Antibacterial and Anti-Inflammatory Polysaccharide from Fructus Ligustri Lucidi Incorporated in PVA/Pectin Hydrogels Accelerate Wound Healing.

In cutaneous wound healing, an overproduction of inflammatory chemokines and bacterial infections impedes the process. Hydrogels can maintain a physiologically moist microenvironment, absorb chemokines, prevent bacterial infection, inhibit bacterial reproduction, and facilitate wound healing at a wound site. The development of hydrogels provides a novel treatment strategy for the entire wound repair process. Here, a series of Fructus Ligustri Lucidi polysaccharide extracts loaded with polyvinyl alcohol (PVA) and pectin hydrogels were successfully fabricated through the freeze-thaw method. A hydrogel containing a 1% mixing weight ratio of FLL-E (named PVA-P-FLL-E1) demonstrated excellent physicochemical properties such as swellability, water retention, degradability, porosity, 00drug release, transparency, and adhesive strength. Notably, this hydrogel exhibited minimal cytotoxicity. Moreover, the crosslinked hydrogel, PVA-P-FLL-E1, displayed multifunctional attributes, including significant antibacterial properties, earlier re-epithelialization, production of few inflammatory cells, the formation of collagen fibers, deposition of collagen I, and faster remodeling of the ECM. Consequently, the PVA-P-FLL-E1 hydrogel stands out as a promising wound dressing due to its superior formulation and enhanced healing effects in wound care.

Pull technique versus open surgical removal of the catheter for peritoneal dialysis: a retrospective cohort study.

BACKGROUND: The open surgical technique (OST) is the main modality for peritoneal dialysis (PD) catheter removal; however, the pull technique (PT) is emerging as a minimally invasive alternative. At present, the safety and relative equivalence of PT and OST are unclear. METHODS: In this retrospective study, we reviewed the medical records of consecutive patients who underwent PD catheter removal via PT or OST at the Xinyang Central Hospital from April 2015 to October 2019. Complication-free survival (CFS) and surgical outcomes 365 days after PD catheter removal were evaluated and compared between groups. RESULTS: The PD catheter was removed in 89 patients. The final sample of 80 patients was selected based on eligibility for inclusion and exclusion criteria. Ten patients experienced complications (PT group, n = 2; OST group, n = 8), including death (n = 6), dialysate leak (n = 3), and incisional dehiscence (n = 1). Epidemiological and preoperative clinical characteristics were similar in all patients. Kaplan-Meier plots for CFS revealed significant differences in prognostic outcomes between the groups. Multivariate analysis revealed that CFS was similar in both groups (with OST as a reference; hazard ratio, 0.21; 95% confidence interval [CI], 0.03-1.27; P = 0.09). We observed significant differences in the operative time, blood loss, operative pain score, and anesthetic use between the groups (all P < 0.001). The length and cost of hospitalization were similar in both the groups. CONCLUSIONS: PT is superior to OST in terms of blood loss, anesthetic use, operative pain score, and operating time without sacrificing safety and survival benefits.

Traditional Chinese Medicine Rhodiola Sachalinensis Borissova from Baekdu Mountain (RsBBM) for Rheumatoid Arthritis: Therapeutic Effect and Underlying Molecular Mechanisms.

