[Expression and characterization of mesophilic GH1 ß-glucosidase CdBglA from acidophilic Cuniculiplasma divulgatum].

ß-glucosidase has important applications in food, pharmaceutics, biomass conversion and other fields, exploring ß-glucosidase with strong adaptability and excellent properties thus has received extensive interest. In this study, a novel glucosidase from the GH1 family derived from Cuniculiplasma divulgatum was cloned, expressed, and characterized, aiming to find a better ß-glucosidase. The amino acid sequences of GH1 family glucosidase derived from C. divulgatum were obtained from the NCBI database, and a recombinant plasmid pET-30a(+)-CdBglA was constructed. The recombinant protein was induced to express in Escherichia coli BL21(DE3). The enzymatic properties of the purified CdBglA were studied. The molecular weight of the recombinant CdBglA was 56.0 kDa. The optimum pH and temperature were 5.5 and 55 ℃, respectively. The enzyme showed good pH stability, 92.33% of the initial activity could be retained when treated under pH 5.5-11.0 for 1 h. When pNPG was used as a substrate, the kinetic parameters Km, Vmax and Kcat/Km were 0.81 mmol, 291.99 µmol/(mg·min), and 387.50 s-1 mmol-1, respectively. 90.33% of the initial enzyme activity could be retained when CdBglA was placed with various heavy metal ions at a final concentration of 5 mmol/L. The enzyme activity was increased by 28.67% under 15% ethanol solution, remained unchanged under 20% ethanol, and 43.68% of the enzyme activity could still be retained under 30% ethanol. The enzyme has an obvious activation effect at 0-1.5 mol/L NaCl and can tolerate 0.8 mol/L glucose. In conclusion, CdBglA is an acidic and mesophilic enzyme with broad pH stability and strong tolerance to most metal ions, organic solvents, NaCl and glucose. These characteristics may facilitate future theoretical research and industrial production.

Diagnostic Value and Clinical Application of Metagenomic Next-Generation Sequencing for Infections in Critically Ill Patients.

Objective: To evaluate the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) for infections in critically ill patients. Methods: Comparison of diagnostic performance of mNGS and conventional microbiological testing for pathogens was analyzed in 234 patients. The differences between immunocompetent and immunocompromised individuals in mNGS-guided anti-infective treatment adjustment were also analyzed. Results: The sensitivity and specificity of mNGS for bacterial and fungal detection were 96.6% (95% confidence interval [CI], 93.5%-99.6%) and 83.1% (95% CI, 75.2%-91.1%), and 85.7% (95% CI, 71.9%-99.5%) and 93.2% (95% CI, 89.7%-96.7%), respectively. Overall, 152 viruses were detected by mNGS, but in which 28 viruses were considered causative agents. The proportion of mNGS-guided beneficial anti-infective therapy adjustments in the immunocompromised group was greater than in the immunocompetent group (48.5% vs 30.1%; P=0.008). In addition, mNGS-guided anti-infective regimens with peripheral blood and BALF specimens had the highest proportion (39.0%; 40.0%), but the proportion of patients not helpful due to peripheral blood mNGS was also as high as 22.0%. Conclusion: mNGS might be a promising technology to provide precision medicine for critically ill patients with infection.

Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis.

BACKGROUND: Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated. RESULTS: In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene-miRNA and miRNA-lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77). CONCLUSION: Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis.

Comparison of endotracheal aspirate and bronchoalveolar lavage fluid metagenomic next-generation sequencing in severe pneumonia: a nested, matched case-control study.

OBJECTIVES: To compare clinical outcomes in patients with severe pneumonia according to the diagnostic strategy used. METHODS: In this retrospective, nested, case-control study, patients with severe pneumonia who had undergone endotracheal aspirate (ETA) metagenomic next-generation sequencing of (mNGS) testing (n = 53) were matched at a ratio of 1 to 2 (n = 106) by sex, age, underlying diseases, immune status, disease severity scores, and type of pneumonia with patients who had undergone bronchoalveolar lavage fluid (BALF) mNGS. The microbiological characteristics and patient's prognosis of the two groups were compared. RESULTS: An overall comparison between the two groups showed no significant differences in bacterial, fungal, viral, or mixed infections. However, subgroup analysis of 18 patients who received paired ETA and BALF mNGS showed a complete agreement rate for the two specimens of 33.3%. There were more cases for whom targeted treatment was initiated (36.79% vs. 22.64%; P = 0.043) and fewer cases who received no clinical benefit after mNGS (5.66% vs. 15.09%; P = 0.048) in the BALF group. The pneumonia improvement rate in the BALF group was significantly higher than in the ETA group (73.58% vs. 87.74%, P = 0.024). However, there were no significant differences in ICU mortality or 28-day mortality. CONCLUSIONS: We do not recommend using ETA mNGS as the first-choice method for analyzing airway pathogenic specimens from severe pneumonia patients.

