Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

Methylene blue ameliorates brain edema in rats with experimental ischemic stroke via inhibiting aquaporin 4 expression.

Brain edema is a common and serious complication of ischemic stroke with limited effective treatment. We previously reported that methylene blue (MB) attenuated ischemic brain edema in rats, but the underlying mechanisms remained unknown. Aquaporin 4 (AQP4) in astrocytes plays a key role in brain edema. We also found that extracellular signal-regulated kinase 1/2 (ERK1/2) activation was involved in the regulation of AQP4 expression in astrocytes. In the present study, we investigated whether AQP4 and ERK1/2 were involved in the protective effect of MB against cerebral edema. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), MB (3 mg/kg, for 30 min) was infused intravenously through the tail vein started immediately after reperfusion and again at 3 h after ischemia (1.5 mg/kg, for 15 min). Brain edema was determined by MRI at 0.5, 2.5, and 48 h after tMCAO. The decreases of apparent diffusion coefficient (ADC) values on diffusion-weighted MRI indicated cytotoxic brain edema, whereas the increase of T2 MRI values reflected vasogenic brain edema. We found that MB infusion significantly ameliorated cytotoxic brain edema at 2.5 and 48 h after tMCAO and decreased vasogenic brain edema at 48 h after tMCAO. In addition, MB infusion blocked the AQP4 increases and ERK1/2 activation in the cerebral cortex in ischemic penumbra at 48 h after tMCAO. In a cell swelling model established in cultured rat astrocyte exposed to glutamate (1 mM), we consistently found that MB (10 µM) attenuated cell swelling, AQP4 increases and ERK1/2 activation. Moreover, the ERK1/2 inhibitor U0126 (10 µM) had the similar effects as MB. These results demonstrate that MB improves brain edema and astrocyte swelling, which may be mediated by the inhibition of AQP4 expression via ERK1/2 pathway, suggesting that MB may be a potential choice for the treatment of brain edema.

Pyrosequencing of the subgingival microbiome in peri-implantitis after non-surgical mechanical debridement therapy.

BACKGROUND AND OBJECTIVES: Peri-implantitis remains a challenge for dental implant therapy, and the prognosis of non-surgical therapy for peri-implantitis is unsatisfactory. In order to reveal the impact of non-surgical mechanical debridement therapy on microbial communities, we investigated the subgingival microbial communities of healthy implants and implants with peri-implantitis, both before and after the therapy. MATERIAL AND METHODS: Subgingival plaques were collected from patients with healthy dental implants (HC; n = 10) and from patients with peri-implantitis (n = 13) before and after non-surgical mechanical debridement therapy. The treatment was conducted using curettes for submucosal debridement followed by irrigation with 0.2% (w/v) chlorhexidine, with re-examination 1 month later. 16S rRNA pyrosequencing was used to analyze the subgingival microbiome, and co-occurrence networks were adopted to explore the interactions between pathogens in the microbial communities. RESULTS: A total of 506 955 high-quality reads were generated, and 2222 operational taxonomic units were finally detected using a 97% similarity cutoff, with a mean of 249 ± 69 per sample. The peri-implantitis sites harbored similar microbial communities before and after the treatment, as demonstrated by the microbial diversity, relative abundance, and prevalence of bacteria. Most importantly, the microbial community structures were stable before and after non-surgical therapy based on the microbial diversity and bacterial composition, as well as the interactions between key pathogens, including Enterobacteriaceae, Selenomonas sputigena, Parvimonas, Eubacterium infirmum, Campylobacter gracilis, Tannerella forsythia, and Fusobacterium, which were measured using a co-occurrence network analysis. Periodontal pathogens were also detected in subgingival plaque after the treatment. Distinct microbial communities were found between the healthy and peri-implantitis sites. CONCLUSION: Our results demonstrate that non-surgical mechanical debridement therapy did not significantly affect the subgingival microbial communities in peri-implantitis, and the stable microbial networks created via interactions among pathogens may be responsible for the poor prognosis of peri-implantitis treatment.

Adaptive modal gain controlling for a high-efficiency cylindrical vector beam fiber laser.

