Shear damage mechanisms of jointed rock mass: a macroscopic and mesoscopic study.

The joints are existing throughout the underground rock mass. It is of great significance to investigate the shear performance of the rock mass to maintain the stability of the underground structure. In this study, we conducted orthogonal tests to determine the proportion of rock-like materials, and used JRC curves to make specimen molds and then prepare the specimens. We conducted straight shear tests and uniaxial compression tests to determine the various mechanical parameters of the rock-like materials. Next, we carried out the compression and shear tests to investigate the shear characteristics of the specimens, and study the damage pattern and shear strength of the jointed rock mass under different confining pressures and roughness levels. The mesoscopic displacements in the shear process of joints were analyzed by using ABAQUS. The test results show that the effect of the confining pressure on the shear strength of the joint plane is relatively obvious, and a larger confining pressure indicates a larger shear strength. The effects of different joint plane roughness and shear rated on the shear characteristics of the joint plane are also significant. The mesoscopic displacement difference inside the joint plane with higher roughness is relatively large, and the stress concentration phenomenon is obvious and lasts longer, which leads to the faster destruction of the specimen with higher roughness and the higher destruction degree. Therefore, we suggest that the priority should be given to the reinforcement of jointed rock mass with high roughness during the construction to prevent sudden destabilization and failure.

Prognostic value of lymph node ratio in patients with non-metastatic cervical cancer treated with radical hysterectomy: A population-based study.

BACKGROUND: The lymph node ratio (LNR) is an emerging prognostic biomarker in multiple malignancies. This study aimed to explore the prognostic role of LNR in patients with non-metastatic cervical cancer undergoing radical hysterectomy. METHODS: Data were extracted from the SEER 17 registry. Univariate and multivariate Cox analyses were performed to identify the prognostic factors associated with cancer-specific survival (CSS). A nomogram was constructed to predict the 5-year and 10-year CSS. Survival analyses stratified by the status of LNR and different adjuvant treatments were performed using the Kaplan-Meier method. RESULTS: A total of 8128 female patients with non-metastatic cervical cancer who underwent radical hysterectomy and regional node examination (≥8) were enrolled. Of these, 1269 (15.6%) were confirmed as lymph node-positive. Cox regression analyses showed that age, race, tumor size, tumor grade, histology, and LNR were significant factors affecting CSS. A nomogram was developed for predicting the 5-year and 10-year CSS, which showed good discrimination and calibration. Patients without lymph node involvement had inferior CSS with adjuvant treatments compared to those who did not receive further treatment. In patients with LNR ≤10%, only those receiving adjuvant radiotherapy had a trend of better CSS. In patients with an LNR between 10% and 30% and more than 30%, concurrent radiochemotherapy (CCRT) proved to be the best treatment. CONCLUSIONS: LNR is an independent prognostic factor in patients with non-metastatic cervical cancer undergoing radical hysterectomy. For patients with negative lymph nodes, no further treatment is recommended. Patients with positive lymph nodes could benefit more from CCRT.

A rapid evaluation method of blasting effect based on optimized image segmentation algorithm and application in engineering.

To quickly determine the blasting block degree and conduct an accurate and objective analysis of the tunnel blasting effect, this study has enhanced and improved upon the traditional genetic algorithm and Otsu algorithm. It has combined it with the marking watershed method and utilized ground digital acquisition to capture images of blasting debris. These images are then used in our custom-developed blasting analysis software to calculate the blasting block degree distribution and provide a quantitative analysis of blasting block degree. The research results show that the optimized image segmentation algorithm effectively improves the traditional threshold segmentation method on the poor effect of segmentation of the edge of the adherent block or the direct application of the watershed segmentation of the over-segmentation problem, to improve the segmentation accuracy based on the new segmentation technology is close to the traditional technology in terms of time. Through the self-developed software, the construction personnel in the project site to quickly obtain the blasting block degree histogram, block degree cumulative curve and other important indicators of the evaluation of the effect of blasting block degree, to provide data support for on-site construction, to assist in the modification of the blasting program, and to improve the efficiency of construction. This study realizes the rapid detection and block identification of blasting blocks, provides data support for the optimization of blasting parameters, and has good application and promotion value.

