Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ~4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

Single-cell sequencing in primary intraocular tumors: understanding heterogeneity, the microenvironment, and drug resistance.

Retinoblastoma (RB) and uveal melanoma (UM) are the most common primary intraocular tumors in children and adults, respectively. Despite continued increases in the likelihood of salvaging the eyeball due to advancements in local tumor control, prognosis remains poor once metastasis has occurred. Traditional sequencing technology obtains averaged information from pooled clusters of diverse cells. In contrast, single-cell sequencing (SCS) allows for investigations of tumor biology at the resolution of the individual cell, providing insights into tumor heterogeneity, microenvironmental properties, and cellular genomic mutations. SCS is a powerful tool that can help identify new biomarkers for diagnosis and targeted therapy, which may in turn greatly improve tumor management. In this review, we focus on the application of SCS for evaluating heterogeneity, microenvironmental characteristics, and drug resistance in patients with RB and UM.

[Sediment Pollution Characteristics and Dredging in the Nanfei River Estuary, Chaohu Lake].

To clarify the endogenous pollution characteristics of sediments in the Nanfei River estuary, Chaohu Lake, and provide a theoretical basis for the dredging works, the organic index, pollution index, and potential ecological risk were determined. The results show that the average total nitrogen (TN), total phosphorus (TP), and organic matter (OM) content of the sediment was 1461 mg·kg-1, 438 mg·kg-1, and 1.77%, respectively, showing enrichment in the surface layer (0-10 cm). The nutrient pollution status and TP pollution index show that the organic pollution level was moderate and the TP pollution was severe. Furthermore, the pollution risk gradually reduced with sediment depth, representing a low risk at depths below 30 cm. Static release results showed that the average release fluxes of NH4+-N and TP in the sediment were 8.04 mg·(m2·d)-1 and 0.19 mg·(m2·d)-1, respectively, and showed highest release potentials consistent with areas of sediment nutrient pollution. Except for Cr and Ni, the concentrations of six heavy metals were higher than the soil background values for Anhui Province, and the concentrations of Hg and Cd far exceeded the standards. According to the assessment of potential ecological risk from heavy metals, the 0-20 cm sediments present a high level of risk and sediments below 30 cm have a low level of risk. Heavy metal leaching toxicity indicated that the risk of heavy metal release after dredging is low and non-hazardous. These results were used to determine the key dredging area (3.93 km2) and depth (30 cm) for the Nanfei River estuary, providing an important basis for future dredging activities.

[Endogenous Pollution and Release Characteristics of Bottom Sediments of Hengshan Reservoir in Yixing City].

To clarify the endogenous pollution and release characteristics of the bottom sediment of Hengshan Reservoir in Yixing City, a typical section of the reservoir was sampled and analyzed. The research results show that the average concentrations of total nitrogen, total phosphorus, and organic matter in the surface sediments of Hengshan Reservoir are 2778 mg·kg-1, 899 mg·kg-1, and 3.1%, respectively. The endogenous pollution is serious, and the downstream sediments are highly polluted upstream of the reservoir. Phosphorus spectroscopic analysis results show that iron-bound phosphorus (Fe-P) and aluminum-bound phosphorus (Al-P) are the main bound phosphorus forms in the sediment, accounting for 28% and 39% of the total phosphorus, respectively. The average concentration of activated phosphorus in the sediment (combination of weakly adsorbed phosphorus, organic phosphorus, and iron phosphorus) is 255 mg·kg-1, accounting for 38% of the total phosphorus. The average release rates of nitrogen and phosphorus in sediments were 18.0 mg·(m2·d)-1 and 0.60 mg·(m2·d)-1. The correlation analysis results show that the organic matter content of the sediment is significantly correlated with the diffusion flux of phosphate, ammonia nitrogen, and ferrous iron (P<0.05), indicating that the mineralization of organic matter in the sediment may be the main release source of nitrogen and phosphorus in the sediment influencing factors.

Electrochemical Oxidative Esterification of Thiophenols: Efficient Access to Sulfinic Esters.

