Invasive pulmonary and central nervous system aspergillosis in a child: A case report and literature review.

RATIONALE: Children with haematological malignancies have a higher risk of developing aggressive pulmonary aspergillosis and a higher mortality rate. The most common site of extrapulmonary aspergillosis in children is the central nervous system (CNS), and the death rate is higher when CNS is affected. Therefore, early diagnosis and treatment of invasive aspergillosis are essential for reducing mortality. PATIENT CONCERNS: We report a case of an 8-year-old girl with acute lymphoblastic leukaemia who developed invasive pulmonary aspergillosis complicated by CNS aspergillosis. Aspergillus was confirmed by metagenomic sequencing of pathogenic microorganisms. DIAGNOSES: Invasive pulmonary and central nervous system aspergillosis. INTERVENTIONS: The patient was treated with combined systemic antifungal agents (voriconazole and liposomal amphotericin B) and intrathecal injection of amphotericin B. OUTCOMES: The treatment was well tolerated and resulted in remarkable clinical and radiological head improvements. LESSONS: Invasive aspergillosis has a high mortality rate and requires early diagnosis and treatment. Pathogenic microbial metagenomic sequencing is a convenient method to assist in the early diagnosis of aspergillosis. Voriconazole is the drug of choice for the treatment of invasive aspergillosis. When CNS aspergillosis occurs, it can be combined with other systemic antifungal drugs and intrathecal injection of amphotericin B.

Interlayer Engineering of VS2 Nanosheets via In Situ Aniline Intercalative Polymerization toward Long-Cycling Magnesium-Ion Batteries.

Rechargeable magnesium batteries (RMBs) show great potential in large-scale energy storage systems, due to Mg2+ with high polarity leading to strong interactions within the cathode lattice, and the limited discovery of functional cathode materials with rapid kinetics of Mg2+ diffusion and desirable cyclability retards their development. Herein, we innovatively report the confined synthesis of VS2/polyaniline (VS2/PANI) hybrid nanosheets. The VS2/PANI hybrids with expanded interlayer spacing are successfully prepared through the exfoliation of VS2 and in situ polymerization between VS2 nanosheets and aniline. The intercalated PANI increases the interlayer spacing of VS2 from 0.57 to 0.95 nm and improves its electronic conductivity, leading to rapid Mg-ion diffusivity of 10-10-10-12 cm2 s-1. Besides, the PANI sandwiched between layers of VS2 is conducive to maintaining the structural integrity of electrode materials. Benefiting from the above advantages, the VS2/PANI-1 hybrids present remarkable performance for Mg2+ storage, showing high reversible discharge capacity (245 mA h g-1 at 100 mA g-1) and impressive long lifespan (91 mA h g-1 after 2000 cycles at 500 mA g-1). This work provides new perspectives for designing high-performance cathode materials based on layered materials for RMBs.

Effects of social factors on the COVID-19 cases and its evolution in Hubei, China.

Introduction: In order to study the impact of social factors on the evolution of the epidemic, this paper takes the COVID-19 in Hubei Province of China as an example to study the impact of social factors such as the permanent population, universities, hospitals, the distance between Wuhan seafood market and 17 cities in Hubei Province, and the distribution of medical supplies on the COVID-19. This is of great significance for helping to develop effective prevention and control measures and response strategies, ensuring public health and social stability. Methods: Time series regression analysis is used to study the impact of various factors on the epidemic situation, multidimensional scale analysis is used to assess the differences among provinces, and Almon polynomial is used to study the lag effect of the impact. Results: We found that these cities can be divided into three groups based on the number of confirmed cases and the time course data of the cases. The results verify that these factors have a great impact on the evolution of the COVID-19. Discussion: With the increase in the number of universities, the number of confirmed cases and new cases has significantly increased. With the increase in population density, the number of new cases has significantly increased. In addition, the farther away from the Wuhan seafood market, the fewer confirmed cases. It is worth noting that the insufficient increase in medical supplies in some cities still leads to a significant increase in new cases. This impact is regional, and their lag periods are also different. Through the comparison with Guangdong Province, it is concluded that social factors will affect COVID-19. Overall, promoting the construction of medical schools and ensuring the reasonable distribution of medical supplies is crucial as it can effectively assist decision-making.

Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

Effect of Stress Ulcers Prophylaxis, Sedative and Statin on Ventilator-Associated Pneumonia: A Retrospective Analysis Based on MIMIC Database.

Background: The use of MV can easily lead to VAP especially in ICU patients. SUP, sedatives, statin and insulin have been proved to prevent VAP and improve the prognosis of patients. Our aim was to analyze the effects of SUP, sedative, statin, and insulin on patients with MV. Methods: The occurrence of VAP and death in MV patients and VAP patients were explored by multivariate logistic regression and Cox regression to analyze analyses. Results: Totally, 5277 cases who received MV in ICU from MIMIC IV database were included. There were 826 (15.7%) cases in VAP-group and 4451 (84.3%) cases in non-VAP group and there were 1914 (36.3%) cases in hospital mortalities altogether. No protective effect of drugs on VAP was found in MV patients. The risk of death was 1.43 times higher in MV patients taking midazolam than in propofol (aHR = 1.43 95% CI: 1.04,1.97). No protective effect of drugs on death was found in VAP patients. Conclusion: Compared with midazolam, propofol is more recommended as sedation regimen in ICU patients with MV. Further high-quality studies are needed to confirm this finding.

High-density lipoprotein reduces microglia activation and protects against experimental autoimmune encephalomyelitis in mice.

Studies have shown that high-density lipoprotein (HDL) is a powerful anti-atherosclerosis factor in vivo and in vitro, with anti-inflammatory effects, and it also plays an important role in the immune system and central nervous system (CNS). In this study, the BV2 microglia inflammation model and experimental autoimmune encephalomyelitis animal model were used to investigate the potential mechanism of HDL in multiple sclerosis. Our results show that HDL inhibits the activation of BV2 microglia in a model of BV2 microglia inflammation and were validated with primary microglia. HDL can down-regulate the expression of TNF-α, IL-6, iNOS and NO. Western blot results showed that HDL could reduce the expression levels of TLR4, CD14, MyD88 and NF-κB p65 LPS-induced microglia. In a mouse model of experimental autoimmune encephalomyelitis, hematoxylin-eosin (HE) staining showed decreased infiltration of inflammatory cells in brain and spinal cord tissues, and Luxol Fast Blue (LFB) staining showed significant improvement in spinal cord demyelination. We found that HDL reduced spinal cord and brain inflammation after EAE induction, inhibited the infiltration of CD68 and Iba-1 positive inflammatory cells, and reduced the production of multiple pro-inflammatory cytokines, including pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. Western blot showed that EAE mice HDL inhibited the activation of ERK1/2 and JNK in MAPK pathway and p-IκBα and P65 in NF-κB pathway. Taken together, our study suggests that HDL may influence microglia activation and inflammatory response in mice by regulating inflammatory signaling pathways, improving induction of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and provides further insights into HDL therapy for multiple sclerosis.

Analysis of influence factors of pharmacodynamics of propofol with target-controlled infusion during anesthetic recovery period.

