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Little is known about the genetics of sclerosing stromal tumor of the ovary, a rare type of sex cord-stromal tumor. Here, the authors use sequencing strategies to show that in a cohort of 26 tumor samples 65% carry a FHL2-GLI2 fusion gene and demonstrate in vitro that the fusion gene has oncogenic properties.

Danofloxacin is a synthetic fluoroquinolone with broad-spectrum activity developed for use in veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff values and the optimum doses of danofloxacin against P. multocida and H. parasuis in piglets. Single dose serum pharmacokinetics was determined in piglets after intravenous and intramuscular administration of 2.5 mg/kg. Danofloxacin was well absorbed and fully bioavailable (95.2%) after intramuscular administration of 2.5 mg/kg. The epidemiological cutoff (ECOFF) values of danofloxacin from 931 P. multocida isolates and 263 H. parasuis isolates were 0.03 and 4 mg/L, respectively. Danofloxacin MICs determined in porcine serum were markedly lower than those measured in artificial broth, with a broth/serum ratio of 4.33 for H. parasuis. Compared to P. multocida, danofloxacin exhibited significantly longer post-antibiotic effects (3.18–6.60 h) and post-antibiotic sub-MIC effects (7.02–9.94 h) against H. parasuis. The mean area under the concentration-time curve/MIC (AUC24h/MIC) targets of danofloxacin in serum associated with the static and bactericidal effects were 32 and 49.8, respectively, for P. multocida, whereas they were 14.6 and 37.8, respectively, for H. parasuis. Danofloxacin AUC24h/MIC targets for the same endpoints for P. multocida were higher than those for H. parasuis. At the current dose of 2.5 mg/kg, the PK/PD cutoff (COPD) values of danofloxacin against P. multocida and H. parasuis were calculated to be 0.125 and 0.5 mg/L, respectively, based on Monte Carlo simulations. The predicted optimum doses of danofloxacin for a probability of target attainment (PTA) of > 90% to cover the overall MIC population distributions of P. multocida and H. parasuis in this study were 2.38 and 13.36 mg/kg, respectively. These PK/PD-based results have potential relevance for the clinical dose optimization and evaluation of susceptibility breakpoints for danofloxacin in the treatment of swine respiratory tract infections involving these pathogens.

The migration path of formation water plays an indispensable role in hydrocarbon accumulation and preservation. The hydrodynamic field controls the content of various ions in formation water and is an important participant in hydrocarbon evolution. Formation water can basically be used to judge the preservation status of oil/gas reservoirs, especially for carbonate reservoirs; the carbonate reservoirs are a typical example in the Gaoqiao area of the Ordos Basin, China. However, it is not easy to evaluate the sealing and integrity of the gas reservoir because hydrocarbon has experienced a multistage charging process and complicated later reconstruction. The geochemical characteristics of Ordovician formation water (100 brine samples from 67 wells in the Ma5 Member) are studied, and their chemical composition is analyzed in the Ordos Basin. The results show that formation water has high overall salinity and is the original sedimentary water of the carbonate reservoir, which is the sealing reservoir and can promote the accumulation of hydrocarbons. This is also associated with stronger water-rock reactions and diagenetic transformations, such as dolomitization. The main (TDS) range is from 40 to 150 g·L−1, with an average of 66.16 g·L−1; the Cl− content in the formation water samples is the highest, followed by Ca2+, Na+, Mg2+, HCO3−, and SO42−. In addition, the (Cl−-Na+)/Mg2+ ratio, Na+/Cl− ratio, Mg2+/Ca2+ ratio, and SO42−×100/Cl− ratio are closely related to gas preservation. The indication function between chemical parameters of formation water and hydrocarbon dynamics can be better understood in carbonate reservoirs by analogy study, so as to improve the accuracy of discriminating favorable hydrocarbon accumulation areas.

ObjectiveThis study aimed to review the applicability and complications rate associated with endoscopic submucosal dissection (ESD) for early gastric cancer in elderly patients.MethodsDatabases of PubMed, Embase, CENTRAL, and ScienceDirect were searched till 15th April 2021. All types of studies comparing ESD in the elderly vs non-elderly were included. Subgroup analysis was conducted for the following groups: ≥80 years vs

Prognostic biomarkers that can reliably predict the disease-free survival (DFS) of locally advanced cervical cancer (LACC) are needed for identifying those patients at high risk for progression, who may benefit from a more aggressive treatment. In the present study, we aimed to construct a multiparametric MRI-derived radiomic signature for predicting DFS of LACC patients who underwent concurrent chemoradiotherapy (CCRT).MethodsThis multicenter retrospective study recruited 263 patients with International Federation of Gynecology and Obetrics (FIGO) stage IB-IVA treated with CCRT for whom pretreatment MRI scans were performed. They were randomly divided into two groups: primary cohort (n = 178) and validation cohort (n = 85). The LASSO regression and Cox proportional hazard regression were conducted to construct the radiomic signature (RS). According to the cutoff of the RS value, patients were dichotomized into low- and high-risk groups. Pearson’s correlation and Kaplan–Meier analysis were conducted to evaluate the association between the RS and DFS. The RS, the clinical model incorporating FIGO stage and lymph node metastasis by the multivariate Cox proportional hazard model, and a combined model incorporating RS and clinical model were constructed to estimate DFS individually.ResultsThe final radiomic signature consisted of four radiomic features: T2W_wavelet-LH_ glszm_Size Zone NonUniformity, ADC_wavelet-HL-first order_ Median, ADC_wavelet-HH-glrlm_Long Run Low Gray Level Emphasis, and ADC_wavelet _LL_gldm_Large Dependence High Gray Emphasis. Higher RS was significantly associated with worse DFS in the primary and validation cohorts (both p

Named entity recognition can deeply explore semantic features and enhance the ability of vector representation of text data. This paper proposes a named entity recognition method based on multi-head attention to aim at the problem of fuzzy lexical boundary in Chinese named entity recognition. Firstly, Word2vec is used to extract word vectors, HMM is used to extract boundary vectors, ALBERT is used to extract character vectors, the Feedforward-attention mechanism is used to fuse the three vectors, and then the fused vectors representation is used to remove features by BiLSTM. Then multi-head attention is used to mine the potential word information in the text features. Finally, the text label classification results are output after the conditional random field screening. Through the verification of WeiboNER, MSRA, and CLUENER2020 datasets, the results show that the proposed algorithm can effectively improve the performance of named entity recognition.

