Case report: Paralytic ileus resulted from nirmatrelvir/ritonavir-tacrolimus drug-drug interaction in a systemic lupus erythematosus patient with COVID-19.

Patients with systemic autoimmune rheumatic diseases are at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and effective antiviral treatments including nirmatrelvir/ritonavir can improve their outcomes. However, there might be potential drug-drug interactions when these patients take nirmatrelvir/ritonavir together with immunosuppressants with a narrow therapeutic window, such as tacrolimus and cyclosporine. We present a case of paralytic ileus resulting from tacrolimus toxicity mediated by the use of nirmatrelvir/ritonavir in a patient with systemic lupus erythematosus (SLE). A 37-year-old female SLE patient was prescribed nirmatrelvir/ritonavir without discontinuing tacrolimus. She presented to the emergency room with symptoms of paralytic ileus including persistent abdominal pain, nausea, and vomiting, which were verified to be associated with tacrolimus toxicity. The blood concentration of tacrolimus was measured >30 ng/mL. Urgent medical intervention was initiated, while tacrolimus was withheld. The residual concentration was brought within the appropriate range and tacrolimus was resumed 8 days later. Physicians must be aware of the potential DDIs when prescribing nirmatrelvir/ritonavir, especially to those taking immunosuppresants like tacrolimus.

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

Experimental evaluation of the impact of ventilation on cooking-generated fine particulate matter in a Chinese apartment kitchen and adjacent room.

Cooking is one of the major contributors to indoor pollution. Fine particulate matter (PM2.5) produced during cooking commonly mix into adjacent rooms and elevates indoor PM2.5 concentrations. The risk of human exposure to cooking-generated PM2.5 is mainly related to the exposure duration and particulate matter (PM) concentration. The PM2.5 concentration is influenced by cooking methods and ventilation patterns. Range hoods and open windows are conventional strategies for lowering the concentration of cooking-generated particles. To decrease PM emissions, kitchen air supply systems have been proposed, providing alternative possibilities for kitchen ventilation patterns. The effects of cooking methods, air supply systems, range hoods, and windows on PM2.5 concentrations must be analyzed and compared. To understand and provide advice on reducing exposure to PM2.5 due to cooking activities, we measured the PM2.5 mass concentration in a kitchen and adjacent room during cooking. The identified factors, including cooking method, range hood use, window status, and air supply system, were varied based on orthogonal design. The delay time between the PM2.5 peak in the kitchen and that in the adjacent room was determined. The degree of exposure risk for cooking-generated PM2.5 was evaluated using the mean exposure dose. The results indicated that the mean PM2.5 mass concentration in the kitchen ranged from 22 to 2296 µg/m3. In descending order, the factors affecting the indoor PM2.5 concentration in the apartment studied were range hood use, cooking methods, window status, and air supply system. The PM2.5 peak in the adjacent room occurred 200-800 s later than that in the kitchen. Other conditions being constant in these experiments, the use of range hoods, air supply systems, and windows reduce exposure doses by 90%, 37%, and 51%, respectively. These research results provide insights for reducing human exposure to cooking-generated PM2.5.

The workload change and depression among emergency medical staff after the open policy during COVID-19: a cross-sectional survey in Shandong, China.