Clinical Value of Metagenomics Next-Generation Sequencing in Bronchoalveolar Lavage Fluid for Patients with Severe Hospital-Acquired Pneumonia: A Nested Case-Control Study.

Background: Metagenomics next-generation sequencing (mNGS) is more efficient in identifying pathogens responsible for pneumonia. However, whether these patients ultimately benefit from this improvement remains unknown. Methods: In this retrospective, nested, case-control study, patients with severe hospital-acquired pneumonia (HAP) who had undergone mNGS of bronchoalveolar lavage fluid while in our intensive care unit from March 2017 to December 2020 (n = 33) were matched in a ratio of 1 to 2 (n = 66) by sex, age, comorbidities, immune status, Acute Physiology and Chronic Health Evaluation II score, severity of pulmonary infection, and use of extracorporeal life support with patients who had undergone conventional microbiological testing only. The primary outcome was 90-day mortality; secondary outcomes being length of intensive care unit stay, duration of mechanical ventilation support, 7-day and 28-day mortality, and efficacy of treatment of pulmonary infection. Results: In the CMT group, 17 patients (25.8%) had negative results, whereas only one (3.0%) had negative results in the mNGS group (P < 0.001). After receipt of microbiology results, antibiotics were altered in 23/33 patients (70.0%) in the mNGS group, but in only 29/66 (43.9%) in the CMT group (P = 0.016). Pulmonary infection-related findings improved in 20/33 patients (60.6%) in the mNGS group in the subsequent 7 days, but in only 25/66 (37.9%) in the CMT group (P = 0.032). However, the 28-day (33.3% vs 31.2%, P = 1.0) and 90-day (48.5% vs 45.5%, P = 0.78) mortality rates did not differ significantly between the two groups. These findings were supported by Cox-regression and Kaplan-Meier survival curve analyses. Conclusion: mNGS is helpful in the treatment of severe HAP but does not improve medium or long-term survival rates, especially in patients with severe comorbidities.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Metagenomic next-generation sequencing technology for detection of pathogens in blood of critically ill patients.

OBJECTIVE: To explore the applicability of metagenomic next-generation sequencing (mNGS) technology for the detection of blood pathogens in intensive care unit patients. METHODS: The clinical data of 63 critically ill patients who could not be diagnosed with blood culture (BC) and who underwent mNGS blood sample testing were retrospectively analyzed. The diagnostic efficacy of mNGS was compared with that of traditional detection methods; the distribution of the pathogens identified by mNGS was analyzed; and the differences in laboratory tests, comorbidities, treatment, and prognosis between the mNGS-positive and mNGS-negative groups were compared. RESULTS: The positive rate of mNGS was 41.3% (26/63), and 16 patients were found to have mixed infections. However, the positive rate of BCs performed simultaneously with mNGS was only 7.9% (5/63). The results of univariate analysis showed that the average length of intensive care unit stay (ß, -8.689 [95% CI, -16.176, -1.202]; P = 0.026) and the time from onset to sequencing (ß, -5.816 [95% CI,-9.936, -1.696]; P = 0.007) of the mNGS-positive group were significantly shorter than those of the mNGS-negative group. More patients in the positive group were adjusted for anti-infective treatment after mNGS (OR, 3.789 [95% CI,1.176, 12.211]; P < 0.001). CONCLUSIONS: Detection of blood pathogens by mNGS has good applicability for critically ill patients who cannot be diagnosed by BC in the early stages of infection, and mNGS should be performed as early as possible to obtain higher pathogen detection rates.

Diagnostic Value of Metagenomic Next-Generation Sequencing for the Detection of Pathogens in Bronchoalveolar Lavage Fluid in Ventilator-Associated Pneumonia Patients.

