Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.

The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings.

Influence of the Anatomical Structure on the Hemodynamics of Iliac Vein Stenosis.

Few reports study the effects of the anatomical structure of the iliac vein on hemodynamics and the methods to reduce and delay in-stent thrombosis. The anatomical structure of iliac vein stenosis was used to establish vascular models with different stenosis rates, taper angle, and left branch tilt angle in the work. The influence of anatomical structure on hemodynamics was revealed through theoretical research and in vitro experimental verification. A real iliac vein model was built based on computed tomography angiography (CTA) images, and hemorheological parameters including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were analyzed by computational fluid dynamics (CFD). The results showed that iliac vein stenosis could significantly increase the wall shear stress (WSS) of the blood vessels at the stenosis site and outside the intersection area, which was easy to produce eddy currents in the distal blood vessels. With the increased taper angle, the proportion of low-wall shear stress areas and the risk of thrombosis increased. A small tilt angle could aggravate the influence of narrow blood vessels on the blood flow characteristics and vascular wall. The numerical simulation results were consistent with the theoretical research results, and the experimental study verified the correctness of the simulation. The work is helpful to further understand the hemodynamic characteristics of the iliac vein, providing a scientific reference for clinical treatment and diagnosis.

Effect of post-discharge pharmacist-led follow-up on drug treatment in patients with deep venous thrombosis in primary hospitals in China.

Warfarin and rivaroxaban were the two most commonly-used anticoagulant drugs for Deep venous thrombosis (DVT). The aim of this study was to explore the effects of post-discharge pharmacist-led follow-up on drug treatment in patients with DVT in primary hospitals from a pharmacological perspective. A total of 125 patients were recruited from July 2017 to June 2019 and randomized to either a control group or an intervention group. The control group was given routine medication guidance, clinical pharmacists followed up at 3 and 6 months after discharge. The intervention group was based on the control group and was followed up weekly for 6 months after discharge. For patients taking warfarin, the percentage of time in therapeutic range (TTR) and TTR>65% were significantly higher in the intervention group (p<0.05) and they also had less frequent dose changes. For patients taking warfarin or rivaroxaban, vascular ultrasonography showed better improvement rate in the intervention group (p<0.05). Pharmacist-led follow-up showed that the medication adherence (p<0.05) were significantly improved. There were lower risks of total and minor hemorrhage events and thrombosis events in the intervention group (p<0.05). Pharmacist-led follow-up not only reduced the risk of hemorrhage and thrombosis events, but also improved adherence to anticoagulation drugs.

LncRNA FGD5-AS1 promotes the malignant phenotypes of ovarian cancer cells via targeting miR-142-5p.

Long non-coding RNAs (lncRNAs) have been reported to participate in regulating gene expression and are related to tumor progression. FGD5 antisense RNA 1 (FGD5-AS1) facilitates the progression of various tumors. However, the expression and function of FGD5-AS1 in ovarian cancer (OC) and its mechanism of action are not yet clear. Real-time polymerase chain reaction (RT-PCR) was employed to explore the expression levels of FGD5-AS1 and miR-142-5p in OC. The relationship between the expression of FGD5-AS1 and clinicopathological indicators of OC patients was analyzed by χ2 test. CCK-8 assay, BrdU assay, and Transwell assay were carried out to detect cell proliferation, migration, as well as invasion, respectively. Subcutaneous tumorigenesis experiment and lung metastasis model were used to examine the biological effects of FGD5-AS1 in OC in vivo. Dual luciferase reporter gene assay or RIP experiment was employed to explore the targeting relationship between FGD5-AS1 and miR-142-5p, as well as miR-142-5p and PD-L1 3'UTR. First, we found that FGD5-AS1 was markedly up-regulated in OC. Moreover, its high expression level was associated with positive local lymph node metastasis and higher T stage in OC patients. Gain-of-function and loss-of-function assays demonstrated that FGD5-AS1 facilitated the proliferation, migration, as well as invasion of OC cells. Mechanistically, it was revealed that FGD5-AS1 targeted miR-142-5p to repress its expression and function. Furthermore, miR-142-5p has a binding site for 3' UTR of PD-L1, and FGD5-AS1 could positively regulate PD-L1 expression via repressing miR-142-5p. The present study reports that FGD5-AS1/miR-142-5p/PD-L1 axis is involved in regulating OC progression.