The lack of effective rheumatoid arthritis (RA) therapies is a persistent challenge worldwide, prompting researchers to urgently evaluate traditional Chinese medicines (TCMs) as potential clinical RA treatments. The present investigation was conducted to evaluate the therapeutic effects and potential molecular mechanisms of the active components isolated from TCM Rhodiola sachalinensis Borissova from Baekdu Mountain (RsBBM) using an experimental adjuvant arthritis model induced by injection of rats with Freund's complete adjuvant. After induction of the adjuvant arthritis rat model, the extract-treated and untreated groups of arthritic rats were evaluated for RsBBM therapeutic effects based on comparisons of ankle circumferences and ELISA-determined blood serum inflammatory factor levels (TNF-α, IL-1ß, and PGE2). In addition, the joint health of rats was evaluated via microscopic examination of hematoxylin-eosin-stained synovial tissues. Furthermore, to explore whether NF-κB and RANK/RANKL/OPG signaling pathways participated in observed therapeutic effects from a molecular mechanistic viewpoint, mRNA and protein levels related to the expression of nuclear factor kappa-B (NF-κB), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-Β ligand (RANKL) were analyzed via quantitative RT-PCR and Western blot analysis, respectively. Treatment of arthritic rats with the extract of RsBBM was shown to reduce ankle swelling, reduce blood serum levels of inflammatory factors, and alleviate arthritis-associated synovial inflammation and joint damage. Moreover, an RsBBM 50% ethanol extract treatment inhibited bone destruction by up-regulating OPG-related mRNA and protein expression and down-regulating RANKL-related mRNA and protein expression, while also reducing inflammation by the down-regulating of the NF-κB pathway activity. The results clearly demonstrated that the extract of RsBBM alleviated adjuvant arthritis-associated joint damage by altering activities of inflammation-associated NF-κB and the RANK/RANKL/OPG signaling pathways. Due to its beneficial effects for alleviating adjuvant arthritis, this RsBBM 50% ethanol extract should be further evaluated as a promising new therapeutic TCM treatment for RA.

A ten-genes-based diagnostic signature for atherosclerosis.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease with a high mortality worldwide. Understanding the atherosclerosis pathogenesis and identification of efficient diagnostic signatures remain major problems of modern medicine. This study aims to screen the potential diagnostic genes for atherosclerosis. METHODS: We downloaded the gene chip data of 135 peripheral blood samples, including 57 samples with atherosclerosis and 78 healthy subjects from GEO database (Accession Number: GSE20129). The weighted gene co-expression network analysis was applied to identify atherosclerosis-related genes. Functional enrichment analysis was conducted by using the clusterProfiler R package. The interaction pairs of proteins encoded by atherosclerosis-related genes were screened using STRING database, and the interaction network was further optimized with the cytoHubba plug-in of Cytoscape software. RESULTS: The logistic regression diagnostic model was constructed to predict normal and atherosclerosis samples. A gene module which included 532 genes related to the occurrence of atherosclerosis were screened. Functional enrichment analysis basing on the 532 genes identified 235 significantly enriched GO terms and 44 significantly enriched KEGG pathways. The top 50 hub genes of the protein-protein interaction network were identified. The final logistic regression diagnostic model was established by the optimal 10 key genes, which could distinguish atherosclerosis samples from normal samples. CONCLUSIONS: A predictive model based on 10 potential atherosclerosis-related genes was obtained, which should shed light on the diagnostic research of atherosclerosis.

A Railway Track Geometry Measuring Trolley System Based on Aided INS.

Accurate measurement of the railway track geometry is a task of fundamental importance to ensure the track quality in both the construction phase and the regular maintenance stage. Conventional track geometry measuring trolleys (TGMTs) in combination with classical geodetic surveying apparatus such as total stations alone cannot meet the requirements of measurement accuracy and surveying efficiency at the same time. Accurate and fast track geometry surveying applications call for an innovative surveying method that can measure all or most of the track geometric parameters in short time without interrupting the railway traffic. We provide a novel solution to this problem by integrating an inertial navigation system (INS) with a geodetic surveying apparatus, and design a modular TGMT system based on aided INS, which can be configured according to different surveying tasks including precise adjustment of slab track, providing tamping measurements, measuring track deformation and irregularities, and determination of the track axis. TGMT based on aided INS can operate in mobile surveying mode to significantly improve the surveying efficiency. Key points in the design of the TGMT's architecture and the data processing concept and workflow are introduced in details, which should benefit subsequent research and provide a reference for the implementation of this kind of TGMT. The surveying performance of proposed TGMT with different configurations is assessed in the track geometry surveying experiments and actual projects.

Optimization of Purification, Identification and Evaluation of the in Vitro Antitumor Activity of Polyphenols from Pinus Koraiensis Pinecones.