BACKGROUND: The sulfinic esters are important and useful building blocks in organic synthesis. OBJECTIVE: The aim of this study was to develop a simple and efficient method for the synthesis of sulfinic esters. MATERIALS AND METHODS: Constant current electrolysis from thiols and alcohols was selected as the method for the synthesis of sulfinic esters. RESULTS AND DISCUSSION: A novel electrochemical method for the synthesis of sulfinic esters from thiophenols and alcohols has been developed. Up to 27 examples of sulfinic esters have been synthesized using the current methods. This protocol shows good functional group tolerance as well as high efficiency. In addition, this protocol can be easily scaled up with good efficiency. Notably, heterocycle-containing substrates, including pyridine, thiophene, and benzothiazole, gave the desired products in good yields. A plausible reaction mechanism is proposed. CONCLUSION: This research not only provides a green and efficient method for the synthesis of sulfinic esters but also shows new applications of electrochemistry in organic synthesis. It is considered that this green and efficient synthetic protocol used to prepare sulfinic esters will have good applications in the future.

Gene Mutation Spectrum of Thalassemia Among Children in Yunnan Province.

Background: Thalassemia is an autosomal genetic disorder, found throughout the world. It is still not treatable and create socio economic problems. In this study, we investigated the prevalence and spectrum features of thalassemia in Yunnan Province, the southwestern area of China. During 2014-2018, a total of 3,539 suspected thalassemia children were detected with α- and ß-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Kunming Children's Hospital. Results: Of these patients, 1,130 were diagnosed thalassemia gene carriers with a carrying rate of 31.92%. Among them, α-thalassemia was 43.63%, ß-thalassemia was 53.98%, cases with both α- and ß- thalassemia was 2.39%. In α-thalassemia patients, the most common mutations was -SEA/αα (52.13%), followed by -α3.7/αα (27.79%), hemoglobin H disease (18.46%), and -α4.2/αα (1.62%). Fifteen gene mutations and 30 genotypes were identified in ß-thalassemia patients, with the five most common mutations CD17 (A>T) (29.51%), CD41-42 (-TTCT) (27.87%), IVS-II-654 (C>T) (14.92%), CD26 (G>A) (6.89%), and CD26/CD27 (2.62%) accounting for 81.81% of the ß-globin gene mutations. Furthermore, we founded two rare mutations CD34 (TGG → TAG) and Int in Chinese populations. Conclusions: Our results suggested that the prevalence and gene mutation spectrum of thalassemia display obviously heterogeneity among children in Yunnan Province. The findings provide the valuable information for premarital and pre-pregnancy screening, prenatal diagnostic services, and designing appropriate prevention programs to control thalassemia for future in this area.

[Costunolide Suppresses Proliferation of K562 Cells through JAK/STAT Signaling Pathway].

OBJECTIVE: To investigate the inhibitory effect of costunolide on the proliferation of human chronic myeloid leukemia cell line K562 cells and the underlying mechanisms. METHODS: The effect of costunolide on the viability of K562 cells was detected by CCK-8 assay. The cell apoptosis and the level of ROS in K562 cells were detected by flow cytometry. The expression level of related proteins were analyzed using Western blot. RESULTS: The CCK-8 viability assay showed that costunolide at the gradient concentrations of 0-50 µmol/L significantly inhibited the proliferation of K562 cells after exposure for 24 h. The IC50 value of costunolide was approximately 15.70±2.13 µmol/L, with statistically significant difference (P＜0.05). Treatment with 15 µmol/L costunolide for 24 and 48 h induced apoptosis of K562 cells with the apoptotic rate significantly increasing from (1.77±0.59) % in the control group to (17.68±2.84) % and (30.65±4.54) % (P＜0.05) respectively. Furthermore, following treatment, the level of ROS was significantly increased, from (3.52±1.08) % to (23.56±3.52) % and (36.68±4.22) % (P＜0.05). The study results also revealed that costunolide treatment significantly inhibited the expression of p-JAK2, p-STAT3 and BCL-2, and increased the expression of BAX, cytochrome C, cleaved-caspase-3 and cleaved-PARP. CONCLUSION: Costunolide suppresses the proliferation of K562 cells through JAK/STAT signaling pathway.