Mobilization and geochemistry of nutrients in sediment evaluated by diffusive gradients in thin films: Significance for lake management.

Investigation of in-situ mobilization of both nitrogen (N) and phosphate (PO43-) in sediment is important for lake management strategy. In this paper, diffusion gradients in thin films (DGT) and DGT induced flux in sediments (DIFS) model are newly designed for in-situ measurement of iron (Fe), PO43-, nitrate (NO3-N) and ammonium (NH4-N), and nutrients' mobility in sediment in Lake Nanhu (China). According to DGT profiles together with physicochemical properties in sediment, (I) PO43- is released from (i) Fe-bound P plus loosely sorbed P in anoxic sediment and (ii) the loosely sorbed P in oxic sediment; (II) anoxic sediment inhibits nitrification and NO3-N release, but it favors denitrification and dissimilatory nitrate reduction to ammonium (DNRA), leading to NH4-N release; (III) Eh and organic matter are two key influence factors on mobility of PO43-, NO3-N and NH4-N. According to DIFS calculation, the dynamics of desorption and diffusion at two sites belong to (i) slow rate of resupply and (ii) fast resupply cases, respectively. Internal loadings are estimated to be 92.74 (PO43-), 268.1 (NH4-N) and -2466 kg a-1 (NO3-N), which reflects sediment mainly acts as a source for PO43- and NH4-N, and a sink for NO3-N in water. Based on sediment P release risk index (SPRRI), P release risks in lake sediments are estimated, ranging from light to relative high level. DGT and SPRRI aid choice of restoration methods for sediment, including sediment dredging, phytoremediation and in-situ inactivation.

Thyroid-disrupting effects and mechanism of thiazole-Zn-induced thyroid cell hypertrophy and hyperplasia in male Sprague-Dawley rats.

Thiazole-Zn is a systemic fungicide synthesized and developed in China that has been used for the prevention and treatment of bacterial and fungal diseases on fruits and vegetables. Thiazole-Zn is a new thyroid disruptor chemical. The purpose of this study was to clarify the thyroid-disrupting property of thiazole-Zn and the mechanism responsible for thyroid hormone (TH) biosynthesis inhibition in male rats induced by thiazole-Zn. First, the effects of different thiazole-Zn doses and exposure times on the thyroid weights, thyroid morphology and serum hormone levels of rats were investigated. The results showed that thiazole-Zn increased thyroid weights and serum thyroid-stimulating hormone (TSH) levels and induced thyroid cell hypertrophy and hyperplasia in a dose-related and time-related manner. Furthermore, measurement of thyroid radioiodine uptake in vivo in rats confirmed that thiazole-Zn inhibited active iodide uptake into the thyroid, which reduced circulating levels of serum T3 and T4. Decreases in circulating THs resulted in a compensatory increase in serum TSH levels through a negative feedback system. Subsequently, sustained excessive stimulation of the thyroid gland by TSH led to thyroid follicular cell hypertrophy and hyperplasia. In addition, thiazole-Zn increased sodium/iodide symporter (NIS) expression in the rat thyroid, and the increased NIS expression promoted and restored iodide uptake into the thyroids of rats. The risk of iodine intake inhibition by thiazole-Zn to humans, especially susceptible individuals, such as children and pregnant women, warrants additional attention.

Overexpression of Axl reverses endothelial cells dysfunction in high glucose and hypoxia.

The receptor tyrosine kinase Axl is involved in diabetic vascular disease. This study aims to investigate the effect of high glucose on endothelial cells injury and Axl expression in hypoxia condition in vitro, and we present details of the mechanism associated with overexpression of Axl rescue the high glucose injury. Our results showed that high glucose impaired both human umbilical vein endothelial cells (HUVECs) and EAhy926 cells angiogenesis in hypoxia condition. In addition, high glucose inhibits Axl and hypoxia-inducible factor 1-α (HIF-1α) protein expression in hypoxia condition. Axl overexpression significantly reversed endothelial cells dysfunction in high glucose/hypoxia. Furthermore, Axl overexpression in EAhy926 cells increases HIF-1α protein synthesis through PI3K/Akt/mTOR/p70 S6K signal pathway but not Mek/Erk in high glucose/hypoxia condition. This study demonstrates that high glucose can alter Axl signaling and HIF-1α in hypoxia condition. Overexpression of Axl may rescue endothelial cells dysfunction and HIF-1α expression through its downstream signals in high glucose/hypoxia.