Introduction: In the middle of December 2022, the Chinese government adjusted the lockdown policy on coronavirus disease 2019 (COVID-19), a large number of infected patients flooded into the emergency department. The emergency medical staff encountered significant working and mental stress while fighting the COVID-19 pandemic. We aimed to investigate the workload change, and the prevalence and associated factors for depression symptoms among emergency medical staff after the policy adjustment. Methods: We conducted a cross-sectional online survey of emergency medical staff who fought against COVID-19 in Shandong Province during January 16 to 31, 2023. The respondents' sociodemographic and work information were collected, and they were asked to complete the 9-item Patient Health Questionnaire (PHQ-9) then. Univariate and multivariate logistic regression analyses were applied to identify the potential associated factors for major depression. Results: Nine hundred and sixteen emergency medical personnel from 108 hospitals responded to this survey. The respondents' weekly working hours (53.65 ± 17.36 vs 49.68 ± 14.84) and monthly night shifts (7.25 ± 3.85 vs 6.80 ± 3.77) increased after the open policy. About 54.3% of the respondents scored more than 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. In univariate analysis, being doctors, living with family members aged ≤16 or ≥ 65 years old, COVID-19 infection and increased weekly working hours after the open policy were significantly associated with a PHQ-9 score ≥ 10 points. In the multivariate analysis, only increased weekly working hours showed significant association with scoring ≥10 points. Conclusion: Emergency medical staff' workload had increased after the open policy announcement, which was strongly associated with a higher PHQ-9 scores, indicating a very high risk for major depression. Emergency medical staff working as doctors or with an intermediate title from grade-A tertiary hospitals had higher PHQ-9 scores, while COVID-19 infection and weekly working hours of 60 or more after the open policy were associated with higher PHQ-9 scores for those from grade-B tertiary hospitals. Hospital administrators should reinforce the importance of targeted emergency medical staff support during future outbreaks.

MiRNA-423 rs6505162 and miRNA-6811 rs2292879 SNP associated with lung cancer in Hainan, China.

BACKGROUND: MicroRNAs (miRNAs) are known to exert significant influence on various physiological processes and diseases, including cancers. The primary objective of this present study was to examine the impact of eight single-nucleotide polymorphisms (SNPs) in miRNA on the susceptibility to lung cancer (LC) within the Chinese Southern population. METHODS: The genotypes of these eight polymorphisms were determined in 132 LC patients and 214 cancer-free controls. RESULTS: In overall analyses, GG genotype of miRNA-6811 rs2292879 polymorphism was significantly correlated with increased risk of LC (GG vs. AA, adjusted OR = 5.10, 95% CI = 1.02-25.43, P=0.047), yet the genotype frequencies of rs2292879 SNP in controls did not met the Hardy-Weinberg equilibrium (HWE) (P=0.001) in present study. Stratified analyses by smoking revealed that miRNA-423 rs6505162 variants significantly decreased the LC risk in heterozygous (CA vs. CC, adjusted OR = 0.14, 95% CI = 0.03-0.81, P=0.028) and recessive (AA vs. CA + CC, adjusted OR = 0.17, 95% CI = 0.03-0.90, P=0.038) genetic models in smoking population. However, miRNA-196A2 rs11614913, miRNA-196A2 rs12304647, miRNA-146A rs2910164, miRNA-16-1 rs1022960, miRNA-608 rs4919510, and miRNA-27a rs895819 polymorphisms were not significantly associated with LC. CONCLUSION: The findings of our study indicate a potential decrease in LC risk among smokers with the miRNA-423 rs6505162 variants, while an increase in risk is associated with miRNA-6811 rs2292879 polymorphisms in the population of Southern Chinese. However, further well-designed research is necessary to fully understand the precise impact of these two SNPs on the development of LC.

Clinical applications of skin traction technique with adjustable tension in treatment of large area skin defects.

OBJECTIVE: To explore the clinical applications of the adjustable skin traction technique in the treatment of large area skin defects. RESEARCH DESIGN: A prospective study. BACKGROUND: The skin is the largest organ of the human body and skin tissue exposed to external environment which makes it vulnerable to damage. There are many reasons for skin defects such as trauma, infection, burns, scars, tumors resection, inflammation, pigmented nevus, etc. Skin traction is the application of pulling force to the trunk or extremities for immobilization, fracture reduction and deformity correction. This technique accurately controls skin expansion which is safe, convenient and accelerates wound healing. METHODS: A prospective study was conducted on 80 patients suffered from large area skin defects in the department of orthopedics, the first affiliated hospital of Zhengzhou University from September 2019 to January 2023. There were 40 patients in the experimental group who underwent skin traction. In contrast, 40 people in the control group underwent skin flaps or skin grafts without skin traction. The inclusion criteria include large area skin defects, normal peripheral skin & blood supply, normal vital organs, no severe coagulation dysfunction etc. Male & female with and without skin traction are 22 & 18 and 25 & 15 respectively. The skin traction device used was a hook and single rod type. The skin defect area was approximately 15 cm × 9-43 cm × 10 cm. RESULTS: Postoperatively, the experimental group with traction showed 2 cases of skin infection, 1 case of skin necrosis and 3 cases of inflammation recurrence. In contrast, the control group without traction showed 8 cases of skin infection, 6 cases of skin necrosis and 10 cases of inflammation recurrence. Skin infection (P = 0.04), skin necrosis (P = 0.02) and inflammatory response (P = 0.03) represented significant differences between two groups. There was also a significant difference in hospitalization costs (P = 0.001). CONCLUSION: Skin traction has huge clinical applications including a shorter hospital stay, faster wound healing, lower hospitalization cost, high satisfaction rate, and a fair skin appearance after surgery. It is an effective method of treating skin and musculoskeletal defects.

