Long-Term Risk of Subsequent Malignant Neoplasms Among Childhood and Adolescent Lymphoma Survivors (1975-2013): A Population-Based Predictive Nomogram.

BACKGROUND: Studies are needed to assess risk factors pertinent to the incidence of secondary malignancies among childhood and adolescent lymphoma survivors. We aimed to identify risk factors pertinent to the incidence of secondary malignancies and subsequently establish a clinically practical predictive nomogram. METHODS: A total of 5561 patients who were diagnosed with primary lymphoma below the age of 20 years between 1975 and 2013 and survived for at least 5 years were identified. Standardized incidence ratio (SIR) and excess risk (ER) analysis were performed by sex, age, and year when primary lymphoma was diagnosed, sites and types of primary lymphoma, and therapy strategies. Univariable and multivariable logistic regression were used to identify independent risk factors for adolescent and childhood lymphoma-related secondary malignancies. Based on 5 factors (age, time from lymphoma diagnosis, gender, lymphoma type, and therapy), a nomogram for predicting the risk of a secondary malignancy for patients with childhood and adolescent primary lymphoma was established. RESULTS: Among 5561 lymphoma survivors, 424 developed a secondary malignancy. Females (SIR = 5.34, 95% CI, 4.73-5.99; ER = 50.58) exhibited a higher SIR and ER than males (SIR = 3.28, 95% CI, 2.76-3.87; ER = 15.53). Blacks were at a higher risk than Caucasians or others. Nodular lymphocyte-predominant Hodgkin lymphoma survivors exhibited typically high SIR (13.13, 95% CI, 6-24.92) and ER (54.79) among all lymphoma classifications. Lymphoma survivors who underwent radiotherapy, whether they received chemotherapy or not, had typically higher SIR and ER. Among all types of secondary malignancies, "bone and joint neoplasms" (SIR = 11.07, 95% CI, 5.52-19.81) and "soft tissue neoplasms" (SIR = 12.27, 95% CI, 7.59-18.76) presented significantly high SIR whereas "breast cancer" and "endocrine cancer" associated with higher ER. The median diagnosis age of secondary malignancies was 36 years old, and the median time interval between the diagnosis of two malignancies was 23 years. A nomogram was constructed to predict the risk of secondary malignancies in patients diagnosed with primary lymphoma before 20 years of age. After internal validation, the AUC and C-index of the nomogram are 0.804 and 0.804, respectively. CONCLUSION AND RELEVANCE: The established nomogram provides a convenient and reliable tool for predicting the risk of a secondary malignancy among childhood and adolescent lymphoma survivors, concluding significant concern for lymphoma survivors with high-risk estimates.

Long-term venovenous extracorporeal membrane oxygenation support for acute respiratory distress syndrome after COVID-19.

INTRODUCTION: Acute respiratory syndrome (ARDS) following coronavirus 2 (SARS-CoV-2) infection is a serious complication often causing irreversible lung injury associated with high mortality. Extracorporeal membrane oxygenation (ECMO) may be initiated in severe cases. We present a case of ARDS following SARS-CoV-2 infection with prolonged duration ECMO (1045 hours, 44 days) without exchanging circuit throughout the whole duration without technical complication. CASE REPORT: A 71-year-old man of acute respiratory failure secondary to SARS-CoV-2 infection was initiated on venovenous ECMO (VV-ECMO). There was no technical complication without exchanging circuit throughout the whole prolonged ECMO duration (1045 hours, 44 days). Despite a great effort to improve his lung mechanics and gas exchange, there was continued clinical and physiological deterioration unfortunately. Following family discussion and with input from the multidisciplinary team (MDT) including palliative care specialists, there was recognition of deterioration despite optimal respiratory support. Shortly thereafter planned withdrawal occurred, and the patient passed away with his family at his bedside. DISCUSSION: This case study illustrates that it may be considered to use long term ECMO as a bridge to recovery or lung transplantation of ARDS patient after SARS-CoV-2 infection with severe lung injury. Benefits from proper long-term ECMO management,it is possible of sparing to exchange circuit throughout the whole prolonged duration without technical complication. CONCLUSION: This case indicates the feasibility of using of a long term VV-ECMO as a bridge to recovery or lung transplantation of ARDS patient after secondary to coronavirus 2 (SARS-CoV-2) infection with severe lung injury without circuit exchange. The optimal duration of VV-ECMO support and optimal diagnostic modalities for critical assessment of native lung recovery or irretrievable severe lung injury still require further investigation.