Objective: To evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) in patients with ventilator-associated pneumonia (VAP). Methods: BALF samples of 72 patients with VAP were collected from August 2018 to May 2020. The diagnostic performance of conventional testing (CT) and mNGS methods were compared based on bacterial and fungal examinations. The diagnostic value of mNGS for viral and mixed infections was also analyzed. Results: The percentage of mNGS positive samples was significantly higher than that estimated by the CT method [odds ratio (OR), 4.33; 95% confidence interval (CI), 1.78-10.53; p < 0.001]. The sensitivity and specificity of mNGS for bacterial detection were 97.1% (95% CI, 93.2-101.0%) and 42.1% (95 CI, 30.7-53.5%), respectively, whereas the positive predictive value (PPV) and the negative predictive value (NPV) were 60.0% (95% CI, 48.7-71.3%) and 94.1% (95% CI, 88.7-99.6%), respectively. A total of 38 samples were negative for bacterial detection as determined by the CT method, while 22 samples were positive as shown by the mNGS method. Conflicting results were obtained for three samples between the two methods of bacterial detection. However, no significant differences were noted between the mNGS and CT methods (OR, 1.42; 95% CI, 0.68-2.97; p = 0.46) with regard to fungal infections. The sensitivity and specificity of mNGS were 71.9% (95% CI, 61.5-82.3%) and 77.5% (95% CI, 67.9-87.1%), respectively. mNGS exhibited a PPV of 71.9% (95% CI, 61.5-82.3%) and an NPV of 77.5% (95% CI, 67.9-87.1%). A total of 9 out of 40 samples were found positive for fungi according to mNGS, whereas the CT method failed to present positive results in these samples. The mNGS and CT methods produced conflicting results with regard to fungal detection of the two samples. A total of 30 patients were virus-positive using mNGS. Furthermore, 42 patients (58.3%) were identified as pulmonary mixed infection cases. Conclusions: mNGS detection using BALF improved the sensitivity and specificity of bacterial identification in patients who developed VAP. In addition, mNGS exhibited apparent advantages in detecting viruses and identifying mixed infections.

Hemophagocytic lymphohistiocytosis is associated with Bartonella henselae infection in a patient with multiple susceptibility genes.

BACKGROUND: Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition, which is often triggered by certain types of infection, cancer and numerous autoimmune diseases; however, of the numerous infectious triggers associated with HLH, the consequences of Bartonella henselae infection have been rarely reported. CASE PRESENTATION: A 48-year-old female presented with a 20-day history of intermittent fever accompanied by systemic rash, fatigue, anorexia and weight loss later she developed shock and unconsciousness. Blood tests showed a reduction of leukocyte, anemia and thrombocytopenia, and pathological results of a bone marrow biopsy confirmed hemophagocytic activity. Metagenomic next-generation sequencing (mNGS) analysis of the lymph node detected the presence of B. henselae. Whole exome sequencing revealed two gene variants, STXBP2 and IRF5, in this adult patient with secondary HLH. Then, she received minocycline and rifampin combination anti-infective therapy. Intravenous immunoglobulin for 5 days followed by a high dose of methylprednisolone were also administered. The patient was successfully discharged from the intensive care unit and remained in good condition after 2 months of follow-up. CONCLUSIONS: mNGS served crucial roles in obtaining an etiological diagnosis, which suggested that screening for B. henselae should be considered in patients with HLH, especially those with a cat at home. In addition, the genetic defects were discovered to not only be present in primary HLH, but also in secondary HLH, even in the elderly.

[Incidence and risk factor analysis of deep venous thrombosis in patients with severe traumatic brain injury].

