Research progress of traditional Chinese medicine monomer in treating diabetic peripheral neuropathy: A review.

Diabetes peripheral neuropathy is one of the most common complications of diabetes. Early symptoms are insidious, while late symptoms mainly include numbness, pain, swelling, and loss of sensation in the limbs, which can lead to disability, foot ulcers, amputation, and so on. At present, the pathogenesis is also complex and diverse, and it is not yet clear. Western medicine treatment mainly focuses on controlling blood sugar and nourishing nerves, but the effect is not ideal. In recent years, it has been found that many drug monomers have shown good therapeutic and prognostic effects in the prevention and treatment of diabetes peripheral neuropathy, and related research has become a hot topic. To understand the specific mechanism of action of traditional Chinese medicine monomers in treatment, this article provides a review of their mechanism research and key roles. It mainly includes flavonoids, phenols, terpenes, saponins, alkaloids, polysaccharides, etc. By nuclear factor-κB (NF-κB), the signaling pathways of adenosine monophosphate-activated protein kinase (AMPK), Nrf2/ARE, SIRT1/p53, etc, can play a role in lowering blood sugar, antioxidant, anti-inflammatory, inhibiting cell apoptosis, and autophagy, promoting sciatic nerve regeneration, and have great potential in the prevention and treatment of this disease. A systematic summary of its related mechanisms of action was conducted, providing ideas for in-depth research and exploration of richer traditional Chinese medicine components, and also providing a relatively complete theoretical reference for clinical research on diabetes peripheral neuropathy treatment.

Preliminary Evaluation of 18F-Labeled Benzylguanidine Analogs as NET Tracers for Myocardial Infarction Diagnosis.

PURPOSE: Heart failure (HF) remains a major cause of late morbidity and mortality after myocardial infarction (MI). To date, no clinically established 18F-labeled sympathetic nerve PET tracers for monitoring myocardial infarction are available. Therefore, in this study, we synthesized a series of 18F-labeled benzyl guanidine analogs and evaluated their efficacy as cardiac neuronal norepinephrine transporter (NET) tracers for myocardial imaging. We also investigated the preliminary diagnostic capabilities of these tracers in myocardial infarction animal models, as well as the structure-activity relationship of these tracers. PROCEDURES: Three benzyl guanidine-NET tracers, including [18F]1, [18F]2, and [18F]3, were synthesized and evaluated in vivo as PET tracers in a myocardial infarction mouse model. [18F]LMI1195 was used as a positive control for the tracers. H&E staining of the isolated myocardial infarction heart tissue sections was performed to verify the efficacy of the selected PET tracer. RESULTS: Our data show that [18F]3 had a moderate decay corrected labeling yield (~10%) and high radiochemical purity (>95%) compared to other tracers. The uptake of [18F]3 in normal mouse hearts was 1.7±0.1%ID/cc at 1 h post-injection (p. i.), while it was 2.4±0.1, 2.6±0.9, and 2.1±0.4%ID/cc in the MI mouse hearts at 1, 2, and 3 days after surgery, respectively. Compared with [18F]LMI1195, [18F]3 had a better myocardial imaging effect in terms of the contrast between normal and MI hearts. The area of myocardial infarction shown by PET imaging corresponded well with the infarcted tissue demonstrated by H&E staining. CONCLUSIONS: With an obvious cardiac uptake contrast between normal mice and the myocardial infarction mouse model, [18F]3 appears to be a potential tool in the diagnosis of myocardial infarction. Therefore, it is necessary to conduct further structural modification studies on the chemical structure of [18F]3 to improve its in vivo stability and diagnostic detection ability to achieve reliable and practical imaging effects.

Identification and Validation of Signature Genes and Their Correlations with Infiltrated Immune Cells in Neonatal Sepsis.

