Dissection of the antitumor mechanism of tetrandrine based on metabolite profiling and network pharmacology.

RATIONALE: Tetrandrine, the Q-marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated. METHODS: The metabolites of tetrandrine in rats were profiled using ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology. RESULTS: A total of 30 metabolites were characterized in rats after ingestion of tetrandrine (10 mg/kg), including 0 in plasma, 7 in urine, 11 in feces, 9 in liver, 8 in spleen, 4 in lung, 5 in kidney, 5 in heart, and 4 in brain. This study was the first to show the metabolic processes demethylation, hydroxylation, and carbonylation in tetrandrine. The pharmacology network results showed that tetrandrine and its metabolites could regulate AKT1, TNF, MMP9, MMP2, PAK1, and so on by involving in proteoglycan tumor pathway, PI3K-Akt signaling pathway, tumor pathway, MAPK signaling pathway, and Rap1 signaling pathway. CONCLUSIONS: The metabolism features of tetrandrine and its potential antitumor mechanism were summarized, providing data for further pharmacological validation.

Hyperbaric oxygen via mediating SIRT1-induced deacetylation of HMGB1 improved cReperfusion inj/reperfusion injury.

Ischemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro-protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF-α, IL-1ß and IL-6 related inflammatory factors. RT-qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro-inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1-induced HMGB1 deacetylation and suppressing MMP-9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1-induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment.

Ligninolytic enzymes from Ganoderma spp: current status and potential applications.

White-rot fungal species belonging to Ganoderma have long been used as medicinal mushrooms in many Asian countries. In recent years, however, attention is not just being paid to their pharmacological properties, but to their other potentially valuable features as well, including their secretion of enzymes which decompose lignin. The current literature regarding lignin-modifying enzymes from the genus Ganoderma, their potential uses, and the components, structures and processes of lignocellulose degradation are discussed. The ligninolytic enzymes from the genus Ganoderma, as well as the number of additional enzymes that participate in lignin degradation, are summarized; further, the potential applications of these enzymes are analyzed and probed in this article. This review will provide insight on the valuable applications of Ganoderma spp. and will serve as a useful reference on the use of lignocellulose degradation as a means of environmental protection.

Applied modern biotechnology for cultivation of Ganoderma and development of their products.

A white-rot basidiomycete Ganoderma spp. has long been used as a medicinal mushroom in Asia, and it has an array of pharmacological properties for immunomodulatory activity. There have been many reports about the bioactive components and their pharmacological properties. In order to analyze the current status of Ganoderma products, the detailed process of cultivation of Ganoderma spp. and development of their products are restated in this review article. These include the breeding, cultivating, extracting bioactive component, and processing Ganoderma products, etc. This article will expand people's common knowledge on Ganoderma, and provide a beneficial reference for research and industrial production.

Rapid classification of hairtail fish and pork freshness using an electronic nose based on the PCA method.

We report a method for building a simple and reproducible electronic nose based on commercially available metal oxide sensors (MOS) to monitor the freshness of hairtail fish and pork stored at 15, 10, and 5 °C. After assembly in the laboratory, the proposed product was tested by a manufacturer. Sample delivery was based on the dynamic headspace method, and two features were extracted from the transient response of each sensor using an unsupervised principal component analysis (PCA) method. The compensation method and pattern recognition based on PCA are discussed in the current paper. PCA compensation can be used for all storage temperatures, however, pattern recognition differs according to storage conditions. Total volatile basic nitrogen (TVBN) and aerobic bacterial counts of the samples were measured simultaneously with the standard indicators of hairtail fish and pork freshness. The PCA models based on TVBN and aerobic bacterial counts were used to classify hairtail fish samples as "fresh" (TVBN ≤ 25 g and microbial counts ≤ 10(6) cfu/g) or "spoiled" (TVBN ≥ 25 g and microbial counts ≥ 10(6) cfu/g) and pork samples also as "fresh" (TVBN ≤ 15 g and microbial counts ≤ 10(6) cfu/g) or "spoiled" (TVBN ≥ 15 g and microbial counts ≥ 10(6) cfu/g). Good correlation coefficients between the responses of the electronic nose and the TVBN and aerobic bacterial counts of the samples were obtained. For hairtail fish, correlation coefficients were 0.97 and 0.91, and for pork, correlation coefficients were 0.81 and 0.88, respectively. Through laboratory simulation and field application, we were able to determine that the electronic nose could help ensure the shelf life of hairtail fish and pork, especially when an instrument is needed to take measurements rapidly. The results also showed that the electronic nose could analyze the process and level of spoilage for hairtail fish and pork.