Temperature-dependent particle number emission rates and emission characteristics during heating processes of edible oils.

The goal of this research is to investigate the temperature-dependent emission rates of particle numbers and emission characteristics during oil heating. Seven regularly used edible oils were studied in a variety of tests to attain this objective. First, total particle number emission rates ranging from 10 nm to 1 µm were measured, followed by an examination within six size intervals from 0.3 µm to 10 µm. Following that, the impacts of oil volume and oil surface area on the emission rate were investigated, and multiple regression models were developed based on the results. The results showed that corn, sunflower and soybean oils had higher emission rates than other oils above 200 °C, with peak values of 8.22 × 109#/s, 8.19 × 109#/s and 8.17 × 109#/s, respectively. Additionally, peanut and rice oils were observed to emit the most particles larger than 0.3 µm, followed by medium-emission (rapeseed and olive oils) and low-emission oils (corn, sunflower and soybean oils). In most cases, oil temperature (T) has the most significant influence on the emission rate during the smoking stage, but its influence was not as pronounced in the moderate smoking stage. The models obtained are all statistically significant (P < 0.001), with R2 values greater than 0.9, and the classical assumption test concluded that regressions were in accordance with the classical assumptions regarding normality, multicollinearity, and heteroscedasticity. In general, low oil volume and large oil surface area were more recommended for cooking to mitigate UFPs emission.

Transition from electromagnetically-induced transparency to absorption in a single microresonator.

Electromagnetically induced transparency (EIT) and absorption (EIA) are two phenomena that can be observed in whispering-gallery-mode (WGM) optical microresonators. Transition from EIT to EIA has potential applications in optical switching, filtering and sensing. In this paper an observation of the transition from EIT to EIA in a single WGM microresonator is presented. A fiber taper is used to couple light into and out of a sausage-like microresonator (SLM) that contains two coupled optical modes with significantly different quality factors. By stretching the SLM axially the resonance frequencies of the two coupled modes are tuned to the same, a transition from EIT to EIA is then observed in the transmission spectra when the fiber taper is moved closer to the SLM. It is the special spatial distribution of the optical modes of the SLM that provide a theoretical basis for the observation.

Broadband hyperbolic thermal metasurfaces based on the plasmonic phase-change material In3SbTe2.

Thermal radiation modulation facilitated by phase change materials (PCMs) needs a large thermal radiation contrast in broadband as well as in a non-volatile phase transition, which are only partially satisfied by conventional PCMs. In contrast, the emerging plasmonic PCM In3SbTe2 (IST) that undergoes a non-volatile dielectric-to-metal phase transition during crystallization offers a fitting solution. Here, we have prepared IST-based hyperbolic thermal metasurfaces and demonstrated their capabilities to modulate thermal radiation. By laser-printing crystalline IST gratings with different fill factors on amorphous IST films, we have achieved multilevel, large-range, and polarization-dependent control of the emissivity modulation (0.07 for the crystalline phase and 0.73 for the amorphous phase) over a broad bandwidth (8-14 µm). With the convenient direct laser writing technique that supports large-scale surface patterning, we have also demonstrated promising applications of thermal anti-counterfeiting with hyperbolic thermal metasurfaces.

Temperature-dependent particle mass emission rate during heating of edible oils and their regression models.