A Tentative Tamdy Orthonairovirus Related to Febrile Illness in Northwestern China.

BACKGROUND: Many novel tick-borne viruses have been discovered by deep-sequencing technology in recent years; however, their medical significance is unknown. METHODS: We obtained clinical data of a patient from Xinjiang, China. Possible pathogens were detected by metagenomic analysis; the causative pathogen Tacheng tick virus 1 (TcTV-1) was found and further confirmed by reverse transcriptase-polymerase chain reaction, viral culture, and sequence analyses. Epidemiological investigation was conducted in the local human population, domestic animals, and ticks by serological/molecular methods. RESULTS: A 62-year-old woman with a history of tick bite in Qinghe, Xinjiang, presented with fever and rashes. These symptoms were relieved after clinical treatment. TcTV-1 (strain QH1) was isolated from the patient's cerebrospinal fluid, throat swabs, and urine on day 47 after illness onset. Although the blood and urine showed viral RNA positive on day 73 after illness onset, the virus was only isolated from urine. Serological detection revealed a virus neutralizing antibody titer of 1:40 and 1:80 on day 47 and 73 after illness onset, respectively. No coinfection with other pathogens was detected, suggesting TcTV-1 may be the potential causative pathogen. We detected anti-TcTV-1 antibodies (immunoglobulin G: 10.1%; immunoglobulin M: 4.8%) in the local human population. The viral RNA was also found in cattle (4.9%), sheep (9.2%), and ticks, including Dermacentor marginatus (14.3%), Dermacentor silvarum (11.8%), Dermacentor nuttalli (6.7%), and Hyalomma asiaticum (4.8%). CONCLUSIONS: TcTV-1 may be associated with a febrile illness syndrome, and epidemiological data of the virus in humans and animals necessitate disease surveillance of TcTV-1 infection in China.

The expression of ERK and JNK in patients with an endemic osteochondropathy, Kashin-Beck disease.

Kashin-Beck disease (KBD) is a chronic, endemic osteochondropathy. Its etiopathogenesis is still obscure until now. Epidemiological observation has shown that low selenium play a crucial role in the pathogenesis of KBD. Extracellular signal-regulated kinases (ERKs) and C-Jun N-terminal kinase (JNK), members of the mitogen-activated protein kinase (MAPK) superfamily, play an important role in cell proliferation and differentiation. Nuclear factor-ĸB (NF-ĸB), an important signaling mediator for inflammatory and immune responses, is involved in the regulation of osteoclastogenesis. In the present study, we investigated the expression of ERK and JNK signal molecular, as well as nuclear factor-ĸB in the pathogenesis of Kashin-Beck disease, evaluated the effect of selenium on ERK signal pathway. The expression levels of ERK and JNK signal pathway, as well as nuclear factor-ĸB were investigated for 218 patients and 209 controls by immunoblot analysis in whole blood. Evaluated the effect of selenium on ERK signal pathway by Na2SeO3 treatment. The protein levels of pRaf-1, pMek1/2 and pErk1/2 decreased significantly in KBD patients, p-JNK and NF-ĸB increased in KBD patients. Furthermore, Na2SeO3 treatment improved the reduction of proteins in ERK signal pathway. These findings indicated that ERK and JNK signaling pathways, as well as the expression level of NF-κB signaling molecular are important contributor to the pathogenesis of KBD. Selenium stimulates the phosphorylation of the ERK signaling pathway.