[Normal values and influencing factors of fractional exhaled nitric oxide for Chinese healthy adults].

OBJECTIVE: To evaluate the normal values of fractional exhaled nitric oxide (FENO) for Chinese adults. METHODS: A total of 200 non-smoking and healthy Chinese adults were recruited according to the inclusion and exclusion criteria. They received lung function and allergen skin prick tests at the Outpatient Department of China-Japan Friendship Hospital from February to August 2011. There were 100 males and 100 females. FENO test was performed according to the standard procedures of American Thoracic Society/European Respiratory Society (ATS/ERS) recommendation. The FENO levels of healthy non-smokers were tested by the NIOXMINO analyzer. All variables, such as age, gender, height, weight, forced expiratory volume at 1 second (FEV(1))% predicted and FEV(1)/FVC, were included for multiple regression analyses. RESULTS: The FENO level of healthy non-smokers was (14.2 ± 5.6)×10(-9) mol/L with the 95% normal range of (3.2 - 25.2)×10(-9) mol/L. The value of FENO was significantly higher in males than females ((15.6 ± 5.5) vs (12.9 ± 5.4)×10(-9) mol/L, t = 3.48, P = 0.001). The FENO level of the subjects aged 60 - 80 years was (15.7 ± 5.4)×10(-9) mol/L and it was higher than those aged 18 - 60 years ((13.8 ± 5.6)×10(-9) mol/L, t = 2.04, P = 0.040). Multiple regression analysis showed that gender was an independent influencing factor of FENO level. CONCLUSIONS: The FENO level of non-smoking and healthy Chinese adults is similar with that of the westerners. Gender is an independent influencing factor of FENO level.

[Wildfire smoke injection heights in China based on multi-angle imaging spectroradiometer (MISR) observations]. / åŸºäºŽå¤šè§’åº¦æˆåƒå ‰è°±ä»ª(MISR)数据的中国野火烟羽喷射高度.

Smoke injection height is a key driving factor for plume transport, which determines the lifetime of smoke aerosol in the atmosphere, transport path and diffusion along with the wind, and impacts on atmospheric environment. In this study, raw data obtained from the latest multi-angle imaging spectroradiometer (MISR) plume height project was extracted and analzyed. The variation of smoke injection heights of wildfire in China was investigated with statistical analysis methods. The effects of fire characteristics (combustion biomass type and fire radiative power) on the smoke injection height were explored. Meanwhile, the influence of smoke injection heights on the atmospheric environment was discussed based on the proportion of higher injection height plumes and the value of smoke aerosol optical depth (AOD). The results showed that smoke injection heights from wildfire ranged from 345 to 7719 m, with 57.1% of which ranging from 500 to 1000 m. Except for an abnormally high value of smoke injection height from a large grassland fire, the rest of smoke injection heights were lower than 3000 m. The biomass type for combustion was an important factor affecting smoke injection heights. The injection heights of the plume caused by forest fire were the highest and had the greatest variability. Smoke injection heights increased with the fire radiation power, but with obvious dispersion (R2=0.19). By setting a simple threshold, the proportion of higher injection plumes which might cause long-distance transportation of air pollutants in China was 10.5%. Combined with the analysis of smoke AOD, it was found that the average smoke injection height from cropland burning was the lowest, but their smoke caused the highest regional air pollution. In contrast, although forest fires could produce the highest smoke injection height, their smoke had a lower average value of AOD, which indicated a relatively weak impact of forest fires on regional air quality.

[Effects of Wastewater Discharge on Antibiotic Resistance Genes and Microbial Community in a Coastal Area].