We propose and experimentally demonstrate an ytterbium-doped fiber laser emitting the single high-order cylindrical vector beams with a high efficiency and a high modal purity based on adaptive modal gain control. By the combination of a high-order pump with a self-designed ytterbium-ring doped fiber, modal dependent gain was tailored and specific transverse mode can be selected in the laser cavity. A model based on multimode propagation-rate equations is built up to demonstrate the behaviors of transverse mode competition in the fiber laser. Modal dependent gain of high-order mode pump are simulated numerically, which agree well with our experiment results. The slope efficiency of the fiber laser reaches 79.61% with a low threshold of 47.73mw. The purity of the generated high-order CVBs are in excess of 95%. Such a strategy enables the controllability of modal gain in a fiber laser and reveals the potential to offer a new and promising way to achieve a high-power fiber laser with an arbitrary single high-order transverse modes output.

On-chip generation of time-and wavelength-division multiplexed multiple time-bin entanglement.

Optical quantum states based on entangled photons are the key resource in quantum-information science. The realization of multiplexed multiple entanglement are necessary for developing high-capacity quantum information process. Silicon-on-insulator (SOI) has recently become a leading platform for generating and processing of non-classical optical states. In this work, by combining the wavelength- and time-division multiplexing technologies, we demonstrate a multiplexing time-bin entangled photon pair source based on a silicon nanowire waveguide and distribute entangled photons into 3(time) × 14(wavelength) channels independently. The indistinguishability of photon pairs in each time channel is confirmed by a fourfold Hong-Ou-Mandal quantum interference. Our work paves a new and promising way to achieve a high capacity quantum communication and to generate a multiple-photon non-classical state.

Quantum frequency conversion for multiplexed entangled states generated from micro-ring silicon chip.

Silicon-on-chip photonic circuits are among some very promising platforms for generating nonclassical photonic quantum state, because of its low loss, small footprint, and compatibility with complementary metal-oxide-semiconductor (CMOS) and telecommunications techniques. Dense wavelength division multiplexing (DWDM) is a leading technique for enhancing the transmission capacity of both classical and quantum communications. To bridge the frequency gap between silicon-chip and other quantum systems, such as quantum memories, a quantum interface is indispensable. Here, we demonstrate a quantum interface for multiplexed energy-time entanglement states, which are generated on a silicon micro-ring cavity that is based on frequency up-conversion. By switching the pump wavelength, energy-time entanglement from any channel can be selected at will after being up-converted. The high visibilities of two-photon interference over three channels after frequency up-conversion clearly prove that the entanglement is fully preserved during the quantum frequency conversion (QFC) process. Our work provides new perspectives regarding channel capacity enhancement in quantum communications and for quantum resources being transferred between two different quantum systems.

Thermo-Mechanical Properties of Glass Fiber Reinforced Shape Memory Polyurethane for Orthodontic Application.

OBJECTIVES: Glass fiber reinforced shape memory polyurethane (GFRSMPU) has great potential to be an alternative kind of material for orthodontic archwires for overcoming the disadvantages of metal wires in terms of esthetic and allergy and deficiency of pure shape memory polyurethane (SMPU) wires in mechanical properties. The objective of this study was to investigate the thermo-mechanical properties and shape recovery functions of GFRSMPU and evaluate the feasibility of using this composite for orthodontic archwires. MATERIAL AND METHODS: GFRSMPU were made from short cut glass fibers and SMPU by mixing extrusion. Scanning electron microscope (SEM) and differential scanning calorimetry (DSC) were performed to investigate the distribution of glass fibers in the mixture and glass transition temperature (Tg). Then the thermo-mechanical properties, including tensile modulus, flexural modulus and stress relaxation effects, were measured. Furthermore, shape recovery functions of GFRSMPU characterized by the shape recovery ratio and force were investigated through shape recovery tests, typodont models and finite element analysis (FEA). RESULTS: SEM images indicated that an excellent dispersity of glass fibers was obtained after double-extrusion. DSC experiments showed Tg was not enormously affected with the existence of glass fibers, but the mechanical properties of GFRSMPU were greatly improved. Shape recovery tests showed reduction of shape recovery ratio of the GFRSMPU material with the addition of glass fibers, but dentition aligning time was reduced by 50% in the simulation performed on identical typodont models with GFRSMPU archwires filled with 30 wt.% glass fibers. The FEA results illustrated that the reacting forces of GFRSMPU archwires with 30 wt.% glass fiber was increased by 96.36% compared with pure SMPU archwires. CONCLUSIONS: The mechanical properties of GFRSMPU can be considerably improved by adding glass fibers, and the shape memory function would be well preserved too. Enhanced SMPU owns a good application prospect in orthodontics for dentation aligning on the preliminary stage, as well as other medical fields.

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma.