OBJECTIVE: To estimate the incidence and risk factors for deep venous thrombosis (DVT) in patients with severe traumatic brain injury (TBI) treated in the intensive care unit (ICU). METHODS: 105 patients with TBI admitted to the First Affiliated Hospital of University of Science and Technology of China from January 2016 to June 2018 were enrolled [Glasgow coma scale (GCS) 3-8; concise injury score for other parts ≤ 3]. All patients did not receive any medication or physical measures to prevent DVT during hospitalization. Bilateral compression Doppler ultrasounds of the double lower limbs and upper limbs were performed to clarify the occurrence of DVT on the first day of admission and twice a week until ICU discharge or the death of patient. The examination was performed by a senior ultrasound doctor. It was defined as DVT as long as any deep vein had thrombosis. Patients were divided into two groups according to whether DVT occurred or not during hospitalization. Clinical data such as body mass index (BMI), coagulation index, platelet count (PLT) and deep venous catheterization were obtained from the clinical chemistry laboratory database and patient files. Logistic regression was used to analyze the risk factors of DVT. Binary Logistic regression was used to calculate the predictive probability of risk factors. The predictive value of risk factors and predictive probability to the occurrence of DVT was analyzed by receiver operating characteristic (ROC) curve. RESULTS: In 105 patients with simple TBI, 42 patients developed DVT during hospitalization, and the incidence of DVT was 40%. Univariate Logistic regression showed that high BMI [odds ratio (OR) = 1.490, 95% confidence interval (95%CI) = 1.174-1.891, P = 0.001], high PLT (OR = 1.023, 95%CI = 1.006-1.040, P = 0.007), shorten activated partial thromboplastin time (APTT; OR = 0.913, 95%CI = 0.853-0.978, P = 0.010) and catheterization in deep vein (OR = 0.114, 95%CI = 0.026-0.493, P = 0.004) were risk factors for DVT. It was shown by multivariate regression analysis that high BMI (OR = 1.378, 95%CI = 1.411-1.665, P = 0.001), high PLT (OR = 1.017, 95%CI = 1.003-1.032, P = 0.020), low APTT (OR = 0.920, 95%CI = 0.860-0.982, P = 0.012) and catheterization in deep vein (OR = 0.113, 95%CI = 0.029-0.443, P = 0.002) were independent risk factors for DVT. The predictive probability formula: Logit P = -4.673+0.321×BMI-0.083×APTT+0.017×PLT-2.181×catheterization in deep vein. It was shown by ROC curve analysis that high BMI, high PLT, low APTT and catheterization in deep vein could predict the occurrence of DVT in severe TBI patients, and the area under ROC curve (AUC) was 0.775, 0.709, 0.709 and 0.680, respectively. The AUC of prediction probability was 0.890, and its sensitivity and specificity were respectively increased to 88.10% and 85.71%. CONCLUSIONS: The incidence of DVT was higher in patients with simple severe TBI. High coagulation, high BMI, high PLT and catheterization in deep vein are the independent risk factors for DVT.

Experimental demonstration of a flexible-grid 1×2 wavelength-selective switch based on silicon microring resonators.

An integrated flexible-grid 1×2 wavelength-selective switch based on reconfigurable add-drop silicon microring resonators using strip waveguides is designed and experimentally demonstrated. By flexibly tuning the resonance of microring resonators and path phase differences via the thermo-optic effect, the transmission spectra with adjustable bandwidths can be formed as desired at the output ports. Our experimental results reveal that the fabricated flexible-grid 1×2 wavelength-selective switch provides crosstalk lower than -10.39 dB. The 3-dB bandwidth varies from 0.38 nm to 1 nm, the in-band ripple is less than 0.52 dB, and the response time is about 17.6 µs.

[Effect of early rehabilitation physiotherapy on muscle quality and function in critically ill patients].