Research on the deformation laws of buildings adjacent to shield tunnels in clay strata.

Earth pressure shields are widely used in tunnel construction due to their low environmental impact and mechanized operations. However, ensuring the stability of the excavation surface during the construction process is crucial. Any instability in the excavation surface can lead to soil destruction, such as body collapse or surface uplift. Additionally, the tunneling process can cause deformation disturbances to nearby buildings. In the case of Beijing Metro Line 17, detailed survey data and construction monitoring data were collected through field surveys and tests. The study combined theoretical analysis and numerical simulations to investigate the impact of shield tunneling in clay layers on neighboring buildings. The focus was on analyzing the physical deformation and the response law of influencing factors, such as stratum parameters and engineering effects on surface settlement, building inclination, and distortion. Furthermore, sensitivity analysis of the deformation impact was conducted, and corresponding measures for deformation control were proposed.

Characteristics of cardiac arrhythmia and heart rate variability in Chinese patients with primary aldosteronism.

We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.

Association Between Mortality Due to Nasopharyngeal Carcinoma and Race in the United States From 2007 to 2016.

BACKGROUND: Asians and Pacific Islanders (API) exhibit increased incidence of nasopharyngeal carcinoma (NPC). However, they are often excluded when the disease is studied. Risk-factors and incidence are well-researched while cancer-specific mortality trends remain unclear. We aimed to determine whether insurance status modifies the association between race and cancer-specific mortality in NPC patients. METHODS: This retrospective cohort study used secondary data analysis from the Surveillance, Epidemiology, and End Results Program database. Patients ≥18 years with histologically confirmed primary NPC from 2007 - 2016 were included. The main outcome assessed was 5-year survival and the main exposure variable was race (API, white, black). Insurance status was classified into uninsured, any Medicaid, and insured (with any insurance). Potential confounders included age, sex, marital status, stage at diagnosis, and surgical treatment. Adjusted Cox regression analysis was used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: 1610 patients were included (72.98% male, 27.02% female). 49.8% were API, 40.5% were Whites, and 9.8% Blacks. Maximum follow-up was 5-years. The adjusted hazards of 5-year cancer-specific death for API and Blacks compared with Whites were 0.77 (95% CI 0.62 - 0.96) and 0.92 (95% CI 0.65 - 1.31), respectively. Cases decreased with age in API and Blacks. 8.2% of cases had localized disease, 45.3% had local spread, and 44.6% had distant metastasis. Insurance status did not modify the association between race and mortality. CONCLUSION: Race is an important prognostic factor to account for in NPC patients. Investigating risk-factors and subtypes stratified by race may explain our findings.

Improved Permeability Model of the Binary Gas Interaction within a Two-Phase Flow and its Application in CO2-Enhanced Coalbed Methane Recovery.

In this paper, we develop a dual-porosity dual-permeability model for binary gas migration to explore the permeability evolution in the matrix and fracture in the process of a gas-water two-phase flow during CO2-enhanced coalbed methane (CO2-ECBM) recovery in coal reservoirs. This mechanistic model accommodates the effects of elastic deformation caused by the effective stress change in the matrix and fracture, the swelling/shrinkage deformation of the matrix caused by adsorption/desorption, the convection and diffusion of gas, and the discharge of water. Specifically, the time-dependent matrix swelling, from initially completely reducing the fracture aperture to finally affecting the coal bulk volume, is considered by the invaded volume fraction involving binary gas intrusion. The model is validated through laboratory data and applied to examine the permeability evolution of CO2-ECBM recovery for 10 000 days. Furthermore, we analyze the sensitivity of some selected initial parameters to capture the key factors affecting CO2-ECBM recovery. Our modeling results show that the permeability evolution can be divided into two stages during the process, where stage I is dominated by effective stress and stage II is dominated by adsorption/desorption. Increasing the injection pressure or initial permeability advances the start of stage II. The decrease in initial water saturation causes the permeability to change more drastically and the time of stage II to appear earlier until a time long enough, after which little effect is seen on the permeability results.