OBJECTIVE: To explore the pharmacodynamic (PD) characteristics of propofol during anesthetic recovery period with target-controlled infusion (TCI), and to identify the clinical variables related to the PD parameters. MATERIALS AND METHODS: 20 patients scheduled for otolaryngology surgery were enrolled. After the surgery was finished, target effect site concentration was gradually decreased, blood samples were measured at 7 time points and the differences between the target and measured plasma concentration were compared. Observer's assessment of alertness/sedation (OAA/S) and Narcotrend index (NI) were used as two PD indicators by fitting sigmoid Emax model. Correlations between PD parameter and clinical variables were evaluated. RESULTS: Performance of the TCI system showed a positive bias at the end of the anesthesia sedation period and a negative bias in the anesthetic recovery period. PD parameters (EC50, r) calculated with OAA/S and NI were significantly different, EC50 of OAA/S was lower than EC50 of NI (1.53 ± 0.70 vs. 2.16 ± 0.99 µg/mL), r of OAA/S was higher than r of NI (57.07 ± 56.39 vs. 4.35 ± 4.42). Propofol dosage and hemodynamic parameters were significantly correlated with EC50 (OAA/S), lean body weight and gender were significantly correlated with EC50 (NI). CONCLUSION: NI provided a more stable and adequate assessment of the depth of anesthesia than OAA/S, and the influence factors should be taken into account for precise dosing.

Risk factors for delirium after coronary artery bypass grafting in elderly patients.

BACKGROUND: Postoperative delirium (POD) is a common complication of major surgery and is associated with fortified morbidity, mortality, and long-term cognitive dysfunction. This study sought to evaluate the incidence and risk factors of delirium in elderly (aged ≥65 years) patients who underwent coronary artery bypass grafting (CABG). METHODS: We performed a retrospective cohort analysis. The clinical data of 1,426 elderly patients who underwent CABG at our hospital from October 2018 to October 2020 were collected and analyzed. Delirium was defined as any positive Confusion Assessment Method for Intensive Care Unit examination following surgery during the intensive care unit (ICU) stay. Risk factors for POD were authenticated via univariate and multivariate logistic regression analyses. The intraoperative and postoperative factors were evaluated using a propensity score-matched regression analysis based on preoperative factors. RESULTS: A total of 39.3% (560 of 1,426) of elderly patients who underwent CABG were diagnosed with delirium. Based on the multivariate analysis, age [odds ratio (OR) 1.013], long-term alcohol consumption (OR 2.026), diabetes (OR 1.51), stroke (OR 1.41), and extracardiac arteriopathy (OR 1.61) were found to be independent predictors of post-cardiac surgery delirium. Conversely, high-density lipoprotein cholesterol levels (HDL-C) ≥1.0 mmol/L (OR 0.71) was found to be a protective factor. Among the intraoperative and postoperative factors evaluated, only a prolonged ICU stay (≥48 h; OR 1.62) was identified as a risk factor for developing delirium in the propensity-score matched analysis, after adjusting for potential confounding variables and selection bias. In contrast to the earlier analysis, the multivariate logistic regression further revealed that peri-procedural myocardial infarction and postoperative arterial oxygen partial pressures were not significantly associated with POD. CONCLUSIONS: The incidence of POD in elderly patients undergoing CABG was high. Factors such as older age, long-term alcohol consumption, diabetes, stroke, and extracardiac arteriopathy were independent risk factors for POD in these patients. In relation to the intraoperative and postoperative factors, after adjusting for preoperative confounding factors, only a prolonged ICU stay was identified as a risk factor for POD. Additionally, high levels of HDL-C may be beneficial in reducing the incidence of delirium.

Long non-coding RNA SOX21-AS1 enhances the stemness of breast cancer cells via the Hippo pathway.

Breast cancer stem cells (BCSCs) have high tumorigenicity and invasiveness, which contributes to recurrence and metastasis. The long non-coding RNA SOX21-AS1 has been previously reported to modulate the properties of breast cancer stem cells via targeting SOX2, although the underlying molecular mechanisms remain unclear. To investigate this issue, we first confirmed that the expression level of SOX21-AS1 is increased in breast cancer tissues and cell lines (MCF-7, MDA-MB-231, CSC-MCF-7, CSC-MDA-MB-231), especially in BCSCs. We demonstrated that SOX21-AS1 promotes the stemness of CSC-MCF-7 cells through western blot detection of stemness-related proteins, as well as side population and sphere formation assays. Overexpression of SOX21-AS1 enhanced the proliferation, migration and invasion of CSC-MCF-7 cells. We also observed that SOX21-AS1 inhibited the Hippo pathway. SOX21-AS1 enhanced the stemness, migration and invasion of CSC-MCF-7 cells by increasing the nuclear localization of YAP and decreasing the level of pYAP. Overall, we conclude that SOX21-AS1 may promote the stemness viability, proliferation, migration and invasion of BCSCs by inhibiting the Hippo pathway. Our findings provide insights into potential biomarkers and prognostic measures for the treatment of breast cancer.

Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury.

Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

Molecular Cloning and Bioinformatics Analysis of DQA Gene from Mink (Neovison vison).

In the present study, we cloned, sequenced, and explored the structural and functional characteristics of the major histocompatibility complex (MHC)-DQA gene from mink (Neovison vison) for the first time. The full-length sequence of DQA gene was 1147-bp-long, contained a coding region of 768-bp, which was predicted to encoding 255 amino acid residues. The comparison between DQA from mink (Neovison vison) and other MHC-DQA molecules from different animal species showed that nucleotide and encoded amino acid sequences of the mink DQA gene exhibited high similarity with the ferret (Mustela pulourius furo). Phylogenetic analysis revealed that mink (Neovison vison) DQA is grouped with that of ferret (Mustela pulourius furo). The cloned sequence contained a 23-amino acid NH2-terminal signal sequence with the signal peptide cutting site located in amino acids 23⁻24, and had three Asn-Xaa-Ser/Thr sequons. Three cysteine residues were also identified (Cys-85, Cys-121, and Cys-138). The 218 to 240 amino acids were predicted to be the transmembrane domains. The prediction of the secondary structure revealed three α-helixes and fourteen ß-sheets in Neovison vison DQA protein, while random coil was a major pattern. In this study, the whole CDS sequence of Neovison vison DQA gene was successfully cloned, which was valuable for exploring the function and antiviral molecular mechanisms underlying the molecule. The findings of the present study have laid the foundation for the disease resistance and breeding of mink.

Diverse secondary C(sp3)-H bond functionalization via site-selective trifluoroacetoxylation of aliphatic amines.

We describe a coinage-metal-catalyzed site-selective oxidation of secondary C(sp3)-H bonds for aliphatic amine substrates. Broad amine scope, good functional compatibility and late-stage diversification are demonstrated with this method. The steric demand of the ß-substituents controlled diastereoselectivities under this catalytic system. The site selectivity favors secondary C(sp3)-H bonds over tertiary ones underscoring the unique synthetic potential of this method.

An Intron Variant of SLC2A9 Increases the Risk for Type 2 Diabetes Mellitus Complicated with Hyperuricemia in Chinese Male Population.

BACKGROUND: The aim of this study was to explore the associations of haplotypes of the glucose transporter 9 (SLC2A9) genes with type 2 diabetes mellitus (T2DM) complicated with hyperuricemia (HUA). METHODS: Overall, 608 Chinese males, enrolled from the Affiliated Hospital of Medical College of Qingdao University in 2009-2012, were genotyped. The subjects included 167 withT2DM (average age of onset (58.07±11.82 yr), 198 with HUA subjects (average age of onset (39.20±9.73) yr), 115 with T2DM complicated with HUA (average age of onset (51.24±10.09) yr), and 128 control subjects (average age (41.92±10.01) yr). Patients genotypes of the SNPs; including rs734553 was determined by PCR method. Each genotype was regressed assuming the co-dominant, dominant and the recessive models of inheritance with covariates of duration of total glucose, uric acid, urea nitrogen, triglyceride, cholesterol, and creatinine levels. RESULTS: Chi-square test revealed that rs734553polymorphism was both significantly associated with HUA as well as T2DM complicated HUA, but not with pure T2DM. After adjustment for age and gender, analysis showed that people with C allele had higher risk of HUA and T2DM complicated HUA than those without C allele. And none of the subjects had the homozygous genotype for SLC2A9 (CC). CONCLUSION: The SLC2A9 mutation increases the risk for T2DM complicated HUA in Chinese population, which suggested that intron variants between two relatively conserved exons could also be associated with diseases. In patients of T2DM complicated with HUA, the diagnosis and detection of SLC2A9 gene variants should be caused enough attention.