Wastewater treatment plants (WWTPs) are important sources of antibiotic resistance genes (ARGs) in aquatic environments. Mobile genetic elements (MGEs) and microbial communities are key factors that affect the proliferation of ARGs. To reveal the effects of WWTPs effluent discharge on the ARGs and microbial community in a coastal area, the structure and distribution of ARGs, MGEs, and microbial community in Shangyu (SY) and Jiaxing (JX) effluent receiving areas (ERAs) and the offshore area of Hangzhou Bay (HB) were investigated via high-throughput quantitative PCR and 16S rRNA high-throughput sequencing. The results showed that multidrug resistance genes were the most abundant ARGs across all the sampling sites. The diversity and abundance of ARGs and MGEs in the ERAs were much higher than those in the HB. Additionally, the diversities of the microbial community in the JX-ERA were higher than those in the SY-ERA and HB. PCoA showed that the distribution of ARGs, MGEs, and microbial communities in the ERAs and HB were significantly different, indicating that the long-term wastewater discharge could alter the distribution of ARGs, MGEs, and microbial communities in the coastal area. The co-occurrence pattern among ARGs, MGEs, and microbial communities revealed that 12 bacterial genera, such as Psychrobacter, Pseudomonas, Sulfitobacter, Pseudoalteromonas, and Bacillus, showed strong positive correlations with ARGs and MGEs. Most potential hosts carried multidrug and ß-lactamase resistance genes.

Investigation of the effects of high cervical spinal cord electrical stimulation on improving neurological dysfunction and its potential mechanism in rats with traumatic brain injury.

To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 ( P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly ( P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group ( P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased ( P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.

The pharmacokinetics of recombinant human interferon-alpha-2b poly(lactic-co-glycolic acid) microspheres in rats.

Interferon-alpha2b (IFN α-2b) microspheres were prepared at various concentrations (5%, 10%, 15%, 20% and 25%) and viscosities (0.39, 0.6, 0.89 and 1.13 dL/g) of poly(lactic-co-glycolic acid) (PLGA) using double emulsion solvent evaporation. The optimal formulation of IFN α-2b microspheres was determined to be 0.89 dL/g PLGA, as assessed by the in vitro release test. The pharmacokinetics of IFN α-2b microspheres was investigated. Nine groups of rats were injected intramuscularly with three doses (0.5, 1 and 2 MIU) of commercial lyophilized IFNα-2b injection or IFN α-2b microspheres. At a dose of 0.5 MIU, the IFN α-2b microsphere released significantly longer than that of the IFN α-2b injection. At a dose of 2 MIU, each pharmacokinetics parameter of microspheres prepared with the IFNa-2b stock solution was manifestly greater than those of the injection. Our study indicated that the IFN α-2b microspheres prepared in 15% of 0.89 dL/g PLGA provided a sustained drug effect for up to 21 days in rats.

[Values of fractional exhaled nitric oxide in the diagnosis of chronic cough].

OBJECTIVE: To evaluate the diagnostic value of fractional exhaled nitric oxide (FeNO) in the diagnosis of chronic cough. METHODS: A total of 106 subjects with chronic cough and normal chest radiographs were recruited from October 2009 to September 2010. Based on the management guidelines of the Chinese Respiratory Society for cough, the golden standard methods were used to make the definite diagnosis of chronic cough, including sputum cell counts, pulmonary function tests, bronchial hyperresponsiveness, 24-h esophageal pH monitoring, skin pricking test and serum immunoglobulin E. All subjects received a FeNO test by a NIOXMINO analyzer. The values of FeNO to diagnose cough variant asthma (CVA) from chronic cough and EB from non-asthma cough were respectively assessed by the receiver operating characteristic (ROC) curves. RESULTS: Among them, the definite diagnoses were cough variant asthma (CVA, n = 39), eosinophilic bronchitis (EB, n = 30) and other causes (n = 37). The FeNO levels in CVA [(54 ± 21) ppb)] (1 ppb = 1 × 10(9) mol/L) were significantly higher than those in EB [(34 ± 17) ppb, P < 0.01] and other causes [(21 ± 10) ppb, P < 0.01]. And the FeNO levels in EB were higher than those in other causes (P < 0.01). To diagnose CVA from chronic cough, the optimal FeNO cutoff value was 40 ppb with a sensitivity of 75%, a specificity of 86%, a positive predictive value of 77%, a negative predictive value of 86% and an accuracy of 81%. To diagnose EB from non-asthma chronic cough, the optimal FeNO cutoff value was 31 ppb with a sensitivity of 63%, a specificity of 92%, a positive predictive value of 88%, a negative predictive value of 92% and an accuracy of 72% respectively. CONCLUSION: There are significant differences between the FeNO levels of different causes of chronic cough. A marked elevation of FeNO level helps to make a final diagnosis of CVA or EB. FeNO test is useful for making the diagnosis and differential diagnosis of chronic cough in clinic practices.