BACKGROUND/AIMS: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma. METHODS: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis. RESULTS: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups. CONCLUSION: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

Glutamate Impairs Mitochondria Aerobic Respiration Capacity and Enhances Glycolysis in Cultured Rat Astrocytes.

OBJECTIVE: To study the effect of glutamate on metabolism, shifts in glycolysis and lactate release in rat astrocytes. METHODS: After 10 days, secondary cultured astrocytes were treated with 1 mmol/L glutamate for 1 h, and the oxygen consumption rates (OCR) and extra cellular acidification rate (ECAR) was analyzed using a Seahorse XF 24 Extracellular Flux Analyzer. Cell viability was then evaluated by MTT assay. Moreover, changes in extracellular lactate concentration induced by glutamate were tested with a lactate detection kit. RESULTS: Compared with the control group, treatment with 1 mmol/L glutamate decreased the astrocytes' maximal respiration and spare respiratory capacity but increased their glycolytic capacity and glycolytic reserve. Further analysis found that 1-h treatment with different concentrations of glutamate (0.1-1 mmol/L) increased lactate release from astrocytes, however the cell viability was not affected by the glutamate treatment. CONCLUSION: The current study provided direct evidence that exogenous glutamate treatment impaired the mitochondrial respiration capacity of astrocytes and enhanced aerobic glycolysis, which could be involved in glutamate injury or protection mechanisms in response to neurological disorders.

Three gangliogliomas: results of GTG-banding, SKY, genome-wide high resolution SNP-array, gene expression and review of the literature.

According to the World Health Organization gangliogliomas are classified as well-differentiated and slowly growing neuroepithelial tumors, composed of neoplastic mature ganglion and glial cells. It is the most frequent tumor entity observed in patients with long-term epilepsy. Comprehensive cytogenetic and molecular cytogenetic data including high-resolution genomic profiling (single nucleotide polymorphism (SNP)-array) of gangliogliomas are scarce but necessary for a better oncological understanding of this tumor entity. For a detailed characterization at the single cell and cell population levels, we analyzed genomic alterations of three gangliogliomas using trypsin-Giemsa banding (GTG-banding) and by spectral karyotyping (SKY) in combination with SNP-array and gene expression array experiments. By GTG and SKY, we could confirm frequently detected chromosomal aberrations (losses within chromosomes 10, 13 and 22; gains within chromosomes 5, 7, 8 and 12), and identify so far unknown genetic aberrations like the unbalanced non-reciprocal translocation t(1;18)(q21;q21). Interestingly, we report on the second so far detected ganglioglioma with ring chromosome 1. Analyses of SNP-array data from two of the tumors and respective germline DNA (peripheral blood) identified few small gains and losses and a number of copy-neutral regions with loss of heterozygosity (LOH) in germline and in tumor tissue. In comparison to germline DNA, tumor tissues did not show substantial regions with significant loss or gain or with newly developed LOH. Gene expression analyses of tumor-specific genes revealed similarities in the profile of the analyzed samples regarding different relevant pathways. Taken together, we describe overlapping but also distinct and novel genetic aberrations of three gangliogliomas.

Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.

OBJECTIVE: To investigate the role of extracellular signal-regulated kinase1/2 (ERK1/2) pathway in the regulation of aquaporin 4 (AQP4) expression in cultured astrocytes after scratch-injury. METHODS: The scratch-injury model was produced in cultured astrocytes of rat by a 10-µL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase (LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2 (p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups. RESULTS: Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury. CONCLUSION: These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.

Pathogenicity of Five Strains of Toxoplasma gondii from Different Animals to Chickens.

Toxoplasma gondii is a protozoan parasite with a broad range of intermediate hosts. Chickens as important food-producing animals can also serve as intermediate hosts. To date, experimental studies on the pathogenicity of T. gondii in broiler chickens were rarely reported. The objective of the present study was to compare the pathogenicity of 5 different T. gondii strains (RH, CN, JS, CAT2, and CAT3) from various host species origin in 10-day-old chickens. Each group of chickens was infected intraperitoneally with 5×10(8), 1×10(8), 1×10(7), and 1×10(6) tachyzoites of the 5 strains, respectively. The negative control group was mockly inoculated with PBS alone. After infection, clinical symptoms and rectal temperatures of all the chickens were checked daily. Dead chickens during acute phage of the infection were checked for T. gondii tachyzoites by microscope, while living cases were checked for T. gondii infection at day 53 post-inoculation (PI) by PCR method. Histopathological sections were used to observe the pathological changes in the dead chickens and the living animals at day 53 PI. No significant differences were found in survival periods, histopathological findings, and clinical symptoms among the chickens infected with the RH, CN, CAT2, and CAT3 strains. Histopathological findings and clinical symptoms of the JS (chicken origin) group were similar to the others. However, average survival times of infected chickens of the JS group inoculated with 5×10(8) and 1×10(8) tachyzoites were 30.0 and 188.4 hr, respectively, significantly shorter than those of the other 4 mammalian isolates. Chickens exposed to 10(8) of T. gondii tachyzoites and higher showed acute signs of toxoplasmosis, and the lesions were relatively more severe than those exposed to lower doses. The results indicated that the pathogenicity of JS strain was comparatively stronger to the chicken, and the pathogenicity was dose-dependent.

