Human epidermal growth factor receptor 2 (HER2) plays a critical role in breast cancer progression in patients with HER2 overexpression, thereby driving the development of targeted drugs and ...advancing therapy strategies targeting this gene. Pyrotinib is a novel irreversible pan-ErbB kinase inhibitor, primarily suppresses the downstream MAPK and PI3K/AKT pathways. Alpelisib, a selective PI3K p110α inhibitor, has been approved for clinical application in HR+, HER2-, PIK3CA mutated breast cancers and is also being developed for use in other breast cancer subtypes. In this study, we hypothesised that combining pyrotinib with alpelisib would yield superior results compared to single-drug treatment. Our data demonstrated that the combination of alpelisib and pyrotinib exhibited a synergistic effect in HER2+ breast cancer both in vitro and in vivo. This combination led to decreased cell proliferation and migration, G0-G1 cell cycle arrest, and increased apoptosis rates. Additionally, the deactivation of ErbB receptors and sustained activation of PI3K/AKT pathway by upstream compensatory pathways induced acquired pyrotinib resistant cells resistant to pyrotinib treatment, thus alpelisib combined with pyrotinib showed a tremendous synergistic effect and reverse pyrotinib resistance in acquired pyrotinib resistant cells by suppressing the activated PI3K/AKT pathway. Our results revealed a combination of pyrotinib and alpelisib as an effective therapeutic strategy in treating HER2+ breast cancer, whether sensitive or resistant to pyrotinib treatment.
Wi-Fi-based human activity recognition has attracted broad attention for its advantages, which include being device-free, privacy-protected, unaffected by light, etc. Owing to the development of ...artificial intelligence techniques, existing methods have made great improvements in sensing accuracy. However, the performance of multi-location recognition is still a challenging issue. According to the principle of wireless sensing, wireless signals that characterize activity are also seriously affected by location variations. Existing solutions depend on adequate data samples at different locations, which are labor-intensive. To solve the above concerns, we present an amplitude- and phase-enhanced deep complex network (AP-DCN)-based multi-location human activity recognition method, which can fully utilize the amplitude and phase information simultaneously so as to mine more abundant information from limited data samples. Furthermore, considering the unbalanced sample number at different locations, we propose a perception method based on the deep complex network-transfer learning (DCN-TL) structure, which effectively realizes knowledge sharing among various locations. To fully evaluate the performance of the proposed method, comprehensive experiments have been carried out with a dataset collected in an office environment with 24 locations and five activities. The experimental results illustrate that the approaches can achieve 96.85% and 94.02% recognition accuracy, respectively.
The 5G network is developing rapidly. However, due to spectrum resource limitation, it is expected to use the 5G network to ensure high resource utilization and network efficiency, while keeping part ...of 4G in the same band for existing 4G users. Dynamic spectrum-sharing (DSS) technology enables 4G/5G wireless networks to coexist in scarce spectrum resources and dynamically allocates spectrum resources in the same band. 4G/5G DSS has been successfully commercialized in some countries such as Germany and Brazil. However, complex 4G/5G DSS networks will introduce intra-frequency interference in the inter-system, which will affect network performance. Therefore, we innovatively proposed two interference mitigation schemes: buffer setting and rate matching. Furthermore, we have verified the practical performance of both schemes in a commercial network for the first time to determine the feasibility of the schemes. From theory, simulation, and practical analysis, both schemes can effectively mitigate the interference of the inter-system introduced by DSS: increasing the network rate by 60% in the interference environment and improving the user experience in the DSS architecture.
ObjectivesTo assess the association between blood circulating vitamin D levels and colorectal cancer risk in the Asian population.DesignThis is a systematic review and dose-response meta-analysis of ...observational studies that investigated the relationship between blood circulating vitamin D levels and colorectal cancer risk in the Asian population.Data sourcesRelevant studies were identified through a literature search in Medline, Embase and Web of Science from 1st January 1980 to 31st January 2019. Eligibility criteria: original studies published in peer-reviewed journals investigating the association between blood circulating vitamin D levels and the risk of colorectal cancer and/or adenoma in Asian countries.Data extraction and synthesisTwo authors independently extracted data and assessed the quality of included studies. Study-specific ORs were pooled using a random-effects model. A dose-response meta-analysis was performed with generalised least squares regression. We applied the Newcastle-Ottawa Scale quality assessment to evaluate the quality of the selected studies.ResultsThe eight included studies encompassed a total of 2916 cases and 6678 controls. The pooled ORs of colorectal cancer for the highest versus lowest categories of blood circulating vitamin D levels was 0.75 (95% CI 0.58 to 0.97) up to 36.5 ng/mL in the Asian population. There was heterogeneity among the studies (I 2=53.9%, P heterogeneity=0.034). The dose-response meta-analysis indicated a significant linear relationship (P non-linearity=0.11). An increment of 16 ng/mL in blood circulating vitamin D level corresponded to an OR of 0.79 (95% CI 0.64 to 0.97).ConclusionsThe results of this meta‐analysis indicate that blood circulating vitamin D level is associated with decreased risk of colorectal cancer in Asian countries. The dose-response meta-analysis shows that the strength of this association among the Asian population is similar to that among the Western population. Our study suggests that the Asian population should improve nutritional status and maintain a higher level of blood circulating vitamin D.
