Genetic effects and causal association analyses of 14 common conditions/diseases in multimorbidity patterns.

BACKGROUND: Multimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but the further mechanisms underlying the association patterns are largely unknown. METHODS: Summary statistics of 14 conditions/diseases were available from the genome-wide association study (GWAS). Linkage disequilibrium score regression analysis (LDSC) was applied to estimate the genetic correlations. Pleiotropic SNPs between two genetically correlated traits were detected using pleiotropic analysis under the composite null hypothesis (PLACO). PLACO-identified SNPs were mapped to genes by Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA), and gene set enrichment analysis and tissue differential expression were performed for the pleiotropic genes. Two-sample Mendelian randomization analyses assessed the bidirectional causality between conditions/diseases. RESULTS: LDSC analyses revealed the genetic correlations for 20 pairs based on different two-disease combinations of 14 conditions/diseases, and genetic correlations for 10 pairs were significant after Bonferroni adjustment (P<0.05/91 = 5.49E-04). Significant pleiotropic SNPs were detected for 11 pairs of correlated conditions/diseases. The corresponding pleiotropic genes were differentially expressed in the brain, nerves, heart, and blood vessels and enriched in gluconeogenesis and drug metabolism, biotransformation, and neurons. Comprehensive causal analyses showed strong causality between hypertension, stroke, and high cholesterol, which drive the development of multiple diseases. CONCLUSIONS: This study highlighted the complex mechanisms underlying the association patterns that include the shared genetic components and causal effects among the 14 conditions/diseases. These findings have important implications for guiding the early diagnosis, management, and treatment of comorbidities.

Accelerated biological aging as a potential risk factor for rheumatoid arthritis.

OBJECTS: Previous studies have suggested a potential correlation between rheumatoid arthritis (RA) and biological aging, but the intricate connections and mechanisms remain elusive. METHODS: In our study, we focused on two specific measures of biological age (PhenoAge and BioAge), which are derived from clinical biomarkers. The residuals of these measures, when compared to chronological age, are defined as biological age accelerations (BAAs). Utilizing the extensive UK Biobank dataset along with various genetic datasets, we conducted a thorough assessment of the relationship between BAAs and RA at both the individual and aggregate levels. RESULTS: Our observational studies revealed positive correlations between the two BAAs and the risk of developing both RA and seropositive RA. Furthermore, the genetic risk score (GRS) for PhenoAgeAccel was associated with an increased risk of RA and seropositive RA. Linkage disequilibrium score regression (LDSC) analysis further supported these findings, revealing a positive genetic correlation between PhenoAgeAccel and RA. PLACO analysis identified 38 lead pleiotropic single nucleotide polymorphisms linked to 301 genes, providing valuable insights into the potential mechanisms connecting PhenoAgeAccel and RA. CONCLUSION: In summary, our study has successfully revealed a positive correlation between accelerated biological aging, as measured by BAAs, and the susceptibility to RA.

Risk factors for skin injuries in cancer patients with peripherally inserted central catheter: A prospective multicenter cohort study.

BACKGROUND: The risk factors for skin injuries remain poorly understood in cancer patients with peripherally inserted central catheters (PICC). We herein aimed at exploring the effect of clinical factors on the risk of PICC-related skin injuries. METHODS: We included 1245 cancer patients with PICC from 16 hospitals in Suzhou, China. The study outcome was in-hospital skin injuries, including contact dermatitis, skin (epidermal) stripping, tension injury, allergic dermatitis, skin tear, maceration, folliculitis, and pressure injury. RESULTS: During hospitalization, 274 patients (22.0%) developed skin injuries after prolonged use of an indwelling catheter. Univariable logistic regression analysis identified several risk factors for PICC-related skin injuries; multivariable logistic regression analysis showed that the following factors independently and significantly (p < 0.05) associated with the risk of PICC-related skin injuries: body mass index (BMI, >25 kg/m2 versus <18.5 kg/m2: odds ratio (OR), 1.79; 95% confidence interval (CI), 1.03-3.11), skin condition (humid vs normal: OR, 2.96; 95% CI, 1.62-5.43), skin indentation (OR, 4.67; 95% CI, 3.31-6.58), allergic history (OR, 2.11; 95% CI, 1.21-3.66), history of dermatitis (OR, 3.05; 95% CI, 1.00-9.28), history of eczema (OR, 3.36; 95% CI, 1.20-9.43), catheter insertion site (under elbow vs. upper arm: OR, 3.32; 95% CI, 1.12-9.90), and PICC maintenance interval (4-5 days vs ⩽3 days: OR, 0.06; 95% CI, 0.01-0.50; 5-7 days vs ⩽3 days: OR, 0.07; 95% CI, 0.02-0.31; 7-9 days vs ⩽3 days: OR, 0.10; 95% CI, 0.02-0.57). CONCLUSIONS: BMI, skin condition, skin indentation, allergic history, history of dermatitis, history of eczema, catheter insertion site, and PICC maintenance interval were independent risk factors for PICC-related skin injuries in cancer patients. This knowledge will guide future studies with formulating optimal treatment strategies for improving the skin health of cancer patients with PICC.