OBJECTIVE: To investigate the effect of early rehabilitation physiotherapy on muscle quality and function in critical patients. METHODS: A prospective randomized controlled study was performed. Adult critically ill patients admitted to intensive care unit (ICU) of Anhui Provincial Hospital from October 1st, 2016 to August 31st, 2017 who had been hospitalized for more than 7 days and had acute physiology and chronic health evaluation II (APACHE II) > 8 were enrolled, and they were divided into treatment group and control group according to random number table method. All patients were given routine treatment, and on this basis, the treatment group was given rehabilitation therapy within 24 hours after admission, including limb active/passive activities, respiratory muscle function training and transcutaneous electrical nerve stimulation, etc. Bedside ultrasound was used to measure the area and cross sectional thickness of left rectus femoris muscle and the cross sectional thickness of middle thigh muscle of patients at 1, 4 and 7 days after treatment; at the same time, the muscle strength of sober patients was evaluated by medical research council (MRC) muscle strength evaluation method, and the mechanical ventilation time, ICU hospitalization time and ICU expenses were recorded. RESULTS: Forty patients were enrolled in this study, with 20 in each group. Compared with the control group, the difference of left rectus femoris muscle area between 1 day and 4 days, 4 days and 7 days, 1 day and 7 days (cm2: 0.19±0.02 vs. 0.31±0.19, 0.02±0.01 vs. 0.08±0.05, 0.04±0.02 vs. 0.38±0.23), and the difference in left rectus femoris thickness (cm: 0.01±0.01 vs. 0.14±0.13, 0.03±0.03 vs. 0.16±0.14) and the difference in middle thigh muscle thickness (cm: 0.02±0.02 vs. 0.11±0.09, 0.03±0.02 vs. 0.16±0.12) between 1 day and 4 days, 1 day and 7 days in the treatment group were significantly reduced (all P < 0.01). The MRC strength score in the treatment group was significantly higher than that of the control group at 7 days (52.06±3.52 vs. 47.94±3.96, P < 0.05). The mechanical ventilation time in the treatment group (n = 15) and the control group (n = 13) were (138.5±34.5) hours and (185.0±40.9) hours, respectively, and the difference between two groups were statistical significance (P < 0.05). Compared with the control group, the incidence rate of ICU acquired muscle weakness (ICUAW) in the treatment group was significantly decreased [5.0% (1/20) vs. 40.0% (8/20), P < 0.05], the length of ICU stay was significantly shortened (days: 17.67±4.91 vs. 22.06±5.94, P < 0.05), and the ICU expenses were significantly reduced (ten thousand yuan: 7.53±2.09 vs. 9.55±1.73, P < 0.05). CONCLUSIONS: Early rehabilitation physiotherapy can improve the muscle quality and function in critical patients, and decrease the length of ICU stay.

Evaluation of costs associated with atmospheric mercury emission reductions from coal combustion in China in 2010 and projections for 2020.

Coal combustion is the most significant anthropogenic mercury emission source in China. In 2013, China signed the Minamata Convention affirming that mercury emissions should be controlled more strictly. Therefore, an evaluation of the costs associated with atmospheric mercury emission reductions from China's coal combustion is essential. In this study, we estimated mercury abatement costs for coal combustion in China for 2010, based on a provincial technology-based mercury emission inventory. In addition, four scenarios were used to project abatement costs for 2020. Our results indicate that actual mercury emission related to coal combustion in 2010 was 300.8Mg, indicating a reduction amount of 174.7Mg. Under a policy-controlled scenario for 2020, approximately 49% of this mercury could be removed using air pollution control devices, making mercury emissions in 2020 equal to or lower than in 2010. The total abatement cost associated with mercury emissions in 2010 was 50.2×109 RMB. In contrast, the total abatement costs for 2020 under baseline versus policy-controlled scenarios, having high-energy and low-energy consumption, would be 32.0×109 versus 51.2×109, and 27.4×109 versus 43.9×109 RMB, respectively. The main expense is associated with flue gas desulfurization. The unit abatement cost of mercury emissions in 2010 was 288×103 RMB/(kgHg). The unit abatement costs projected for 2020 under a baseline, a policy-controlled, and an United Nations Environmental Programme scenario would be 143×103, 172×103 and 1066×103 RMB/(kgHg), respectively. These results are much lower than other international ones. However, the relative costs to China in terms of GPD are higher than in most developed countries. We calculated that abatement costs related to mercury emissions accounted for about 0.14% of the GDP of China in 2010, but would be between 0.03% and 0.06% in 2020. This decrease in abatement costs in terms of GDP suggests that various policy-controlled scenarios would be viable.

[Efficacy and safety of colistimethate sodium in critical patients: an in vitro study by using of Monte Carlo simulation].

