Crafting Docetaxel-Loaded Albumin Nanoparticles Through a Novel Thermal-Driven Self-Assembly/Microfluidic Combination Technology: Formulation, Process Optimization, Stability, and Bioavailability.

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges. Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated. Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX. Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.

XB130 inhibits healing of diabetic skin ulcers through the PI3K/Akt signalling pathway.

BACKGROUND: Diabetic skin ulcers, a significant global healthcare burden, are mainly caused by the inhibition of cell proliferation and impaired angiogenesis. XB130 is an adaptor protein that regulates cell proliferation and migration. However, the role of XB130 in the development of diabetic skin ulcers remains unclear. AIM: To investigate whether XB130 can regulate the inhibition of proliferation and vascular damage induced by high glucose. Additionally, we aim to determine whether XB130 is involved in the healing process of diabetic skin ulcers, along with its molecular mechanisms. METHODS: We conducted RNA-sequencing analysis to identify the key genes involved in diabetic skin ulcers. We investigated the effects of XB130 on wound healing using histological analyses. In addition, we used reverse transcription-quantitative polymerase chain reaction, Western blot, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, immunofluorescence, wound healing, and tubule formation experiments to investigate their effects on cellular processes in human umbilical vein endothelial cells (HUVECs) stimulated with high glucose. Finally, we performed functional analysis to elucidate the molecular mechanisms underlying diabetic skin ulcers. RESULTS: RNA-sequencing analysis showed that the expression of XB130 was up-regulated in the tissues of diabetic skin ulcers. Knockdown of XB130 promoted the healing of skin wounds in mice, leading to an accelerated wound healing process and shortened wound healing time. At the cellular level, knockdown of XB130 alleviated high glucose-induced inhibition of cell proliferation and angiogenic impairment in HUVECs. Inhibition of the PI3K/Akt pathway removed the proliferative effects and endothelial protection mediated by XB130. CONCLUSION: The findings of this study indicated that the expression of XB130 is up-regulated in high glucose-stimulated diabetic skin ulcers and HUVECs. Knockdown of XB130 promotes cell proliferation and angiogenesis via the PI3K/Akt signalling pathway, which accelerates the healing of diabetic skin ulcers.

[Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks: a Meta analysis]. / 脐带挤压与延迟断脐对胎龄<34周早产儿早期预后影响的Meta分析.

OBJECTIVES: To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis. RESULTS: A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05). CONCLUSIONS: Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

Emerging roles of growth differentiation factor-15 in brain disorders (Review).

Brain disorders, such as Alzheimer's and Parkinson's disease and cerebral stroke, are an important contributor to mortality and disability worldwide, where their pathogenesis is currently a topic of intense research. The mechanisms underlying the development of brain disorders are complex and vary widely, including aberrant protein aggregation, ischemic cell necrosis and neuronal dysfunction. Previous studies have found that the expression and function of growth differentiation factor-15 (GDF15) is closely associated with the incidence of brain disorders. GDF15 is a member of the TGFß superfamily, which is a dimer-structured stress-response protein. The expression of GDF15 is regulated by a number of proteins upstream, including p53, early growth response-1, non-coding RNAs and hormones. In particular, GDF15 has been reported to serve an important role in regulating angiogenesis, apoptosis, lipid metabolism and inflammation. For example, GDF15 can promote angiogenesis by promoting the proliferation of human umbilical vein endothelial cells, apoptosis of prostate cancer cells and fat metabolism in fasted mice, and GDF15 can decrease the inflammatory response of lipopolysaccharide-treated mice. The present article reviews the structure and biosynthesis of GDF15, in addition to the possible roles of GDF15 in Alzheimer's disease, cerebral stroke and Parkinson's disease. The purpose of the present review is to summarize the mechanism underlying the role of GDF15 in various brain disorders, which hopes to provide evidence and guide the prevention and treatment of these debilitating conditions.

Corrigendum: Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/ß-Catenin Signaling Pathway.

[This corrects the article DOI: 10.3389/fphar.2020.523962.].

Alkaloid Extract of Moringa oleifera Lam. Exerts Antitumor Activity in Human Non-Small-Cell Lung Cancer via Modulation of the JAK2/STAT3 Signaling Pathway.