Body surface area is a potential obesity index: Its genetic determination and its causality for later-life diseases.

OBJECTIVE: This study aimed to identify novel genetic factors that contribute to body surface area (BSA) and explore its relationship with complex traits and diseases. METHODS: Based on more than 330,000 European individuals in the UK Biobank, the first large-scale genome-wide association study for BSA was performed. Comprehensive genetic analysis and enrichment analysis were then performed to explore the biological function of the identified loci. The genetic correlations and causal associations between BSA and other anthropometry parameters, early growth indices, and later-life diseases, respectively, were assessed by complex genetic approaches. RESULTS: Genome-wide association study analysis identified a total of 456 conditionally independent single-nucleotide polymorphism mapping genes with known functions in the regulation of adipogenesis and metabolism and enriched in adipogenesis-related pathways. BSA was highly genetically correlated with obesity phenotypes, and all the studied anthropometry parameters from the UK Biobank were significantly positively associated with BSA. BSA was phenotypically associated with 13 chronic diseases and genetically associated with 6 diseases. Mendelian randomization analyses showed that BSA has a causal effect in increasing the risk of some diseases. CONCLUSIONS: These findings increase understanding of genetic determinants for BSA and its relationship with complex traits and diseases, and BSA could be regarded as a potential obesity trait.

Relationship between indwelling site and peripheral venous catheter-related complications in adult hospitalized patients: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: This systematic review and meta-analysis aimed to compare the incidence of PVC-related complications between catheterisation in the forearm and back of the hand in adult patients. BACKGROUND: A peripheral intravenous catheter (PVC) is often inserted as part of care during patients' hospitalisation. The catheter is typically inserted in the forearm or at the back of the hand in usual practice. Studies have not yet reached a consensus on the optimal insertion site in any clinical setting. DESIGN: We performed a systematic review and meta-analysis based on PRISMA guidelines. METHODS: We searched the following electronic databases: PubMed, Cochrane Library, Embase, and CINAHL. Randomised controlled trials, cohort studies, case-control studies and cross-sectional studies from inception to July 2021 reporting the incidence of PVC-related complications at the forearm and back of the hand were included. Fixed-effects models and random-effects models were used to derive the pooled risk ratios. RESULTS: Twenty-four studies involving 16562 PVCs met our inclusion criteria. The meta-analysis showed that compared with PVC placement in the back of the hand, placement in the forearm was associated with a higher incidence of total complications and infiltration/extravasation. However, the differences between the PVC indwelling sites were not significant (total complications: P = 0.43; phlebitis: P = 0.35; infiltration/extravasation: P = 0.51). Both incidence of total complications and infiltration/extravasation analyses showed high heterogeneity (total complications: I2  = 60%; infiltration/extravasation: I2  = 58%). CONCLUSION: Available evidence suggests that there is no significant difference between PVC placement in the forearm and at the back of the hand in terms of the incidence of complications, thus making both approaches suitable. RELEVANCE TO CLINICAL PRACTICE: For patients who need indwelling PVC, medical staff can choose the best indwelling site, and both forearm and back of the hand are suitable.

[Inventory and Distribution Characteristics of Anthropogenic Ammonia Emissions in Zhejiang Province from 2008 to 2018].

As ammonia is the main component of PM2.5, long time series of ammonia emission characteristics are an important basis for studying the historical causes of PM2.5 pollution. In this study, the activity data of various anthropogenic ammonia emissions from 11 cities were collected in Zhejiang. The anthropogenic ammonia emissions inventory in Zhejiang was established using emission factors, and then a 1 km×1 km spatial grid distribution was carried out using ArcGIS software. The results showed that from 2008 to 2018, the ammonia emissions from anthropogenic sources in Zhejiang exhibited a downward trend, with an average annual decline rate of approximately 3.97%. The ammonia emissions were 108.52 kt in 2018, and the emission intensity was 1.03 t·km-2, in which there was 90.02 kt from agricultural sources and 18.50 kt from non-agricultural sources. The ammonia emissions of Hangzhou, Jiaxing, and Wenzhou were higher than those of the other cities, accounting for 14.72%, 11.86%, and 11.80% of the total ammonia emissions, respectively. The spatial distribution characteristics showed that ammonia emissions were mainly distributed in the northern part of Zhejiang, showing an emission trend of "high in the north and low in the south." Uncertainty analysis showed that the simulated average value of ammonia emissions was 108.37 kt, and the uncertainty range in the 95% confidence interval was -5.40%-5.60%.