[The values of fractional exhaled nitric oxide in the diagnosis and treatment of chronic cough].

OBJECTIVE: To evaluate the values of fractional exhaled nitric oxide (FENO) in the diagnosis and treatment of chronic cough. METHODS: Based on the protocol from The Chinese Respiratory Society guidelines for management of cough, 75 consecutive subjects with chronic cough and normal chest radiographs were recruited from the outpatient clinic of the Department of Respiratory Diseases in China-Japan Friendship Hospital from January to June 2010. All the patients accepted FENO tests, sputum cell counts, pulmonary function tests, bronchial hyperresponsiveness (BHR), serum IgE, cough symptom scores and Leicester cough Questionnaire (LCQ) before and after treatment of 4 weeks. RESULTS: The final diagnosis of the subjects included 29 with cough variant asthma (CVA), 19 with eosinophilic bronchitis (EB) and 27 with other causes (Others). FENO levels in CVA (58 ± 26) ppb were significantly higher than those in EB (36 ± 18) ppb and Others (20 ± 7) ppb, and the FENO levels in EB were higher than Others (F = 28.2, P < 0.01). FENO levels showed significant correlations with sputum eosinophils, BHR, cough symptom scores, non-specific IgE, and LCQ scores. The mean baseline FENO level of the subjects whose coughs were relieved after inhaled corticosteroid therapy was (63 ± 42) ppb, higher than those of the non-responders (28 ± 13) ppb (t = 3.91, P < 0.01). There were significant correlations between the percentage of FENO decrease and the percentage of sputum eosinophil decrease or the cough symptom score decrease. CONCLUSION: FENO could be used as a inflammation marker of chronic cough because of its good correlation with sputum eosinophils, AHR, atopy, and cough symptoms. FENO also has a potential to predict the response of anti-inflammatory therapy because FENO decrease is correlated with the decrease of eosinophilic inflammation and improvement of cough symptoms.

[A cloud detection algorithm for MODIS images combining Kmeans clustering and multi-spectral threshold method].

An improved method for detecting cloud combining Kmeans clustering and the multi-spectral threshold approach is described. On the basis of landmark spectrum analysis, MODIS data is categorized into two major types initially by Kmeans method. The first class includes clouds, smoke and snow, and the second class includes vegetation, water and land. Then a multi-spectral threshold detection is applied to eliminate interference such as smoke and snow for the first class. The method is tested with MODIS data at different time under different underlying surface conditions. By visual method to test the performance of the algorithm, it was found that the algorithm can effectively detect smaller area of cloud pixels and exclude the interference of underlying surface, which provides a good foundation for the next fire detection approach.

Adjuvant treatment with Angong Niuhuang pills in treating traumatic brain damage: a meta-analysis of randomized controlled trials.