Preventive and Therapeutic Effects of Thymol in a Lipopolysaccharide-Induced Acute Lung Injury Mice Model.

Acute lung injury (ALI) is a life-threatening syndrome which causes a high mortality rate worldwide. In traditional medicine, lots of aromatic plants-such as some Thymus species-are used for treatment of various lung diseases including pertussis, bronchitis, and asthma. Thymol, one of the primary active constituent derived from Thymus vulgaris (thyme), has been reported to exhibit potent anti-microbial, anti-oxidant, and anti-inflammatory activities in vivo and in vitro. The present study aims to investigate the protective effects of thymol in lipopolysaccharide (LPS)-induced lung injury mice model. In LPS-challenged mice, treatment with thymol (100 mg/kg) before or after LPS challenge significantly improved pathological changes in lung tissues. Thymol also inhibited the LPS-induced inflammatory cells influx, TNF-α and IL-6 releases, and protein concentration in bronchoalveolar lavage fluid (BALF). Additionally, thymol markedly inhibited LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that thymol effectively inhibited the NF-κB activation in the lung. Taken together, these results suggested that thymol might be useful in the therapy of acute lung injury.

Copper-catalyzed remote (δ) C(sp3)-H bond amination: a practical strategy to construct pyrrolidine derivatives.

We report a copper-catalyzed remote C(sp3)-H bond amination reaction that converts acyclic amines to pyrrolidines. This reaction occurs selectively at the carbon δ to the amine functionality. Primary, secondary and tertiary C-H bonds are all suitable for the amination reactions in the presence of an inexpensive and commercially available copper catalyst.

Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice.

CONTEXT: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD). OBJECTIVE: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). MATERIALS AND METHODS: Male BALB/c mice were treated with standardized myrtol for 1.5 h prior to exposure of atomized LPS. Six hours after LPS challenge, lung injury was determined by the neutrophil recruitment, cytokine levels and total protein concentration in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissue. Additionally, pathological changes and NF-κB activation in the lung were examined by haematoxylin and eosin staining and western blot, respectively. RESULTS: In LPS-challenged mice, standardized myrtol at a dose of 1200 mg/kg significantly inhibited the neutrophile counts (from 820.97 ± 142.44 to 280.42 ± 65.45, 103/mL), protein concentration (from 0.331 ± 0.02 to 0.183 ± 0.01, mg/mL) and inflammatory cytokines level (TNF-α: from 6072.70 ± 748.40 to 2317.70 ± 500.14, ng/mL; IL-6: from 1184.85 ± 143.58 to 509.57 ± 133.03, ng/mL) in BALF. Standardized myrtol also attenuated LPS-induced MPO activity (from 0.82 ± 0.04 to 0.48 ± 0.06, U/g) and pathological changes (lung injury score: from 11.67 ± 0.33 to 7.83 ± 0.79) in the lung. Further study demonstrated that standardized myrtol prevented LPS-induced NF-κB activation in lung tissues. DISCUSSION AND CONCLUSION: Together, these data suggest that standardized myrtol has the potential to protect against LPS-induced airway inflammation in a model of ALI.

[Values of different biomarkers for diagnosis of Henoch-Schönlein purpura in children].