Concurrent chemoradiotherapy using gemcitabine and nedaplatin in recurrent or locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with recurrent or locally advanced head and neck squamous cell carcinoma (HNSCC) typically have limited treatment options and poor prognosis. AIM: To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC. METHODS: This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days. Intensity-modulated radiation therapy with a conventional fraction was delivered 5 days per week. Objective response rate (ORR), disease control rate, and toxicity were observed as primary endpoints. Overall survival (OS) and progression free survival were recorded and analyzed as secondary endpoints. RESULTS: A total of 24 patients with HNSCC were enrolled. During the median 22.4-mo follow-up, both ORR and disease control rate were 100%. The one-year OS was 75%, and one-year progression-free survival (PFS) was 66.7% (median PFS was 15.1 mo). Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients, and patients who achieved complete response had better survival than those in the PR group (all P < 0.05). The most common grade 1-4 (100%) or grade 3-4 toxicities (75%) were hematological, and the most common grade 3-4 non-hematological toxicity was mucositis in 17 (71%) patients. CONCLUSION: Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability. Considering the high adverse event rate, the optimized dose and schedule must be further explored.

False-negative aldosterone-to-renin ratio in a primary aldosteronism patient complicated with primary polydipsia: case report.

Aldosterone-to-renin ratio is the most reliable screening method of primary aldosteronism and has been widely used in clinical practice, but the index is influenced by many factors, some of which cause it false-negative, consequently leading to primary aldosteronism underdiagnosed. We report a rare case of a 27-year-old woman complaining of elevated arterial blood pressure and spontaneous hypokalemia but whose aldosterone-to-renin ratio were negative consecutively. She also had symptoms of polydipsia and polyuria for more than 20 years, with the volume of water intake and urine output up to 17 liters per day. Confirmatory tests of saline infusion test and captopril challenge test could not suppress plasma aldosterone concentration to the cutoff value. Abdominal contrast-enhanced CT suggested an adenoma on the right adrenal gland. After excluding other known causes of hypertension with hypokalemia, the patient was ultimately diagnosed with aldosterone-producing adenoma complicated with primary polydipsia. Complete clinical remission was achieved after unilateral adrenalectomy. The histopathology showed typical features of adrenocortical adenoma which was positive for CYP11B2 by immunohistochemistry, and next-generation sequencing results of tumor tissues revealed a missense mutation of the KCNJ5 gene [chr11:128781619, c.451 (exon 2) G>A]. All these findings supported the diagnosis of aldosterone-producing adenoma. This study has shown that negative aldosterone-to-renin ratio screening result cannot simply exclude primary aldosteronism. Comprehensive patient's evaluation should be taken to avoid missed diagnosis in clinical work, especially for those who have potentially curative surgery.

Class I myosin mediated endocytosis and polarization growth is essential for pathogenicity of Magnaporthe oryzae.

In eukaryotes, myosin provides the necessary impetus for a series of physiological processes, including organelle movement, cytoplasmic flow, cell division, and mitosis. Previously, three members of myosin were identified in Magnaporthe oryzae, with class II and class V myosins playing important roles in intracellular transport, fungal growth, and pathogenicity. However, limited is known about the biological function of the class I myosin protein in the rice blast fungus. Here, we found that Momyo1 is highly expressed during conidiation and infection. Functional characterization of this gene via RNA interference (RNAi) revealed that Momyo1 is required for vegetative growth, conidiation, melanin pigmentation, and pathogenicity of M. oryzae. The Momyo1 knockdown mutant is defective in formation of appressorium-like structures (ALS) at the hyphal tips. In addition, Momyo1 also displays defects on cell wall integrity, hyphal hydrophobicity, extracellular enzyme activities, endocytosis, and formation of the Spitzenkörper. Furthermore, Momyo1 was identified to physically interact with the MoShe4, a She4p/Dim1p orthologue potentially involved in endocytosis, polarization of the actin cytoskeleton. Overall, our findings provide a novel insight into the regulatory mechanism of Momyo1 that is involved in fungal growth, cell wall integrity, endocytosis, and virulence of M. oryzae. KEY POINTS: • Momyo1 is required for vegetative growth and pigmentation of M. oryzae. • Momyo1 is essential for cell wall integrity and endocytosis of M. oryzae. • Momyo1 is involved in hyphal surface hydrophobicity of M. oryzae.