Efficacy of Four Scoring Systems in Predicting Intravenous Immunoglobulin Resistance in Children with Kawasaki Disease in a Children's Hospital in Beijing, North China.

OBJECTIVE: To evaluate the predictive efficacies of 4 existing scoring systems for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) in hospitalized children with KD in a children's hospital affiliated with the Capital Institute of Pediatrics, Beijing, China. STUDY DESIGN: We retrospectively analyzed 1569 children with KD treated at our children's hospital between January 2010 and December 2015. Age, sex, clinical manifestations, and pretreatment hematologic indicators were recorded. Scores were assigned using 4 existing scoring systems: Egami, Kobayashi, San Diego, and Formosa. A 4-case table test was used to determine prediction efficacies. RESULTS: There were 63 IVIG-resistant cases (41 males, 22 females; average age, 2.5 years). Nine cases were classified as high risk for IVIG resistance by the Egami system, and this system had a sensitivity of 14% and a specificity of 86%. Ten cases had Kobayashi high-risk scores, and this system had a sensitivity of 16% and a specificity of 85%. The San Diego system assigned 60 cases as high-risk, and had a sensitivity of 95% and specificity of 3%. Finally, 27 cases had Formosa scores in the high-risk category, and this system had a sensitivity of 43% and a specificity of 47%. CONCLUSIONS: None of the evaluated systems for assessing the risk for IVIG resistance displayed the combination of sensitivity and specificity necessary for screening. Our analyses show that the 4 scoring systems have limited utility in predicting IVIG resistance among patients with KD in our population.

Plasma MASP-1 concentration and its relationship to recovery from coronary artery lesion in children with Kawasaki disease.

BACKGROUND: This study investigated prognostic factors for early recovery of coronary artery lesion (CAL) in children with Kawasaki disease (KD). METHODS: Patients hospitalized for KD were enrolled less than 2 wk from the onset of illness and divided into two groups: KD with CAL and KD without CAL. The CAL group was further divided into two subgroups according to the degree of CAL: mild (n = 31) and moderate/severe (n = 6) and further divided into two subgroups according to the age: younger than 1 y (n = 9) and older than 1 y (n = 28). Lectin pathway-related factors MASP-1, CD59, and C5b-9 were measured, along with C-reactive protein, white blood cell counts, erythrocyte sedimentation rate, and platelet count. Patients were followed up for 3 mo. Correlation between the measured factors and the length of time of recovery from CAL was analyzed. RESULTS: Plasma concentrations of MASP-1 in the CAL group were significantly lower than those without CAL. MASP-1 and gender positively correlated with the recovery time of CAL. There was no difference in MASP-1 between mild and moderate/severe CAL. At 3-mo follow-up, there was a positive correlation between plasma MASP-1 concentration and recovery time of the patients with CAL older than 1 y. CONCLUSION: Plasma MASP-1 concentration at the early stage of KD is predictive of length of time of recovery from CAL.

Elevated Inducible Nitric Oxide Levels and Decreased Hydrogen Sulfide Levels Can Predict the Risk of Coronary Artery Ectasia in Kawasaki Disease.

Kawasaki disease (KD) is a vasculitis disease in children that is associated with coronary artery ectasia (CAE). We investigated whether inducible nitric oxide synthase (i-NOS) and hydrogen sulfide (H2S) could be used to predict CAE secondary to KD. We enrolled 65 children with KD (35 cases with CAE and 30 cases without CAE), 33 healthy children, and 32 children with fever but without vasculitis disease (febrile group). We measured plasma nitric oxide (NO), total nitric oxide synthase (Total-NOS), i-NOS, constructive nitric oxide synthase (c-NOS) levels, and H2S content in all patients. Plasma NO, Total-NOS, i-NOS, and H2S were higher in KD children than in healthy and febrile children (P < 0.05). The i-NOS level was higher in KD children with CAE compared to those without CAE, while the H2S was lower (both P < 0.05). Using a combination of i-NOS (higher than 10 U/mL) and H2S (lower than 3.31 µmol/L) to predict CAE had 80 % sensitivity and 81 % specificity (P < 0.05). Elevated plasma i-NOS and decreased plasma H2S levels in the acute phase of KD have good predictive value for CAE and may be used to guide appropriate clinical treatment and prevent future cardiovascular complications.