Background and Objective: There is increasing demand to identify accurate and reliable molecular biomarkers for early diagnosis of neonatal sepsis. We aimed to identify and verify signature genes in neonatal sepsis through comprehensive bioinformatics analysis. Methods: A Gene Expression Omnibus data set was used to identify differentially expressed genes (DEGs) in patients with neonatal sepsis and healthy controls by functional and disease enrichment analysis. Gene set enrichment analysis, screening of DEGs using 2 machine algorithms, analysis of receiver operating characteristic curves, and correlation analysis with infiltrating immune cells was performed. Results: We identified 433 DEGs: 144 downregulated and 289 upregulated. Gene Ontology analysis identified DEGs for T cell activation, positive regulation of cytokine production, secretory granule cavity, cytoplasmic vesicle cavity, immune receptor activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified DEGs for hematopoietic cell lineage, cytokine-cytokine receptor interaction, and coronavirus disease (COVID-19). Disease Ontology analysis identified DEGs for hematopoietic system diseases, skin system diseases, and bacterial infectious diseases. We also gained understanding of the enrichment of various functions and pathways by gene set enrichment analysis. In the neonatal sepsis group, Gene Ontology analysis results were significant for coagulation, endocytosis, white cell migration, myeloid leukocyte-mediated immunity, and phagocytosis; KEGG analysis results were significant for chemokine signaling pathway, complement and coagulation cascade, leukocyte migration across endothelium, regulation of actin cytoskeleton, and toll-like receptor signaling pathway. We screened 2 signature DEGs (GSN and SEMA4B) using the least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms and verified their diagnostic accuracy by receiver operating characteristic curves. We correlated GSN and SEMA4B expression levels with the infiltration levels of 22 types of immune cell. Conclusion: GSN and SEMA4B expression accurately predicted early-stage neonatal sepsis, which is beneficial for early clinical diagnosis and treatment.

Carboxymethylcellulose based self-healing hydrogel with coupled DOX as Camptothecin loading carrier for synergetic colon cancer treatment.

The self-healing hydrogels have important applications in biomedication as drug release carrier. In this research, the Doxorubicin (DOX) was coupled onto oxidized carboxymethylcellulose (CMC) (CMC-Ald) to fabricate self-healing hydrogel with intrinsic antitumor property and loaded with Camptothecin (CPT) for synergetic antitumor treatment. The DOX coupled CMC-Ald (CMC-AD) was reacted with poly(aspartic hydrazide) (PAH) to fabricate injectable self-healing hydrogel. The coupled DOX avoided the burst release of the drug and the 100 % CPT loaded hydrogel could take the advantages of both drugs to enhance the synergetic antitumor therapeutic effect. The in vitro and in vivo results revealed the CPT loaded CMC-AD/PAH hydrogel showed enhanced antitumor property and reduced biotoxicity of the drugs. These properties demonstrate that the CMC-AD/PAH hydrogel has great application prospects in biomedication.

Biodegradable hydrogel from pectin and carboxymethyl cellulose with Silibinin loading for lung tumor therapy.

Serious side effects of chemotherapy drugs greatly limited the anticancer performance, while targeted drug delivery could improve the therapeutic effect and reduce side effects. In this work, biodegradable hydrogel was fabricated from pectin hydrazide (pec-H) and oxidized carboxymethyl cellulose (DCMC) for localized Silibinin delivery in lung adenocarcinoma treatment. The self-healing pec-H/DCMC hydrogel showed blood compatibility and cell compatibility both in vitro and in vivo, and could be degraded by enzymes. The hydrogel also formed fast fit for injectable applications and showed sustained drug release characteristic sensitive to pH based on acylhydrzone bond cross-linked networks. The Silibinin, as a specific lung cancer inhibiting drug targets TMEM16A ion channel, was loaded into the pec-H/DCMC hydrogel to treat the lung cancer in mice model. The results showed that the hydrogel loaded Silibinin significantly enhanced the anti-tumor efficiency in vivo and greatly reduced the toxicity of the Silibinin. Based on the dual effect of improving efficacy and reducing side effects, the pec-H/DCMC hydrogel with Silibinin loading have broad application prospects to inhibit lung tumor growth in clinic.

Monoubiquitinated MxIRT1 acts as an iron receptor to determine MxIRT1 vacuole degradation or plasma membrane recycling via endocytosis.