Carboxylate breaks the arene C-H bond via a hydrogen-atom-transfer mechanism in electrochemical cobalt catalysis.

Combined computational and experimental studies elucidated the distinctive mechanistic features of electrochemical cobalt-catalyzed C-H oxygenation. A sequential electrochemical-chemical (EC) process was identified for the formation of an amidylcobalt(iii) intermediate. The synthesis, characterization, cyclic voltammetry studies, and stoichiometric reactions of the related amidylcobalt(iii) intermediate suggested that a second on-cycle electro-oxidation occurs on the amidylcobalt(iii) species, which leads to a formal Co(iv) intermediate. This amidylcobalt(iv) intermediate is essentially a cobalt(iii) complex with one additional single electron distributed on the coordinating heteroatoms. The radical nature of the coordinating pivalate allows the formal Co(iv) intermediate to undergo a novel carboxylate-assisted HAT mechanism to cleave the arene C-H bond, and a CMD mechanism could be excluded for a Co(iii/i) catalytic scenario. The mechanistic understanding of electrochemical cobalt-catalyzed C-H bond activation highlights the multi-tasking electro-oxidation and the underexplored reaction channels in electrochemical transition metal catalysis.

[Effect of Dehydrocostus Lactone on Proliferation of K562 Cells and Its Mechanism].

OBJECTIVE: To explore the inhibitory effect of dehydrocostus lactone on the proliferation of human chronic myeloid leukemia K562 cells and the underlying mechanisms. METHODS: Cell viability was evaluated by CCK-8 assay. Flow cytometry was used to assess the effect of dehydrocostus lactone on the cell cycle and apoptosis of K562 cells. The levels of BCR/ABL-STATs-related molecules were analyzed by using Western blot. RESULTS: The CCK-8 assay showed that dehydrocostus lactone at graded concentration of 4, 6, 8, 10, 12 µmol/L could significantly inhibit the proliferation of K562 cells after exposure for 24 h. The proliferation inhibition rate was (24.32±3.05%), (42.91±3.89%), (46.35±4.93%), (77.06±5.42%) and (89.04±4.25%) respectively, showing statistically significantly different from (2.08±0.27%) in the control (P＜0.05). Also, the treatment with 5 and 10 µmol/L of dehydrocostus lactone induced K562 cell apoptosis, the apoptotic rate of K562 cells was significantly higher than that the control group (P＜0.05), and up-regulated the expression level of BAX and p21. Furthermore, dehydrocostus lactone (5 and 10 µmol/L) also increased the percentage of cells in G2/M [(8.53±1.71)% to (17.42±2.72) and (31.79±4.38%)](P＜0.05). The study results also revealed that dehydrocostus lactone significantly inhibited the expression of BCR/ABL STAT3, STAT5, CyclinB1, CDK1 and BCL-2, and up-regulated the expression level of BAX and p21. CONCLUSION: Dehydrocostus lactone can suppress the proliferation of K562 cells and induce the apoptosis of K562 cells through BCR/ABL-STAT signaling pathways.

A de novo ANK1 mutation associated to hereditary spherocytosis: a case report.

BACKGROUND: Hereditary spherocytosis (HS) is a type of hemolytic anemia caused by abnormal red cell membrane skeletal proteins with few unique clinical manifestations in the neonate and infant. An ANK1 gene mutation is the most common cause of HS. CASE PRESENTATION: The patient was a 11-month-old boy who suffered from anemia and needed a regular transfusion therapy at an interval of 2-3 months. Hematological investigations showed moderate anemia (Hb80 g/L). Red cells displayed microcytosis (MCV76.4 fl, MCH25.6 pg, MCHC335 g/L). The reticulocytes were elevated (4.8%) and the spherocytes were increased (10%). Direct antiglobulin test was negative. Biochemical test indicated a slight elevation of bilirubin, mainly indirect reacting (TBIL32.5 µmol/L, IBIL24 µmol/L). The neonatal HS ratio is 4.38, obviously up the threshold. Meanwhile, a de novo ANK1 mutation (exon 25:c.2693dupC:p.A899Sfs*11) was identified by next-generation sequencing (NGS). Thus, hereditary spherocytosis was finally diagnosed. CONCLUSIONS: Gene detection should be considered in some hemolytic anemia which is difficult to diagnose by routine means. We identified a novel de novo ANK1 heterozygous frameshift mutation in a Yi nationality patient while neither of his parents carried this mutation.