Depolymerization of Free-Radical Polymers with Spin Migrations.

The mechanism of depolymerization is one of the most essential issues in chemical engineering and materials science. In this work, we investigate the depolymerization reactions of three typical free-radical poly(alpha-methylstyrene) tetramers by using first-principles density functional theory. The calculated results show that these reactions all need to overcome the energy barriers in the range of 0.58 to 0.77 eV, and that breaking the C-C bond at the chain end leads to the dissociation of alpha-methylstyrene monomers from the polymers. Electronic-structure analysis indicates that the reactions occur easily at the CR3 unsaturated end, and that the frontier molecular orbitals that participate in the reactions are mainly localized at the unsaturated ends. Meanwhile, spin population analysis presents the unique net spin-transfer process in free-radical depolymerization reactions. We hope the current findings can contribute to understanding the free-radical depolymerization mechanism and help guide future experiments.

Early decreased plasma levels of factor B and C5a are important biomarkers in children with Kawasaki disease.

BACKGROUND: The mechanisms underpinning Kawasaki disease (KD) are incompletely understood. There is an unmet need for specific biomarkers for the early diagnosis of KD. METHODS: Eighty-five KD patients suffering from acute-phase and subacute-phase KD, 40 healthy children, and 40 febrile children comprised the study cohort. An enzyme-linked immunosorbent assay was used to measure plasma levels of C1q, C1q-circulating immune complex (C1q-CIC), mannan-binding lectin-associated serine protease (MASP)-1, factor B, C4d, C3d, C5a, C5b-9 and CD59. RESULTS: Plasma concentrations of factor B and C5a in the acute phase were lower than those in healthy and febrile control groups (all P < 0.05). Compared with acute-phase KD patients, plasma concentrations of C1q, factor B, and C3d in KD patients were increased significantly (P < 0.05), but those of C4d, MASP-1 and CD59 decreased significantly (P < 0.05), in patients with sub-acute KD. CONCLUSION: These data suggest that more than one pathway in the complement system is activated in KD. Importantly, decreased plasma concentrations of factor B and C5a in the acute phase (6-10 d) could be employed as biomarkers for the early diagnosis of KD.

Electronic delocalization in small water rings.

Water clusters are known to form through hydrogen bonding. However, this study shows that the formation of small water clusters such as (H2O)n with n = 3 or 4 involves strong electron delocalization. Our first-principles calculations reveal that the electron delocalization originates from both the H and O atomic orbitals and extends to the ring center, enriching the bonding characteristics of water clusters.

Efficacy and safety of radiofrequency ablation and laparoscopic adrenalectomy for primary aldosteronism: a meta­analysis.