IRON-REGULATED TRANSPORTER 1 (IRT1) is critical for iron uptake in roots, and its exocytosis to the plasma membrane (PM) is regulated by the iron status sensed by the histidine-rich domain (HRM). However, studies on the fate of IRT1 after fusion with PM in response to iron conditions are still limited. In this study, we found that K165 and K196 regulate the monoubiquitination of MxIRT1 (mUb-MxIRT1), which acts as a receptor delivering signals from HRM to downstream effectors such as clathrin to determine the fate of MxIRT1. Iron supply led MxIRT1 in the PM to monoubiquitin-dependent endocytosis which could be inhibited by endocytosis inhibitor TyrA23 or in the double site-directed mutant K165/K196R. Subsequently, the endocytosis pathway to the vacuole was inhibited by vacuolar protease inhibitor Leupeptin in excessive iron conditions and the inability of being able to respond to iron change, indicated by the protein accumulating in the PM, contributed to iron toxicity in K165/K196R transgenic Arabidopsis. With iron availability decreasing again, MxIRT1 could dock close to the PM waiting for to be recycled. Another monoubiquitination site, K26, was necessary for MxIRT1 Endoplasmic Reticulum (ER) export as site-directed mutant K26R lost the ability of PM targeting, and co-localized with the COPII subunit of the coat protein OsSec24. Therefore, after K26-directed ER export and iron-induced PM fusion, mUb-MxIRT1 determines subsequent vacuolar degradation or recycling to the PM via endocytosis for maintaining iron homeostasis.

Application of Pelvic Magnetic Resonance Imaging Scan Combined with Serum Pyruvate Kinase Isozyme M2, Neutrophil Gelatinase-Associated Lipocalin, and Soluble Leptin Receptor Detection in Diagnosing Endometrial Carcinoma.

Objective: To explore the application value of pelvic magnetic resonance imaging (MRI) scan combined with serum pyruvate kinase isozyme M2 (PKM2), neutrophil gelatinase-associated lipocalin (NGAL), and soluble leptin receptor (sOB-R) detection in diagnosing endometrial carcinoma (EC). Methods: The clinical data of 45 patients with pathologically confirmed EC treated in our hospital from May 2019 to May 2020 were retrospectively analyzed. All patients received pelvic MRI scan, serum PKM2, NGAL and sOB-R detection was performed, and the combination of the two was performed so as to analyze the diagnostic application value of the three modalities. Results: Compared with the joint detection, the number of true positive cases, sensitivity, specificity, and accuracy rate obtained by a single application of pelvic MRI or serum PKM2, NGAL, and sOB-R detection were obviously lower; the area under the ROC curve of the joint detection was obviously larger than that of single detection; the results of the joint detection were better than those of single detection (P < 0.05); the combined diagnosis obtained the highest sensitivity. Conclusion: Combining pelvic MRI with serum PKM2, NGAL, and sOB-4 detection can effectively promote the diagnostic accuracy for EC, presenting significant clinical diagnostic value.

Short stature associated with a novel mutation in the aggrecan gene: A case report and literature review.

BACKGROUND: Mutations in the aggrecan (ACAN) gene are identified in patients with: spondyloepiphyseal dysplasia, Kimberley type; short stature with advanced bone age (BA); in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans; and spondyloepimetaphyseal dysplasia, ACAN type. Heterozygous mutations contribute to spondyloepiphyseal dysplasia, Kimberley type (MIM#608361), which is a milder skeletal dysplasia. In contrast, homozygous mutations cause a critical skeletal dysplasia, which is called spondyloepimetaphyseal dysplasia, ACAN type (MIM#612813). Lately, investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA, in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans (MIM#165800). We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature, BA acceleration, and premature growth cessation. CASE SUMMARY: A 2-year-old male patient visited us due to growth retardation. The patient presented symmetrical short stature (height 79 cm, < -2 SD) without facial features and other congenital abnormalities. Whole-exome sequencing revealed a heterozygous pathogenic variant c. 871C>T (p. Gln291*) of ACAN, which was not yet reported in cases of short stature. This mutation was also detected in his father and paternal grandmother. According to the Human Gene Mutation Database, 67 ACAN mutations are registered. Most of these mutations are genetically inheritable, and very few children with short stature are associated with ACAN mutations. To date, heterozygous ACAN mutations have been reported in approximately 40 families worldwide, including a few individuals with a decelerated BA. CONCLUSION: Heterozygous c. 871C>T (p. Gln291*) variation of the ACAN gene was the disease-causing variant in this family. Collectively, our newly discovered mutation expanded the spectrum of ACAN gene mutations.

LINC01087 Promotes the Proliferation, Migration, and Invasion of Thyroid Cancer Cells by Upregulating PPM1E.