OBJECTIVE: To screen biomarkers which can be used as an auxiliary method in the diagnosis of Henoch-Schönlein purpura (HSP) and to evaluate their diagnostic values by receiver operating characteristic (ROC) curve analysis. METHODS: A total of 127 children diagnosed with HSP between April 2012 and March 2014 were included in the HSP group and an equal number of healthy children were included in the control group. Twelve parameters, i.e., serum amyloid protein A (SAA), interleukin-6 (IL-6), immunoglobulins (IgA, IgG, IgM, and IgE), C-reactive protein (CRP), white blood cell (WBC) count, complements C3 and C4, anti-streptolysin O, and ferritin, were analyzed. The values of the screened biomarkers for diagnosis of HSP were assessed by ROC curve analysis. RESULTS: The HSP group had significantly higher levels of SAA, IL-6, CRP, WBC, IgA, and IgM than the control group (P<0.05). The areas under the ROC curve of SAA, IL-6, WBC, IgA, and IgM for the diagnosis of HSP were higher than 0.7 (P<0.05). The optimal cut-off values of SAA, IgA, IgM, WBC, and IL-6 for the diagnosis of HSP were 3.035 µg/mL, 1579.5 mg/L, 922.5 mg/L, 8.850 × 109/L, and 7.035 pg/mL, respectively; the corresponding sensitivities of the optimal cut-off values for the diagnosis of HSP were 95.1%, 75.6%, 72.3%, 78.0%, and 63.4%, respectively, and the corresponding specificities were 90.2%, 85.4%, 82.4%, 70.7%, and 80.5%, respectively. CONCLUSIONS: SAA, IgA, IgM, WBC, and IL-6 are valuable biomarkers for clinical diagnosis of HSP and among them SAA seems to be the best one.

Population Pharmacokinetics in China: The Dynamics of Intravenous Voriconazole in Critically Ill Patients with Pulmonary Disease.

Pharmacokinetic research in China on the use of voriconazole in critically ill adult patients with different pulmonary diseases remains to be explored. This study evaluated the population pharmacokinetics of the use of voriconazole (VRC) in critically ill patients to determine covariate effects on VRC pharmacokinetics by NONMEM, which could further optimize VRC dosing in this population. A one-compartment model with first-order absorption and elimination best fit the data, giving 4.28 L/h clearance and 93.4 L volume of distribution of VRC. The model variability, described as an approximate percentage coefficient of interindividual variability in clearance and volume of distribution, was 72.94% and 26.50%, respectively. A significant association between Cmin and drug response or grade 2 hepatotoxicity was observed (p=0.002, <0.001, respectively, 1.5-4.0 µg/mL) via logistic multivariate regression. Monte Carlo simulations at 100, 150, 200, and 250 mg dosage predicted effectiveness at 45.99%, 99.76%, 98.76%, and 67.75% within the 1.5-4.0 µg/mL range, suggesting that a 150 or 200 mg intravenous dose twice daily is best suited to achieve the target steady state trough concentration range in critically ill patients with pulmonary disease.

Study on the diversity of Bacteroides and Clostridium in patients with primary gout.

To analyze the diversity of both Bacteroides and Clostridium in patients with primary gout and the difference from that of normal individuals. And to investigate the relationship between the primary gout and the intestinal flora. Fecal samples of 90 cases with the primary gout and 94 cases normal comparison group were selected, together with the cases that match the filter criteria. The DNA is extracted from the feces. 16S rRNA specific primers of both Bacteroides and Clostridium were adopted for the PCR amplification. The molecular fingerprints of Bacteroides and Clostridium in both the primary gout group and the normal control group were obtained through DGGE and subjected for further analysis on both the diversity and the similarity. Compared with normal individuals, the number of bands and Shannon-Weaver (H') of Bacteroides in patients with primary gout was not reduced, but significantly decreased in Clostridium. Furthermore, the intra-group and inter-group similarity of both Bacteroides and Clostridium were lower. The primary gout has caused the structural change of both Bacteroides and Clostridium, inducing the low similarity, especially for Clostridium. It has statistic significance. The gut predominant flora may play an important role in the development of primary gout.