OBJECTIVE: To compare the efficacy (including blood pressure, medication reduction, serum potassium, and clinical success) and safety parameters (including operative time, length of hospital stay, blood loss, hypertension crisis rate, and complication rate) of radiofrequency ablation (RFA) and laparoscopic adrenalectomy (LA) in the treatment of primary aldosteronism (PA). METHODS: Literature search was performed on PubMed, EMBASE, The Cochrane Library (Issue 8, 2023), Web of Science, China National Knowledge Infrastructure, and Wanfang from inception to August 2023. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Quality assessment was conducted using the Newcastle-Ottawa scale. The Stata 12.0 software was used for statistical analyses. Pooled odds ratios (OR) with corresponding 95% confidence interval (CI) were calculated for categorical outcomes, while mean difference (MD) with corresponding 95% CI were calculated for continuous outcomes. RESULTS: A total of 5 studies involving 204 patients (LA, n = 127; and RAF, n = 77) were included. LA had better diastolic blood pressure control than RFA (WMD = 5.19; 95% CI 0.96-9.43); however, the RFA demonstrated better shorter operative time (WMD = - 57.99; 95% CI - 116.54 to 0.57), and shorter length of hospital stay (OR - 1.6; 95% CI - 2.37 to - 0.83) compared to LA. All remaining parameters were comparable between the interventions. CONCLUSION: While grossly comparable in efficacy as treatment options for PA, RFA may allow for shorter operative time and hospital stay, less intraoperative blood loss, and lower hospitalization costs. However, LA has better diastolic blood pressure control. Even so, we still need larger prospective studies, specifically with comparative hypertension response (short and long term) and number of post-procedural antihypertensive medication requirement.

Potential non-invasive biomarkers in tumor immune checkpoint inhibitor therapy: response and prognosis prediction.

Immune checkpoint inhibitors (ICIs) have dramatically enhanced the treatment outcomes for diverse malignancies. Yet, only 15-60% of patients respond significantly. Therefore, accurate responder identification and timely ICI administration are critical issues in tumor ICI therapy. Recent rapid developments at the intersection of oncology, immunology, biology, and computer science have provided an abundance of predictive biomarkers for ICI efficacy. These biomarkers can be invasive or non-invasive, depending on the specific sample collection method. Compared with invasive markers, a host of non-invasive markers have been confirmed to have superior availability and accuracy in ICI efficacy prediction. Considering the outstanding advantages of dynamic monitoring of the immunotherapy response and the potential for widespread clinical application, we review the recent research in this field with the aim of contributing to the identification of patients who may derive the greatest benefit from ICI therapy.

SEER-Based Survival Nomogram (1998-2015) Based on 'Stage, Lymph Node Dissection, Tumor Size and Degree of Differentiation, and Therapies' for Prognosis of Primary Pulmonary Sarcoma.

Objective: Primary pulmonary sarcoma (PPS) is very rare in terms of incidence, henceforth, the clinical evidence pertinent to the prognosis of PPS is limited. The aim of this study was to construct a nomogram for evaluating the overall survival (OS) of patients diagnosed with PPS based on the stage, lymph node dissection, tumor size and degree of differentiation, and therapies. Methods: A total of 515 patients diagnosed with PPS during the period of 1998 to 2015 were obtained from the surveillance, epidemiology, and end results database and randomly segregated into 'training group' and 'validation group' with a ratio of 7:3. Regression analysis was executed for the training group to obtain the independent factors influencing prognosis of PPS patients. A nomogram was constructed as per the results obtained through multivariate Cox regression analysis subsequently validated using C index, receiver operating characteristic (ROC) curve, and calibration curves. Results: Age, tumor size, histology type, lymph node surgery, summary stage and differentiation grade were independent factors affecting the prognosis. C index was 0.775 and 0.737 for both training group, and validation group, respectively. Areas under the ROC curve of 1-year, 3-year, and 5-year OS were 87.6 (95% CI: 83.8-91.3), 90.1 (95% CI: 86.2-94.0) and 90.6 (95% CI: 85.8-95.4), respectively, in training group. Area under the curve values of 1-year, 3-year, and 5-year OS in the validation group were 83.1 (95% CI: 75.8-90.5), 82.9 (95% CI: 73.2-92.7) and 87.0 (95% CI: 75.9-98.1), respectively. Based on the nomogram, patients were segregated into low-risk group and high-risk group (degree of risk: cutoff score 193). OS of low-risk group was significantly higher when compared to high-risk group (P < .001) in the training group and validation group. Radiotherapy was a risk factor for the low-risk group and adjuvant chemotherapy has not exhibited influence on OS pertinent to low-risk group. However, adjuvant radiotherapy or chemotherapy both significantly improved the prognosis of PPS patients (P < .001) in the high-risk group. Conclusion: Constructed nomogram could have a strong predictive ability with higher accuracy for the prognosis of patients with PPS. Patients at low risk could not benefit from adjuvant radiotherapy or chemotherapy, while the prognosis clearly improved in the high-risk populations treated with either radiotherapy or chemotherapy.