Inhibition of autophagy induced by PTEN loss promotes intrinsic breast cancer resistance to trastuzumab therapy.

This study aims to explore the effects of the phosphatase and tension homolog (PTEN) expression level on autophagic status and on the resistance of breast cancer to trastuzumab treatment. PTEN and LC3I/II were knocked down with shRNA expression vectors, which were transfected into estrogen receptor (ER)-positive breast cancer cell lines. After trastuzumab treatment, the changes in the autophagy signal transduction pathways and autophagic proteins (LC3I/II, p62, LAMP, and cathepsin B) in these stably transfected cells were detected using western blot. The cells were also orthotopically implanted into nude mice to explore the influence of PTEN knockdown on tumor size, cell viability, and autophagic proteins after trastuzumab treatment. Similar determinations were performed using the LC3I/II overexpressed shPTEN breast cancer cells (LC3I/II-shPTEN). Downregulation of PTEN and autophagic proteins LC3-I and LC3-II was observed in resistant human breast cancer samples. Knockdown of PTEN and PTEN+ LC3I/II with shRNA in breast cancer cells resulted in increased resistance to trastuzumab. Consistently, trastuzumab treatment could not effectively reduce tumor size. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B, and PI3K-Akt-mTOR and the signaling pathway protein Akt were found in PTEN knockdown cells, compared to the PTEN normal group, after trastuzumab administration, both in vitro and in vivo. However, these findings were reversed with the LC3I/II-shPTEN treatment. Therefore, the loss of PTEN may promote the development of primary resistance to trastuzumab in breast cancer via autophagy defects.

Effects of random food deprivation and refeeding on energy metabolism, behavior and hypothalamic neuropeptide expression in Apodemus chevrieri.

Maintaining adaptive control of behavior and physiology is the main strategy used by animals in responding to changes of food resources. To investigate the effects of random food deprivation (FD) and refeeding on energy metabolism and behavior in Apodemus chevrieri, we acclimated adult males to FD for 4weeks, then refed them ad libitum for 4weeks (FD-Re group). During the period of FD, animals were fed ad libitum for 4 randomly assigned days each week, and deprived of food the other 3days. A control group was fed ad libitum for 8weeks. At 4 and 8weeks we measured body mass, thermogenesis, serum leptin levels, body composition, gastrointestinal tract morphology, behavior and hypothalamic neuropeptide expression. At 4weeks, food intake, gastrointestinal mass, neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expressions increased and thermogenesis, leptin levels, pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) expressions decreased in FD compared with controls. FD also showed more resting behavior and less activity than the controls on ad libitum day. There were no differences between FD-Re and controls at 8weeks, indicating significant plasticity. These results suggested that animals can compensate for unpredictable reduction in food availability by increasing food intake and reducing energy expended through thermogenesis and activity. Leptin levels, NPY, AgRP, POMC, and CART mRNA levels may also regulate energy metabolism. Significant plasticity in energy metabolism and behavior was shown by A. chevrieri over a short timescale, allowing them to adapt to food shortages in nutritionally unpredictable environments.

Seasonal changes in body mass, serum leptin levels and hypothalamic neuropeptide gene expression in male Eothenomys olitor.