Photodetector spectral responsivity is usually affected by photosensitive surface temperatures. The Photosensitive Surface Temperatures (PSTs) of the long wavelength-type InGaAs detector used in the Polarized Scanning Atmospheric Corrector (PSAC), which adopts an active Constant-Current Cooling (CCC) scheme, can be changed with ambient temperature. To correct this responsivity temperature characteristic, a Responsivity Temperature Dependence Correction (RTDC) model was established with parameters obtained using an instrument-level experiment. Moreover, a detector-level experiment under ambient conditions was also explored to acquire model parameters. The instrument-level and detector-level experimental results show that the responsivity of a PSAC 2250 nm channel operating on orbit (PST ≈ −65 °C) with a 35 °C PST difference is reduced by approximately 1.2% and 1.5% compared with a laboratory-based radiometric test (PST ≈ −30 °C). The 1.08% responsivity change (−61 °C < PST < −38 °C) in the temperature drift simulation experiment is reduced to approximately 0.38% and 0.34%, respectively. The consistency between the two experimental results preliminarily verifies the substitutability of this detector-level experiment for this type of detector. The RTDC experiments are applicable to other spaceborne remote sensors. The detector-level experiment explored herein provides a reference for realizing RTDC under ambient temperature conditions at low costs.

In the above article [1], the affiliation of the coauthor Qiu Chen is currently listed incorrectly. His correct affiliation should be stated as “Major of Electrical Engineering and Electronics, Graduate School of Engineering, Kogakuin University, Tokyo, Japan.” Furthermore, it is necessary to rectify the biographical details of the coauthor Qiu Chen as follows:

Abstract The present study investigated the anti-atherosclerotic potential of myricitrin in hypercholesterolemic rats. Rats were divided into the following groups: sham (standard food), control [1% high-cholesterol diet (HCD)], 1 μM myricitrin + 1% HCD, 10 μM myricitrin + 1% HCD, 100 μM myricitrin + 1% HCD, and the positive control (10 mg/kg body weight atorvastatin). The dose was given to rats via oral gavage for 45 consecutive days. Feeding of rats with 1% HCD caused substantial increases in the levels of LDL, cholesterol, and triglycerides (TG), while high-density lipoprotein (HDL) was reduced. However, rats supplemented with myricitrin had reduced levels of cholesterol, LDL, and TG to near-normal levels, whereas HDL was increased. Catalase, superoxide dismutase (SOD), glutathione peroxidase (Gpx), and reduced glutathione (GSH) levels were substantially reduced in the HCD-fed rats compared with sham rats. However, the rats supplemented with 100 μM myricitrin showed > 50% increases in these levels. Lipid peroxidation and reactive oxygen species (ROS) levels were reduced following myricitrin treatment. The aortic cell wall area was significantly increased by 14.5% in HCD-fed rats. However, rats supplemented with 1, 10, and 100 μM myricitrin showed significant reductions in the aortic cell wall area of 2.3%, 4%, and 27.5%, respectively. This is the first report of the anti-atherosclerotic and hypolipidemic effects of myricitrin in hypercholesterolemic rats. Myricitrin decreased the level of total serum cholesterol and the role of aortic atherosclerosis in hypercholesterolemic rats.

As a new cement-matrix composite material, fiber-reinforced concrete performs excellently in freeze–thaw resistance, tensile resistance, and seepage resistance. Since resistivity can be used to evaluate the performance of concrete, the resistivity of basalt–polypropylene fiber-reinforced concrete (BPFRC) was investigated in this study. Various parameters such as fiber type, fiber content, and water–binder ratio were also analyzed. The resistivity of the BPFRC was tested by an improved two-electrode alternating current (AC) method, and the differences in resistivity were analyzed using scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP). The results showed that adding fiber affected the resistivity of the BPFRC, and the basalt fiber had a more significant effect than the polypropylene fiber. The resistivity of the BPFRC was sensitive to the water–binder ratio, which showed a negative correlation. In addition, a 365-day resistivity model for the BPFRC was established by considering variables such as fiber, water–binder ratio, ambient temperature, and ambient relative humidity. The hydration equations of various cementitious materials were derived, and a time-varying resistivity model for the BPFRC was developed. Finally, the established resistivity model of the BPFRC lays a foundation for the further building of the relationship between resistivity and BPFRC performance.

Purpose: To analyze clinical toxicity and quality-of-life (QOL) outcomes among patients with stage I non-small cell lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT) as a function of radiation dose and volume parameters. Methods and Materials: In this institutional review board–approved study, 55 patients with stage I NSCLC who received SBRT (12 Gy × 4) and completed QOL forms were analyzed. Clinical symptoms and QOL outcomes were measured at baseline and at 3, 6, 12, 18, 24, and 36 months after SBRT. Clinical toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Lung-Trial Outcome Index (FACT-L-TOI) instrument. Dosimetric parameters including the mean lung radiation dose and the volume of normal lung receiving greater than 5, 10, 13, or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student t tests and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxic effects. The Kaplan-Meier method was used to estimate rates of local control (LC), disease-free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3-year LC, DFS, and OS were 93%, 65%, and 84%, respectively, with a 5.5% rate of grade-3 toxic effects and no grade 4 or 5 toxic effects. Clinically meaningful declines in patient-reported QOL (FACT-L-TOI, lung cancer subscale, physical well-being, and/or functional well-being) posttreatment significantly correlated with increased dosimetric parameters such as V10, V13, and V20. Conclusion: Although lung SBRT was associated with excellent LC and minimal clinical toxic effects for early-stage NSCLC, clinically meaningful declines in QOL were significantly correlated with increasing lung dose and volume parameters.

Abstract Although liver‐humanized animals are desirable tools for drug development and expansion of human hepatocytes in large quantities, their development is restricted to mice. In animals larger than mice, a precondition for efficient liver humanization remains preliminary because of different xeno‐repopulation kinetics in livers of larger sizes. Since rats are ten times larger than mice and widely used in pharmacological studies, liver‐humanized rats are more preferable. Here, Fah–/–Rag2–/–IL2rg–/– (FRG) rats are generated by CRISPR/Cas9, showing accelerated liver failure and lagged liver xeno‐repopulation compared to FRG mice. A survival‐assured liver injury preconditioning (SALIC) protocol, which consists of retrorsine pretreatment and cycling 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC) administration by defined concentrations and time intervals, is developed to reduce the mortality of FRG rats and induce a regenerative microenvironment for xeno‐repopulation. Human hepatocyte repopulation is boosted to 31 ± 4% in rat livers at 7 months after transplantation, equivalent to approximately a 1200‐fold expansion. Human liver features of transcriptome and zonation are reproduced in humanized rats. Remarkably, they provide sufficient samples for the pharmacokinetic profiling of human‐specific metabolites. This model is thus preferred for pharmacological studies and human hepatocyte production. SALIC may also be informative to hepatocyte transplantation in other large‐sized species.

Interfacial transition zone (ITZ) is an important component of a concrete-like material. Accurately simulating the ITZ's characteristics of the concrete-like materials is a difficult process in numerical simulation. This article proposed a random three-phase mesostructural modeling method using the incorporation of random aggregate generation, Minkowski sum theory, and polygon union techniques. It was found that this method can better simulate the mesostructure and ITZ characteristics of concrete-like materials. By using this method, a random three-phase mesostructural model had been built for conducting a finite element analysis to investigate the effective permeability parameters of concrete. A good agreement between numerical and experimental results indicates the feasibility of this method in the concrete-like material analysis.