The incidence of colorectal cancer (CRC) is common and reliable biomarkers are lacking. We aimed to systematically and comprehensively compare the ability of various combinations of serum ...inflammatory signatures to predict the prognosis of CRC. Moreover, particular attention has been paid to the clinical feasibility of the newly developed inflammatory burden index (IBI) as a prognostic biomarker for CRC.
The discrimination capacity of the biomarkers was compared using receiver operating characteristic curves and Harrell's C-index. Kaplan-Meier curves and log-rank tests were used to compare survival differences between the groups. Cox proportional hazard regression analysis was used to determine the independent prognostic factors. Logistic regression analysis was used to assess the relationship between IBI, short-term outcomes, and malnutrition.
IBI had the optimal prediction accuracy among the systemic inflammation biomarkers for predicting the prognosis of CRC. Taking IBI as a reference, none of the remaining systemic inflammation biomarkers showed a gain. Patients with high IBI had significantly worse overall survival than those with low IBI (56.7% vs. 80.2%; log-rank P<0.001). Multivariate Cox regression analysis showed that continuous IBI was an independent risk factor for the prognosis of CRC patients (hazard ratio = 1.165, 95% confidence interval CI = 1.043-1.302, P<0.001). High IBI was an independent risk factor for short-term outcomes (odds ratio OR = 1.537, 95% CI = 1.258-1.878, P<0.001), malnutrition (OR = 2.996, 95% CI = 1.471-6.103, P=0.003), and recurrence (OR = 1.744, 95% CI = 1.176-2.587, p = 0.006) in CRC patients.
IBI, as a reflection of systemic inflammation, is a feasible and promising biomarker for assessing the prognosis of CRC patients.
Malnutrition is associated with poor overall survival (OS) in breast cancer patients; however, the most predictive nutritional indicators for the prognosis of patients with breast cancer are not ...well-established. This study aimed to compare the predictive effects of common nutritional indicators on OS and to refine existing nutritional indicators, thereby identifying a more effective nutritional evaluation indicator for predicting the prognosis in breast cancer patients.
This prospective study analyzed data from 776 breast cancer patients enrolled in the "Investigation on Nutritional Status and its Clinical Outcome of Common Cancers" (INSCOC) project, which was conducted in 40 hospitals in China. We used the time-dependent receiver operating characteristic curve (ROC), Kaplan-Meier survival curve, and Cox regression analysis to evaluate the predictive effects of several nutritional assessments. These assessments included the patient-generated subjective nutrition assessment (PGSGA), the global leadership initiative on malnutrition (GLIM), the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI). Utilizing machine learning, these nutritional indicators were screened through single-factor analysis, and relatively important variables were selected to modify the PNI. The modified PNI, termed the cholesterol-modified prognostic nutritional index (CPNI), was evaluated for its predictive effect on the prognosis of patients.
Among the nutritional assessments (including PGSGA, GLIM, CONUT, NRI, and PNI), PNI showed the highest predictive ability for patient prognosis (time-dependent ROC = 0.58). CPNI, which evolved from PNI, emerged as the superior nutritional index for OS in breast cancer patients, with the time-dependent ROC of 0.65. It also acted as an independent risk factor for mortality (p < 0.05). Moreover, the risk of malnutrition and mortality was observed to increase gradually among both premenopausal and postmenopausal age women, as well as among women categorized as non-overweight, overweight, and obese.
The CPNI proves to be an effective nutritional assessment tool for predicting the prognosis of patients with breast cancer.