The present study examined seasonal changes in body mass and energy metabolism in the Chaotung vole (Eothenomys olitor) and the physiological mechanisms underpinning these changes. Seasonal changes in the following parameters were measured in male E. olitor, body mass, food intake, thermogenesis, enzyme activity, masses of tissues and organs, hormone concentrations and expression of hypothalamic arcuate nucleus energy balance genes including neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART). Body mass was constant over the year, but the masses of tissues and organs differed significantly between seasons. There were significant changes in body fat mass and serum leptin levels over the four seasons. E. olitor showed significant seasonal changes in food intake and thermogenesis, uncoupling protein 1 (UCP1) content, enzyme activity, and serum tri-iodothyronine (T3) and thyroxine (T4) levels. Moreover, mRNA expression in the hypothalamus showed significant seasonal changes. All of our results suggested that E. olitor had constant body mass over the year, which was inconsistent with the prediction of the 'set-point' hypothesis. However, body fat mass and serum leptin levels were significantly different among the four seasons, providing support for the 'set-point' hypothesis. The changes in leptin, NPY, AgRP, POMC, and CART mRNA levels may play a role in the regulation of energy intake in E. olitor. Furthermore, the role of leptin and hypothalamic neuropeptide gene in the regulation of energy metabolism and body mass may be different in animals that are acclimated to different seasons.

Study of the mechanism of action of sand therapy on atherosclerosis based on the two-phase flow-Casson model.

BACKGROUND: Sand therapy is a non-pharmacological physiotherapy method that uses the natural environment and resources of Xinjiang to treat through the heat transfer and magnetic effects of sand. OBJECTIVE: Employing the two-phase flow-Casson blood flow model, we investigate the mechanism of atherosclerosis prevention via sand therapy, offering a biomechanical theoretical rationale for the prevention of atherosclerosis through sand therapy via the prism of computational fluid dynamics (CFD). METHODS: Sand therapy experiments were conducted to obtain popliteal artery blood flow velocity, and blood was considered as a two-phase flow composed of plasma and red blood cells, and CFD method was applied to analyze the hemodynamic effects of Casson's blood viscosity model before and after sand therapy. RESULTS: (1) The blood flow velocity increased by 0.24 m/s and 0.04 m/s at peak systolic and diastolic phases, respectively, after sand therapy; the axial velocity of blood vessels increased by 28.56% after sand therapy. (2) The average red blood cell viscosity decreased by 0.00014 Pa ⋅ s after sand therapy. (3) The low wall shear stress increased by 1.09 Pa and the high wall shear stress reached 41.47 Pa after sand therapy. (4) The time-averaged wall shear stress, shear oscillation index and relative retention time were reduced after sand therapy. CONCLUSION: The increase of blood flow velocity after sand therapy can reduce the excessive deposition of cholesterol and other substances, the decrease of erythrocyte viscosity is beneficial to the migration of erythrocytes to the vascular center, the increase of low wall shear stress has a positive effect on the prevention of atherosclerosis, and the decrease of time-averaged wall shear stress, shear oscillation index and relative retention time can reduce the occurrence of thrombosis.

Modulating Th1/Th2 drift in asthma-related immune inflammation by enhancing bone mesenchymal stem cell homing through targeted inhibition of the Notch1/Jagged1 signaling pathway.

Asthma, a disease intricately linked to immune inflammation, is significantly influenced by the immune regulatory effect of bone mesenchymal stem cells (BMSCs). This study aims to investigate changes in the homing of BMSCs in bronchial asthma, focusing on the Notch homolog (Notch)1/Jagged1 signaling pathway's role in regulating T helper 1(Th1)/T helper 2(Th2) drift. Additionally, we further explore the effects and mechanisms of homologous BMSCs implantation in asthma-related immune inflammation. Following intervention with BMSCs, a significant improvement in the pathology of rats with asthma was observed. Simultaneously, a reduction in the expression of inflammatory cells and inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin(IL)-4, and IL-13 was observed in bronchoalveolar lavage fluid (BALF). Furthermore, there was an increase in the expression of Th1 cytokine Interferon-γ（IFN-γ）and the transcription factor T-box expressed in T cell (T-bet), while the expression of Th2 cytokine IL-13 and transcription factor GATA binding protein (GATA)-3 decreased in lung tissue. This indicates that the Th1/Th2 drift leans towards Th1, which a crucial in ameliorating asthma inflammation. Importantly, inhibition of the Notch1 signaling pathway led to an increased expression of the Stromal cell-derived factor-1(SDF-1)/C-X-C motif chemokine receptor (CXCR)4 chemokine axis. Consequently, the homing ability of bone marrow mesenchymal stem cells to asthma-affected lung tissue was significantly enhanced. BMSCs demonstrated heightened efficacy in regulating the cytokine/chemokine network and Th1/Th2 balance, thereby restoring a stable state during the immune response process in asthma. In conclusion, inhibiting the Notch signaling pathway enhances the expression of the SDF-1 and CXCR4 chemokine axis, facilitating the migration of allogeneic BMSCs to injured lung tissues. This, in turn, promotes immune regulation and improves the Th1/Th2 imbalance, thereby enhancing the therapeutic effect on asthmatic airway inflammation.