Background: Lymph node (LN) metastasis is considered one of the most important risk factors affecting the prognosis of distal cholangiocarcinoma (DCC). This study aimed to demonstrate the superiority of log odds of positive lymph nodes (LODDS) compared with other LN stages, and to establish a novel prognostic nomogram to predict the cancer-specific survival (CSS) of DCC.Methods: From the Surveillance, Epidemiology and End Results (SEER) database, the data of 676 patients after DCC radical operation were screened, and patients were randomly divided into training (n = 474) and validation sets (n = 474). The prognostic evaluation performance of the LODDS and American Joint Commission on Cancer (AJCC) N stage and lymph node ratio (LNR) were compared using the Akaike information criteria, receiver operating characteristic area under the curve (AUC), and C-index. Multivariate Cox analysis was used to screen independent risk factors, and a LODDS-based nomogram prognostic staging model was established. The nomogram's precision was verified by C-index, calibration curves, and AUC, and the results were compared with those of the AJCC TNM staging system.Results:Compared with the other two stages of LN metastasis, LODDS was most effective in predicting CSS in patients with DCC. Multivariate analysis proved that LODDS, histologic grade, SEER historic stage, and tumor size were independent risk factors for DCC. The C-index of the nomogram, based on the above factors, in the validation set was 0.663. The 1-, 3-, and 5-y AUCs were 0.735, 0.679, and 0.745, respectively. Its good performance was also verified by calibration curves. In addition, the C-index and Kaplan-Meier analysis showed that the nomogram performed better than the AJCC TNM staging system.Conclusion:For postoperative patients with DCC, the LODDS stage yielded better prognostic efficiency than the AJCC N and LNR stages. Compared with the AJCC TNM staging system, the nomogram, based on the LODDS, demonstrated superior performance.

Atherosclerosis is a multifaceted disease characterized by the formation and accumulation of plaques that attach to arteries and cause cardiovascular disease and vascular embolism. A range of diagnostic techniques, including selective coronary angiography, stress tests, computerized tomography, and nuclear scans, assess cardiovascular disease risk and treatment targets. However, there is currently no simple blood biochemical index or biological target for the diagnosis of atherosclerosis. Therefore, it is of interest to find a biochemical blood marker for atherosclerosis. Three datasets from the Gene Expression Omnibus (GEO) database were analyzed to obtain differentially expressed genes (DEG) and the results were integrated using the Robustrankaggreg algorithm. The genes considered more critical by the Robustrankaggreg algorithm were put into their own data set and the data set system with cell classification information for verification. Twenty-one possible genes were screened out. Interestingly, we found a good correlation between RPS4Y1 , EIF1AY , and XIST . In addition, we know the general expression of these genes in different cell types and whole blood cells. In this study, we identified BTNL8 and BLNK as having good clinical significance. These results will contribute to the analysis of the underlying genes involved in the progression of atherosclerosis and provide insights for the discovery of new diagnostic and evaluation methods.

Large volumes of crude oil accidentally released into the sea may cause irreversible adverse impacts on marine and coastal environments. Large swath optical imagery, acquired using platforms such as the moderate-resolution imaging spectroradiometer (MODIS), is frequently used for massive oil spill detection, attributing to its large coverage and short global revisit, providing rich data for oil spill monitoring. The aim of this study was to develop a suitable approach for massive oil spill detection in sun glint optical imagery. Specifically, preprocessing procedures were conducted to mitigate the inhomogeneous light field over the spilled area caused by sun glint, enhance the target boundary contrast, and maintain the internal homogeneity within the target. The image was then segmented into super-pixels based on a simple linear clustering method with similar characteristics of color, brightness, and texture. The neighborhood super-pixels were merged into target objects through the region adjacency graph method based on the Euclidean distance of their colors with an adaptive termination threshold. Oil slicks from the generated bright/dark objects were discriminated through a decision tree with parameters based on spectral and spatial characteristics. The proposed approach was applied to oil spill detection in MODIS images acquired during the Montara oil spill in 2009, with an overall extraction precision of 0.8, recall of 0.838, and F1-score of 0.818. Such an approach is expected to provide timely and accurate oil spill detection for disaster emergency response and ecological impact assessment.

The affine scale-invariant feature transform (ASIFT) algorithm is a feature extraction algorithm with affinity and scale invariance, which is suitable for image feature matching using unmanned aerial vehicles (UAVs). However, there are many problems in the matching process, such as the low efficiency and mismatching. In order to improve the matching efficiency, this algorithm firstly simulates image distortion based on the position and orientation system (POS) information from real-time UAV measurements to reduce the number of simulated images. Then, the scale-invariant feature transform (SIFT) algorithm is used for feature point detection, and the extracted feature points are combined with the binary robust invariant scalable keypoints (BRISK) descriptor to generate the binary feature descriptor, which is matched using the Hamming distance. Finally, in order to improve the matching accuracy of the UAV images, based on the random sample consensus (RANSAC) a false matching eliminated algorithm is proposed. Through four groups of experiments, the proposed algorithm is compared with the SIFT and ASIFT. The results show that the algorithm can optimize the matching effect and improve the matching speed.

Cardiovascular diseases (CVDs) are major causes of mortality and morbidity in the modern society. The rupture of atherosclerotic plaque can induce thrombus formation, which is the main cause of acute cardiovascular events. Recently, many studies have demonstrated that there are some relationships between microbiota and atherosclerosis. In this review, we will focus on the effect of the microbiota and the microbe-derived metabolites, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and lipopolysaccharide (LPS), on the stability of atherosclerotic plaque. Finally, we will conclude with some therapies based on the microbiota and its metabolites.