Molecular classification of human papilloma virus-negative head and neck squamous cell carcinomas: Cell cycle-based classifier and prognostic signature.

The molecular classification of human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs) remains questionable. Differentially expressed genes were detected between tumor and normal tissues and GSEA showed they are associated with cell cycle pathways. This study aimed to classify HPV-negative HNSCCs based on cell cycle-related genes. The established gene pattern was correlated with tumor progression, clinical prognosis, and drug treatment efficacy. Biological analysis was performed using HNSCC patient sample data obtained from the Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Gene Expression Omnibus (GEO) databases. All samples included in this study contained survival information. RNA sequencing data from 740 samples were used for the analysis. Previously characterized cell cycle-related genes were included for unsupervised consensus clustering. Two subtypes of HPV-negative HNSCCs (C1, C2) were identified. Subtype C1 displayed low cell cycle activity, 'hot' tumor microenvironment (TME), earlier N stage, lower pathological grade, better prognosis, and higher response rate to the immunotherapy and targeted therapy. Subtype C2 was associated with higher cell cycle activity, 'cold' TME, later N stage, higher pathological grade, worse prognosis, and lower response rate to the treatment. According to the nearest template prediction method, classification rules were established and verified. Our work explored the molecular mechanism of HPV-negative HNSCCs in the view of cell cycle and might provide new sights for personalized anti-cancer treatment.

Recent Updates on the Efficacy of Mitocans in Photo/Radio-Therapy for Targeting Metabolism in Chemo/Radio-Resistant Cancers: Nanotherapeutics.

Conventional therapeutic modalities against the cancers such as surgery, chemotherapy (CT) and radiotherapy (RT) have limited efficacy due to drug resistance, and adverse effects. Recent developments in nanoscience emphasized novel approaches to overcome the aforementioned limitations and subsequently improve overall clinical outcomes in cancer patients. Photodynamic therapy (PDT), photothermal therapy (PTT), and radiodynamic therapy (RDT) can be used as cancer treatments due to their high selectivity, low drug resistance, and low toxicity. Mitocans are the therapeutic molecules that can produce anti-cancer effects by modulating mitochondria functions and they have significant implications in cancer therapy. Mitochondria- targeted therapy is a promising strategy in cancer treatment as these organelles play a crucial function in the regulation of apoptosis and metabolism in tumor cells and are more vulnerable to hyperthermia and oxidative damage. The aim of this review is used to explore the targeting efficacy of mitocans in the nanotherapeutic formulation when combined with therapies like PDT, PTT, RDT. We searched several databases include Pubmed, relemed, scopus, google scholar, Embase and collected the related information to the efficacy of mitocans in nanotherapeutics when combined with photo-radiotherapy to target chemo/radio-resisant tumor cells. In this review, we vividly described research reports pertinent to the selective delivery of chemotherapy molecules into specific sub-organelles which can significantly improve the efficiency of cancer treatment by targeting tumor cell metabolism. Furthermore, the rational design, functionalization and application of various mitochondrial targeting units, including organic phosphine/sulfur salts, quaternary ammonium salts, transition metal complexes, and mitochondria-targeted cancer therapy such as PDT, PTT, RDT, and others were summarized. Mainly, the efficacy of these modalities against mtDNA and additional nanotherapeutic strategies with photosensitizers, or radiotherapy to target mitochondrial metabolism in tumor cells with chemo/radio-resistance were delineated. This review can benefit nanotechnologists, oncologists, and radiation oncologists to develop rational designs and application of novel mitochondrial targeting drugs mainly to target metabolism in chemo/radio-resistant cancer cells in cancer therapy.