Oral exposure of sulpiride promotes the proliferation of Brown-Norway rat prostates.

The aim of the present study was to establish an animal model of prostatic hyperplasia to explore the mechanisms of this disease. Sulpiride, a specific type 2 dopamine receptor antagonist, causes prostate toxicity by stimulating prolactin (PRL) production. Male Brown-Norway (BN) rats were treated intragastrically (i.g.) with sulpiride (40 and 120 mg/kg daily) and vehicle (i.g., daily) for 4 weeks. The results demonstrated that sulpiride-treatment resulted in increased prostate size, prostate lobe weight, epithelial height and acinar luminal area. Furthermore, prostate lobe weight, epithelial height and acinar luminal area of lateral lobes (LP) significantly increased. These effects were dose dependent. Sulpiride treatment increased serum PRL, follicle-stimulating hormone and testosterone levels, while serum luteinizing hormone levels were reduced. Immunohistochemical analysis revealed that proliferating cell nuclear antigen and B-cell lymphoma-2 were significantly increased in certain sulpiride treated groups. Furthermore, estrogen receptor (ER)-α and androgen receptors were upregulated, while ERß was downregulated in LP. The expression of stromal cell biomarkers, including vimentin, fibronectin and α-smooth muscle actin were significantly increased in LP following 40 mg/kg sulpiride administration. These results suggest that sulpiride causes LP hyperplasia in BN rats by promoting proliferation and inhibiting prostate cell apoptosis via ERα and AR signaling.

Long non-coding RNA urothelial cancer associated 1 can regulate the migration and invasion of colorectal cancer cells (SW480) via myocardin-related transcription factor-A.

Colorectal cancer (CRC) is the third leading cause of cancer-associated mortalities. Long non-coding RNAs (lncRNAs) have been identified as key regulators in the occurrence and development of CRC. The lncRNA urothelial cancer associated 1 (UCA1) has been demonstrated to promote the development of numerous different types of cancer. In the present study, a novel molecular mechanism of UCA1, regulating the migratory and invasive capabilities of SW480 CRC cells was identified. UCA1 promoted the migration and invasion of SW480 cells by suppressing phosphorylation of myocardin-related transcription factor-A (MRTF-A). Our findings indicated that UCA1 competes with extracellular signal-regulated kinases1/2 to inhibit the phosphorylation of MRTF-A. These novel discoveries may reveal additional functions of UCA1, which may support future clinical development of novel drug targets.

Proteomic analysis of human prostate cancer PC-3M-1E8 cells and PC-3M-2B4 cells of same origin but with different metastatic potential.

Prostate cancer (PCa) is the second most frequently diagnosed cancer and the fifth leading cause of death from cancer in men worldwide. Increased understanding of the prostate cancer metastasis mechanisms will help identify more efficient intervention strategies to prevent or treat this deadly disease in the future. To identify the candidate proteins that contribute to metastasis of PCa, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis was performed to explore differentially expressed proteins between two homologous human prostate cancer cell lines including highly-metastatic PC-3M-1E8 cell line and poorly-metastatic PC-3M-2B4 cell line. Here, a total of 58 proteins were identified to be significantly differentially expressed between PC-3M-1E8 and PC-3M-2B4 cells, which were further verified using real-time quantitative PCR and western blot analysis. The bioinformatic analysis suggested that the differentially expressed proteins, like MMP1 and FHL1, may contribute to the higher metastatic ability of PC-3M-1E8 cells than PC-3M-2B4 cells. In addition, functional analyses proved MMP1's positive effect on the higher metastatic ability of PC-3M-1E8 cells than PC-3M-2B4 cells. These findings provided a unique resource to specifically reveal the complex molecular regulatory mechanisms underlying the progression of prostate cancer from poorly-metastatic to highly-metastatic stage.