This study is aimed at investigating the effect and mechanism of LINC01087 on the malignant evolution of thyroid cancer cells. The expression levels of LINC01087, miR-135a-5p, and PPM1E in thyroid carcinoma tissues were detected by QRT-PCR. Cell viability was detected using the CCK-8 method. Transwell assay was used to assess the ability of cells to invade. The targeting relationship between LINC01087 and miR-135a-5p was detected by dual luciferase reporting assay. In comparison with normal thyroid tissues and cells, the expression level of LINC01087 in thyroid cancer tissues and TPC-1 and K1 cells increased, and the expression level of miR-135a-5p in thyroid cancer tissues and TPC-1 and K1 cells decreased. LINC01087 knockdown and the high expression of miR-143-3p inhibited the proliferation, invasion, and EMT processes of TPC-1 and K1 in thyroid cancer cells. LINC01087 negatively targeted miR-135a-5p. Has-miR-135a-5p inhibited the malignant evolution and EMT of thyroid cancer by targeting PPM1E. The PPM1E overexpression can reverse the inhibitory effect of LINC01087 gene knockdown on the proliferation, migration, and invasion of thyroid cancer cells. LINC01087 can promote the proliferation and apoptosis of thyroid cancer cells, and its mechanism may be related to the miR-135a-5p/PPM1E axis.

HRM and CRAC in MxIRT1 act as iron sensors to determine MxIRT1 vesicle-PM fusion and metal transport.

The IRON-REGULATED TRANSPORTER1 (IRT1) is critical for iron uptake in roots, and its exocytosis to the plasma membrane (PM) is regulated by detergent-resistant membranes. However, studies on IRT1 exocytosis and function in response to iron status are limited. Presently, we found that the histidine-rich motif (HRM) of MxIRT1 could bind to iron directly and HRM determined the delivery of MxIRT1 to the PM, after which the cholesterol recognition amino acid consensus (CRAC) motif-regulated MxIRT1 mediated metal transport. IMAC assay revealed that H192 was the vital site for HRM binding to Fe2+, and metal-binding activity was stopped after the deletion of HRM (MxIRT1∆HM) or in H192 site-directed mutants (H192A). MxIRT1∆HM or H192A in transgenic yeast and Arabidopsis failed to localize in the PM and displayed impaired iron absorption. In the PM, Y266 in CRAC was required for metal transport; Y266A transgenic Arabidopsis displayed the same root length, Cd2+ flux, and Fe concentration as Arabidopsis mutant irt1 under iron-deficient conditions. Therefore, H192 in HRM may be an iron sensor to regulate delivery of MxIRT1 vesicles to the PM after binding with iron; Y266 in CRAC acts as an iron sensor for active metal transport under iron-deficient conditions.

Diallyl Disulfide (DADS) Ameliorates Intestinal Candida albicans Infection by Modulating the Gut microbiota and Metabolites and Providing Intestinal Protection in Mice.

Diallyl disulfide (DADS), a garlic extract also known as allicin, has been reported to have numerous biological activities, including anticancer, antifungal, and inflammation-inhibiting activities, among others. Although many studies have assessed whether DADS can treat Candida albicans infection in vitro, its in vivo function and the underlying mechanism are still not clear. Accumulated evidence has implicated the gut microbiota as an important factor in the colonization and invasion of C. albicans. Thus, this study aimed to identify the mechanism by which DADS ameliorates dextran sulfate (DSS)-induced intestinal C. albicans infection based on the systematic analysis of the gut microbiota and metabolomics in mice. Here, we determined the body weight, survival, colon length, histological score, and inflammatory cytokine levels in the serum and intestines of experimental mice. Fecal samples were collected for gut microbiota and metabolite analysis by 16S rRNA gene sequencing and LC-MS metabolomics, respectively. DADS significantly alleviated DSS-induced intestinal C. albicans infection and altered the gut microbial community structure and metabolic profile in the mice. The abundances of some pathogenic bacteria, such as Proteobacteria, Escherichia-Shigella, and Streptococcus, were notably decreased after treatment with DADS. In contrast, SCFA-producing bacteria, namely, Ruminiclostridium, Oscillibacter, and Ruminococcaceae_UCG-013, greatly increased in number. The perturbance of metabolites in infectious mice was improved by DADS, with increases in secondary bile acids, arachidonic acid, indoles and their derivatives, which were highly related to the multiple differentially altered metabolic pathways, namely, bile secretion, arachidonic acid metabolism, and tryptophan metabolism. This study indicated that DADS could modulate gut microbiota and metabolites and protect the gut barrier to alleviate DSS-induced intestinal C. albicans infection in mice. Moreover, this work might also provide novel insight into the treatment of C. albicans infection using DADS.

