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.

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.

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.

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.

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.

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.

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.

Brucella meningoencephalitis in children with status epilepticus A case report and literature review / 中国热带医学

@#Abstract: Objective　To investigate the clinical characteristics and incidence of Brucella encephalitis and meningitis in children. Methods We report the clinical data of a child with Brucella melitensis meningitis in children, and summarize the incidence, diagnosis methods and treatment of Brucella encephalitis or meningitis in children, taking into account the relevant domestic and foreign literature from January 2014 to December 2020. Results　A 4-year-old girl was admitted to the hospital with status epilepticus on March 15, 2021 because of interrupted right limb numbness for 16 hours and convulsions for 2 hours. She had 2 non-febrile convulsions three months before admission and was diagnosed with epilepsy. This incident was acute, accompanied by low fever, with epilepsy as the main manifestation. Cerebrospinal fluid test suggested central nervous system infection, but the nature of infection could not be determined by routine and biochemistry of cerebrospinal fluid.The cerebrospinal fluid next generation sequencing confirmed that the pathogen of the infection was B. melitensis, which was further verified by the peripheral blood antibody test. After effective antibiotics combined with a full course of treatment, the patient recovered after six months of treatment. A total of 60 articles were retrieved in the database, including 29 in Chinese. During this period, a total of 7 cases of brucellosis in children with nervous system involvement were reported, one of which was a case report, and the other 6 cases were mentioned in the comprehensive analysis of children with brucellosis. Conclusions　Brucella encephalitis or meningitis in children has a low incidence and various clinical features, which are easy to be misdiagnosed or missed.

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.

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.

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.

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.

[Effectiveness of Xuebijing in treatment of multiple organ dysfunction syndrome: a Meta analysis].

OBJECTIVE: To systematical evaluate the effect of Xuebijing injection in the treatment of multiple organ dysfunction syndrome (MODS). METHODS: With the keywords including Xuebijing, multiple organ dysfunction syndrome, multiple organ dysfunction and multiple organ failure, PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP and Wanfang Data from the database start until March 4th, 2018 were searched for relevant randomized controlled trials (RCTs) related to Xuebijing injection combined conventional treatment versus conventional treatment alone for MODS. The control group received conventional western medicine treatment, including etiological treatment, antibiotics, mechanical ventilation, nutritional support, and comprehensive treatment to maintain fluid, electrolyte, acid and alkali balance. The experimental group was given traditional western medicine combined with Xuebijing injection. The observation parameters included 7-day and 28-day mortality, acute physiology and chronic health evaluation II (APACHE II) and Marshall score, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the number of platelets, activated partial thromboplastin time (APTT) and prothrombin time (PT). According to the inclusion and exclusion criteria, two evaluators independently screened the literature, extracted data and evaluated the methodological quality of the included studies. RevMan 5.3 software was used for Meta analysis. Funnel plot was used to analyze publication bias. RESULTS: A total of 35 RCTs and 2 131 patients were enrolled, including 1 076 in the experimental group and 1 055 in the control group. The results of Meta analysis showed that compared with control group, Xuebijing combined conventional treatment was in favor to decrease the mortality of patients with MODS [7-day mortality: odds ratio (OR) = 0.42, 99% confidence interval (99%CI) = 0.26-0.69, P < 0.000 01; 28-day mortality: OR = 0.31, 99%CI = 0.21-0.45, P < 0.000 01], also could obviously reduce critical condition degree of APACHE II score and the organ function of Marshall score [APACHE II: mean difference (MD) = 3.24, 99%CI = 2.00-4.49, P < 0.000 01; Marshall score: MD = 1.95, 99%CI = 0.50-3.40, P = 0.000 5]. Meanwhile, the results of conventional western medicine combined with Xuebijing in the removal of IL-6 and TNF-α, platelets increase and improvement of PT were better than those of conventional western medicine (IL-6: MD = 5.56, 99%CI = 1.44-9.68, P = 0.000 5; TNF-α: MD = 4.97, 99%CI = 3.44-6.50, P < 0.000 01; platelets: MD = -50.79, 99%CI = -74.84 to -26.74, P < 0.000 1; PT: MD = 4.55, 99%CI = 3.96-5.14, P < 0.000 01), however, there was no obvious advantage in improving APTT (MD = 0.96, 99%CI = -5.08-7.00, P = 0.68). The analysis of funnel map showed that the effect points of various studies were mainly centered on the amount of combined effect, and the "inverted funnel" type was generally symmetrical distribution. However, because the number of the included studies was less, the literature bias could not be completely eliminated. CONCLUSIONS: Xuebijing injection may through its strong cytokines clearance, platelet increase and blood coagulation improvement to protect the organ function in patients with MODS, so as to reduce the mortality and improve the prognosis.