Novel Implications of Nanoparticle-Enhanced Radiotherapy and Brachytherapy: Z-Effect and Tumor Hypoxia.

Radiotherapy and internal radioisotope therapy (brachytherapy) induce tumor cell death through different molecular signaling pathways. However, these therapies in cancer patients are constrained by dose-related adverse effects and local discomfort due to the prolonged exposure to the surrounding tissues. Technological advancements in nanotechnology have resulted in synthesis of high atomic elements such as nanomaterials, which can be used as radiosensitizers due to their photoelectric characteristics. The aim of this review is to elucidate the effects of novel nanomaterials in the field of radiation oncology to ameliorate dose-related toxicity through the application of ideal nanoparticle-based radiosensitizers such as Au (gold), Bi (bismuth), and Lu (Lutetium-177) for enhancing cytotoxic effects of radiotherapy via the high-Z effect. In addition, we discuss the role of nanoparticle-enhanced radiotherapy in alleviating tumor hypoxia through the nanodelivery of genes/drugs and other functional anticancer molecules. The implications of engineered nanoparticles in preclinical and clinical studies still need to be studied in order to explore potential mechanisms for radiosensitization by minimizing tumor hypoxia, operational/logistic complications and by overcoming tumor heterogeneity in radiotherapy/brachytherapy.

Selenoprotein P gene r25191g/a polymorphism and quantification of selenoprotein P mRNA level in patients with Kashin-Beck disease.

Kashin-Beck disease (KBD) is an endemic and deformable osteoarthrosis. Epidemiological study has revealed that lower Se level is the principal environmental factor in the pathogenesis of KBD. Selenoprotein P (SEPP1) is a special selenoprotein, which is the primary form of Se in vivo. Our aim was to investigate the putative association of SEPP1 r25191g/a single nucleotide polymorphism (SNP) with KBD risk and the SEPP1 transcriptional levels in whole blood and articular cartilage tissue of KBD cases and controls, respectively. One hundred and sixty-seven cases with KBD and 166 control subjects from Shaanxi province of China were included in the present study. The detection of SNP r25191g/a in the 3' untranslated region was performed using an efficient technique, tetra-primer amplification refractory mutation system PCR. A quantitative analysis of SEPP1 mRNA in KBD and control groups by real-time PCR was also performed. The present results show no significant difference in genotype and allele distribution of SNP r25191g/a between individuals with KBD and controls (P = 0·279 and 0·428, respectively). There was also no association between SNP r25191g/a and risk of KBD (OR 1·153; 95 % CI 0·533, 2·496). However, the frequency of the rare genotype AG of SNP r25191g/a was significantly lower in Chinese population than in the Caucasians. It was shown that the SEPP1 mRNA expression in whole blood was lower in KBD patients than in the control group (0·149-fold, P < 0·001), but that it was much higher in articular cartilage tissue (4·53-fold, P = 0·012). Our aim was to lay a foundation for us to further study the association between the pathogenesis of KBD and SEPP1.

APOE2 promotes the development and progression of subretinal neovascularization in age-related macular degeneration via MAPKs signaling pathway.