Systematic evaluation for the causal effects of blood metabolites on osteoporosis: Genetic risk score and Mendelian randomization.

Purpose: Osteoporosis is associated with metabolic alterations, but the causal roles of serum metabolites on osteoporosis have not been identified. Methods: Based on the large individual-level datasets from UK Biobank as well as GWAS summary datasets, we first constructed genetic risk scores (GRSs) for 308 of 486 human serum metabolites and evaluated the effect of each GRS on 2 major osteoporosis phenotypes, i.e., estimated bone miner density (eBMD) and fracture, respectively. Then, two-sample Mendelian Randomization (MR) was performed to validate the casual metabolites on osteoporosis. Multivariable MR analysis tested whether the effects of metabolites on osteoporosis are independent of possible confounders. Finally, we conducted metabolic pathway analysis for the metabolites involved in bone metabolism. Results: We identified causal effects of 18 metabolites on eBMD and 1 metabolite on fracture with the GRS method after adjusting for multiple tests. Then, 9 of them were further validated with MR as replication, where comprehensive sensitive analyses proved robust of the causal associations. Although not identified in GRS, 3 metabolites were associated with at least three osteoporosis traits in MR results. Multivariable MR analysis determined the independent causal effect of several metabolites on osteoporosis. Besides, 23 bone metabolic pathways were detected, such as valine, leucine, isoleucine biosynthesis (p = 0.053), and Aminoacyl-tRNA biosynthesis (p = 0.076), and D-glutamine and D-glutamate metabolism (p = 0.004). Conclusions: The systematic causal analyses strongly suggested that blood metabolites have causal effects on osteoporosis risk.

Genetic Risk for Osteoporosis and the Benefit of Adherence to Healthy Lifestyles.

Objectives: We aimed to explore how healthy lifestyles and genetic factors influence the risk of Osteoporosis (OP). Methods: In this prospective cohort study, we first performed a genome-wide association study (GWAS) of estimated bone mineral density (eBMD) and constructed the genetic risk score (GRS) based on the effect of single nucleotide polymorphism (SNP) on eBMD. We then assessed the effect of three-level GRS and adherence to healthy lifestyles on the risk of OP and fracture, respectively. Finally, we assessed the joint effects of GRS and lifestyle on the OP and fracture risk. Results: People with higher GRS have a lower risk of OP and fracture. Negative associations were detected between healthy lifestyle factors and the risk of OP and fracture. Compare with the group with high GRS and favorable lifestyles, the group with low GRS and unfavorable lifestyles had a high Hazard Ratio (HR). Conclusion: The findings suggest that adherence to healthy lifestyles can reduce the risk of OP and fracture in people with different genetic risks.

Systematic Evaluation of Rheumatoid Arthritis Risk by Integrating Lifestyle Factors and Genetic Risk Scores.

Background: Effective identification of high-risk rheumatoid arthritis (RA) individuals is still a challenge. Whether the combined effects of multiple previously reported genetic loci together with lifestyle factors can improve the prediction of RA risk remains unclear. Methods: Based on previously reported results and a large-scale Biobank dataset, we constructed a polygenic risk score (PRS) for RA to evaluate the combined effects of the previously identified genetic loci in both case-control and prospective cohorts. We then evaluated the relationships between several lifestyles and RA risk and determined healthy lifestyles. Then, the joint effects of healthy lifestyles and genetic risk on RA risk were evaluated. Results: We found a positive association between PRS and RA risk (OR = 1.407, 95% confidence interval (CI) = 1.354~1.463; HR = 1.316, 95% CI = 1.257~1.377). Compared with the low genetic risk group, the group with intermediate or high genetic risk had a higher risk (OR = 1.347, 95% CI = 1.213~1.496; HR = 1.246, 95% CI = 1.108~1.400) (OR = 2.169, 95% CI = 1.946~2.417; HR = 1.762, 95% CI = 1.557~1.995). After adjusting for covariates, we found protective effects of three lifestyles (no current smoking, regular physical activity, and moderate body mass index) on RA risk and defined them as healthy lifestyles. Compared with the individuals with low genetic risks and favorable lifestyles, those with high genetic risks and unfavorable lifestyles had as high as OR of 4.637 (95%CI = 3.767~5.708) and HR of 3.532 (95%CI = 2.799~4.458). Conclusions: In conclusion, the integration of PRS and lifestyles can improve the prediction of RA risk. High RA risk can be alleviated by adopting healthy lifestyles but aggravated by adopting unfavorable lifestyles.