BackgroundLiver cancer is one of the most malignant human cancers, with few treatments and a poor prognosis. Erianin (ERN) is a natural compound with multiple pharmacological activities that has been reported to have numerous excellent effects against liver cancer in experimental systems. However, its application in vivo has been limited due to its poor aqueous solubility and numerous off-target effects. This study aimed to improve the therapeutic efficacy of ERN by developing novel ERN-loaded tumor-targeting nanoparticles.ResultsIn this study, ERN was loaded into liposomes by ethanol injection (LP-ERN), and the resulting LP-ERN nanoparticles were treated with transferrin to form Tf-LP-ERN to improve the solubility and enhance the tumor-targeting of ERN. LP-ERN and Tf-LP-ERN nanoparticles had smooth surfaces and a uniform particle size, with particle diameters of 62.60 nm and 88.63 nm, respectively. In HepG2 and SMMC-7721 cells, Tf-LP-ERN induced apoptosis, decreased mitochondrial membrane potentials and increased ERN uptake more effectively than free ERN and LP-ERN. In xenotransplanted mice, Tf-LP-ERN inhibited tumor growth, but had a minimal effect on body weight and organ morphology. In addition, Tf-LP-ERN nanoparticles targeted tumors more effectively than free ERN and LP-ERN nanoparticles, and in tumor tissues Tf-LP-ERN nanoparticles promoted the cleavage PARP-1, caspase-3 and caspase-9, increased the expression levels of Bax, Bad, PUMA, and reduced the expression level of Bcl-2. Moreover, in the spleen of heterotopic tumor model BALB/c mice, ERN, LP-ERN and Tf-LP-ERN nanoparticles increased the expression levels of Nrf2, HO-1, SOD-1 and SOD-2, but reduced the expression levels of P-IKKα+β and P-NF-κB, with Tf-LP-ERN nanoparticles being most effective in this regard. Tf-LP-ERN nanoparticles also regulated the expression levels of TNF-α, IL-10 and CCL11 in serum.ConclusionTf-LP-ERN nanoparticles exhibited excellent anti-liver cancer activity in vivo and in vitro by inducing cellular apoptosis, exhibiting immunoregulatory actions, and targeting tumor tissues, and did so more effectively than free ERN and LP-ERN nanoparticles. These results suggest that the clinical utility of a Tf-conjugated LP ERN-delivery system for the treatment of liver cancer warrants exploration.

BackgroundThe efficacy and safety of chimeric antigen receptor T (CAR-T) cell therapy in the treatment of non-Hodgkin’s lymphoma has already been demonstrated. However, patients with a history of/active secondary central nervous system (CNS) lymphoma were excluded from the licensing trials conducted on two widely used CAR-T cell products, Axicabtagene ciloleucel (Axi-cel) and Tisagenlecleucel (Tisa-cel). Hence, the objective of the present review was to assess whether secondary CNS lymphoma patients would derive a benefit from Axi-cel or Tisa-cel therapy, while maintaining controllable safety.MethodTwo reviewers searched PubMed, Embase, Web of Science, and Cochrane library independently in order to identify all records associated with Axi-cel and Tisa-cel published prior to February 15, 2021. Studies that included secondary CNS lymphoma patients treated with Axi-cel and Tisa-cel and reported or could be inferred efficacy and safety endpoints of secondary CNS lymphoma patients were included. A tool designed specifically to evaluate the risk of bias in case series and reports and the ROBINS-I tool applied for cohort studies were used.ResultsTen studies involving forty-four patients were included. Of these, seven were case reports or series. The other three reports were cohort studies involving twenty-five patients. Current evidence indicates that secondary CNS lymphoma patients could achieve long-term remission following Axi-cel and Tisa-cel treatment. Compared with the non-CNS cohort, however, progression-free survival and overall survival tended to be shorter. This was possibly due to the relatively small size of the CNS cohort. The incidence and grades of adverse effects in secondary CNS lymphoma patients resembled those in the non-CNS cohort. No incidences of CAR-T cell-related deaths were reported. Nevertheless, the small sample size introduced a high risk of bias and prevented the identification of specific patients who could benefit more from CAR-T cell therapy.ConclusionSecondary CNS lymphoma patients could seem to benefit from both Axi-cel and Tisa-cel treatment, with controllable risks. Thus, CAR-T cell therapy has potential as a candidate treatment for lymphoma patients with CNS involvement. Further prospective studies with larger samples and longer follow-up periods are warranted and recommended.

BackgroundRecent studies have shown that the systemic inflammation and nutritional indicators are prognostic for a variety of malignancies. However, only limited data have so far demonstrated their usefulness in gastrointestinal mesenchymal tumors (GIST).MethodsWe retrospectively analyzed the data of GIST patients who underwent radical surgery in Beijing hospital from October 2004 to July 2018. The area under the receiver operating characteristic curve (AUC) was used to compare several commonly used inflammatory and nutritional indicators. The indicators with largest AUC were further analysis. Optimal cut-off values of those indicators in predicting recurrence-free survival (RFS) were determined. Kaplan-Meier curve and the time-dependent receiver operating characteristic (ROC) curve were used to assess the prognostic values. We then used univariate and multivariate Cox regression analyses to identify prognostic factors that were associated with RFS.ResultsIn total, 160 patients who underwent surgery for GIST were included in the study. The median survival time was 34.5 months, with 1-, 3-, and 5-year RFS rates of 96.1%, 84.7%, and 80.8%, respectively. The inflammatory and nutritional indicators with largest AUC were Systemic immunoinflammatory Index (SII) and Geriatric Nutrition Risk Index (GNRI), reached 0.650 and 0.713, respectively. The optimal cutoff of GNRI and SII were 98.3, and 820.0, respectively. Univariate analysis showed that GNRI, SII, KI67, surgery method, tumor location, tumor size, and mitotic index were all significant prognostic indicators of RFS. After multivariate Cox analysis, independent prognostic factors for RFS in GIST included tumor location, mitotic index, tumor size, and GNRI (HR=2.802,95% CI: 1.045 to 7.515, p = 0.041). Besides, SII also tended to be associated with RFS (HR = 2.970, 95% CI: 0.946 to 9.326, p = 0.062).ConclusionsHigh GNRI is an independent prognostic factor for RFS in GIST, while SII can be considered as a prognostic factor. GNRI and SII can be used as tools to evaluate the prognosis of patients before surgery, helping doctors to better treat high-risk patients.

BackgroundCurrently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.MethodsTwo reviewers independently searched the Embase, PubMed, Web of Science, and Cochrane Library, to identify studies related to the use of the three CAR-T cell products for treating hematologic malignancies published up to October 5, 2020. We pooled the overall response rate, complete response rate, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome of three products, and then performed subgroup analysis based on the type of product and type of tumor.ResultsThirty-three studies involving 2,172 patients were included in the analysis. All three products showed promising results in patients with different pathological subtypes and clinical characteristics that included those who did not meet the eligibility criteria of licensing trials, with overall response rates of nearly 70% or above and complete response rates of more than 50%. However, high rates of severe immune effector cell-associated neurotoxicity syndrome in patients undergoing axicabtagene ciloleucel treatment and life-threatening cytokine release syndrome in patients with leukemia undergoing tisagenlecleucel treatment required special attention in practice (31%; 95% CI: 0.27–0.35 and 55%; 95% CI: 0.45–0.64, respectively). Moreover, lisocabtagene maraleucel that showed a favorable efficacy and safety in the licensing trial lacked corresponding real-world data.ConclusionBoth axicabtagene ciloleucel and tisagenlecleucel showed considerable efficacy in practice, but need special attention with respect to life-threatening toxicity that can occur in certain situations. Lisocabtagene maraleucel demonstrated excellent efficacy and safety profiles in the licensing trial, but lacked corresponding real-world data. Additional data on the three products are needed in rare histological subtypes to benefit a broader patient population.