[Association between polymorphisms of inflammatory factor genes and coronary heart disease].

OBJECTIVE: To investigate the association between genetic polymorphisms of inflammatory factors and susceptibility to coronary heart disease(CHD) in southern Chinese Han population. METHODS: Using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) method, the genotypes of five inflammatory factors (BRCA1-associated protein, a disintegrin and metalloproteinase 8, inter-alpha-trypsin inhibitor H3, interleukin-15, cyclooxygenase-2) were anaylzed in 283 CHD patients diagnosed by angiography and 176 controls. RESULTS: In these inflammatory factors, the 270T/C and 90A/G polymorphisms of the BRAP gene showed a significant association with CHD. The allele and genotype frequencies of BRAP gene were consistent with those predicted by Hardy-Weinberg equilibrium (chi-square=0.878, P> 0.05; chi-square=0.776, P> 0.05, respectively). The frequencecies of 270C and 90G alleles in CHD patients was significantly higher than those of the control group (29.51% vs. 21.31%, P=0.006; 30.04% vs. 21.31%, P=0.004, respectively). Compared with 270TT and 90AA, 270CC and 90GG genotypes had a significantly increased CHD risk by Logistic regression analysis (OR=4.51, 95%CI: 1.41-14.45, P=0.011; OR=5.09, 95%CI: 1.60-16.26, P=0.006, respectively). This association was still signifcant after adjustment for the sex, age, smoke, hypertension, diabetes, plasma total cholesterol and low density lipoprotein levels. No evidence of association was found for other single nucleotide polymorphisms. CONCLUSION: The 270T/C and 90A/G polymorphisms in the BRAP gene may contribute to an increased risk of CHD among southern Chinese Han population.

[Correlation between loss of heterozygosity on chromosome 1p and 19q and expression of MGMT, p53 and Ki-67 proteins in gliomas].

OBJECTIVE: To study the correlation of loss of heterozygosity (LOH) on chromosome 1p and 19q with the expression of MGMT, p53 and Ki-67 proteins in gliomas. METHODS: One hundred and forty six cases of gliomas (45 oligodendrogliomas, 42 oligodendroastrocytomas, and 59 astrocytomas) were included in this study. Their tissue and blood samples were retrospectively analyzed by PCR-denaturing high-performance liquid chromatography (DHPLC) for 1p and 19q status and by immunohistochemistry for MGMT, p53 and Ki-67 expression patterns. The correlation among them and with clinicopathological characteristics were analyzed by chi-square test and t-test. RESULTS: In the oligodendrogliomas, the positive rate of 1p LOH was 59.8%, significantly higher than 33.9% in astrocytomas (P = 0.002), and 1p and 19q LOH was 42.5%, significantly higher than 16.9% in astrocytomas (P = 0.001). Combined with LOH on 1p and 19q, low MGMT expression (65.5%), and high Ki-67 expression (54%) were more frequent in oligodendrogliomas, whereas high p53 expression was more frequent in astrocytomas and mixed tumors (75.2%). 1p LOH (72.5%) and low MGMT (87.5%) expressions were more frequent in grade II oligodendrogliomas, whereas high expressions of p53 (83.0%) and Ki-67 (76.6%) were more frequent in grade III oligodendrogliomas. In addition, high Ki-67 expression was more frequent in grade III astrocytomas. LOH on 1p and 19q LOH was more frequent in nontemporal oligodendrogliomas (55.6%) than that in temporal ones (22.2%, P = 0.002). Non-random associations were found between LOH 1p and 19q LOH, MGMT and p53 protein expressions, and MGMT and Ki-67 protein expressions (all P < 0.05), whereas mutual exclusions were found between LOH on 1p and 19q and p53 expression, and LOH 1p and Ki-67 expression. CONCLUSIONS: There is a significant interrelationship of the investigated molecular markers and clinicopathological features of gliomas, which support a promising role of molecular markers in guiding diagnostic assessment and clinical management of gliomas.