Individualized Whole Course Nutrition Management for Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs. METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group. RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05). CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.

Identification of causal metabolites related to multiple autoimmune diseases.

Observational studies provide evidence that metabolites may be involved in the development of autoimmune diseases (ADs), but whether it is causal is still unknown. Based on the large-scale genome-wide association studies (GWAS) summary statistics, we performed two-sample Mendelian randomization (MR) to evaluate the causal associations between human blood metabolites and multiple ADs, which were inflammatory bowel disease (IBD), ulcerative colitis (UC), crohns disease (CD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). After Bonferroni adjustment, we identified 6 causal features of metabolites, i.e., glycerol 2-phosphate for T1D, hexadecanedioate, phenylacetylglutamine and laurylcarnitine for RA, glycine and arachidonate (20:4n6) for CD. Comprehensive sensitive analysis was further performed to validate the robustness of associations. We also observed some overlaps of metabolites among different ADs, implying similar or shared underlying mechanisms in such pathogenic processes. Multivariable MR analysis was then conducted to avoid potential pleiotropic effect of other complex traits. After controlling for several common traits, multivariable MR analysis ruled out most of potential pleiotropic effects and validated independence of identified metabolites. Finally, metabolic pathway analysis was performed based on suggestive metabolites for each AD respectively and a total of seven metabolic pathways were identified. In conclusion, this study provided novel insights into investigating causal role of blood metabolites in development of multiple ADs through a comprehensive genetic pathway.

Risk factors for peripheral venous catheter failure: A prospective cohort study of 5345 patients.

PURPOSE: The objective of this study was to determine the independent risk factors associated with peripheral venous catheter (PVC) failure and develop a model that can predict PVC failure. METHODS: This prospective, multicenter cohort study was carried out in nine tertiary hospitals in Suzhou, China between December 2017 and February 2018. Adult patients undergoing first-time insertion of a PVC were observed from catheter insertion to removal. Logistic regression was used to identify the independent risk factors predicting PVC failure. RESULTS: This study included 5345 patients. The PVC failure rate was 54.05% (n = 2889/5345), and the most common causes of PVC failure were phlebitis (16.3%) and infiltration/extravasation (13.8%). On multivariate analysis, age (45-59 years: OR, 1.295; 95% CI, 1.074-1.561; 60-74 years: OR, 1.375; 95% CI, 1.143-1.654; ⩾75 years: OR, 1.676; 95% CI, 1.355-2.073); department (surgery OR, 1.229; 95% CI, 1.062-1.423; emergency internal/surgical ward OR, 1.451; 95% CI, 1.082-1.945); history of venous puncture in the last week (OR, 1.298, 95% CI 1.130-1.491); insertion site, number of puncture attempts, irritant fluid infusion, daily infusion time, daily infusion volume, and type of sealing liquid were independent predictors of PVC failure. Receiver operating characteristic curve analysis indicated that a logistic regression model constructed using these variables had moderate accuracy for the prediction of PVC failure (area under the curve, 0.781). The Hosmer-Lemeshow goodness of fit test demonstrated that the model was correctly specified (χ2 = 2.514, p = 0.961). CONCLUSION: This study should raise awareness among healthcare providers of the risk factors for PVC failure. We recommend that healthcare providers use vascular access device selection tools to select a clinically appropriate device and for the timely detection of complications, and have a list of drugs classified as irritants or vesicants so they can monitor patients receiving fluid infusions containing these drugs more frequently.

Continuous quality improvement of nutrition management during radiotherapy in patients with nasopharyngeal carcinoma.

AIM: To investigate the effect of implementing a model for continuous quality improvement in the nutritional management of patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy. DESIGN METHODS: In the intervention group (n = 77), a model for the continuous quality improvement of efforts at nutrition management was implemented. These efforts included the development of a new process for nutrition management, a system to provide nutritional support and the use of targeted intervention plans to improve nutrition. The time from diagnosis to the administration of radiation therapy, the severity of oral mucositis and dietary factors were recorded and considered in the development of targeted nutrition intervention and nutrition education. The control group (n = 71) followed the original procedures for nutrition management. RESULTS: The study found that the CQI model can decrease the severity of oral mucositis caused by radiation and improve nutritional status in affected patients.