Human papillomavirus infection and follow-up on positive results in 7222 female samples obtained from 2016 to 2019 in Hefei, China.

BACKGROUND: Human papillomavirus (HPV) infection rates in women vary regionally. This study analyzed HPV infection in women of different age groups in Hefei, China, performed follow-up on positive cases, and discussed infection prognoses. METHODS: Samples (7,222) of exfoliated cervical cells were collected in Hefei and tested with an HPV assay kit against 27 HPV genotypes. Statistical software was used to analyze the data. RESULTS: The total positive rate of infection was 17.13% (1,068 women), and the 51-60-year age group had the highest HPV infection rate (19.82%). There were statistically significant differences between rates in the 21-30 and 31-40 (P = 0.002), 21-30 and 41-50 (P = 0.0003), 21-30 and 51-60 (P = 0.00003), and 51-60 and >60 age groups (P = 0.046). High-risk infection (15.67%) and single infection (13.01%) were the main types of HPV infection. The dominant genotypes of high-risk infection were HPV 52 (2.42%), HPV 16 (2.01%), HPV 53 (1.43%), HPV 58 (1.32%) and HPV 66 (1.01%). We conducted follow-up on cases in 69 of 94 women who had a history of 1-4 years of positive infection, and in 18 (seven treated, 11 untreated) patients, infection status turned negative (26.09%). Seventeen of the fifty-one women whose infections did not turn negative received treatment. Persistent infection was predominantly observed in high-risk genotypes (56 of 69). CONCLUSIONS: The results recommend that women in Hefei improve health awareness and receive a 9-valent vaccine. Additionally, women with persistent infections should consult a gynecologist to prevent cervical lesions.

Influence of family environment on the development of speech and language in pre-lingually deaf children after cochlear implantation.

OBJECTIVE: To investigate the influence of family environment on the development of speech and language in pre-school children after cochlear implantation. METHODS: A total of 88 pre-lingually deaf children, aged 2-5 years, who received cochlear implantation, were included in this study. All families completed a self-report family environment questionnaire (FES). The deaf children's linguistic progress was assessed by Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) at 0, 3, 6 and 12 months after implantation. RESULTS: The family environment was the significant factor associated with CAP and SIR at 6 months post-implantation. The children in families with higher levels of Cohesion, Intellectual-Cultural Orientation and the ability to express emotion effectively had better auditory and speech abilities, while children in families with low intimacy and high incompatibility exhibited a delay in the development of auditory speech (P < .05). CONCLUSIONS: The development of speech and language in pre-lingually deaf children after cochlear implantation can be influenced by family environment and parents' roles.

Elevation of stromal cell-derived factor 1 and C-X-C chemokine receptor type 4 in white matter damage treatment with recombinant human erythropoietin and human umbilical cord mesenchymal stem cells in a rat model of preterm birth.

OBJECTIVES: To investigate the role of stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) in the premature brain with white matter damage (WMD) undergoing treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) and recombinant human erythropoietin (rhEPO). EXPERIMENTAL DESIGN: Three-day-old Sprague-Dawley (SD) rats were randomly divided into sham operation group, hypoxia-ischemia (HI) group, rhEPO treated HI group, hUC-MSCs treated HI group, and rhEPO + hUC-MSCs treated HI group. WMD was established in all groups except the Sham group. SDF-1 and CXCR-4 levels in each group were detected at postnatal day (P) 5, P7, and P14. Pathological changes were assessed via HE staining at P14 and neuroethological tests were performed at P28. OBSERVATIONS AND CONCLUSIONS: The rhEPO and hUC-MSCs intervention reduced injury area, increased body weight at P7, and improved neurobehavioral scores at P28. Furthermore, their combined use proved even more beneficial. SDF-1 levels in the rhEPO group were higher than those in the other groups and highest in the hUC-MSCs + rhEPO group (all p < .01). SDF-1 levels in the hUC-MSCs + rhEPO and rhEPO groups were increased at P5 and reached a peak at P7. CXCR-4 levels in the hUC-MSCs group were higher than those in the other groups and highest in the hUC-MSCs + rhEPO group (all p < .01). CXCR-4 levels were also increased at P5 and highest at P14. SIGNIFICANCE: hUC-MSCs + rhEPO might reduce nerve cell damage and improve neurobehavioral development, in connection with increased SDF-1 and CXCR-4 expression, in premature rats with WMD due to hypoxic-ischemic injury.