In this study, an efficient purification method for the polyphenols of Pinus koraiensis pinecone (PPP) has been developed. AB-8 resin was verified to offer good adsorption and desorption ratio for PPP. Response surface methodology (RSM) indicated that the optimized purification parameters for PPP were 1.70 mg GAE/mL phenolic sample concentration, 22.00 mL sample volume, and 63.00% ethanol concentration. Under these conditions, the experimental purity of PPP was 27.93 ± 0.14% (n = 3), which matched well with the predicted purity of 28.17%. Next, the antiproliferative effects of PPP on seven cancer cell lines, including A375 (human skin melanoma cancer cell line), A549 (human lung cancer cell line), SH-SY5Y (human neuroblastoma cell line), LOVO (human colon cancer stem cell line), MCF-7 (human breast cancer cell line), HeLa (human cervical cancer line), and HT29 (human colon cancer line), were examined by MTT assays. The results indicated that PPP had the highest capacity for inhibiting LOVO cells growth with an EC50 value of 0.317 ± 0.0476 mg/mL. Finally, Ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS) was used to tentatively identify twenty-four peaks in the purified PPP, of which five representative peaks were identified as catechin, methyl quercetin, o-vanillin, luteolin and coronaric acid. Our results demonstrate that Pinus koraiensis pinecone is a readily available source of polyphenols, and the purified PPP could be a promising natural antitumor agent for applications in functional foods.

Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Efficacy of small back optic zone design on myopia control for corneal refractive therapy (CRT): a one-year prospective cohort study.

BACKGROUND: To investigate the control effect on the axial length elongation using corneal refractive therapy (CRT) with different optical zone diameters (BOZDs). We also sought to compare the difference in higher-order aberrations (HOAs), treatment zone (TZ) size and Zernike defocus coefficient with different BOZDs and seek the optimal parameter for predicting axial elongation. METHODS: This prospective cohort study included 7- to 14-year-olds fitted with orthokeratology (ortho-K) lenses of 5-mm (5-mm group) or 6-mm BOZD (6-mm group). Axial length (AL), corneal topography, HOAs and Zernike defocus coefficient were obtained at baseline, and 1, 3, 6, 9 and 12 months follow-up visits. Multivariate regression analyses were used to explore the association between AL change and ocular biometric parameters. Receiver operating characteristic (ROC) curve analysis was used to determine the best diagnostic value for AL change in ocular biometric parameters. RESULTS: In total, 301 participants completed the one-year follow-up. The mean AL change in the 5-mm group (0.13 ± 0.18 mm) was less than that in the 6-mm group (0.27 ± 0.15 mm) at the 12 months visit. The TZ size and decentration were smaller, while the Zernike defocus coefficient and HOAs were higher in the 5-mm group (all P < 0.05). Older age and smaller TZ size were protective factors against AL elongation in multiple regression. In predicting AL elongation, TZ diameter yielded an area under the ROC curve of 0.684 with a cut-off value of 3.82 mm. CONCLUSION: The 5-mm group showed 0.14 mm (51.8%) less axial elongation than the 6-mm group. The 5-mm BOZD produced a smaller TZ size, higher Zernike defocus coefficient and higher HOA after reshaping of the cornea. TZ size was the best predictor of AL elongation. TZ diameter less than 3.82 mm may lead to AL elongation less than 0.2 mm in one year.

Comparison of ultrasonic and CO2laser pretreatment methods on enzyme digestibility of corn stover.

To decrease the cost of bioethanol production, biomass recalcitrance needs to be overcome so that the conversion of biomass to bioethanol becomes more efficient. CO(2) laser irradiation can disrupt the lignocellulosic physical structure and reduce the average size of fiber. Analyses with Fourier transform infrared spectroscopy, specific surface area, and the microstructure of corn stover were used to elucidate the enhancement mechanism of the pretreatment process by CO(2) laser irradiation. The present work demonstrated that the CO(2) laser had potential to enhance the bioconversion efficiency of lignocellulosic waste to renewable bioethanol. The saccharification rate of the CO(2) laser pretreatment was significantly higher than ultrasonic pretreatment, and reached 27.75% which was 1.34-fold of that of ultrasonic pretreatment. The results showed the impact of CO(2) laser pretreatment on corn stover to be more effective than ultrasonic pretreatment.