Oral exposure of low-dose bisphenol A promotes proliferation of dorsolateral prostate and induces epithelial-mesenchymal transition in aged rats.

Bisphenol A (BPA) is a well-known endocrine disruptor compound reported to have prostate toxicity. This study aimed to assess the effect of BPA on the proliferation of dorsolateral prostate (DLP) and the expression of epithelial-mesenchymal transition (EMT)-related genes in aged rats. Male aged SD rats were treated with BPA (10.0, 30.0, and 90.0 µg/kg i.g., daily) or vehicle (i.g., daily) for 3 months. Treatment with BPA resulted in increased the expression of PCNA, DLP weight and DLP epithelial height compared with the control group (P < 0.01); such effects were more obvious at higher BPA doses. 90 µg/kg BPA significantly increased the estrogen to androgen ratio (P < 0.05). The EMT chip showed the BPA induced upregulation of vimentin, Snail, Twist1, and transforming growth factor beta 1, as well as the downregulation of E-cadherin in the DLP. Immunohistochemical data showed that the expression of vimentin, estrogen receptor subtypes, and androgen receptor increased and the expression of E-cadherin decreased in 30 and 90 µg/kg BPA groups. It was concluded that environmental exposure to low doses of BPA might promote the proliferation of DLP in aged rats by increasing the estrogen to androgen ratio and inducing EMT.

[CYTOCOMPATIBILITY AND PREPARATION OF BONE TISSUE ENGINEERING SCAFFOLD BY COMBINING LOW TEMPERATURE THREE DIMENSIONAL PRINTING AND VACUUM FREEZE-DRYING TECHNIQUES].

OBJECTIVE: To study the preparation and cytocompatibility of bone tissue engineering scaffolds by combining low temperature three dimensional (3D) printing and vacuum freeze-drying techniques. METHODS: Collagen (COL) and silk fibroin (SF) were manufactured from fresh bovine tendon and silkworm silk. SolidWorks2014 was adopted to design bone tissue engineering scaffold models with the size of 9 mm x 9 mm x 3 mm and pore diameter of 500 µm. According to the behavior of composite materials that low temperature 3D printing equipment required, COL, SF, and nano-hydroxyapatite (nHA) at a ratio of 9 : 3 : 2 and low temperature 3D printing in combination with vacuum freeze-drying techniques were accepted to build COL/SF/nHA composite scaffolds. Gross observation and scanning electron microscope (SEM) were applied to observe the morphology and surface structures of composite scaffolds. Meanwhile, compression displacement, compression stress, and elasticity modulus were measured by mechanics machine to analyze mechanical properties of composite scaffolds. The growth and proliferation of MC3T3-E1 cells were evaluated using SEM, inverted microscope, and MTT assay after cultured for 1, 7, 14, and 21 days on the composite scaffolds. The RT-PCR and Western blot techniques were adopted to detect the gene and protein expressions of COL I, alkaline phosphatase (ALP), and osteocalcin (OCN) in MC3T3-E1 cells after 21 days. RESULTS: COL/SF/nHA composite scaffolds were successfully prepared by low temperature 3D printing technology and vacuum freeze-drying techniques; the SEM results showed that the bionic bone scaffolds were 3D polyporous structures with macropores and micropores. The mechanical performance showed that the elasticity modulus was (344.783 07 ± 40.728 55) kPa; compression displacement was (0.958 41 ± 0.000 84) mm; and compression stress was (0.062 15 ± 0.007 15) MPa. The results of inverted microscope, SEM, and MTT method showed that a large number of cells adhered to the surface with full extension and good cells growth inside the macropores, which demonstrated a satisfactory proliferation rate of the MC3T3-E1 cells on the composite scaffolds. The RT-PCR and Western blot electrophoresis revealed gene expressions and protein synthesis of COL I, ALP, and OCN in MC3T3-E1 cells. CONCLUSION: Low temperature 3D printing in combination with vacuum freeze-drying techniques could realize multi-aperture coexisted bionic bone tissue engineering scaffolds and control the microstructures of composite scaffolds precisely that possess good cytocompatibility. It was expected to be a bone defect repair material, which lays a foundation for further research of bone defect.