OBJECTIVE: To evaluate the efficacy and safety of colistimethate sodium (CMS) for the treatment of critical patients infected by pan-drug resistant Acinetobacter baumannii (PDR-AB) or pan-drug resistant Pseudomonas aeruginosa (PDR-PA). METHODS: 321 isolates of PDR-AB and 204 isolates of PDR-PA from critical patients admitted to 35 intensive care units (ICUs) of grade two or above were collected from the Anhui Antimicrobial Resistance Investigation Net (AHARIN) program from September 2012 to September 2015, while the minimal inhibitory concentrations (MIC) of colistin were determined by the E-test. A series of Monte Carlo simulations was performed for CMS regimens (1 MU q8h, 2 MU q8h, and 3 MU q8h, and MU meant a million of unit), and the probability of achieving a 24-hour area under the drug concentration time curve (AUC24)/MIC ratio > 60 and risk of nephrotoxicity for each dosing regimen was calculated. Each simulation was run over three CLCr ranges: < 60, ≥ 60-90, ≥ 90-120 mL/min. The probability of target attainment (PTA) for the AUC24/MIC ratio was calculated using the partial MIC value, while the cumulative fraction of response (CFR) was determined by integrating each PTA with the MIC distributions, the value greater than or equal to 90% or more than 80% was set as the optimal dosing regimen or suboptimal dosing regimen respectively. The probability of average 24-hour serum concentrations up to 4 mg/L for three dosage regimens was used to predict the risks of nephrotoxicity. RESULTS: All 321 isolates of PDR-AB and 204 isolates of PDR-PA were susceptible to colistin, the MIC50/90 against PDR-AB were 0.5 mg/L and 1.0 mg/L, and those against PDR-PA were 0.5 mg/L and 1.5 mg/L, respectively. When recommended dose (1 MU q8h) was used for patients with CLCr of < 60 mL/min, high CFR value (89.78% for PDR-AB, 81.06% for PDR-PA) were obtained, but with a high risks of nephrotoxicity (> 32.51%). Moreover, low value of PTA (< 66.56%) was yielded for isolates with MIC of ≥ 1 mg/L. Recommended dose also yielded a low CFR value (56.97%-69.31% for PDR-AB, 44.76%-56.94% for PDR-PA) in patients with CLCr of ≥ 60-120 mL/min. When dose was increased to 2 MU q8h, CFR (77.45%-92.87%) and the risks of nephrotoxicity (< 0.15%) was optimal for patients with CLCr ≥ 60-120 mL/min, but low value of PTA (< 75.36%) was also yielded for isolates with MIC of ≥ 1 mg/L. The most aggressive dose of 3 MU q8h provided high CFR (> 89.24%) even in patients with CLCr ≥ 90-120 mL/min, and PTA was < 76.20% only for isolates with MIC of ≥ 1.5 mg/L, but this dosing scheme was associated with unacceptable risks of nephrotoxicity (> 33.68%). CONCLUSIONS: Measurement of MIC, individualized CMS therapy and therapeutic drug-level monitoring should be considered to achieve the optimal drug exposure and ensure the safety of CMS.

Silicon three-mode (de)multiplexer based on cascaded asymmetric Y junctions.

A three-mode (de)multiplexer based on two cascaded asymmetric Y junctions is proposed and experimentally demonstrated on a silicon-on-insulator platform for mode-division multiplexing applications. Within a bandwidth from 1537 to 1566 nm, the best demultiplexing crosstalk of the fabricated device, composed of a three-mode multiplexer, a multimode straight waveguide, and a three-mode demultiplexer, is up to -31.5 dB, while in the worst case it is -9.7 dB. The measured maximum insertion loss is about 5.7 dB at a wavelength of 1550 nm. The mode crosstalk and insertion loss can be further improved by high-quality fabrication processes.

Low-level prenatal mercury exposure in north China: an exploratory study of anthropometric effects.

In order to investigate anthropometric effects of mercury (Hg) exposure, we examined the status of human prenatal exposure to Hg species, including total mercury (THg), methylmercury (MeHg) and inorganic mercury (IHg), in North China, as well as their potential effects on fetal and infant growth. Hg concentrations in various bioindicators were measured from 50 Chinese women and newborns in 2011. The participants were followed for 12 months to collect anthropometric information. Linear and two-level regression analyses were performed to determine the associations between Hg levels and body growth. The geometric mean levels of THg in the placenta, cord blood, fetal hair, and maternal blood, hair, and urine were 25.88 µg/kg dry wt, 2.73 µg/L, 572.98 µg/kg, 2.29 µg/L, 576.54 µg/kg, and 0.58 µg/g creatinine, respectively. Nearly 100% of Hg presented as IHg in urine, and the percentage of IHg in other bioindicators was 14.86-48.73%. We observed significantly negative associations between Hg levels in some matrixes and anthropometry of neonates (weight and height) and infants (height) (p < 0.05). THg levels in maternal hair were also negatively associated with infant growth rate of weight during 12 months after delivery (p = 0.017). This study suggests that low-level prenatal Hg exposure could play a role in attenuating fetal and infant growth, and the effects of MeHg and IHg are different.