Targeting DNA repair pathway offers an important therapeutic strategy for Homo sapiens (human) cancers. However, the failure of DNA repair inhibitors to markedly benefit patients necessitates the development of new strategies. Here, we show that exosome component 1 (EXOSC1) promotes DNA damages and sensitizes human kidney renal clear cell carcinoma (KIRC) cells to DNA repair inhibitor. Considering that endogenous source of mutation (ESM) constantly assaults genomic DNA and likely sensitizes human cancer cells to the inhibitor, we first analyzed the statistical relationship between the expression of individual genes and the mutations for KIRC. Among the candidates, EXOSC1 most notably promoted DNA damages and subsequent mutations via preferentially cleaving C site(s) in single-stranded DNA. Consistently, EXOSC1 was more significantly correlated with C>A transversions in coding strands than these in template strands in human KIRC. Notably, KIRC patients with high EXOSC1 showed a poor prognosis, and EXOSC1 sensitized human cancer cells to poly(ADP-ribose) polymerase inhibitors. These results show that EXOSC1 acts as an ESM in KIRC, and targeting EXOSC1 might be a potential therapeutic strategy.

Abstract Background Zoledronic acid is the most potent osteoclast inhibitor and is widely used for advanced cancer patients with bone metastasis, but its role on cancer stem cells (CSCs) remains unclear. In the present study, we aimed to identify the stemness phenotypic characteristics of CSCs derived from cervical cancer cells and explore the anti-cancer efficiency of zoledronic acid on these cells, as well as the possible molecular mechanisms. Methods Stemness phenotypic identification of cervical cancer cells derived CSCs was performed via sphere formation efficiency (SFE), tumorigenesis, immunofluorescence staining, Transwell assay, and western blot. Anti-cancer efficiency of zoledronic acid on these cells (including proliferation, stemness phenotype, apoptosis, and cell cycle) was carried out through MTT assay, SFE, transwell, DAPI staining, flow cytometry, immunofluorescence, TUNEL staining, and western blot, both in vitro and in vivo. Results Enhanced self-renewal ability, including SFE and tumorigenesis, was verified in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Specifically, the expression of ALDH1, Sox2, CD49f, Nanog, and Oct4 was significantly up-regulated in cervical cancer cells derived CSCs. Furthermore, enhanced migratory ability was observed in these cells along with up-regulated N-cadherin and Vimentin and down-regulated E-cadherin. Zoledronic acid inhibited cervical cancer cells derived CSCs proliferation in vitro and in vivo. The stemness phenotype of these CSCs including tumor sphere formation, migration, as well as the expression of the aforementioned associated markers was also suppressed. In addition, zoledronic acid significantly induced apoptosis and cell cycle arrest of cervical cancer cells derived CSCs in a dose-dependent manner. Mechanistically, the expression of phosphorylated Erk1/2 and Akt was significantly increased in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Zoledronic acid inhibited phosphorylated Erk1/2 and Akt in cervical cancer cells derived CSCs. IGF-1, a potent stimulator for Erk1/2 and PI3K/Akt, attenuated the aforementioned anti-cancer effect of zoledronic acid. Conclusions Zoledronic acid inhibited the growth of cervical cancer cells derived CSCs through attenuating their stemness phenotype, inducing apoptosis, and arresting cell cycle. The suppression of phosphorylated Erk1/2 and Akt was involved in this process.

To deal with the inconsistency of the minimum variance (MV) benchmark in evaluating non-Gaussian disturbance systems, this paper proposed a new benchmark, which combined entropy with output mean value. For a cascade control system, the new benchmark was constructed by analyzing the weakness of the MV benchmark and the pure Renyi entropy benchmark. In order to estimate the more accurate performance of the unknown system, an improved estimation of distribution algorithm based on entropy criterion is given. It can identify the disturbance distribution and calculate the new index evaluation value. Finally, different disturbance distributions were used to verify the consistency of the new index. The experimental results show that the proposed index and algorithms are consistent and effective in evaluating the performance of the unknown systems with non-Gaussian disturbance.

Streaming media transmission requires strict quality of service (QoS) parameters such as maximum delay and delay jitter. An effective streaming media routing algorithm is a key factor in ensuring QoS. The existing solution only considers a single parameter indicator in the performance parameters such as bandwidth, delay, and utilization of the link, and fails to comprehensively measure the data flow in the network. It is not possible to comprehensively measure the relationship between the business attributes and the QoS parameters. Firstly, the deterministic upper bounds of QoS parameters in streaming media networks are solved by using network calculus theory, and the QoS parameters are normalized, and a multi-constrained QoS resource allocation model is established; the separation of control and forwarding planes is defined by using software-defined networking (SDN) to deploy the multi-constrained QoS resource allocation model in the control plane; the QoS routing system of streaming media network based on the SDN is designed and implemented, including flow table scheduling model, routing function, measurement and forwarding modules. In the routing function module of the SDN controller, a multi-constrained QoS routing algorithm based on network calculus is implemented. Experimental results show that the proposed multi-constrained QoS resource allocation model based on network calculus and the multi-constrained centralized QoS routing algorithm based on the SDN have good performance.

Brain extraction is a process of removing non-brain tissue in the brain magnetic resonance (MR) images and serves as a first step towards more delicate brain segmentation. Although many brain extraction methods have been proposed in the literature, most of them are either laborious or time consuming, and lack of instant visualization. This leads to a time lag between image acquisition and comprehensive visualization. Especially for intraoperative image based neurosurgery navigation, the time lag from image acquisition to brain visualization should be reduced as much as possible. In this paper, we propose an end-to-end fast brain extraction and visualization framework. The input is a T1-weighted MR volume and the output is comprehensive brain visualization. An improved brain extraction tool (BET) algorithm is proposed to evolve a 3D active mesh model to fit the brain surface in the 3D image. Then the brain mask is generated per slice using a polygon fill algorithm. At last, a ray-casting volume rendering algorithm is used to visualize the brain surface with the help of the generated mask. All the operations are performed using the modern OpenGL pipelines running on a graphics processing unit (GPU). Experiments were performed on two publicly available datasets and one clinical dataset to compare our method with five state-of-the-art methods including the original BET in terms of segmentation accuracy and time cost. Our method achieved mean Dice coefficients of 96.8%, 97.1%, 98.5% and mean time cost of 361 ms, 341 ms, 502 ms on the three datasets, outperforming all the other methods.