Serratus Anterior Plane Block Combined with General Analgesia and Patient-Controlled Serratus Anterior Plane Block in Patients with Breast Cancer: A Randomized Control Trial.

INTRODUCTION: Anterior serratus muscle plane block is a novel regional block technique for blockade of the sensory plane of the lateral cutaneous branch of the intercostal nerve (T2-T9), which effectively relieves the pain of patients and improves the quality of recovery. This study aimed to observe the early effectiveness and safety of serratus anterior plane block combined with general anesthesia and patient-controlled serratus anterior plane block in early postoperative recovery in breast cancer. METHODS: The study involved a total of 84 patients undergoing radical mastectomy in our hospital. The patients were randomly divided into three groups: the serratus anterior block + general anesthesia + patient-controlled serratus anterior plane block group (PCSAPB group), the serratus anterior block + general anesthesia + patient-controlled intravenous analgesia group (PCIA group), and the general anesthesia + PCIA group (control group), with n = 28 cases in each group. RESULTS: The visual analogue scale (VAS) scores of the three groups were compared before and after the operation (P < 0.001), and the anxiety visual analogue scale (AVAS) scores after operation were compared among the three groups (P < 0.001). The total number of postoperative analgesic pumps in the PCSAPB group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions in the three groups was statistically significant (P < 0.05). CONCLUSION: The combination of anterior serratus plane block and general anesthesia and patient-controlled anterior serratus plane block reduced pain and adverse events, alleviating anxiety, improving the quality of early postoperative recovery among patients with breast cancer after modified radical mastectomy.

The immunogenic maturation of goat monocyte-derived dendritic cells and upregulation of toll-like receptors by five antigens of Haemonchus contortus in-vitro.

Previously, it was found that several proteins of Haemonchus contortus were involved in the stimulation of the host immune system. However, the information about the selection of superlative antigens with immunogenic efficacies on host DCs is lacking. In the current study, the stimulatory effects of five recombinant proteins (elongation factor-1α, arginine kinase, ES-15, ES-24, and ADP-ribosylation factor 1) of H. contortus on the maturation of goat monocyte-derived dendritic cells (md-DCs) were reported. Recombinant proteins were purified separately in E. coli expression and incubated with isolated goat peripheral blood mononuclear cells (PBMC). Immunofluorescence assay (IFA) results confirmed the binding of these molecules to the md-DC's surface as compared to control groups. In the flow cytometry analysis, recombinant proteins induced md-DC stimulation via the up-regulation of the expression of the costimulatory molecule (CD80) and MHC-II. Quantitative RT-PCR data showed a significant increase in the expression of specific genes of the WNT and toll-like receptor (TLR) signaling pathways. The result of ELISA indicated the higher levels of cytokine (IL-10, IL-12, IFN-γ, and TNF-α) secretion in the md-DC compared to the negative (pET-32a His-Tag) and blank (PBS) control groups. The data gives valuable support in the selection of potential antigens for future studies on the immunomodulation of the host against the infection of H. contortus.

[Association of the polymorphism of synaptobrevins/vesicle-associated membrane proteins 8 gene with coronary heart disease in Chinese Han population].

OBJECTIVE: To investigate the association of synaptobrevins/vesicle-associated membrane proteins 8 (VAMP8) gene rs1010 polymorphism with coronary heart disease (CHD) in Chinese Han population. METHODS: The allele and genotype frequencies of the VAMP8 gene rs1010 locus in 185 CHD patients and 149 controls were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. RESULTS: There was polymorphism of the VAMP8 gene rs1010 locus in the studied population. The distribution of VAMP8 genotypes was in Hardy-Weinberg equilibrium. The frequency of the A allele in the CHD group was significantly higher than that in control (67.3% vs 53.0%, P< 0.05). Multiple logistic regression analysis showed that genotypes AA and AG were independent risk factors of coronary heart disease. The odds ratio (OR) of (AA+AG) genotype versus GG genotype was 1.969,95% CI: 1.032-3.755. CONCLUSION: The VAMP8 rs1010 polymorphism was associated with CHD risk in Chinese Han population, the A allele might serve as a genetic risk factor of coronary heart disease.

Molecular analyses of glioblastoma stem-like cells and glioblastoma tissue.