[Phenotype and functions of natural killer cells in septic patients and its clinical significance].

OBJECTIVE: To investigate the possible mechanism of natural killer cells (NK cells) in immune dysfunction in sepsis by monitoring the phenotype and function of periphery NK cells in patients with sepsis. METHODS: A retrospective study was conducted. The patients with systemic inflammatory response syndrome (SIRS, n=59) or sepsis (n=65) admitted to Department of Critical Care Medicine of Anhui Provincial Hospital from August 2011 to August 2013 were enrolled. Blood samples were collected within 48 hours after intensive care unit (ICU) admission, the phenotype and function of periphery NK cells were determined by flow cytometry. Twenty-eight healthy people served as controls. RESULTS: The proportion and number of peripheral blood CD3⁻ CD56⁺ NK cells in SIRS and sepsis groups were normal, and no statistical difference was found when compared with those of the healthy control group [cell proportion: 0.102 ± 0.019, 0.102 ± 0.108 vs. 0.106 ± 0.018, F = 0.018, P = 0.982; cell number (× 106/L): 182.46 ± 65.98, 172.97 ± 63.51 vs. 179.25 ± 60.44, F=0.349, P=0.706]. It was shown by NK cell degranulation detection that there was no significant difference in the expression of CD107 and interferon-γ (IFN-γ) secretion [CD107: 0.135 ± 0.050, 0.140 ± 0.058, 0.128 ± 0.070, F = 0.583, P = 0.560; IFN-γ (kU/L): 14.36 ± 4.74, 12.49 ± 4.21, 13.45 ± 5.04, F=1.616, P=0.202] among healthy control group, SIRS group, and sepsis group. It was shown by antibody dependent cytotoxic effect (ADCC) test that there was no difference in the expression of CD107 among healthy control group, SIRS group, and sepsis group (0.574 ± 0.166, 0.643 ± 0.165, 0.581 ± 0.157, F = 0.808, P = 0.448). When compared with healthy controls, the secretion of IFN-γ was increased in SIRS patients (kU/L: 40.5 ± 13.2 vs. 28.4 ± 9.6, P = 0.001), while reduced in sepsis patients (kU/L: 19.8 ± 6.7 vs. 28.4 ± 9.6, P<0.01). Compared with SIRS group, only NK cell surface inhibitory receptors CD158e (KIR 3DL1) expression in sepsis group was significantly increased (0.203 ± 0.057 vs. 0.079 ± 0.021, t = 15.762, P<0.001), and there were no significant differences in the other phenotype between the two groups. Compared with SIRS group, the IFN-γ production of the sepsis group was significantly lowered (kU/L: 0.280 ± 0.040 vs. 0.310 ± 0.038, t = 3.390, P = 0.009), and the level of IL-12 was also significantly decreased (ng/L: 0.15 ± 0.03 vs. 0.30 ± 0.08, t = 32.832, P < 0.001). CONCLUSIONS: It was showed by NK cell phenotype and function assay that the function of NK cells in patients with sepsis was impaired and led to a poor production of IFN-γ. The IFN-γ mediated immune dysfunction may be a main reason for the disorder of NK cell function, which laid the foundation of the clinical immune intervention practice to improve to NK cell function.

Associations of methylmercury and inorganic mercury between human cord blood and maternal blood: a meta-analysis and its application.

Considering the different ability of placental transfer, an assessment of the cord:maternal blood ratio for both methylmercury (MeHg) and inorganic mercury (IHg) is needed especially for interpreting the low-level prenatal exposure. In this study, we conducted a Monte Carlo-based meta-analysis to comprehensively estimate that ratio for MeHg (RMeHg) and IHg (RIHg). The obtained values followed log-normal distributions, with a mean (standard deviation) of 1.89 (0.98) and 1.01 (0.55) for RMeHg and RIHg, respectively. We also estimated the percentage of MeHg in the blood by means of THg in cord and maternal blood using the RMeHg and RIHg, and obtained a value very close to the measured one (relative deviation, -0.4%). In conclusion, the fetus is exposed to approximately twice as much MeHg and to the same level of IHg as in maternal blood; the introduced model provides a rough but reasonable estimate of the percentage of MeHg in the blood.