This study aimed to evaluate the analgesic efficacy of astilbin and its underlying mechanisms. Astilbin suppressed the symptoms of acetic acid–induced writhing, lengthened the latency period on the hot plate, and reduced the licking and biting response of formalin-injected mice, suggesting its analgesic efficacy on the central nervous system. Astilbin suppressed neuronal nitric oxide synthase and enhanced serotonin and norepinephrine in serum and brains of mice after 30 s of thermal stimulation, but it failed to influence their levels before thermal stimulation. Among six chosen antagonists, only nimodipine, a calcium channel blocker, strongly enhanced the abirritation of astilbin, as indicated by the lengthened latency period of mice treated with nimodipine plus astilbin in the hot plate test. The expression levels of c-Fos and phosphorylated calmodulin-dependent protein kinase II and c-Jun N-terminal kinase in the brains were reduced in the astilbin-treated mice. Astilbin-mediated analgesia is partially related to Ca2+ channels.

Petroleum extraction, transportation, and consumption in the marine environment contribute to a large portion of anthropogenic oil spills into the ocean. While previous research focuses more on large oil spill accidents from oil tankers or offshore oil platforms, there are few systematic records on occasional regional oil spills. In this study, optical imagery from Landsat-8 OLI was used to detect oil slicks on the ocean surface through spatial analysis and spectral diagnosis in the northern South China Sea (NSCS). The source of the slicks was identified through datasets from traffic density and platform locations. A total of 632 oil slicks were detected in the NSCS from 2015 to 2019, where 57 were from platforms sources, and 490 were from ships. The average area of the detected slicks was 4.8 km2, and half of the slicks had areas 2. Major oil spill hot spots included coastal Guangdong (ship origins), southeast and northeast Dongsha Island (ship origins), middle of south Beibu Gulf (ship and platform origins), and southeast Pearl River Estuary (platform origins). Through this study, we demonstrate the capability of medium-resolution optical imagery in monitoring regional oil spills. Such results and methods may help in near real-time oil spill monitoring and further environmental assessments.

Bacterial contamination is an important factor causing food security issues. Among the bacteria, Escherichia coli is one of the main pathogens of food-borne microorganisms. However, traditional bacterial detection approaches cannot meet the requirements of real-time and on-site detection. Thus, it is of great significance to develop a rapid and accurate detection of bacteria in food to ensure food safety and safeguard human health. The pathogen heat-treatment module was designed in this paper based on the techniques including nanoprobe, pathogen heat-treatment, graphene transparent electrode (GTE), and adenosine triphosphate (ATP) bioluminescence technology. The system mainly consists of two parts: one is the optical detection unit; the other is the data processing unit. And it can quickly and automatically detect the number of bacterial colonies in food such as milk etc. The system uses not only the probe to capture and enrich E. coli by antigen-antibody interaction but also the heat treatment to increase the amount of ATP released from bacterial cells within five minutes. To enhance the detecting accuracy and sensitivity, the electric field generated by GTE is adopted in the system to enrich ATP. Compared to the other conventional methods, the linear correlation coefficient of the system can be reached 0.975, and the system meets the design requirements. Under the optimal experimental conditions, the detection can be completed within 25 min, and the detectable concentration of bacteria is in the range of 3.1 × 101–106 CFU/mL. This system satisfies the demands of a fast and on-site inspection.

As the prevalence of obesity increases, so does the occurrence of obesity-related complications, such as cardiovascular and cerebrovascular diseases, diabetes, and some cancers. Increased adipose tissue is the main cause of harm in obesity. To better understand obesity and its related complications, we analyzed the mRNA expression profiles of adipose tissues from 126 patients with obesity and 275 non-obese controls. Using an integrated bioinformatics method, we explored the functions of 113 differentially expressed genes (DEGs) between them. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses revealed that upregulated DEGs were enriched in immune cell chemotaxis, complement-related cascade activation, and various inflammatory signaling pathways, while downregulated DEGs enriched in nutrient metabolism. The CIBERSORT algorithm indicated that an increase in macrophages may be the main cause of adipose tissue inflammation, while decreased γδ T cells reduce sympathetic action, leading to dysregulation of adipocyte thermogenesis. A protein-protein interaction network was constructed using the STRING database, and the top 10 hub genes were identified using the cytoHubba plug-in in Cytoscape. All were confirmed to be obesity-related using a separate dataset. In addition, we identified chemicals related to these hub genes that may contribute to obesity. In conclusion, we have successfully identified several hub genes in the development of obesity, which provide insights into the possible mechanisms controlling obesity and its related complications, as well as potential biomarkers and therapeutic targets for further research.

Adalimumab, as a TNF inhibitor biologic for the treatment of rheumatoid arthritis, is one of the top-selling drugs worldwide. As its various patents have gradually expired, experiments on its biosimilars are constantly being implemented. In this review, we summarized clinical trials of seven biosimilars currently approved by the FDA and/or EMA for the treatment of rheumatoid arthritis, namely: ABP 501 (Amjevita/Amgevita/Solymbic), BI 695501 (Cyltezo), SB5 (Imraldi/Hadlima), GP2017 (Hyrimoz/Hefiya/Halimatoz), MSB11022 (Idacio), FKB327 (Hulio), and PF-06410293 (Abrilada). Overall, these biosimilars showed similar efficacy, safety, and immunogenicity to adalimumab. All biosimilar switching trials indicated that switching from adalimumab to a biosimilar does not have a significant impact on efficacy, safety, and immunogenicity.

BackgroundGlucocorticoid is one of the common and important strategies for the treatment of chimeric antigen receptor T (CAR-T) cell therapy-related toxicity. However, there has been a theoretical concern about whether glucocorticoids use can impact the expansion of CAR-T cells and thus impair its efficacy. Hence, we reviewed studies related to the Axicabtagene ciloleucel (Axi-cel), a first-class and widely used CAR-T cell product, to elucidate the association between glucocorticoids administration and efficacy of Axi-cel.MethodWe systematically searched PubMed, Embase, Web of Science, and Cochrane Library to identify studies of Axi-cel that used glucocorticoids as an intervention for the treatment of CAR-T cell-related adverse events and respectively evaluated any efficacy endpoints of intervention and controlled cohorts, published up to February 17, 2020. There were no restrictions on research type and language.ResultsA total of eight studies with 706 patients were identified in the systematic review. Except for one study found that high cumulative dose, prolonged duration and early use of glucocorticoids could shorten progression-free survival and/or overall survival, and another study that found a negative effect of glucocorticoids administration on overall survival in univariate analysis but disappeared in multivariate analysis, none of other studies observed a statistically significant association between glucocorticoids administration and progression-free survival, overall survival, complete response, and overall response rate.ConclusionOur study indicated that the association between glucocorticoids therapy and the efficacy of CAR-T cell may be affected by cumulative dose, duration, and timing. There is currently no robust evidence that glucocorticoids can damage the efficacy of CAR-T cell, but the early use of glucocorticoids should be cautiously recommended.

Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.