BACKGROUND: The Angong Niuhuang pill (ANP) has been widely used in the adjuvant treatment of patients with traumatic brain injury (TBI). However, the efficacy and adverse reactions of this drug are controversial. In this study, it was aimed to evaluate the effectiveness and safety of ANP on patients with TBI by a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Embase, Cochrane Library, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wangfang databases were systematically searched from their establishment until June 2020. RCTs of ANP treating TBI were enrolled. Odds risk (OR) was used to assess the total effective rate and safety and mean difference (MD) and 95% confidence interval (CI) were used to assess the quantitative data. Tthe included literature's quality was evaluated by RevMan 5.3. The sensitivity and publication bias was evaluated by Stata 16.0. RESULTS: Twelve studies were identified in this systematic review, including 1,568 participants. The metaanalysis results suggested that ANP combined with routine treatment obviously improved the postoperative GCS [MD =1.97, 95% CI (1.22, 2.72), P<0.01] and GOS [OR =2.28, 95% CI (1.60, 3.22), P<0.01] of patients with TBI. ANP also increased Mg2+ concentration and decreased pulmonary infection. In addition, ANP significantly reduced NSE, gastrointestinal bleeding, and liver and kidney function damage. CONCLUSIONS: Based on limited evidence, ANP adjuvant therapy may have a clinical benefit in improving the prognosis of patients with TBI and reducing the associated complications. At the same time, more studies with larger sample sizes and high quality are required to determine the safety and effectiveness of ANP adjuvant therapy.

Preparation and characteristics of interferon-alpha poly(lactic-co-glycolic acid) microspheres.

By a double emulsion solvent evaporation method, interferon-alpha (IFN-alpha) microspheres were prepared with poly(lactide-co-glycolide) (PLGA) and their characteristics, such as morphology, drug loading, encapsulation efficiency, in vitro release and degradation were evaluated. The IFN-alpha microspheres were prepared by different viscosities from 0.17-1.13 dL g(-1) and concentrations between 5-25% of PLGA, which not only affected the drug loading and encapsulation efficiency of IFN-alpha microspheres, but also strongly influenced the in vitro release. With smooth and porous surface, the drug loading and encapsulation efficiency of the microspheres prepared by 15% 0.89 dL g(-1) PLGA were 7.736% and 77.38%, respectively. The DSC curve of microspheres indicated IFN-alpha was loaded inside the microspheres. The degradation of microspheres was homogeneous and the mass loss was over 80% in 6 weeks. The release profile of microspheres showed a sustained fashion and the IFN-alpha released from microspheres maintained its bioactivity for 7 days.

[An improved method for forest fire spot detection based on variance between-class].

An improved method using variance between-class and smoke plume mask is described. The brightness temperature threshold of potential fire pixels was adjusted to be 305 K. Based on the variance between-class of TIR channel brightness temperature and a smoke plume detection algorithm, the improved algorithm can separate the hot fire spots from the background and seek out the cool fire spots, respectively, with suitable thresholds of variance between-class. This algorithm has been used in the forest fires that happened in Fujian province and Heilongjiang province. Study shows that detection results with the algorithm are more satisfactory. It is adapted in different environments and can be more accurately detected the high-temperature fire spot and the smoder at low temperature. It increases the ability and accuracy to detect fire spots.

[Gas pipeline leak detection based on tunable diode laser absorption spectroscopy].

The principle of tunable diode laser absorption spectroscopy and harmonic detection technique was introduced. An experimental device was developed by point sampling through small multi-reflection gas cell. A specific line near 1 653. 7 nm was targeted for methane measurement using a distributed feedback diode laser as tunable light source. The linearity between the intensity of second harmonic signal and the concentration of methane was determined. The background content of methane in air was measured. The results show that gas sensors using tunable diode lasers provide a high sensitivity and high selectivity method for city gas pipeline leak detection.

[Distribution Characteristics of Antibiotic Resistance Genes in Wastewater Treatment Plants].