Lung cancer is one of the most common malignant tumors diagnosed worldwide. Moringa oleifera Lam. is a valuable medicinal plant native to India and Pakistan. However, the antilung cancer activity of M. oleifera alkaloid extract (MOAE) is unknown. The present study aimed to evaluate the regulatory effect of MOAE on A549 cells by examination of the proliferation, apoptosis, cell cycle, and migration of cells and to elucidate the possible mechanism of action of MOAE. We tested five types of cancer cells and four types of lung cancer cells and found MOAE exerted the strongest growth inhibitory effect against A549 cells but had low toxicity to GES-1 cells (human gastric mucosal epithelial cells). Simultaneously, MOAE induced apoptosis and increased the expression of the apoptosis-related proteins caspase-3 and caspase-9 in A549 cells. Furthermore, MOAE induced cell cycle arrest in the S phase through a decrease in the expression of the proteins cyclin D1 and cyclin E and an increase in the expression of the protein p21. MOAE also inhibited the migratory ability of A549 cells and decreased the expression of the migration-related proteins, matrix metalloproteinase (MMP) 2 and MMP9. In addition, the phosphorylation level of JAK2 and STAT3 proteins was decreased in MOAE-treated A549 cells. Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.

Effects of viral infection and microbial diversity on patients with sepsis: A retrospective study based on metagenomic next-generation sequencing.

BACKGROUND: The study aims to investigate the performance of a metagenomic next-generation sequencing (NGS)-based diagnostic technique for the identification of potential bacterial and viral infections and effects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients. METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February 1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for blood cultures and metagenomic NGS when the patients' body temperature was higher than 38 °C. Patients' demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded. The correlations between pathogen types and sepsis severity and survival rate were evaluated. RESULTS: NGS produced higher positive results (105 of 118; 88.98%) than blood cultures (18 of 118; 15.25%) over the whole study period. Concomitant viral infection correlated closely with sepsis severity and had the negative effect on the survival of patients with sepsis. However, correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis. CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and the survival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviral drugs combined with antibiotics may be beneficial to ICU sepsis patients.

Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/ß-Catenin Signaling Pathway.

Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), ß-catenin, phosphorylated glycogen synthase 3ß, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (ß-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and ß-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/ß-catenin signaling pathway.

Automating Spine Curvature Measurement in Volumetric Ultrasound via Adaptive Phase Features.

Ultrasound volume projection imaging (VPI) has been recently suggested. This novel imaging method allows a non-radiation assessment of spine deformity with free-hand 3-D ultrasound imaging. This paper presents a fully automatic method to evaluate the spine curve in VPI images corresponding to different projection depth of the volumetric ultrasound, thus making it possible to analyze 3-D spine deformity. The new automatic method is based on prior knowledge about the geometric arrangement of the spinous processes. The frequency bandwidth of log-Gabor filters is adaptively adjusted to calculate the oriented phase congruency, facilitating the segmentation of the spinous column profile. And the spine curvature angle is finally calculated according to the inflection points of the curve over the segmented spinous column profile. The performance of the automatic method is evaluated on spine VPI images among patients with different scoliotic angles. The curvature angles obtained using the proposed method have a high linear correlation with those by the manual method (r = 0.90, p < 0.001) and X-ray Cobb's method (r = 0.87, p < 0.001). The feasibility of 3-D spine deformity assessment is also demonstrated using VPI images corresponding to various projection depth. The results suggest that this method can substantially improve the recognition of the spinous column profile, especially facilitating the applications of 3-D spine deformity assessment.

BCLAF1 promotes cell proliferation, invasion and drug-resistance though targeting lncRNA NEAT1 in hepatocellular carcinoma.