Particulate matter emitted by heated cooking oil is hazardous to human health. To develop effective mitigation strategies, it is critical to know the amount of the emitted particles. The purpose of this research is to estimate the temperature-dependent particle mass emission rates of edible oils and to develop models for source strength based on the multiple linear regression method. First, this study examined seven commonly used oils by heating experiments. The emission rates of PM2.5 and PM10 were measured, and the effects of parameters such as oil volume and surface area on the emission rates were also analysed. Following that, the starting smoke points (Ts') and aggravating smoke points (Tss') of tested oils were determined. The results showed that oils with lower smoke points had greater emission rates. Notably, the experiments performed observed that peanut, rice, rapeseed and olive oil generated PM2.5 much faster at 240 °C (2.22, 1.50, 0.82 and 0.80 mg/s, respectively, at the highest emission conditions) than that of sunflower, soybean, and corn oil (0.15, 0.12 and 0.11 mg/s, respectively). The temperature, volume, and surface area of oils all had a significant impact on the particle mass emission rate, with oil temperature being the most influential. The regression models obtained were statistically significant (P < 0.001), with the majority of R2 values greater than 0.85. Using sunflower, soybean and corn oils, which have higher smoke points and lower emission rates, and smaller pans for cooking is therefore recommended based on our research findings.

Initiating or switching to insulin degludec/insulin aspart in adults with type 2 diabetes in Malaysia / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings.@*Methodology@#ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS).@*Results@#Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: –1.3% [95% CI: –1.61 to –0.90]) and fasting plasma glucose levels (ED: –1.8 mmol/L [95% CI: –2.49 to –1.13]) were significantly reduced (p<0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients.@*Conclusion@#Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes.

Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.

Evaluation of the Glymphatic System Using the DTI-ALPS Index in Patients with Spontaneous Intracerebral Haemorrhage.

Objective: To investigate the function of the human glymphatic system (GS) in patients with spontaneous intracerebral haemorrhage (sICH) using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS). Methods: Twenty patients with sICH and 31 healthy controls (HCs) were recruited for DTI and susceptibility-weighted imaging scanning. The diffusivity along the perivascular spaces, as well as the projection fibres and association fibres, was evaluated separately. The DTI-ALPS index of each subject was also calculated. Two-sample t-tests and paired t-tests were performed to analyse the difference in ALPS scores between patients and HCs, as well as that between the lesion side and contralateral side. Pearson correlation analysis was used to observe the relationship between disease duration and GS function. Results: The DTI-ALPS index on the lesion side was significantly lower than that of the contralateral side in patients with sICH (p < 0.01, t = -5.77), and it was also significantly lower than that of the ipsilateral side of HCs (p < 0.01, t = -9.50). No significant differences were found in the DTI-ALPS index on the nonlesion side between patients and HCs (p = 0.96, t = 0.05) or between the left and right cerebral hemispheres of HCs (p = 0.41, t = -0.83). The DTI-ALPS index of the lesion side in patients with sICH was significantly correlated with disease duration (p = 0.018, r = 0.537). Conclusions: The present study confirmed that GS dysfunction on the ipsilateral side of the lesion is impaired in patients with haemorrhagic stroke, indicating that the GS may be a separate system in the left and right cerebral hemispheres. The DTI-ALPS index can reflect disease duration. These findings have significant implications for understanding sICH from a new perspective.

Disseminated Mycobacterium szulgai involving lung, lymph nodes and bone: a case report.

Nontuberculous mycobacteria (NTM) refer to a large group of mycobacteria other than Mycobacterium tuberculosis complex and Mycobacterium leprae. Mycobacterium szulgai (M. szulgai) is a slow growing species of nontuberculous mycobacteria (NTM), which can cause infection in multiple organs, including the lungs. Using the technique of next-generation sequencing (NGS), we diagnosed disseminated M. szulgai infection in a patient with no obvious immunodeficiency. We report on a 66-year-old female patient who presented with enlarged cervical lymph nodes and an intermittent fever. Imaging showed multiple, enlarged, abnormal lymph nodes, a pulmonary mass and rib lesions that strongly suggested neoplasia. There was no significant improvement in symptoms after intermittent antibiotic treatment. The pathological results of multiple biopsies did not support the diagnosis of tumors. The diagnosis of M. szulgai infection was confirmed by NGS. The patient started standard treatment with clarithromycin, ethambutol, and moxifloxacin in July 2020. Since then and over the 10-month follow-up period, there has been a progressive reduction in the size of the enlarged lymph nodes and lung lesions, and no recurrence of fever or other symptoms. M. szulgai is a potential cause of infection (including of disseminated disease) even in patients with no obvious immunosuppression. The potential usefulness of the NGS of clinical samples should be highlighted.