Discrete element simulation of vibration compaction of slag subgrade.

In this study, to improve the compaction quality and parameters of slag, discrete element models of irregular rock particles (10-60 mm) and circular soil particles (5 mm) were established based on on-site slag screening results. The motion of the vibratory roller was captured by coupling the roadbed model with the roller model in a simulation in which the roller vibrated and compacted the slag subgrade. The results indicated that (1) the best compaction was achieved when the small particle content was 40%, the medium particle content was 20%, and the large particle content was 40%. (2) When the slag was dominated by small rock particles, the optimum compaction frequency was 28 Hz, and when large rock particles dominated, the optimum compaction frequency was 33 Hz. (3) Rock particles were the primary particles that experienced stress in the vibration compaction, and the compressive force and displacement depended on the particle size. (4) The longitudinal and vertical displacements and rotation angles of the soil and rock particles were examined. The results of this study are conducive for advancing the understanding of slag compaction and improving the working efficiency and compaction quality of rollers.

Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-Specific Transcriptome and Molecular Subtype.

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach also revealed expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of using transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to the identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling. SIGNIFICANCE: The development of an approach to interrogate molecular subtypes, cancer-associated pathways, and differentially expressed genes through RNA sequencing of plasma extracellular vesicles lays the foundation for liquid biopsy-based longitudinal monitoring of patient tumor transcriptomes.

Berberine inhibits the migration and invasion of T24 bladder cancer cells via reducing the expression of heparanase.

Berberine, a quaternary amine and isoquinoline alkaloid, has been proposed to have antimetastatic effects on many types of tumor cells; however, its exact inhibitory mechanisms with bladder cancer cells remain unclear. We used berberine and siRNA technology to interfere the expression of heparanase in bladder cancer T24 cells, detected the expression of heparanase mRNA and protein by reverse transcription PCR and Western blot respectively, and investigated their effects on the migration and invasion of T24 bladder cancer cells using transwell chamber. Our results showed that both mRNA and protein of heparanase were highly expressed in human bladder cancer T24 cells and markedly downregulated by both heparanase-specific siRNA (hpa-siRNA) and berberine. The tumor cell migration assay indicated that transfection of hpa-siRNA and treatment with berberine both attenuated the migration and invasion of T24 cells. Therefore, berberine inhibits the metastasis and invasion of bladder cancer cell, possibly via blocking the heparanase expression and thus may be used clinically to reduce the recurrence of bladder cancer.

Management of missed Monteggia fractures with ulnar osteotomy, open reduction, and dual-socket external fixation.

BACKGROUND: Open reduction of the radial head is usually necessary in the treatment of a missed Monteggia fracture. However, the best way to stabilize the reduction remains controversial. The purpose of this study is to present our experience using the dual-socket external fixator to stabilize the ulna osteotomy and capture the reduction of the radial head. METHODS: We reviewed 33 patients with missed Monteggia fracture who underwent open reduction, ulnar osteotomy, and dual-socket external fixation from 2004 to 2010. The average age of this group was 7 years and the average time to surgical treatment after the fracture was 15 months. We treated all patients with open reduction of the radial head, fully releasing the capsular contracture, removing the fibrous scar tissue within the joint, performing ulnar osteotomy, and fixing the osteotomy with dual-socket external fixation. The clinical and radiographic follow-up averaged 38 months. Descriptive statistics utilized the Student test to compare the preoperative and postoperative functional movement of elbow and forearm. RESULTS: All patients had excellent clinical and radiographic outcomes without losing motion of the elbow and forearm, and all patients maintained reduction of the radial head at the final follow-up. There were no significant differences in the motion of the elbow and forearm between preoperative and postoperative examinations. Delayed union of the ulna occurred in 2 cases, both successfully treated with autologous iliac crest bone graft at 7 months after the operation. Three cases had early redislocation of the radial head, and these were treated successfully by changing the position of the ulnar osteotomy and readjusting the external fixators. CONCLUSIONS: Dual-socket external fixation has the major advantage of permitting and capturing the optimal position of the ulna osteotomy to achieve the best possible reduction of the radial head. A further advantage is the possibility of easily changing the position of the ulnar osteotomy by adjustment of the fixator should the radial head subluxate or redislocate in the early postoperative period as had occurred in 3 of our cases. We conclude that our procedure of fully releasing the capsular contractures, removing scar tissue, ulnar osteotomy, reduction of the radial head, and fixation of the osteotomy with dual-socket external fixation is a safe and effective way to manage children with a missed Monteggia fracture. LEVEL OF EVIDENCE: Therapeutic level IV.