BACKGROUND: Neovascular age-related macular degeneration (nvAMD) is one of the main pathological features of wet AMD. Apolipoprotein E2 is involved in the formation of nvAMD but the molecular mechanism has not been reported. METHODS: The APOE alleles in AMD patients were detected by genotyping. Mouse models were divided into 4 groups according to transfection different gene segments and laser-induced treatment. APOE2, VEGF, PDGF-BB, b-FGF and inflammatory cytokines (including p-NF-κB, TNF-α, IL-1ß and IL-6) were tested by ELISA in mice retinal lysate. The formation of nvAMD in the indicated treatment groups at 3rd, 7th and 14th day after laser-induced damage were detected by FFA. Besides, qRT-PCR was used to determine the mRNA levels of p38, JNK and ERK in ARPE-19 cells. Finally, the inflammatory cytokines and MAPK proteins (including P38, p-P38, JNK, p-JNK, ERK and p-ERK) were detected by western blot. RESULTS: The statistics of APOE alleles showed that APOE2 allele carriers were more likely to nvAMD. VEGF, PDGF-BB, b-FGF and related inflammatory cytokines were up-regulated significantly after treatment with APOE2, which were reduced after silencing the MAPK family genes, however. Further, the expression levels of neovascular growth factors and inflammatory cytokines were highly consistent between mouse models and ARPE-19 cells. Besides, the phosphorylation levels of p38, JNK and ERK were affected by APOE2. CONCLUSION: nvAMD was affected directly by the overexpression of VEGF, PDGF-BB and b-FGF, which were regulated by APOE2 through activating MAPKs pathway.

[Expression of PI3K/Akt signal pathway in acute myocardial ischemia].

OBJECTIVE: To explore the influence of the PI3K/Akt-mediated signal pathway in acute myocardial ischemia (AMI) rats, the expression of pAkt, Akt, Caspase3 and p38 in myocardium and somatic muscles of AMI rats were detected. METHODS: The rats model of AMI were established by peritoneal injecting isoprinosine (ISO), and were detected by electrocardiogram and haemodynamics. The expressions of pAkt, Caspase3 and p38 in somatic muscles and cardiac muscles of AMI and normal rats were detected by Dot blot hybridization and Western blot. RESULTS: In contrast with normal rats, electrocardiogram of AMI rats showed a lower displacement of ST segment (> or = 0.1 mv). The expression of pAkt, Caspase3 and p38 were higher than those in normal rats (P < 0.05). No apparent changes were observed in expression of Akt (P = 0.477). CONCLUSION: Expressions of pAkt, Akt and correlated apoptosis molecule Caspase3 and p38 in cardiac and somatic muscles of AMI rats were higher than those in normal rats. No apparent changes were observed in expression of Akt.

Predictive tool for intravenous immunoglobulin resistance of Kawasaki disease in Beijing.

OBJECTIVE: To construct a predictive tool for the efficacy of intravenous immunoglobulin (IVIG) therapy in children with Kawasaki disease (KD) in Beijing, China. DESIGN: This was a cohort study. Data set (including clinical profiles and laboratory findings) of children with KD diagnosed between 1 January 2010 and 31 December 2015 was used to analyse the risk factors and construct a scoring system. Data set of children with KD diagnosed between 1 January 2016 and 1 December 2016 was used to validate this model. SETTING: Children's Hospital Capital Institute of Pediatrics and Beijing Children's Hospital. PATIENTS: 2102 children diagnosed with KD. INTERVENTIONS: No. MAIN OUTCOME MEASURES: Responsiveness to IVIG. RESULTS: The predictive tool included C reactive protein ≥90 mg/L (3 points), neutrophil percentage ≥70% (2.5 points), sodium ion concentration <135 mmol/L (3 points), albumin <35 g/L (2.5 points) and total bilirubin >20 µmol/L (5 points), which generated an area under the the receiver operating characteristic curve of 0.77 (95% CI 0.71 to 0.82) for the internal validation data set, and 0.69 (95% CI 0.58 to 0.81) and 0.63 (95% CI 0.53 to 0.72) for two external validation data sets, respectively. If a total of ≥6 points were considered high-risk for IVIG resistance, sensitivity and specificity were 56% and 79% in the internal verification, and the predictive ability was similar in the external validation. CONCLUSIONS: The predictive tool is helpful in early screening of high-risk IVIG resistance of KD in the Beijing area. Consequently, it will guide the clinician in selecting appropriate individualised regimens for the initial treatment of this disease, which is important for the prevention of coronary complications.