Ultra-deep clastic reservoirs generally have poor physical properties and low single-well productivity, but Well BZ9, which is newly drilled in the Kuqa Depression of Tarim Basin, NW China, ...encounters a thick high-quality reservoir in the Bashijiqike Formation of Lower Cretaceous deeper than 7600 m and produces a high-yield industrial gas flow. In order to reveal the characteristics and genesis of the Bashijiqike Formation reservoir and reduce the exploration risk of ultra-deep oil and gas layers, we discussed its characteristics, genetic mechanism and oil & gas exploration significance based on cores, well logging and experimental analysis, combined with regional temperature–pressure conditions and burial evolution history. The following research results were obtained. First, the rock types of ultra-deep reservoir of the Bashijiqike Formation in this area are medium- and fine-grained feldspathic litharenite and lithic arkose with point-line contact between grains, and its reservoir space is dominated by primary intergranular pores. At present, it is still at its middle diagenetic stage. Second, different from other ultra-deep fractured low-porosity sandstone reservoirs, this set of ultra-deep reservoir is a pore-type reservoir with porosity of 4–13%, permeability of 0.1–50.0 mD and better porosity and permeability correlation. Third, during the sedimentation of the Bashijiqike Formation, thick sand bodies of delta front were widely developed, medium- and fine-grained sandstones accounted for more than 85% and grains had strong compressive capacity. After that, this reservoir experienced long-term shallow burial during the early–medium stage and rapid deep burial during the late stage, and the burial compaction effect was weaker. During the late stage, a canopy structure was formed from the overlying Paleogene thick gypsum salt bed due to thrust and compression, and it further suppressed vertical compaction. In the meantime, the study area was far from the orogenic belt and the structural transition zone, so the lateral compressive stress was weak. Therefore, the primary intergranular pores were preserved in large quantities. It is concluded that coarse lithology, weak compaction and low tectonic stress are the key factors to the development of this ultra-deep high-quality reservoir. In addition, the development of large-scale effective reservoirs deeper than 7000 m provides favorable material conditions for the high-abundance enrichment of natural gas and the reserves of trillion cubic meters in the Kuqa Depression, and the oil and gas exploration potential is huge.
Serum choline levels were associated with multiple chronic diseases. However, the association between serum choline and all-cause mortality in Chinese adults with hypertension remains unclear. The ...purpose of this study is to explore the association between serum choline concentrations and all-cause mortality risk in Chinese adults with hypertension, a high-risk population.
A nested, case-control study was conducted that included 279 patients with all-cause death, and 279 matched, living controls, derived from the China Stroke Primary Prevention Trial (CSPPT). Baseline serum choline concentrations were measured by liquid chromatography with tandem quadrupole mass spectrometry (LC-MS/MS). Multivariate logistic regression analysis was used to assess the association of serum choline levels and all-cause mortality risk, with adjustment of pertinent covariables, including folic acid and homocysteine.
The median age of all participants was 64.13 years interquartile range (IQR), 57.33-70.59 years. The median serum choline concentration for cases (9.51 μg/mL) was higher than that in controls (7.80 μg/mL) (P = 0.009). When serum choline concentration was assessed as a continuous variable (per SD increased), there was a positive relation between serum choline levels and all-cause mortality risk odds ratios (OR), 1.29; 95% confidence intervals (95%CI), 1.06-1.57; P = 0.010. There was an increased all-cause mortality risk for participants in quartiles 2-4 (≥ 4.00 μg/mL; OR, 1.79; 95%CI, 1.15-2.78 compared with quartile 1 (< 4.00 μg/mL). In addition, non-drinking was found to promote the incidence of all-cause mortality for those with high choline concentrations.
High serum choline concentrations were associated with increased all-cause mortality risk among Chinese adults with hypertension, compared to lower choline concentrations. Trial registration clinicaltrials.gov Identifier: NCT007948885; UTL: https://clinicaltrials.gov/ct2/show/NCT00794885?term=NCT00794885&draw=2&rank=1.
The fractured reservoir is one of the significant petroleum reservoir types in China, representing over one-third of total reserves. The Kuqa Depression in the Tarim Basin is dominated by fractured ...low-porosity sandstone gas reservoirs with characteristic tight matrix, developed fractures, and edge and bottom water. However, the continued development of these reservoirs has led to various problems, including strong reservoir heterogeneity, low well control, complex gas-water relationships, and early water invasion. Addressing these issues requires a detailed understanding of the reservoir’s geological characteristics. One method for achieving a fine reservoir description is through the use of 3D geological modeling. This high-level, comprehensive characterization technique is widely used throughout the entire life cycle of oil and gas field development. A 3D geological model can accurately predict the actual underground reservoir characteristics and provide a geological basis for later numerical simulation work. Based on a study of the geological characteristics of the Kuqa Depression in the Tarim Basin, a 3D geological modeling technique was developed, which includes structural modeling, facies modeling, petrophysical modeling, and fracture modeling. This technology has been successfully applied to many deep gas reservoirs in the Kuqa Depression of the Tarim Basin, leading to enhanced gas recovery.
This paper is concerned with the asymptotic behavior of solutions to reaction-diffusion equations with dynamic boundary conditions as well as L1-initial data and forcing terms. We first prove the ...existence and uniqueness of an entropy solution by smoothing approximations. Then we consider the large-time behavior of the solution. The existence of a global attractor for the solution semigroup is obtained in L1(Ω¯,dν). This extends the corresponding results in the literatures.
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