Evaluation of antioxidant and antiproliferative properties of three Actinidia (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) extracts in vitro.

The total phenolic content, total flavonoid content, vitamin C content, and antioxidant activities of ethanol extracts from different kiwifruit varieties (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) were determined in this study. Multiple scavenging activity assays including the hydroxyl radical, O(2) (-)·radical, DPPH, and the ABTS(+) radical scavenging activity assays were used to identify the antioxidant activities of Actinidia extracts. The cell viability of HepG2 and HT-29 cells was also examined in this study. The results demonstrated that the Actinidia kolomikta extract had a higher antioxidant activity than the other two Actinidia extracts. There is a positive correlation between antioxidant activity and the polyphenols and vitamin C content in all three extracts (R(2) ≥ 0.712, p < 0.05). The Actinidia arguta extract had the highest inhibitory effect on HepG2 and HT-29 cell growth. These results provide new insight into the health functions of fruit and demonstrate that Actinidia extracts can potentially have health benefits.

Evaluation of Corrosion Residual Life Prediction Methods for Metal Pipelines.

The analysis of the basic characteristics of various research methods is highly needed to predict the residual life of the pipeline accurately, help managers understand the operational risks, and provide a reference for developing pipeline transportation and maintenance inspection plans and anti-corrosion measures. Based on a comprehensive investigation of the existing research on the residual life of the pipeline, this paper finds that the current mainstream life prediction method, based on historical statistical data, has the shortcomings of inconsistent modeling methods, inconsistent basic data, and a lack of comparative evaluation among methods. Moreover, considering the in-depth study of BP neural network modeling, grey theory modeling, time series modeling, and exponential smoothing modeling, optimal prediction models using different methods based on the same historical data are established. These optimal modeling methods are discussed, and the feasible modeling path for the accurate prediction of the pipeline's residual life is given by comparing the prediction accuracy of each model. In addition, the findings serve as a guide for developing an anti-corrosion strategy by highlighting the contribution of the prediction results of the residual life to pipeline decision-making. By comparison, it is found that the accuracy of the four prediction models is as follows: the grey theory prediction model, the exponential smoothing prediction model, the BP neural network prediction model, and the time series prediction model, from high to low, respectively.

An investigation into the causes of abnormal waste of Ortho-K lenses.

Purpose: To investigate the reasons for wasting orthokeratology (OK) lenses due to breakage or loss, provide more comprehensive guidelines for the clinical care of lenses and minimize time and costs for patients due to excessive broken and lost lenses. Methods: A survey was administered to clinic outpatients who had broken or lost their OK lenses before the regularly scheduled replacement cycle (1-1.5 years). The association between the frequency of OK lens breakage and daily care was assessed using Fisher's exact test and multivariable ordered logistic regression analysis. Results: A total of 306 valid questionnaires were collected. Among the subjects, 141 were male, and 165 were female, with a mean age of 10.57 ± 2.00 years (range: 6-18 years). In the investigation of the causes of OK lens waste, 81.4% of the patients reported lens breakage, 13.1% lost their lenses, and 5.6% of patients experienced both fragmentation and lens loss. More than half of the patients (52.90%) used incorrect lens cleaning techniques. In further analysis of the relationship between the frequency of OK lens fragmentation within a year and daily care habits, a significant difference was observed between the caregiver (P = 0.03) and whether the lenses were cleaned promptly after removal (P < 0.001). Mothers as daily caregivers of OK lenses had a lower frequency of fragmentation in a year compared to nanny or grandparents (P = 0.014, OR = 0.33, 95% CI = 0.13, 0.80). The failure to clean the lenses according to eye care practitioners' guidance was a risk factor for the frequent breakage of OK lenses (P < 0.001. OR = 5.29, 95% CI = 3.15, 8.89). Conclusions: The causes of OK lens waste were mainly attributed to caregivers, care practices and some unexpected situations that can be avoided through optometrists' reminders. Regardless of the reasons for noncompliant behavior leading to breakage or loss of OK lenses, all of the complications can probably be addressed by better and more frequent reinforcement of care procedures by practitioners. Better clinical guidance measures and more frequent reminders could prevent a large proportion of abnormal waste of OK lenses.