Thrombospondin-2 predicts response to treatment with intravenous immunoglobulin in children with Kawasaki disease.

OBJECTIVE: To investigate the predictive value of thrombospondin-2 (TSP-2) in assessing the response to intravenous immunoglobulin (IVIG) in children with acute Kawasaki disease (KD). METHODS: This was a cohort study with controls. 71 children with KD were recruited as the case group, including IVIG non-responder (n=17) and IVIG responder (n=54), and healthy children (n=27) and febrile children (n=30) were used as control groups. ELISA was used to measure plasma TSP-2 and TSP-1 levels. The rank-sum test was used to compare groups of non-normally distributed data. Predictive value was evaluated through the receiver operating characteristic (ROC) curve. RESULTS: Compared with the control groups, the plasma TSP-2 levels in acute KD were significantly elevated (TSP-2: 31.00 (24.02, 39.28) vs 21.93 (17.00, 24.73) vs 16.23 (14.00, 19.64) ng/mL, P<0.001). The plasma TSP-2 level in the IVIG non-responder was significantly higher than the responder group (37.58 (31.86, 43.98) vs 27.84 (21.88, 33.48) ng/mL, P=0.002). When using an ROC curve to analyse the predictive effect of TSP-2 on non-responsiveness to IVIG treatment, the area under the curve was 0.752 (0.630, 0.875) (P=0.002). When the cut-off value for TSP-2 was 31.50 ng/mL, the sensitivity was 82.35%, the specificity was 64.81%. CONCLUSION: The plasma TSP-2 level was elevated in acute KD and it might be a novel predictor for IVIG resistance, which could help guide clinicians to choose individualised initial therapeutic regimens.

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.

Association of nineteen polymorphisms from seven DNA repair genes and the risk for bladder cancer in Gansu province of China.

BACKGROUND: Balance of DNA damage and proper repair plays an important role in progression of bladder cancer. Here we aimed to assess the associations of nineteen polymorphisms from seven DNA repair-associated genes (PRAP1, OGG1, APEX1, MUTYH, XRCC1, XRCC2 and XRCC3) with bladder cancer and their interactions in the disease in a Han Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: A chip-based TaqMan genotyping for the candidate genes was performed on 227 bladder cancer patients and 260 healthy controls. APEX1 rs3136817, MUTYH rs3219493, three SNPs (rs3213356, rs25487 and rs1799782) in XRCC1, and three SNPs (rs1799794, rs861531 and rs861530) in XRCC3 showed significant associations with the risk of bladder cancer. In haplotype analysis, elevated risks of bladder cancer were observed in those with either haplotype GT (OR = 1.56, P = 0.003) of APEX1, or GGGTC (OR = 2.05, P = 0.002) of XRCC1, whereas decreased risks were in individuals with either GCGCC (OR = 0.40, P = 0.001), or GCGTT (OR = 0.60, = 0.005) of XRCC1, or CCC (OR = 0.65, P = 0.004) of MUTYH, or TTTAT (OR = 0.36, P = 0.009) of XRCC3. Interaction analysis showed that the two-loci model (rs1799794 and rs861530) was the best with the maximal testing accuracy of 0.701, and the maximal 100% cross-validation consistency (P = 0.001). CONCLUSIONS: Polymorphisms and haplotypes of DNA repair genes are associated with the risk of bladder cancer, and of which the SNPs (rs1799794 and rs861530) in XRCC3 gene might be two major loci in relation to the susceptibility to bladder cancer in a northwest Chinese population.

[Study of prevention and control of delirium in ventilated patients by simulating blockage of circadian rhythm with sedative in intensive care unit].

OBJECTIVE: To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). METHODS: A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. RESULTS: (1) There were no significant differences in gender, age, acute physiology and chronic health evaluation II (APACHEII) score among groups. (2) Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. (3) Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). (4) Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75±26.78 vs. 102.00±26.31 and 100.31±25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75±1.04 vs. 7.00±1.52, P < 0.05). (5) The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = -0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05). CONCLUSIONS: Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients.

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.