Establishment of a prediction model for mechanical ventilation in ICU patients with nasal high-flow oxygen therapy / 中华急诊医学杂志

Objective:To establish the prediction model of the ultimate risk of mechanical ventilation for patients undergoing nasal high-flow oxygen therapy in the intensive care unit (ICU), provide clinicians with a convenient and effective prediction method and accurate treatment timing, and improve the prognosis of ICU patients.Methods:Patients admitted to the ICU of our hospital from January 2019 to December 2021 were retrospectively enrolled. General clinical data of the patients were collected, including vital signs, biochemical indices of blood gas, inflammatory indices, acute comorbidities, APACHE Ⅱ score, length of stay in ICU and total length of stay, within 24 h after admission. Statistical analysis was performed on the above indicators and a chart was constructed.Results:Finally, 362 patients were enrolled in this study, and were divided into the transnasal high flow oxygen therapy group (HFNC group) and noninvasive positive pressure ventilation group (NIPPV group) according to whether mechanical ventilation was finally performed. The univariate and binary Logistic multivariate regression analysis showed that APACHE Ⅱ score ( OR=1.323, 95% CI: 1.818-1.483), ROX index ( OR=0.371, 95% CI: 0.226-0.609), total length of stay ( OR=1.097, 95% CI: 1.003-1.200) and complicating acute respiratory failure ( OR=2.456, 95% CI: 1.368-4.506) were independent influencing factors for determining whether patients underwent mechanical ventilation. Based on the above independent influencing factors, the lipopograms were constructed. The goodness of fit R2 and C-index of the model were 0.892 and 0.985, respectively through evaluation and verification model. The calibration curve of the model fitted well with the ideal curve, and the areas under the ROC curve of the rosettes and independent factors were 0.985, 0.959, 0.899, 0.656 and 0.576, respectively, indicating that the model was more effective than the independent index in predicting risk. Decision curve analysis also showed that the rosette had high clinical benefit. Conclusions:There are many related factors affecting whether patients undergo mechanical ventilation after nasal high-flow oxygen therapy. In this paper, after univariate and multivariate analysis, the most valuable indicators are combined to establish a line chart with better predictive performance to assess patients' risk, which can further provide clinicians with simple and effective prediction methods and improve the prognosis of patients.

Evaluation on the efficacy of moxifloxacin hydrochloride based on physiological pharmacokinetic models / 药学学报

This study is to establish and validation in vivo models of moxifloxacin based on the theory of physiologically based pharmacokinetics (PBPK), and then to predict the distribution of moxifloxacin in human venous return and organ such as lung, spleen and so on. The efficacy of moxifloxacin and its pharmaceutical preparations were quantified by comparing the pharmacokinetic parameters with the minimum inhibitory concentration of related pathogenic bacterium. The results showed that the anti-infection efficacy of pharmaceutical moxifloxacin preparation in the corresponding organs was basically the same. The PBPK model of moxifloxacin preparations can be more accurately described the pharmacokinetic of anti-infective drugs in human, it is suitable for the efficacy evaluation of anti-infective drugs and provides a strong basis for the corresponding scientific research and scientific supervision.

Mechanism of miR-455-3 in suppressing epithelial-mesenchymal transition and angiogenesis of non-small cell lung cancer cells.