Antibiotics De-Escalation in the Treatment of Ventilator-Associated Pneumonia in Trauma Patients: A Retrospective Study on Propensity Score Matching Method.

BACKGROUND: Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia (VAP) in trauma patients. METHODS: This retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy (de-escalation group) or non-de-escalation therapy (non-de-escalation group). Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation. RESULTS: Among the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups (28.6% vs. 23.8%, P = 0.620). The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group (11 [8-13] vs. 14 [8-19] days, P = 0.045). The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group (6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively). Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, high injury severity score, multi-drug resistant (MDR) infection, and inappropriate initial antibiotics were associated with patients' 28-day mortality, while high APACHE II score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation. CONCLUSIONS: De-escalation strategy in the treatment of trauma patients with VAP could reduce the duration of antibiotics treatments and expense of hospitalization, without increasing the 28-day mortality and MDR infection.

Modulating the release of proteins from a loaded carrier of alginate/gelatin porous spheres immersed in different solutions.

BACKGROUND: A biodegradable porous particle for the controlled biofactor delivery which assembly of pores in scaffolds can improve the permeation and diffusion of drugs or growth factors. OBJECTIVE: Porous-spheres in millimeter scale were prepared by mixing sodium alginate and gelatin interpenetrating networks with cross-linkers; interconnected open pores were fabricated through solvent casting and particulate leaching. METHODS: Morphological characteristics, degradation, and bovine serum albumin (BSA) release rates of the porous-spheres immersed in three different solutions, namely, deionized distilled water, simulated body fluid (SBF), and phosphate-buffered saline (PBS), were detected. RESULTS: Porous-spheres with a large amount of gelatin exhibited an increase in water absorption rates without affecting scaffold strength and no cytotoxicity was elicited. Highly interconnected pores with a diameter of 100-200 µm were uniformly distributed in scaffolds. The weight loss in PBS was faster than that in other solutions; the highest release rate of BSA in SBF was observed for 2 h. The release rates also exhibited linear patterns from 2 h to 24 h in all of the groups. CONCLUSIONS: After 1 d of immersion in solutions, BSA release rates in scaffolds logarithmically decreased for 14 d. The degradation of porous-spheres also showed an inverse pattern.

[Isoalantolactone Inhibits Proliferation of K562/A02 Cells through Caspase-Dependent Apoptotic Pathway].

OBJECTIVE: To explore the apoptosis-inducing effects of isoalantolactone on chronic myeloid leukemia drug-resistant cell line K562/A02. METHODS: K562/A02 cells were treated with 0, 6.25, 12.5, 25, 50, and 100 µmol/L isoalantolactone for 12 h, 24 h, and 48 h. The cell viability was analyzed with CCK8 assay. The effects of isoalantolactone on mitochondrial membrane potential (MMP), reactive oxygen species(ROS) and apoptosis of K562/A02 cells were measured by flow cytometry. The apoptosis related proteins were analyzed by using Western blot after treatment with isoalantolactone. RESULTS: Isoalantolactone effectively inhibited the proliferation of K562/A02 cells in dose- and time-dependent manner, the IC50 value of isoalantolactone in K562/A02 cells at 24 h was about (15±1.42) µmol/L (P<0.05). Flow cytometric analysis displayed that after treatment of K562/A02 cells with 0, 10, 15, and 20 µmol/L of isoalantolactone, apoptotic rate were 1.35±0.52%, 18.07±4.03%, 27.53±3.01%, and 34.99±4.91%, respectively, mitochondrial membrane potential was 96.42±3.59%, 74.25±6.91%, 60.97±5.69%, and 31.28±4.95%, respectively. Otherwise, isoalantolactone induced accumulation of intracellular reactive oxygen species(ROS) in K562/A02 cells (5.03±1.43%, 17.55±3.85%, 32.09±3.23%, and 44.38±5.92%). Meanwhile, isoalantolactone significantly down-regulated the expression of BCL-2 protein and up-regulated the expression of BAX, cytochrome C, cleaved-caspase-9, cleaved-caspase-3, and cleaved-PARP. CONCLUSION: Isoalantolactone significantly inhibits K562/A02 cell proliferation mainly via caspase-dependent apoptotic pathway.