Tailored Supersaturable Immediate Release Behaviors of Hypotensive Supersaturating Drug-Delivery Systems Combined with Hot-Melt Extrusion Technique and Self-Micellizing Polymer.

The short-term immediate release of supersaturated drug-delivery systems (SDDSs) presents an interesting process that can be tailored to multi-stage release events including initial release after dosing and dissolution, evolved release over longer dissolution periods for biological absorption, and terminal release following the end of immediate release. However, although comprehensive analysis of these critical release behaviors is often ignored yet essential for understanding the supersaturable immediate-release events for supersaturable solid formations when employing new techniques or polymers matched to a particular API. Hot-melt extrusion (HME) has become a popular continuous thermodynamic disordering technique for amorphization. The self-micellizing polymer Soluplus® is reported to be a potential amorphous and amphiphilic graft copolymer frequently used in many nano/micro supersaturable formulations. Our current work aims to develop hypotensive supersaturating solid dispersion systems (faSDDSHME) containing the BCS II drug, felodipine, when coordinately employing the HME technique and self-micellizing Soluplus®, and to characterize their amorphization as well as immediate release. Other discontinuous techniques were used to prepare control groups (faSDDSSE and faSDDSQC). Tailored initial/evolved/terminal three-stage supersaturable immediate-release behaviors were identified and possible mechanisms controlling the release were explored. HME produced the highest initial release in related faSDDSHME. During the evolved-release period, highly extended "spring-parachute" process was found in HME-induced amorphization owing to its superior supersaturation duration. Due to the enhanced crystallization inhibition effect, faSDDSHME displayed the strongest terminal release as measured by solubility. For release mechanisms associated with HME, molecular interaction is not the likely dominant mechanism responsible for the improved properties induced by faSDDSHME. For release mechanisms involved with the polymer Soluplus® itself, they were found to inhibit drug recrystallization, spontaneously solubilize the drug and lead to improved molecular interactions in all SDDS systems, which were the factors responsible for the improved release. These mechanisms play an important role for the generation of an extended multi-stage immediate release produced via HME or self-micellizing polymer. This study provides a deeper understanding on amorphization and superior multi-stage supersaturable immediate-release behaviors for a particular hypotensive supersaturated delivery system combined with an HME-based continuous manufacturing technique and self-micellizing polymer strategy.

Association of necrotizing enterocolitis with antimicrobial exposure in preterm infants <32 weeks gestational age:A multicenter prospective case-control study.

Objective: To assess the risk of necrotizing enterocolitis (NEC) and explore the relationship between antibiotic overexposure and disease occurrence in a large prospective birth cohort. Methods: Based on a prospective birth cohort, the study collected hospitalization data of very preterm infants (VPIs) having gestational age of less than 32 weeks from January 1, 2018, to June 30, 2021 via the China Northern Neonatal Network. Infants diagnosed with NEC ≥ stage II were included in the case group, and each case was matched for GA and birth weight for the control group. Furthermore, the risk factors for NEC were determined by statistical analyses. Results: A total of 6425 VPIs were included in this study, and 167 (2.6%) of these subjects were diagnosed with NEC ≥ stage II. The study also included 984 extremely preterm infants (gestational age <28 weeks), including 50 (5.1%) infants diagnosed with NEC ≥ stage II. In the matched case-control study, subjects had a total of antibiotic days-of-therapy for 9015 days, of which broad-spectrum antibiotics (BSAs) accounted for 77%. The antibiotic spectrum index per antibiotic day in the case group was significantly higher and was an independent risk factor for the occurrence of NEC (p = 0.001, OR = 1.13). Conclusion: The cohort of VPIs was overexposed to antiboitics. Unreasonable combination of antibiotics and overexposure to BSAs may increase the risk of NEC in preterm infants.

Quantification of Losartan Potassium Polymorphs Using Powder X-Ray Diffraction.