Nuclear factor of activated T cells (NFAT) is a transcription factor with a multidirectional regulatory function, that is widely expressed in immune cells, including cells in the cardiovascular system, and non-immune cells. A large number of studies have confirmed that calcineurin/NFAT signal transduction is very important in the development of vascular system and cardiovascular system during embryonic development, and plays some role in the occurrence of vascular diseases such as atherosclerosis, vascular calcification, and hypertension. Recent in vitro and in vivo studies have shown that NFAT proteins and their activation in the nucleus and binding to DNA-related sites can easily ɨnduce the expression of downstream target genes that participate in the proliferation, migration, angiogenesis, and vascular inflammation of vascular wall related cells in various pathophysiological states. NFAT expression is regulated by various signaling pathways, including CD137-CD137L, and OX40-OX40L pathways. As a functionally diverse transcription factor, NFAT interacts with a large number of signaling molecules to modulate intracellular and extracellular signaling pathways. These NFAT-centered signaling pathways play important regulatory roles in the progression of atherosclerosis, such as in vascular smooth muscle cell phenotypic transition and migration, endothelial cell injury, macrophage-derived foam cell formation, and plaque calcification. NFAT and related signaling pathways provide new therapeutic targets for vascular diseases such as atherosclerosis. Hence, further studies of the mechanism of NFAT in the occurrence and evolution of atherosclerosis remain crucial.

Vascular calcification is a high incidence and high risk disease with increasing morbidity and high mortality, which is considered the consequence of smooth muscle cell transdifferentiation initiating the mechanism of accumulation of hydroxyl calcium phosphate. Vascular calcification is also thought to be strongly associated with poor outcomes in diabetes and chronic kidney disease. Numerous studies have been accomplished; however, the specific mechanism of the disease remains unclear. Development of the genome project enhanced the understanding of life science and has entered the post-genomic era resulting in a variety of omics techniques used in studies and a large amount of available data; thus, a new perspective on data analysis has been revealed. Omics has a broader perspective and is thus advantageous over a single pathway analysis in the study of complex vascular calcification mechanisms. This paper reviews in detail various omics studies including genomics, proteomics, transcriptomics, metabolomics and multiple group studies on vascular calcification. Advances and deficiencies in the use of omics to study vascular calcification are presented in a comprehensive view. We also review the methodology of the omics studies and omics data analysis and processing. In addition, the methodology and data processing presented here can be applied to other areas. An omics landscape perspective across the boundaries between genomics, transcriptomics, proteomics and metabolomics is used to examine the mechanisms of vascular calcification. The perspective combined with various technologies also provides a direction for the subsequent exploration of clinical significance.

The kinase PDK1 is a crucial regulator for immune cell development by connecting PI3K to downstream AKT signaling. However, the roles of PDK1 in CD4+ T cell differentiation, especially in T follicular helper (Tfh) cell, remain obscure. Here we reported PDK1 intrinsically promotes the Tfh cell differentiation and germinal center responses upon acute infection by using conditional knockout mice. PDK1 deficiency in T cells caused severe defects in both early differentiation and late maintenance of Tfh cells. The expression of key Tfh regulators was remarkably downregulated in PDK1-deficient Tfh cells, including Tcf7, Bcl6, Icos, and Cxcr5. Mechanistically, ablation of PDK1 led to impaired phosphorylation of AKT and defective activation of mTORC1, resulting in substantially reduced expression of Hif1α and p-STAT3. Meanwhile, decreased p-AKT also suppresses mTORC2-associated GSK3β activity in PDK1-deficient Tfh cells. These integrated effects contributed to the dramatical reduced expression of TCF1 and ultimately impaired the Tfh cell differentiation.

Although the strain-dependent effects of Bacteroides vulgatus on alleviating intestinal inflammatory diseases have been demonstrated, the literature has rarely focused on the underlying causes of this effect. In this study, we selected four B. vulgatus strains (FTJS5K1, FTJS7K1, FSDTA11B14, and FSDLZ51K1) with different genomic characteristics and evaluated their protective roles against dextran sulfate sodium- (DSS-) induced colitis. Compared to the other three tested strains, B. vulgatus 7K1 more strongly ameliorated the DSS-induced weight loss, shortening of the colon length, increased disease activity index scores, colonic tissue injury, and immunomodulatory disorder. In contrast, B. vulgatus 51K1 significantly worsened the DSS-induced alterations in the tumor necrosis factor-alpha (TNF-α) concentration and colonic histopathology. A comparative genomic analysis of B. vulgatus 7K1 and 51K1 showed that the beneficial effects of B. vulgatus 7K1 may be associated with some of its specific genes involved in the production of short-chain fatty acids or capsular polysaccharides and enhancement of its survivability in the gut. In conclusion, these findings indicate that the supplementation of B. vulgatus 7K1 is a potentially efficacious intervention for alleviating colitis and provides scientific support for the screening of probiotics with anticolitis effect.

The accurate design of ship routing plans in arctic areas is not easy, considering that navigation conditions (e.g., weather, visibility, and ice thickness) may change frequently. A ship’s crew identifies sea ice in arctic channels with the help of radar echoes, and ship maneuvering decisions are made to avoid navigation interference. Ship officials must manually and consistently change the ship’s route of travel, which is time-consuming and tedious. To address this issue, we propose a near-field route optimization model for the purpose of automatically selecting an optimal route with the help of radar echo images. The ship near-field route optimization model uses a multiobjective optimal strategy considering factors of minimum navigation risk and steaming distance. We verified the model’s performance with the support of the Xuelong voyage dataset. This research finding can help a ship’s crew to design more reasonable navigation routes in polar channels.

Wearing safety rope while working at the loft and over the side of a ship is an effective means to protect seafarers from accidents. However, there are no active and effective monitoring methods on ships to control this issue. In this article, a one-stage system is proposed to automatically monitor whether the crew is wearing safety ropes. When the system detects that a crew enters the work area without a safety rope, it will warn the supervisor. In this regard, a safety rope wearing detection dataset is established. Then a data augmentation algorithm and a boundary loss function are designed to improve the training effect and the convergence speed. Furthermore, features from different scales are extracted to get the final detection results. The obtained results demonstrate that the proposed approach YOLO-SD is effective at different on-site conditions and can achieve high precision (97.4%), recall rate (91.4%), and mAP (91.5%) while ensuring real-time performance (38.31 FPS on average).

Given the insufficient understanding of the characteristics and controlling factors of the low-permeability sandstone reservoir in the Heshui area, the Ordos Basin, the present study examined the microscale mineral and pore structure of Chang 2 reservoir. It analyzed its major controlling factors using a series of methods, including imaging and indirect methods. The results show that the rocks of Chang 2 reservoir in the study area are dominated by lithic arkose and feldspathic detritus quartz sandstone. The reservoir space develops intragranular pores, feldspar dissolved pores, lithic dissolved pores, and intercrystallite pores. Microcracks can occasionally be found. The average porosity is 10.5%, and the average permeability is 2.2 mD, featuring a low-porosity-ultralow-permeability reservoir. During the reservoir development, traps formed by small-scale nose-shaped uplifts resulting from the tectonic effects provide opportunities for good reservoir space. Sedimentation and diagenetic processes control the degree of development and direction of the evolution of reservoir porosity to a certain degree. Multisegment capillary pressure curve and long missing zone were corresponding to relatively good pore-throat structures. Illite was the predominant diagenetic clay minerals that determine the reservoir quality. These three effects all contribute to the overall development of the reservoir.