Enterogenous infection of Candida albicans in immunocompromised rats under severe acute pancreatitis.

BACKGROUND: Opportunistic infection of Candida albicans (C. albicans) has become a serious problem in immunocompromised patients. The study aimed to explore the mechanism of enterogenous infection of C. albicans in immunocompromised rats under severe acute pancreatitis (SAP). METHODS: Sprague Dawley (SD) rats (n=100) were randomly assigned into 5 groups as the following: blank group, cyclophosphamide+ceftriaxone+SAP group, cyclophosphamide+ceftriaxone group, cyclophosphamide+SAP group, and cyclophosphamide group. The rats were sacrificed at 5 and 10 days, and their jejunum, colon, mesenteric lymph nodes, pancreas, intestinal content, and blood were quickly collected to detect C. albicans. A region of the 25S rRNA gene was chosen and amplified by polymerase chain reaction (PCR) to differentiate C. albicans genotypes. The amplified products were further sequenced and compared to judge their homology. RESULTS: Compared with the Cyclophosphamide group, the combination of immunosuppressants and broad-spectrum antibiotics significantly increased the colonization of C. albicans in intestine in 5 and 10 days. Pure SAP stress did not increase the opportunistic infection of C. albicans. The PCR products of C. albicans isolates all belonged to the genotype A family, and sequence alignment showed that the amplified fragments were homologous. CONCLUSION: The damage of immune system and broad-spectrum antimicrobial agents are important risk factors for opportunistic fungal infection. Intestinal tract is an important source for genotype-A C. albicans to translocate and invade into bloodstream.

Effect of Candida albicans on Intestinal Ischemia-reperfusion Injury in Rats.

BACKGROUND: Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperfusion injury (IIRI), and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI. METHODS: Fifty female Wistar rats were divided into five groups according to the status of C. albicans infection and IIRI operation: group blank and sham; group blank and IIRI; group cefoperazone plus IIRI; group C. albicans plus cefoperazone and IIRI (CCI); and group C. albicans plus cefoperazone and sham. The levels of inflammatory factors tumor necrosis factor (TNF)-µ, interleukin (IL)-6, IL-1ß, and diamine oxidase (DAO) measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier. RESULTS: The levels of inflammatory factors TNF-µ, IL-6, and IL-1ß in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO (serum: 44.13 ± 4.30 pg/ml, intestine: 346.21 ± 37.03 pg/g) and Chiu scores (3.41 ± 1.09) which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number of C. albicans translocated into blood was most in group CCI ([33.80 ± 6.60] ×102 colony forming unit (CFU)/ml). CONCLUSION: Intestinal C. albicans infection worsened the IIRI-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. albicans translocation and dissemination.

[Value of amino-terminal pro-brain natriuretic peptide as a predictive marker of symptomatic patent ductus arteriosus in preterm infants].