Comparative analysis of clinicopathological characteristics of central necrotizing breast cancer and basal cell-like breast cancer.

Purpose: This study aims to compare the clinicopathological and immunohistochemical characteristics of centrally necrotizing carcinoma of the breast (CNC) and basal-like breast cancer (BLBC), as well as to analyze the characteristics of the molecular typing of the CNC. Methods: The clinicopathological features of 69 cases of CNC and 48 cases of BLBC were observed and compared. EnVision immunohistochemical staining was performed to detect the expressions of hypoxia-inducible factor 1α (HIF-1α), breast cancer susceptibility gene 1 (BRCA1), and vascular endothelial growth factor (VEGF) in CNC and BLBC. Results: The age of the 69 patients ranged from 32 to 80 years, with an average of 54.55 years. Gross examination showed that most tumors were well-defined single central nodules with a diameter of 1.2~5.0 cm. Microscopically, there is a large necrotic or acellular area in the center of the tumor, mainly composed of tumor coagulative necrosis with varying degrees of fibrosis or hyaline degeneration. A small amount of cancer tissue remained in the form of a ribbon or small nest around the necrotic focus. Among 69 cases of CNC, the proportion of basal cell type (56.5%) was significantly higher than that of lumen type A (18.84%), lumen type B (13.04%), HER2 overexpression (5.8%), and nonexpression (5.8%). A total of 31 cases were followed up for 8~50 months, with an average of 33.94 months. There have been nine cases of disease progression. When compared to BLBC, there were no significant differences in BRCA1 and VEGF protein expression in response to CNC (p > 0.05), but there were significant differences in protein expression in HIF-1α (p < 0.05). Conclusion: The molecular typing of CNC showed that over half of those were BLBC. No statistically significant difference in the expression of BRCA1 was observed between CNC and BLBC; thus, we predict that targeted therapy for BRCA1 in BLBC may also have considerable effects in CNC patients. The expression of HIF-1α is significantly different in CNC and BLBC, and perhaps HIF-1α can be used as a new entry point to distinguish between the two. There is a significant correlation between the expression of VEGF and HIF-1α in BLBC, and there was no significant correlation between the expression levels of the two proteins in CNC.

Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats: a potential role of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: To verify the hypothesis that electroacupuncture inhibits the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis regulating the expression of glial fibrillary acidic protein (GFAP) in the hippocampus of acute myocardial ischemia (AMI) rats. METHODS: Sixty-six healthy male Sprague-Dawley rats were randomly divided into five groups: Sham, AMI (Model), electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment (EA), non-acupoint electroacupuncture (Control), and Model + corticosterone (Model + CORT). AMI was induced occlusion of the left anterior descending coronary artery, followed by 3 d of electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment. In the Control group, electroacupuncture was applied at points lying 5 and 10 mm from the base of the tail. The AMI + CORT group was injected with CORT (20 mg/kg) in saline. Hemorheology, electrocardiography (ECG), hematoxylin and eosin staining, and expression of glycogen phosphorylase BB (GPBB) and heart-type fatty acid-binding protein (H-FABP) were used to assess cardiac function. The effects of adrenocorticotropic hormone (ACTH) and CORT were evaluated by enzyme-linked immunosorbent assay. Protein expression in the Sham and Model groups were screened by tandem mass tag-based quantitative proteomics analysis. Protein expression was evaluated by Western blotting (vimentin and GFAP) and immunofluorescence staining (GFAP). RESULTS: Compared with the Sham group, the hemorheology indicators, heart rate, ECG-ST segment elevation, and GPBB and H-FABP levels were higher in Model rats. The EA group showed reductions in these indicators compared with the Model group. Similarly, in Model rats, the expression of ACTH and CORT were significantly increased compared with the Sham group. The EA group also showed reduced expression of ACTH and CORT. Importantly, proteomics analysis showed that vimentin was differentially expressed in Model rats. Compared with the Sham group, vimentin and GFAP expression in the hippocampus was increased in the Model group but decreased in the AMI + EA group. Additionally, intraperitoneal injection of CORT aggravated the expression of GPBB, H-FABP and GFAP. CONCLUSIONS: Our results suggested that electroacupuncture may protect against cardiac injury induced by AMI through regulation of HPA axis hyperactivity, and that hippocampal GFAP may play an important role in the regulation.