The tumor-suppressing role of miR-455-3p has been reported in lung cancer, but the working mechanism remains to be fully elucidated. This study aims to explore the possible mechanism of miR-455-3p in regulating epithelial-mesenchymal transition (EMT) progression and angiogenesis in non-small cell lung cancer (NSCLC) cells.The expressions of miR-455-3p, HSF1, GLS1, and EMT-related proteins (E-cadherin, N-cadherin, vimentin, and Snail-1) in both NSCLC tissues and cell lines were determined by RT-qPCR and western blot. After cell transfection, cell proliferation and angiogenesis ability on NSCLC cells were assessed by MTT and tube formation assay. The binding of miR-455-3p with HSF1 was measured by luciferase reporter gene assay, while the interaction between HSF1 and GLS1 was determined by co-immunoprecipitation assay (Co-IP).HSF1 was highly expressed in NSCLC tissues and cells. Inhibition of HSF1 expression or overexpression of miR-455-3p in NSCLC cells can suppress cell proliferation, angiogenesis ability, and EMT progression. miR-455-3p was found to negatively regulate HSF1 expression. Co-transfection of miR-455-3p overexpression and HSF1 inhibition in NSCLC cells showed that miR-455-3p can partially counteract the effect of HSF1 in NSCLC cells. HSF1 can interact with GLS1 and elevate the expression of GLS1. GLS1 can partially abolish the suppressive effect of miR-455-3p in NSCLC cells.miR-455-3p can bind HSF1 to suppress the GLS1 in NSCLC cells, therefore suppressing EMT progression and angiogenesis of NSCLC cells.

Optimization of Ecological Water Supplement Scheme for Improved Suitable Habitat Area for Rare Migratory Birds in Nature Reserves Using Interval-Parameter Fuzzy Two-Stage Stochastic Programming Model.

The optimization of ecological water supplement scheme in Momoge National Nature Reserve (MNNR), using an interval-parameter two-stage stochastic programming model (IPTSP), still experiences problems with fuzzy uncertainties and the wide scope of the obtained optimization schemes. These two limitations pose a high risk of system failure causing high decision risk for decision-makers and render it difficult to further undertake optimization schemes respectively. Therefore, an interval-parameter fuzzy two-stage stochastic programming (IPFTSP) model derived from an IPTSP model was constructed to address the random variable, the interval uncertainties and the fuzzy uncertainties in the water management system in the present study, to reduce decision risk and narrow down the scope of the optimization schemes. The constructed IPFTSP model was subsequently applied to the optimization of the ecological water supplement scheme of MNNR under different scenarios, to maximize the recovered habitat area and the carrying capacity for rare migratory water birds. As per the results of the IPFTSP model, the recovered habitat areas for rare migratory birds under low, medium and high flood flow scenarios were (14.06, 17.88) × 103, (14.92, 18.96) × 103 and (15.83, 19.43) × 103 ha, respectively, and the target value was (14.60, 18.47) × 103 ha with a fuzzy membership of (0.01, 0.83). Fuzzy membership reflects the possibility level that the model solutions satisfy the target value and the corresponding decision risk. We further observed that the habitat area recovered by the optimization schemes of the IPFTSP model was significantly increased compared to the recommended scheme, and the increases observed were (5.22%, 33.78%), (11.62%, 41.88%) and (18.44%, 45.39%). In addition, the interval widths of the recovered habitat areas in the IPFTSP model were reduced by 17.15%, 17.98% and 23.86%, in comparison to those from the IPTSP model. It was revealed that the IPFTSP model, besides generating the optimal decision schemes under different scenarios for decision-makers to select and providing decision space to adjust the decision schemes, also shortened the decision range, thereby reducing the decision risk and the difficulty of undertaking decision schemes. In addition, the fuzzy membership obtained from the IPFTSP model, reflecting the relationship among the possibility level, the target value, and the decision risk, assists the decision-makers in planning the ecological water supplement scheme with a preference for target value and decision risk.

N-Methylation of Amines with Methanol in Aqueous Solution Catalyzed by a Water-Soluble Metal-Ligand Bifunctional Dinuclear Iridium Catalyst.

The N-methylation of amines with methanol in aqueous solution was proposed and accomplished by using a water-soluble metal-ligand bifunctional dinuclear iridium catalyst. In the presence of [(Cp*IrCl)2(thbpym)][Cl]2 (1 mol %), a range of desirable products were obtained in high yields under environmentally benign conditions. Notably, this research exhibited the potential of transition metal-catalyzed activation of methanol as a C1 source for the construction of the C-N bond in aqueous solution.