Wastewater treatment plants (WWTPs) are regarded as the main source for antibiotic resistant genes (ARGs). To explore the features regarding the distribution of ARGs in wastewater with complicated composition in treatment plants, wastewater samples from a chemical industry park that produced antibiotics were selected. qPCR was applied to detect the type and abundance of ARGs in the wastewater flows from the WWTPs. The results indicated that 16 types of ARGs were detected from the wastewater from the WWTPs, among which sulfonamide resistance genes and tetracycline resistance genes were the dominant ARGs that appeared in the wastewater. Additionally, intI 1 was detected and its abundance was correlated with that of sulfonamide resistance genes. This indicated that intI 1 may promote the migration and transformation of sulfonamide resistance genes. The pharmaceutical factories in the park mainly synthesize macrolide antibiotics. Because of the selective pressure, the absolute abundance of ermB in the wastewater was much higher than that in the other industrial wastewater. The total ARGs decreased by 1.16 log via traditional biological treatment process, and the total ARGs decreased by 2.46 log via the Fenton process. The results showed that the removal effects of deep treatment processes on ARGs were better than that of biological treatment in this wastewater treatment process. Highly abundant and movable ARGs already exist in the water body, and their release from WWTPs without effective treatment poses high risks to the environment.

Effects of Brain Temperature on the Outcome of Patients with Traumatic Brain Injury: A Prospective Observational Study.

A prospective observational study collected temperature data from 51 patients in 11 neurosurgical centers and follow-up outcome information at 6 months in 49 patients. Brain temperature (Tbr) was measured directly by an intraventricular temperature sensor. Axillary temperature (Tax) and rectal temperature (Tre) were measured by electric thermometers. Tbr was 0.4 to 1.5°C higher than body temperature. Tre correlated well with the Tbr (coefficient: 0.7378; p < 0.05). Among all patients, Glasgow Coma Scale (GCS) scores on admission were significantly lower in the patients with post-operatively extreme peak temperature (Tpeak, < 37°C or >39°C in first 24 h) and major temperature variation (Tvari > 1°C in first 12 h; p < 0.05, p < 0.01, respectively). Among the patients with no temperature intervention, the extreme Tpeak group showed a lower Glasgow Outcome Scale-Extended (GOS-E) score at 6 months (p < 0.05) with lower GCS scores on admission (p < 0.01), compared with the moderate Tpeak group. Remarkably, the major Tvari group showed significantly lower GOS-E scores (p < 0.05) with the same GCS scores as the minor Tvari group. Thus, Tre is the better candidate to estimate Tbr. Spontaneously extreme Tpeak in TBI represents both more serious injury on admission and worse prognosis, and Tvari might be used as a novel prognostic parameter in TBI. Brain temperature is therefore one of the critical indicators evaluating injury severity, prognostication, and monitoring in the management of TBI. This prospective observational study has been registered in ClinicalTrials.gov ( https://clinicaltrials.gov ), and the registration number is NCT03068143.

Recombinant interferon-alpha2b poly(lactic-co-glycolic acid) microspheres: pharmacokinetics-pharmacodynamics study in rhesus monkeys following intramuscular administration.

AIM: Investigation into pharmacokinetic-pharmacodynamic properties of interferon- alpha (IFN-alpha)2b-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) in rhesus monkey primates. METHOD: IFN-alpha2b was loaded with biodegradable PLGA with 3 inherent viscosities using a double emulsion and solvent evaporation method. The particle size, surface morphology, and in vitro release profiles were investigated. Two groups of rhesus monkeys (n=3) were injected intramuscularly with either 3 MIU/kg commercial IFN-alpha2b lyophilized powder or IFN-alpha2b-loaded PLGA microspheres (inherent viscosity of 0.89 dL/g). In vitro release was determined by Lowry protein assay. The serum IFN and neopterin levels were determined by the enzyme-linked immunosorbent assay (ELISA) method to evaluate biological activity of the microspheres in rhesus monkeys. RESULTS: The IFN-alpha2b microspheres with 3 inherent viscosities (0.39, 0.89, and 1.13 dL/g) were entirely spherical and had a smooth surface. The average diameter of each type was 45.55, 81.23, and 110.25 microm, respectively. The in vitro release was 30 d. The pharmacokinetic-pharmacodynamic properties between the IFN-alpha2b microspheres and IFN-alpha2b lyophilized powder were significantly different (P<0.05). CONCLUSION: The drug residence time for the IFN-alpha2b of the PLGA microsphere with an inherent viscosity of 0.89 dL/g in plasma significantly increased and had a longer time of biological effects in rhesus monkeys following intramuscular administration.