Glioblastoma is a common, malignant brain tumor whose disease incidence increases with age. Glioblastoma stem-like cells (GSCs) are thought to contribute to cancer therapy resistance and to be responsible for tumor initiation, maintenance, and recurrence. This study utilizes both SNP array and gene expression profiling to better understand GSCs and their relation to malignant disease. Peripheral blood and primary glioblastoma tumor tissue were obtained from patients, the latter of which was used to generate GSCs as well as a CD133pos./CD15pos. subpopulation. The stem cell features of GSCs were confirmed via the immunofluorescent expression of Nestin, SOX2, and CD133. Both tumor tissue and the isolated primary cells shared unique abnormal genomic characteristics, including a gain of chromosome 7 as well as either a partial or complete loss of chromosome 10. Individual genomic differences were also observed, including the loss of chromosome 4 and segmental uniparental disomy of 9p24.3→p21.3 in GSCs. Gene expression profiling revealed 418 genes upregulated in tumor tissue vs. CD133pos./CD15pos. cells and 44 genes upregulated in CD133pos./CD15pos. cells vs. tumor tissue. Pathway analyses demonstrated that upregulated genes in CD133pos./CD15pos. cells are relevant to cell cycle processes and cancerogenesis. In summary, we detected previously undescribed genomic and gene expression differences when comparing tumor tissue and isolated stem-like subpopulations.

Effect of the Standardized Management of Cancer Pain on Patients with Bone Metastasis of Lung Cancer in China.

OBJECTIVE: This study investigates the effect of the standardized management of cancer pain on patients with bone metastasis of lung cancer in China. PATIENTS AND METHODS: A total of 123 patients with bone metastasis of lung cancer were selected from the Respiratory Department of the Affiliated Hospital of North China University of Science and Technology. Among these patients, 62 patients who had not received standardized management of cancer pain from March 12, 2018, to September 11, 2018, were selected as the control group. In contrast, 61 patients who had received the standardized management of cancer pain from September 12, 2018, to March 11, 2019, were selected as the observation group. The former cohort accepted the conventional management of cancer pain, while the latter accepted the strict, standardized management of cancer pain. The demographic statistics, disease characteristics, and painkiller application of patients in these two groups were analyzed. Then, the analgesic effect and level of satisfaction were compared between these two groups. RESULTS: No significant differences were noticed between these two groups in terms of age, gender, smoking status, type of pathology, education level, previous treatment, and the Eastern Cooperative Oncology Group score, as well as other demographic and disease characteristics. As for the use of painkillers, opioid analgesics accounted for a higher proportion in the observation group than in the control group. Compared with the control group, pain improvement and patient satisfaction after analgesic treatment were significantly higher in the observation group (p < 0.05). CONCLUSION: The standardized management of cancer pain can considerably alleviate the pain of patients with bone metastasis of lung cancer and improve their quality of life. Furthermore, this type of management can increase satisfaction.

[Regulation of P38 and MKK6 on HMGB1 expression in alveolar macrophages induced by cyclic mechanical stretch.].

The aim of the present study was to investigate the role of mitogen-activated protein kinase kinase 6 (MKK6)-P38 signaling pathway in cyclic mechanical stretch-induced high mobility group box 1 protein (HMGB1) expression in alveolar macrophages. In the study, Sprague-Dawley rats were anesthetized and then sacrificed by bloodletting. The lungs were lavaged six times with prechilled PBS. Alveolar macrophages were isolated from lavage samples. Recombinant plasmids were transfected into alveolar macrophages with liposome DOTAP. Alveolar macrophages transfected with P38(AF)/pGFP and MKK6b(E)/pGFP plasmids were taken as treated groups, while the groups that transfected with pcDNA3 plasmid and pGFP plasmid served as blank transfection group and control group, respectively. All the groups were then cultured in 6-well Bioflex cell culture plates and exposed to cyclic mechanical stretch at 20% elongation using Flexercell 4000T cell stretching unit. The results showed that the transfection of MKK6b(E) led to a marked increases in P38 kinase activity compared with control group. In contrast, the transfection of P38(AF) significantly inhibited P38 kinase activity. Compared with control group, HMGB1 protein and mRNA expression in MKK6b(E) transfected cells increased markedly, while HMGB1 expression in P38(AF) transfected cells decreased markedly. These results suggest that MKK6-P38 MAPK signaling pathway regulates the expression of HMGB1 induced by cyclic mechanical stretch in alveolar macrophages.