BACKGROUND: Losartan potassium, a common antihypertensive drug on the market, has multiple polymorphs, of which form I is used as a pharmaceutical crystal form. Form I can be partially converted to form III under some circumstances. The quantification of losartan potassium polymorphs is important to control the quality of pharmaceuticals. OBJECTIVE: To establish a method to determine the contents of losartan potassium polymorphs. METHODS: Pure form I and form III of losartan potassium were obtained by recrystallization, and characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy, Raman spectroscopy, and thermal analysis. A powder X-ray diffraction method was developed to characterize form I and form III of losartan potassium. Peak area and weight percentage were used to establish calibration curve. RESULTS: The calibration curve was linear over the range of 1-50% (w/w), using the characteristic peak area ratio of form I at 11.13° 2θ and form III at 5.64° 2θ as the quantitative parameter. The precisions were excellent between 0.6-4.9%, and the limit of quantification was 2.02% (w/w). CONCLUSIONS: This PXRD method can be used to analyze mixtures of losartan potassium polymorphs (forms I and III) quantitatively and control the quality of bulk drug. HIGHLIGHTS: This is a new method of quantifying the amount of form III in polymorphic forms of losartan potassium using data obtained by PXRD. It is consistent, sensitive, and accurate.

Clinical significance of combined detection of anti-Mullerian hormone and follicular output rate in women of late reproductive age.

OBJECTIVE: This study was designed to explore the clinical significance of anti-Mullerian hormone (AMH) combined with follicular output rate (FORT) in women of late reproductive age. METHODS: A total of 258 women (age range: 35-45 years old) who underwent pre-pregnancy examination in our hospital were collected as the research group (RG), among whom 184 were treated with in vitro fertilization-embryo transfer (IVF-ET). Concurrently, 126 women aged 24-30 years who came to our hospital for pre-pregnancy examination were enrolled as the control group (CG). AMH and FORT were detected and compared between the two groups to analyze the clinical significance of the two in women of late reproductive age. RESULTS: Compared with the CG, AMH was decreased statistically in the RG (P<0.05). AMH was statistically higher in the regular menstrual group than in the menstrual disorder group (P<0.05), and FORT was statistically higher in the pregnancy group in comparison with the non-pregnancy group (P<0.05). AMH decreased with age (P<0.05), while FORT did not correlate with any notable difference among the three subgroups (P>0.05). High, medium and low AMH groups showed no significant difference in the number of retrieved oocytes and transplantable embryos, as well as FORT (P<0.05). A lower AMH level, was correlated with fewer number of retrieved oocytes and transplantable embryos, and higher the FORT level. Significant differences were present among the high, middle and low FORT groups regarding the number of retrieved oocytes and transplantable embryos, the clinical pregnancy rate and AMH level (P<0.05). The lower the level of FORT was, the less the number of retrieved oocytes and transplantable embryos was, the lower clinical pregnancy rate was, and the higher the AMH level was. CONCLUSIONS: AMH decreases gradually in women with an increase of age, and FORT can effectively predict pregnancy outcome. AMH detection combined FORT is of great significance in predicting the ovarian reserve function in women of late reproductive age.

Effect of Immune Cell Infiltration on Occurrence of Pulmonary Hypertension in Pulmonary Fibrosis Patients Based on Gene Expression Profiles.

Pulmonary hypertension (PH) is a frequent complication in patients with pulmonary fibrosis (PF), whereas the mechanism was not well-understood. This study aimed to explore the influence of immune cell infiltration on PH status based on the genomic expression profiles. Microarray data of GSE24988 were downloaded from the GEO database, including 116 lung tissue samples derived from PF patients with various PH status. Proportion of infiltrated immune cells was evaluated using CIBERSORT, a gene expression-based de-convolution algorithm. A random forest classifier was constructed and out of bag (OOB) cross-validation was carried out for PH prediction. The proportions of immune infiltration cells varied differently in PH samples except T regulatory cells (p-value = 0). Compared with non-PH samples, increased number of naive B cells and plasma cells were identified in PH samples, whereas activated dendritic cells and M2 macrophages were relatively lower (p < 0.05). In the random forest model, these four types of immune cells obtained a higher variable importance score than other cells, including mean decreased accuracy and mean decreased gini evaluation. We ran the OOB cross-validation in each sample of datasets (training set and testing set) and obtained 79 and 69% accuracy, respectively. Abnormal proportions of four types of immune cells were identified in PH samples compared with non-PH samples, suggesting their involvement in PH development. In summary, the immune cell infiltration in PF patients is associated with the PH status of patients, which deserves further investigation in the future.