AIMS: In the present research, we aimed to investigate the effect of Bcl-2-associated transcription factor 1 (BCLAF1) on hepatocellular carcinoma and further explore the special molecular mechanism. MAIN METHODS: The expression of BCLAF1 was analyzed in tumor tissues and different hepatocellular cancer cell lines by real-time RT-PCR and Western blot. Cell proliferation and invasion was explored using MTT and Transwell assay respectively. In addition, luciferase reporter assay was performed to determine the binding activity of BCLAF1 and Nuclear enrichment-rich transcription factor 1 (NEAT1) promoter. Finally, the IC50 for 5-Fluorouracil (5-Fu) was measured by MTT assay, and Western blot was used to determine the expression of P-glycoprotein (P-gp) and multidrug resistance protein1 (MRP1). KEY FINDING: The result revealed that BCLAF1 was highly expressed in hepatocellular carcinoma tissues and cells. In addition, BCLAF1-siRNA inhibited the proliferation and invasion of hepatocellular carcinoma cells, and overexpression of BCLAF1 promoted proliferation and invasion. Furthermore, luciferase reporter assay demonstrated that BCLAF1 directly interact with lncNEAT1 promoter and improved NEAT1 expression, and BCLAF1 promoted proliferation and invasion through targeting lncRNA NEAT1. What's more, BCLAF1 promoted 5-Fu resistance and the expression of P-gp and MRP1 in hepatocellular carcinoma cells by targeting NEAT1. SIGNIFICANCE: The results of the present study suggested that BCLAF1 might be a new gene related to proliferation and drug-resistance of hepatocellular carcinoma. In the future, the search for a deep and reasonable mechanism for the role of BCLAF1 will help us to understand its function more comprehensively, and finally find a new method for the treatment of human cancer.

Quantitative generation of microfluidic flow by using optically driven microspheres.

Microfluidic flow generation plays a fundamental role in microfluidic systems and shows potential for applications in basic biology and clinical medicine. In this study, an enabling technology is proposed to quantitatively generate microfluid flow through the automatic movement of a microsphere in liquid by using optical tweezers. A closed-loop control strategy with visual servoing feedback is introduced to achieve high precision and robustness. The theoretical solution of the generated microfluid is obtained on the basis of Stokes equations. An experimental method is proposed, and experiments are performed to verify the effectiveness of our approach. This method does not impose any dedicated fabrication of microtool, and the microfluidic flow can be dexterously adjusted by controlling the direction, speed, and distance of the microsphere from a target location. To the best of our knowledge, this is the first demonstration of optically actuating liquids through the translational movement of microspheres with closed-loop control. The proposed method will be useful in various biomedical applications needing quantitative, precise and controllable localized microfluid.

An automatic measurement method of spinal curvature on ultrasound coronal images in adolescent idiopathic scoliosis.

This study proposed a new automatic measurement method of spinal curvature on ultrasound coronal images in adolescent idiopathic scoliosis (AIS). After preprocessing of Gaussian enhancement, the symmetric information of the image was extracted using the phase congruency. Then bony features were segmented from the soft tissues and background using the greyscale polarity. The morphological methods of image erosion and top-bottom-hat transformation, and geometric moment were utilized to identify the spinous column profile from the transverse processes. Finally, the spine deformity curve was obtained using robust regression. In-vivo experiments based on AIS patients were performed to evaluate the performance of the developed method. The comparison results revealed there was a significant correlation (y=0.81x, r=0.86) and good agreement between the new automatic method and the manual measurement method. It can be expected that this novel method may help to provide effective and objective deformity assessment method during the ultrasound scanning for AIS patients.

Role and mechanism of matrine alone and combined with acitretin for HaCaT cells and psoriasis-like murine models.