Rheumatoid arthritis and osteoporosis: shared genetic effect, pleiotropy and causality.

Rheumatoid arthritis (RA) is associated with increased localized and generalized bone loss, but the complex genetic mechanism between them is still unknown. By leveraging large-scale genome-wide association studies summary statistics and individual-level datasets (i.e. UK Biobank), a series of genetic approaches were conducted. Linkage disequilibrium score regression reveals a shared genetic correlation between RA and estimated bone mineral density (eBMD) (rg = -0.059, P = 0.005). The PLACO analysis has identified 74 lead (8 novel) pleiotropic loci that could be mapped to 99 genes, the genetic functions of which reveal the possible mechanism underlying RA and osteoporosis. In European, genetic risk score (GRS) and comprehensive Mendelian randomization (MR) were utilized to evaluate the causal association between RA and osteoporosis in European and Asian. The increase in GRS of RA could lead to a decrease of eBMD (beta = -0.008, P = 3.77E-6) and a higher risk of facture [odds ratio (OR) = 1.012, P = 0.044]. MR analysis identified that genetically determined RA was causally associated with eBMD (beta = -0.021, P = 4.14E-05) and fracture risk (OR = 1.036, P = 0.004). Similar results were also observed in Asian that osteoporosis risk could be causally increased by RA (OR = 1.130, P = 1.04E-03) as well as antibodies against citrullinated proteins-positive RA (OR = 1.083, P = 0.015). Overall, our study reveals complex genetic mechanism between RA and osteoporosis and provides strong evidence for crucial role of RA in pathogenesis of osteoporosis.

Negative emotions and their management in Chinese convalescent cervical cancer patients: a qualitative study.

OBJECTIVE: The aim of the study was to understand the experience of negative emotions and coping styles of patients with cervical cancer during the rehabilitation period. METHODS: A descriptive qualitative research method was used. Purposive sampling was used to recruit participants. Semi-structured interviews were conducted with 18 cervical cancer patients and the data were analysed using content analysis. RESULTS: The analysis identified three relevant themes. Theme 1: Negative emotions in convalescent cervical cancer patients mainly comprised fear of recurrence, worries about sex and feelings of inferiority. Theme 2: Patients used positive and negative coping styles to manage negative emotions. Theme 3: Patients expressed a strong need for rehabilitation information. CONCLUSIONS: Patients with cervical cancer exhibited negative emotions during the rehabilitation period. To help these patients, medical staff should develop an understanding of their needs by communicating more with patients and providing them with targeted care to help them return to society more quickly.

Impact of Volume Management on Volume Overload and Rehospitalization in CAPD Patients.

Heart failure due to volume overload is a major reason for rehospitalization in continuous ambulatory peritoneal dialysis patients. Strict volume control provides better cardiac functions and blood pressure in this population. Volume management, which is a volume control strategy, may decrease volume overload and related complications. Using a quasi-experimental design, 66 continuous ambulatory peritoneal dialysis patients were randomly assigned to the intervention group ( n = 34) and control group ( n = 32). The patients were followed up for 6 months with scheduled clinic and/or telephone visits; the intervention group adopted volume management strategy, while the control group adopted conventional care. Volume overload and cardiac function were compared between the two groups at the baseline and at 6 months. At Month 6, the intervention group resulted in significant improvement in volume overloaded status, cardiac function, and volume-overload-related rehospitalization. Volume management strategy allows for better control of volume overload and is associated with fewer volume-related readmissions.

Sexual Dysfunction among Chinese Nurses: Prevalence and Predictors.

This study aimed to estimate the prevalence of and identify the factors influencing female sexual dysfunction (FSD) among Chinese nurses. A cross-sectional survey was conducted from March 2013 to May 2014 among 6 hospitals in Suzhou, China. In total, 2,030 married female nurses were included in the analysis. Data on the sociodemographic, lifestyle, and self-reported health status of the participants were collected, and the participants were asked to complete the Chinese version of the 19-item Female Sexual Function Index (FSFI) questionnaire. In total, 1,035 (50.99%) participants were found to have FSD. Logistic regression analysis showed that increasing age and higher body mass index, lower salary, and poor/very poor self-reported health status were risk factors for FSD; however, regular social activity and physical exercise were protective factors for FSD. The findings of this study suggest that further interventional studies are warranted to study the sexual health among Chinese nurses in detail.

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.

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.

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.