The complex pore structure of low-permeability sandstone reservoir makes it difficult to characterize the heterogeneity of pore throat. Taking the reservoir of Sanjianfang formation in QL oilfield as an example, the fractal dimension of different storage spaces is calculated by using fractal theory based on casting thin section, scanning electron microscope, and high-pressure mercury injection, and the correlation between porosity, permeability, and contribution of different storage space permeabilities is analyzed. The results show that the reservoir of Sanjianfang formation in QL oilfield mainly develops small pores, fine pores, and micropores, and the fractal dimension of micropore structure is between 2.6044 and 2.9982, with an average value of 2.8316. The more complex the pore structure is, the stronger the microheterogeneity is. The higher the fractal dimension, the more complex the pore structure and the smaller the porosity and permeability. The fractal dimensions of small pores, fine pores, and micropores increase successively with the decrease in pore radius, and the microstructure heterogeneity of large pores is weaker than that of small pores. It provides a theoretical basis for the exploration and development of low-permeability sandstone reservoirs.

Vascular calcification is the transformation of arterial wall mesenchymal cells, particularly smooth muscle cells (SMCs), into osteoblast phenotypes by various pathological factors. Additionally, vascular transformation mediates the abnormal deposition of calcium salts in the vascular wall, such as intimal and media calcification. Various pathological types have been described, such as calcification and valve calcification. The incidence of vascular calcification in patients with diabetes is much higher than that in nondiabetic patients, representing a critical cause of cardiovascular events in patients with diabetes. Because basic research on the clinical transformation of vascular calcification has yet to be conducted, this study systematically expounds on the risk factors for vascular calcification, vascular bed differences, sex differences, ethnic differences, diagnosis, severity assessments, and treatments to facilitate the identification of a new entry point for basic research and subsequent clinical transformation regarding vascular calcification and corresponding clinical evaluation strategies.

Background. The optimal timing of temporary ileostomy closure with respect to the time of adjuvant chemotherapy following sphincter-saving surgery for rectal cancer remains unclear. The aim of this study is to investigate the clinical and oncological outcomes of ileostomy closure before, during, and after adjuvant chemotherapy following curative rectal cancer resection. Methods. Patients diagnosed with rectal adenocarcinoma who underwent low anterior resection and temporary loop ileostomy during May 2015 and September 2019 were retrospectively evaluated. Patients undergoing ileostomy closure before adjuvant chemotherapy (Group I) were compared to patients undergoing closure during (Group II) and after (Group III) adjuvant chemotherapy. Results. A total of 225 patients were evaluated for eligibility, and 132 were finally selected and divided into 3 groups (24 in Group I, 53 in Group II, and 55 in Group III). No significant differences were observed in operative time, postoperative hospital stay, postoperative complications, total adjuvant chemotherapy cycles, and low anterior resection syndrome scores among the three groups. There was no significant difference in disease-free survival (p=0.834) and overall survival (p=0.462) between the three groups. Conclusion. Temporary ileostomy closure before adjuvant chemotherapy following curative rectal cancer resection can achieve a clinical and oncological safety level equal to stoma closure during or after chemotherapy in selected patients.

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which causes an enormous socioeconomic burden. Previous studies demonstrated that the apoptosis of nucleus pulposus (NP) cells and the dyshomeostasis of extracellular matrix (ECM) contributed to the pathogenesis of IDD, and effective therapies were still lacking. Quercetin, a natural flavonoid possessing a specific effect of autophagy stimulation and SIRT1 activation, showed some protective effect on a series of degenerative diseases. Based on previous studies, we hypothesized that quercetin might have therapeutic effects on IDD by inhibiting the apoptosis of NP cells and dyshomeostasis of ECM via the SIRT1-autophagy pathway. In this study, we revealed that quercetin treatment inhibited the apoptosis of NP cells and ECM degeneration induced by oxidative stress. We also found that quercetin promoted the expression of SIRT1 and autophagy in NP cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) reversed the protective effect of quercetin on apoptosis and ECM degeneration. Moreover, SIRT1 enzymatic activity inhibitor EX-527, suppressed quercetin-induced autophagy and the protective effect on NP cells, indicating that quercetin protected NP cells against apoptosis and prevented ECM degeneration via SIRT1-autophagy pathway. In vivo, quercetin was also demonstrated to alleviate the progression of IDD in rats. Taken together, our results suggest that quercetin prevents IDD by promoting SIRT1-dependent autophagy, indicating one novel and effective therapeutic method for IDD.

Ventilation corridors in cities can decrease air pollution and alleviate heat island problems but there remains a need to fully assess their effectiveness. Few urban managers have been able to take city-scale approaches to the construction of urban ventilation corridors. This study aimed to introduced the Ventilation Corridor Planning (VCP) model, which is a multi-criteria evaluation method combined with a geographical information system (GIS) to determine where the ventilated environment is most appropriate. Specifically, the VCP model took Bozhou, China as the research object and contained two scales, including mesoscale and local scale. In mesoscale scale, we got three outputs to build urban ventilation corridors, including 1) background wind environment, 2) ventilation potential, 3) heat island intensity. In local scale, we used traditional computational fluid dynamics (CFD) model to verify the impact of VCP criteria. The results revealed that compared with the traditional CFD model, the proposed VCP model has advantages in establishing a comprehensive evaluation standard. In addition, the application of VCP model in macro and micro also enhances the efficiency of ventilation corridor construction. Overall, this study introduced a effective modeling method to urban ventilation corridors planning, and provide a way to study the urban climate.

The microseismic signal is easily affected by observation noise and the inaccurate estimation of traditional methods will seriously reduce the location accuracy of the microseismic event. Therefore, based on the continuous wavelet spectrum and the similarity coefficient, a fast and efficient microseismic time delay estimation method is proposed. Firstly, the original signals are denoised by continuous wavelet transform. Subsequently, the time-frequency transform of the original signal by continuous wavelet transform, time-frequency signal extraction is the process of band-pass filtering, which can further reduce the influence of noise interference on the time delay estimation. Finally, we calculated the similarity between the time-frequency signals via the time domain and frequency domain integration. The similarity function is based on correlation and proposed according to the time-frequency transformation provided by the phase spectrum to evaluate the similarity between two noisy signals. The time delay estimation is determined by searching for the similarity function peak. The experimental results show the precision and accuracy of the method over the cross-correlation method and generalized cross-correlation phase transformation method, especially when the signal-to-noise ratio is low. Therefore, a new time delay estimation method for non-stationary random signals is presented in this paper.