BACKGROUND: Acitretin and matrine have been used in the treatment of psoriasis in China. This study was designed to investigate the role and related mechanisms of matrine alone and in combination with acitretin in the treatment of psoriasis in vitro and in vivo. METHODS: HaCaT cells were treated with matrine at different concentrations of 0 (blank control), 0.2, 0.4, 0.8, and 1.6 mg/mL for 24, 48, 72 h, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay was used to assess the growth and proliferation of HaCaT cells. Cell cycle and apoptosis were detected by flow cytometry. Expression of protein was detected by Western blotting. Autophagy was observed by transmission electron microscopy. Then HaCaT cells were assigned to normal saline (NS) control group, matrine (0.4 mg/mL) group, acitretin (10 µmol/L) group, and matrine plus acitretin group, and the above methods were repeated. In animal experiments, the cumulative score (erythema, scaling, thickening) as a measure of the severity of inflammation was used to measure the skin performance of mice after treated with matrine 50 mg/kg, acitretin 4.5 mg/kg or combination of the two drugs on the psoriasis-like mouse models, respectively. Pathological findings of the lesions were observed, and the protein expressions in the lesions were detected by immunohistochemistry. RESULTS: Cell proliferation inhibition was seen in HaCaT cells with treatment of matrine in a dose- and time-dependent manner (P < 0.01, respectively). Cell cycle G0/G1 phase arrest was observed in a dose-dependent way (P < 0.01). The expression of p21 (P < 0.05), LC3II/I (P < 0.01), and Beclin 1 (P < 0.01) increased and the expression of cyclin D1 (P < 0.05) decreased with increasing doses of matrine. Compared with the blank control, more autophagosomes were seen in HaCaT cells treated with matrine at 0.4 mg/mL by transmission electron microscopy (2.667 ±â€Š1.202 vs. 21.33 ±â€Š1.453, t = 9.899, P < 0.01). Cell proliferation inhibition and degree of the G0/G1 phase arrest was significantly higher in matrine plus acitretin group than those in matrine, acitretin, or the NS control group (P < 0.01, respectively). Compared with matrine or acitretin group, the expression of p21 (P < 0.05, P < 0.05) and LC3II/I (P < 0.01, P < 0.05) in matrine plus acitretin group increased significantly and the expression of cyclin D1 (P < 0.01, P < 0.05) and p62 (P < 0.05, P < 0.05) was reduced significantly. Compared with matrine or acitretin, matrine plus acitretin significantly down-regulated the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway (P < 0.05) and its downstream p-p70S6K (P < 0.05). In addition, the cumulative score of mice in the matrine plus acitretin group was significantly better than that in the matrine or acitretin group (1.480 ±â€Š0.230 vs. 2.370 ±â€Š0.241, P < 0.01; 1.480 ±â€Š0.230 vs. 2.888 ±â€Š0.341, P < 0.01). The expression of LC3 protein in the matrine plus acitretin group was also higher than that in the matrine, acitretin, or the NS control group (P < 0.05, respectively). CONCLUSIONS: Matrine has therapeutic potentials for psoriasis. Matrine and acitretin show synergistic effect via cell cycle arrest and autophagy induction by PI3K/Akt/mTOR pathway.

A Novel Method to Measure the Sagittal Curvature in Spinal Deformities: The Reliability and Feasibility of 3-D Ultrasound Imaging.

The objective of this study was to test the reliability of sagittal spinal curvature measurements using 3-D ultrasound in patients with adolescent idiopathic scoliosis (AIS). Ultrasound spinous process angle (USSPA) and ultrasound laminae angle (USLA) were measured on sagittal ultrasound images, while the Cobb angle (XCA) was measured on sagittal X-ray images. Intra-class correlation coefficients (ICC) for the intra- and inter-observer variability, linear regression analysis and Bland-Altman method, including mean absolute difference (MAD), were investigated to evaluate the reliability and validity of the two ultrasound angles compared with XCA. Excellent measurement reliabilities were demonstrated for both ultrasound angles (ICC ≥ 0.91). Moderate to good and significant linear correlations and good agreement were demonstrated between the ultrasound methods and XCA (Thoracic [R2 ≥ 0.574] / Lumbar [R2 ≥ 0.635]). No significant differences were found for the MADs between both corrected ultrasound angles and XCA. Sagittal ultrasound angles were demonstrated to be reliable for assessing sagittal curvature using spinous processes and laminae and to have good and significant correlations with XCAs. Since it is non-ionizing and relatively low cost, this method opens the possibility of providing frequent curve monitoring and evaluation, and screening for AIS patients, particularly based on sagittal profiles.

Clinical Application of Bioprosthesis in China: Current Status and Future.

China is one of the countries which have a high incidence of heart valvular disease, but the use of biological valve is limited in China before because the majority of patients are young patients suffering from rheumatic heart disease. The biological valve has a good application prospect in China. On the one hand, the new generation of biological valves have been significantly improved in the aspects of anti-calcification treatment, anti-metabolism, material quality control, valve frame mechanics design, and leaflet sewing technology, and the application effect is improved; on the other hand, surgeons should adapt to the new concept changes, and correctly understand and rationally apply biological valves, master valve repair, atrial fibrillation ablation and other techniques, combined with interventional, minimally invasive techniques, etc., according to the specific conditions of the disease and choose the surgery type to ensure the patients' long-term life quality.

Analysis and correction of stray thermal radiation in infrared optical systems including an experimental case study.