Quantitative analyses of the correlation between dynamic contrast-enhanced MRI and intravoxel incoherent motion DWI in thyroid nodules.

This study investigated the correlation between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) to differentiate thyroid nodules. Quantitative DCE-MRI parameters, including the transfer constant (K trans), rate constant (K ep) and volume fraction of the extracellular extravascular space (V e), were calculated. The diffusion coefficient (D), pseudo-diffusion coefficient (D* ), and perfusion fraction (f) were derived from biexponential fitting of IVIM DWI. A total of 38 nodules, including 22 malignant and 16 benign nodules, were analyzed. The K trans, K ep and V e for benign lesions were 1.32 ± 0.76 min-1, 6.44 ± 1.44 min-1, and 2.02 ± 0.89 min-1, respectively, and for malignant lesions, the values were 0.84 ± 0.30 min-1, 5.43 ± 1.38 min-1, and 1.71 ± 0.83 min-1, respectively (P = 0.027, 0.036, and 0.257, respectively). The D, f, and D* for benign lesions were 1.51 ± 0.52 mm2/s, 26.63 ± 8.75%, and 15.84 ± 8.71 mm2/s, respectively, and for malignant lesions, the values were 0.68 ± 0.17 mm2/s, 31.63 ± 10.72%, and 11.10 ± 4.21 mm2/s, respectively (P [< 0.0001, 0.135, 0.058], respectively). No significant correlations were found between IVIM DWI and DCE-MRI quantitative parameters (all P > 0.05). In benign nodules, a moderate inverse correlation was found between D and K ep (r = -0.54, P = 0.031). IVIM DWI shows no significant correlation with perfusion parameters derived from DCE-MRI; however, IVIM DWI combined with quantitative DCE-MRI may be a useful imaging tool for the assessment of thyroid nodules in clinical studies.

Intravoxel incoherent motion and ADC measurements for differentiating benign from malignant thyroid nodules: utilizing the most repeatable region of interest delineation at 3.0 T.

BACKGROUND: There is a growing need for a reproducible and effective imaging method for the quantitative differentiation of benign from malignant thyroid nodules. This study aimed to investigate the performances of intravoxel incoherent motion (IVIM) parameters and the apparent diffusion coefficient (ADC) in differentiating malignant from benign thyroid nodules derived from the most repeatable region of interest (ROI) delineation. METHODS: Forty-three patients with 46 pathologically confirmed thyroid nodules underwent diffusion-weighted imaging (DWI) with 8 b values. Two observers measured the intravoxel incoherent motion (IVIM) parameters (D, f and D*) and the apparent diffusion coefficient (ADC), ADC600 and ADC990 values using whole-lesion (W-L) ROI and IVIM parameters using single-section (S-S) ROI delineation. The intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to evaluate the intra- and interobserver variability. The diagnostic performance of these parameters was evaluated by generating receiver operating characteristic (ROC) curves. RESULTS: The ICC values of all IVIM with W-L ROI delineation were higher than those with S-S ROI delineation, and excellent intra- and interobserver reproducibility was obtained. According to the Bland-Altman plots, the 95% limits of agreement of the IVIM parameters determined by the W-L ROIs revealed smaller absolute intra- and interobserver variability than those determined by S-S ROIs. The D and ADC600 values obtained from the W-L ROIs were the most powerful parameters in differentiating benign from the malignant nodules [area under the ROC curve = 0.962 and 0.970, P = 0.771]. CONCLUSIONS: The W-L ROI of the thyroid was considered an effective method for obtaining IVIM measurements with excellent reproducibility for differentiating benign from malignant nodules.