. Multiple logistic regression was used to assess the association between trajectory membership and readmission risk. ResultsDuring follow-up, 229 patients were readmitted, accounting for 20.6% of the cohort. Four KCCQ trajectories were identified: persistently declining scores (n=228, 20.6%), persistently improving scores (n=110, 9.9%), stable intermediate scores (n=545, 49.1%), and stable high scores (n=226, 20.4%). Compared with the stable intermediate group, the persistently declining group had a higher risk of readmission in the fully adjusted model (OR=2.099, 95% CI: 1.027–4.315, P=0.043), whereas the stable high-score group had a lower risk (OR=0.260, 95% CI: 0.127–0.494, P<0.001). The association between the persistently improving trajectory and readmission was not statistically significant (OR=0.614, 95% CI: 0.306–1.154, P=0.147). ConclusionsKCCQ symptom score trajectories during the vulnerable phase of heart failure show marked heterogeneity and are associated with readmission within 6 months. A persistently declining trajectory is associated with higher readmission risk, whereas a stable high-score trajectory is associated with lower risk. Longitudinal monitoring of KCCQ score changes may help inform post-discharge risk stratification and follow-up management in patients with heart failure.
9.Epidemiological characteristics of imported dengue fever cases in Fengtai District, Beijing, from 2007 to 2025
Yan MENG ; Yang YANG ; Xiao-xing YANG ; Jun-yong YANG ; Ruo-yi DU ; Li-na TIAN ; Ruo-xi LI ; Gui-yin LIN ; Xiao-li RUAN ; Jian-jun ZHANG ; Zhen-jiang XIN ; Li-li TIAN
Acta Parasitologica et Medica Entomologica Sinica 2026;33(3):180-186
Objective We reviewed and analyzed the epidemiological data of 83 imported dengue fever cases reported in Fengtai District, Beijing, from 2007 to 2025, to delineate their epidemiological characteristics and guide the dengue fever prevention and control strategy in the future. Methods Data on dengue fever cases in Fengtai District from 2007 to 2025 were collected to identify the epidemic factors and characteristics using descriptive epidemiological method. Results All 83 dengue fever cases reported in this region over the past two decades have been imported from abroad or other domestic areas, with Southeast Asian countries being identified as the primary source of imported infections, accounting for 42 cases (50.60%), followed by 15 cases (18.07%) from Chinese provinces other than Beijing. The remaining import sources included 13 cases from South Asia,8 from African countries, and each from Oceania, South America, and Europe. Disease onset was found concentrated between May and November. The sex ratio (male-to-female) is 1.59:1. The age of onset ranged from 14 to 61 years old, with a median age of 36. The largest proportion of cases was observed among cadres and office workers (31 cases, 37.35%), followed by businessmen (13 cases, 15.67%), and householders or the unemployed (10 cases,12.05%). Travel visit was identified as the primary reason for their exposure history. Conclusions All dengue fever cases reported in Fengtai from 2007 to 2025 were imported, with an increasing trend of imported cases in Beijing originating from other Chinese provinces. It is essential to strengthen health education for foreign travelers and returning residents, enhance clinical diagnosis and treatment training for medical personnel, eliminate mosquito breeding sites, and reduce mosquito density through active patriotic health campaigns.
10.Correlation between serum zinc level and prognosis of patients with sepsis
Xiao-Gang WANG ; Jia-Jun MA ; Rui-Xin ZHU ; Li-Bing ZHOU ; Sai-Hu HUANG ; Shui-Yan WU ; Wen-Si NIU ; Jie HUANG ; Zhen-Jiang BAI
Parenteral & Enteral Nutrition 2025;32(5):278-282
Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725~0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.


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