MicroRNA-629-3p Promotes Interleukin-13-Induced Bronchial Epithelial Cell Injury and Inflammation by Targeting FOXA2.

OBJECTIVE: Asthma is a chronic pulmonary inflammatory disease. MicroRNA (miR)-629-3p expression is reported to be up-regulated in the sputum of asthma patients. Nonetheless, miR-629-3p's role and mechanism in asthma remain largely unknown. This study is aimed at exploring miR-629-3p's role in regulating the injury and inflammation of bronchial epithelial cells. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of miR-629-3p and forkhead box a2 (FOXA2) mRNA in 16HBE cells treated with interleukin-13 (IL-13). 16HBE cell viability was evaluated using the cell counting kit-8 (CCK-8) assay, and cell apoptosis was analyzed by a flow cytometer. The levels of C-C motif chemokine ligand 11 (CCL11), C-C motif chemokine ligand 26 (CCL26), C-C motif ligand 2 (CCL-2)/mono-cyte chemotactic protein-1 (MCP-1), interleukin-1 beta (IL-1b), and interleukin 6 (IL-6) in 16HBE cell supernatant were detected through enzyme-linked immunosorbent assay (ELISA). The downstream target genes of miR-629-3p were predicted through bioinformatics. Besides, the targeted relationship between miR-629-3p and FOXA2 mRNA 3'-UTR was verified by dual-luciferase reporter gene assay. Western blot was utilized to determine the regulatory effects of miR-629-3p on the expression of FOXA2 protein in 16HBE cells. RESULTS: MiR-629-3p expression was significantly enhanced in IL-13-stimulated 16HBE cells while the FOXA2 mRNA and protein levels were significantly down-regulated. The transfection of miR-629-3p mimics inhibited 16HBE cells' viability, and promoted the apoptosis and the secretion of chemokines CCL11, CCL26, CCL-2/MCP-1, IL-1b, and IL-6 of 16HBE cells, whereas inhibiting miR-629-3p had the opposite effects. Moreover, FOXA2 was identified as a downstream miR-629-3p target, and its overexpression reversed the effects of the miR-629-3p on 16HBE cells. CONCLUSION: MiR-629-3p promotes IL-13-induced 16HBE cells' injury and inflammation by targeting FOXA2.

A review: extraction, phytochemicals, and biological activities of rambutan (Nephelium lappaceum L) peel extract.

Rambutan (Nephelium lappaceum L.) peels are produced during application process. Drying methods of rambutan peel, including open sun, oven, oven vacuum, and freeze-drying, have been describes in this study. The extraction technologies of dried rambutan peels were reviewed, such as maceration and hot extraction, microwave-assisted extraction, ultrasonic-assisted extraction, and supercritical fluid extraction. The phytochemicals of rambutan peel extracts were analyzed, and the purification and stability of geraniin was reviewed. Rambutan peel extracts exhibit wide bioactivities in vitro and in vivo, and these bioactivities depend chiefly on the phenolic contents and profiles in the different extracts. The safety of rambutan peel extracts was analyzed. In addition, rambutan peel extracts could be used as important components to make different products, which are potentially applied in food, medicine, and cosmetic. However, the extracts efficiency must be further increased using some emerging technologies. Furthermore, the bioactive mechanism and bioavailability of the extract in human system should be further evaluated.