Acid-sensitive ROS-triggered dextran-based drug delivery system for advanced chemo-photodynamic synergistic therapy.

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.

Modelling oil trajectories and potentially contaminated areas from the Sanchi oil spill.

Oil spills are major threats to marine ecosystems. Here, we establish a three-dimensional oil spill model to simulate and project the short- and long-term trajectories of oil slicks and oil-contaminated water that leaked from the Sanchi wreckage. The pollution probability in surrounding areas for the period up to 180 days after the Sanchi sank is statistically analysed. The short-term simulations are consistent with synchronous SAR images and observational reports. The potentially polluted areas depend on the properties of the released oil. The coastal areas most likely to be affected by the bunker oil are located in the Ryukyu Island Chain, Tsushima Strait, on the south and east coasts of Japan. Approximately 50% to 70% of oil particles remain in the ocean and mainly expand along the Ryukyu Island Chain and the region southeast of the Sanchi wreck. Subsurface oil-contaminated water is likely to enter the Sea of Japan along the Tsushima Strait. Due to the rapid evaporation rate of condensate oil, the potentially polluted area is confined to regions within a 100 × 100 km area around the location of the shipwreck, and the contaminated region is closely associated with the surface wind.

Deep learning Radiomics of shear wave elastography significantly improved diagnostic performance for assessing liver fibrosis in chronic hepatitis B: a prospective multicentre study.

OBJECTIVE: We aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images. DESIGN: A prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2). RESULTS: AUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied. CONCLUSION: DLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients. TRIAL REGISTRATION NUMBER: NCT02313649; Post-results.

Long noncoding RNA ROR1-AS1 enhances lung adenocarcinoma metastasis and induces epithelial-mesenchymal transition by sponging miR-375.

PURPOSE: The vital role of long noncoding RNAs (lncRNAs) in tumor progression have been identified in numerous studies. In this research, lncRNA ROR1-AS1 was explored to verify its function during the development of lung adenocarcinoma (LAC). METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure ROR1-AS1 expression of LAC tissues. Function assays including wound healing assay and transwell assay were conducted to detect the effect of knockdown of ROR1-AS1 on the metastasis of LAC, and luciferase assays and RNA immunoprecipitation assay (RIP) were also performed to explore the underlying mechanism. RESULTS: ROR1-AS1 expression level was significantly higher in LAC samples compared with that in adjacent tissues, which was associated with patients' prognosis. Knockdown of ROR1-AS1 inhibited cell migration and cell invasion of LAC cells via suppressing epithelial-mesenchymal transition (EMT) process. Furthermore, it was discovered that ROR1-AS1 acted as a competing endogenous RNA via sponging miR-375 in LAC. CONCLUSIONS: These results suggested that ROR1-AS1 could act as a sponge for miR-375 and promo//e cell migration and invasion through suppressing the process of EMT in LAC, which may offer a potential therapeutic target in LAC.

Genomics of neonatal sepsis: has-miR-150 targeting BCL11B functions in disease progression.