In infrared systems, the stray radiation from optical elements and mechanical structures is an important factor affecting quantitative measurements because the irradiance on detectors due to stray radiation depends on the operating temperature of the optical system. Without correcting for this effect, the accuracy of quantitative measurements made with such systems is degraded. To better understand this phenomenon, we derive herein a mathematical model that describes stray radiation as a function of temperature and use the model to quantitatively analyze the stray radiation of an infrared system at different operating temperatures. To test the theory, we use it to calculate the stray radiation from an experimental infrared system comprising a Cassegrain reflector in the first stage and a transmission mirror in the second stage. The maximum relative error between theory and experiment was 8.72%. At the same time, a corrective measure of stray radiation is provided to account for the effect of stray radiation on quantitative measurements. The relative error of quantitative measurements decreases from 2.16% to 0.31%. The measurement accuracy of the infrared system has been improved effectively.

A fast 3-D ultrasound projection imaging method for scoliosis assessment.

Applying ultrasound for scoliosis assessment has been an attractive topic over the past decade. This study proposed a new fast 3-D ultrasound projection imaging method to evaluate the spine deformity. A narrow-band rendering method was used to generate the coronal images based on B-mode images and their corresponding positional data. The non-planar reslicing method, which followed the natural spine curve, was used to project the complete spine data into the coronal image. The repeatability of the new method was tested. A comparison experiment on the reconstructed images and the processing time between the conventional 3-D rendering method and the developed projection imaging method was also performed among 70 patients with scoliosis. The intra- and inter-operator tests results demonstrated very good repeatability (ICC ≥ 0.90). The mean processing times for the developed projection method and conventional rendering method were 15.07 ± 0.03 s and 130.31 ± 35.07 s, respectively. The angle measurement results showed a high correlation (y = 0.984x, r = 0.954) between the images obtained using the two methods. The above results indicated that the developed projection imaging method could greatly decrease the processing time while preserving the comparative image quality. It can be expected that this novel method may help to provide fast 3-D ultrasound diagnosis of scoliosis in clinics.

Long noncoding RNA expression profile from cryptococcal meningitis patients identifies DPY19L1p1 as a new disease marker.

AIMS: LncRNAs play a vital role in the pathological and physiological process. This study aimed to explore the involvement of lncRNAs in cryptococcal meningitis. METHODS: Microarray was performed in cryptococcal meningitis patients, and then, GO and KEGG pathways were analyzed. Coexpression relationship between lncRNA and mRNA was explored. The expressions of the lncRNAs and mRNAs, and their changes after treatment were detected by PCR. RESULTS: A total of 325 mRNAs (201 upregulated and 124 downregulated) and 497 lncRNAs (263 upregulated and 234 downregulated) were identified. The top three enriched GO terms for the mRNAs were arachidonic acid binding, activin receptor binding, and replication fork protection complex. The top three pathways in KEGG were asthma, one carbon pool by folate, and allograft rejection. A total of 305 coexpression relationships were found between 108 lncRNAs and 87 mRNAs. LncRNA-DPY19L1p1 was significantly increased in patients and decreased after treatment. ROC analysis revealed DPY19L1p1 was a potential diagnostic marker (AUCROC  = 0.9389). Furthermore, the target genes of DPY19L1p1 in cis or trans regulation were mainly involved in immune-related pathways like the interleukin signaling pathway. CONCLUSIONS: This study analyzed the differential lncRNA profile in cryptococcal meningitis patients and revealed DPY19L1p1 could be used for treatment evaluation and disease diagnosis.

Case report and review of the literature of primary gastrointestinal amyloidosis diagnosed with enteroscopy and endoscopic ultrasonography.

Here, we report a rare case of primary gastrointestinal amyloidosis in a stable condition after being followed up for three years. The patient was admitted to the hospital in 2014. Tests showed decreased levels of hemoglobin and ferritin. Transoral and transanal enteroscopy showed multiple nodular protuberances in the esophagus, ileum, colon and rectum. Endoscopic ultrasonography indicated the nodular protuberances stemmed from the submucosa and partially invaded the intrinsic myometrium. Pathological examinations found multiple small nodules in the submucosa and dyed structures, which were positive for special Congo red dyeing. After treatment with oral iron supplements, the levels of hemoglobin and ferritin became normal. It is concluded that the patient represents a case of primary gastrointestinal amyloidosis with multiple nodular protuberances in the digestive tract with controllable moderate abdominal discomfort and anemia and a benign course. Enteroscopy and endoscopic ultrasonography play an important role in the diagnosis of primary gastrointestinal amyloidosis.