OBJECTIVE: To study the value of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting symptomatic patent ductus arteriosus (sPDA) in preterm infants. METHODS: Preterm infants born at a gestational age (GA) of ≤ 32 weeks and diagnosed with patent ductus arteriosus (PDA) by echocardiography within 48 hours after birth between June 2014 and April 2015 were selected as subjects. Their clinical manifestations were observed, and serum NT-proBNP levels were measured and echocardiography was performed at 3 and 5 days after birth. The infants were divided into sPDA group and asymptomatic PDA (asPDA) group based on their clinical manifestations and the results of echocardiography. The correlations between serum NT-proBNP level and echocardiographic indices were analyzed. Serum NT-proBNP levels were compared between the two groups. The receiver operator characteristic (ROC) curve was applied to determine the sensitivity and specificity of serum NT-proBNP in the prediction of sPDA. RESULTS: A total of 69 preterm infants were enrolled in this study, with 13 infants in the sPDA group and 56 infants in the asPDA group. Serum NT-proBNP level was positively correlated with the diameter of the arterial duct (r=0.856; P<0.05)and the ratio of left atrial diameter to aortic root diameter (LA/AO) (r=0.713; P<0.05). At 3 and 5 days after birth, the serum NT-proBNP levels in the sPDA group were significantly higher than those in the asPDA group (P<0.05). The area under the ROC curve (AUC) for the prediction of sPDA by NT-proBNP levels at 3 days after birth was 0.949 (95% CI: 0.892-1.000; P<0.001), with a cut-off value of 27 035 pg/mL (sensitivity: 92.3%; specificity: 94.6%); the AUC for the prediction of sPDA by NT-proBNP levels at 5 days after birth was 0.924 (95% CI: 0.848-1.000; P<0.001), with a cut-off value of 6 411 pg/mL (sensitivity: 92.3%; specificity: 92.9%). CONCLUSIONS: NT-proBNP may be a quantitative index for shunt volume. The measurement of serum NT-proBNP levels on 3 and 5 days after birth may be useful to predict sPDA in preterm infants.

Sedation and analgesia with fentanyl and etomidate for intrathecal injection in childhood leukemia patients.

In this study, we tried to find a safe as well as fast effective treatment for sedation and analgesia for intrathecal injection in childhood leukemia patients, relieving treatment difficulties and pain, increasing the success rate of single intrathecal injection.The patients were divided into the experimental group (fentanyl combined with etomidate) and the control group (lidocaine only) randomly. The experimental group was given fentanyl 1 to 2 µg/kg intravenously first, then etomidate 0.1 to 0.3 mg/kg intravenously after the pipe washed. The patients younger than 1.5 years or who did not achieve satisfied sedative and analgesic situation received an additional time of etomidate (0.1-0.3 mg/kg). The patients were given oxygen at the rate of 4-5 L/min during the whole operation, and the finger pulse oximeter was used simultaneously to detect the changes in heart rate (HR) and blood oxygen saturation (SpO2). The doctors who performed the procedures assessed the quality of sedation and analgesia.In the experimental group, the patients' HR increased slightly after given fentanyl combined with etomidate. The patients' SpO2 was stable. Most patients achieved a good sedative and analgesic state within 1 to 2 minutes, and no case of respiration depression or cardiac arrhythmias occurred during the whole operation. The wake-up time was 55.42 ±â€Š20.62 min. In the control group, the patients were not very cooperative during the intrathecal injection, which made the procedures very difficult.During intrathecal injection, pain obviously reduced and the success rate of single lumbar puncture increased. It is safe and effective to apply fentanyl combined with etomidate for sedation and analgesia.

The cytokine and chemokine profiles in patients with hand, foot and mouth disease of different severities in Shanghai, China, 2010.

BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.

The Role of MicroRNA in Hepatitis C Virus Replication.

Hepatitis C virus (HCV) infection is a major global health problem. There is no effective vaccine and the current treatment regimen with pegylated interferon α and ribavirin is associated with significant adverse events. Therefore, there is an urgent need to identify new antiviral targets for HCV therapy. In recent years, a growing number of microRNAs (miRNAs) have been reported to be able to regulate HCV replication and infection by interacting with the HCV genome directly or by regulating host innate immunity to build a nonspecific antiviral state within cells. In this review, we discuss HCV virology and standard of care followed by miRNA in general, and then give a brief overview of miRNAs involved in HCV infection and discuss their potential application as a therapeutic option for the treatment of HCV infection.