BACKGROUND: Neonatal sepsis is an inflammatory systemic syndrome, which is a major cause of morbidity and mortality in premature infants. We analyzed the expression profile data of E-MTAB-4785 to reveal the pathogenesis of the disease. METHODS: The expression profile dataset E-MTAB-4785, which contained 17 sepsis samples and 19 normal samples, was obtained from the ArrayExpress database. The differentially expressed genes (DEGs) were analyzed by the Bayesian testing method in limma package. Based on the DAVID online tool, enrichment analysis was conducted for the DEGs. Using STRING database and Cytoscape software, protein-protein interaction (PPI) network and module analyses were performed. Besides, transcription factor (TF)-DEG regulatory network was also constructed by Cytoscape software. Additionally, miRNA-DEG pairs were searched using miR2Disease and miRWalk 2.0 databases, followed by miRNA-DEG regulatory network was visualized by Cytoscape software. RESULTS: A total of 275 DEGs were identified from the sepsis samples in comparison to normal samples. TSPO, MAPK14, and ZAP70 were the hub nodes in the PPI network. Pathway enrichment analysis indicated that CEBPB and MAPK14 were enriched in TNF signaling pathway. Moreover, CEBPB and has-miR-150 might function in neonatal sepsis separately through targeting MAPK14 and BCL11B in the regulatory networks. These genes and miRNA might be novel targets for the clinical treatment of neonatal sepsis. CONCLUSION: TSPO, ZAP70, CEBPB targeting MAPK14, has-miR-150 targeting BCL11B might affect the pathogenesis of neonatal sepsis. However, their roles in neonatal sepsis still needed to be confirmed by further experimental researches.

[Prognostic value of differences between peripheral arterial and venous blood gas analysis in patients with septic shock].

OBJECTIVE: To investigate the value of the difference between peripheral arterial and venous blood gas analysis for the prognosis of patients with septic shock after resuscitation. METHODS: Patients with septic shock aged 18 to 80 years admitted to intensive care unit (ICU) of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine from May 2016 to December 2017 were enrolled. The peripheral arterial blood and peripheral venous blood gas analysis were measured simultaneously after the early 6 hours resuscitation, including pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), base excess (BE), bicarbonate (HCO3-) and lactate (Lac) level, and the difference values between peripheral arterial and venous blood were calculated. According to the 28-day survival, the patients were divided into survival group and death group. Multiple Logistic regression analysis was used to analyze the risk factors of death, and the receiver operating characteristic curve (ROC) was used to analyze the prognostic value of blood gas analysis parameters for prognosis. RESULTS: A total of 65 patients with septic shock resuscitation were enrolled in the study, 35 survived while 30 died during the 28-day period. (1) There was no significant difference in gender, age, and mean arterial pressure (MAP), central venous pressure (CVP), central venous oxygen saturation (ScvO2) and norepinephrine (NE) dose between the two groups. (2) The arterial and venous Lac, the difference of Lac (ΔLac) and PCO2 (ΔPCO2) between arterial and venous blood in death group were significantly higher than those in survival group [arterial Lac (mmol/L): 7.40±3.10 vs. 4.82±2.91, venous Lac (mmol/L): 9.17±3.27 vs. 5.81±3.29, ΔLac (mmol/L): 1.77±0.54 vs. 0.99±0.60, ΔPCO2 (mmHg, 1 mmHg = 0.133 kPa): 9.64±5.08 vs. 6.70±3.71, all P < 0.01], and there was no significant difference in the other arterial and venous blood gas analysis index and its corresponding differential difference between two groups. (3) Multiple Logistic regression analysis showed that ΔPCO2 [ß = 0.247, odd ratio (OR) = 1.280, 95% confidential interval (95%CI) = 1.057-1.550, P = 0.011], and ΔLac (ß = 2.696, OR = 14.820, 95%CI = 2.916-75.324, P = 0.001) were the independent risk factors for the prognosis of septic shock. (4) It was shown by ROC curve analysis that arterial blood Lac, ΔLac and ΔPCO2 had predictive value on prognosis of septic shock, the area under ROC curve (AUC) was 0.792, 0.857, 0.680, respectively (all P < 0.05). When the best cut-off value of arterial Lac was 4.00 mmol/L, the sensitivity was 100%, and the specificity was 62.86% for predictor of death in 28-day; when the best cut-off value of ΔLac was 1.25 mmol/L, the sensitivity was 93.33%, and the specificity was 68.57% for predictor of death in 28-day; when the best cut-off value of ΔPCO2 was 4.35 mmHg, the sensitivity was 83.33%, and the specificity was 37.14% for predictor of death in 28-day. CONCLUSIONS: Compared to other parameters, the difference between peripheral arterial and venous blood gas analysis, ΔPCO2 and ΔLac had the best correlation with the prognosis of septic shock. The ΔPCO2 and ΔLac are the independent prognostic predictors for 28-day survival.