Search

Abstract Background Colorectal cancer (CRC) exhibits a high incidence globally, with the liver being the most common site of distant metastasis. At the time of diagnosis, 20–30% of CRC patients already present with liver metastases. Colorectal liver metastasis (CRLM) is a major cause of mortality among CRC patients. The pathogenesis of CRLM involves complex molecular mechanisms and the hepatic immune microenvironment, but current clinical prevention and treatment are significantly limited. Recent studies have revealed that the major facilitator superfamily domain containing protein-2a (Mfsd2a) plays a pivotal role in the development and metastasis of various cancers. For instance, Mfsd2a inhibits gastric cancer initiation and progression and may impact angiogenesis. However, the mechanisms by which Mfsd2a influences CRC progression and liver metastasis remain unclear. Methods In this study, we conducted a survival analysis of Mfsd2a in colorectal cancer using data from the GEPIA and GEO databases, and examined the expression differences between primary tumor (PT) and liver metastasis (LM). We further assessed the clinical significance and prognostic relevance of Mfsd2a through immunohistochemical analysis of tissue samples from 70 CRLM patients. Moreover, Kaplan-Meier analysis was used to perform survival analysis on these patients. The biological function of Mfsd2a in CRLM was confirmed by a series of experiments conducted both in vitro and in vivo. Additionally, we investigated downstream molecular pathways using western blot, Co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques. Results We observed that Mfsd2a expression is reduced in LM compared to PT, and higher Mfsd2a levels are associated with better prognosis in CRLM patients. Furthermore, function assays demonstrated that Mfsd2a suppresses CRC cells proliferation, migration, invasion, and EMT in vitro, while also delaying tumor growth and liver metastasis in vivo. Mechanistically, Mfsd2a interacts with S100A14, enhancing its expression and inhibiting phosphorylation of STAT3. In addition, the STAT3 activator colivelin partially reversed the inhibitory effect of Mfsd2a overexpression on the progression of colorectal cancer and liver metastasis. Conclusion In summary, Mfsd2a inhibits colorectal cancer progression and liver metastasis by interacting with S100A14, thereby suppressing the phosphorylation of STAT3. Mfsd2a functions as a tumor suppressor in CRLM and could be a promising therapeutic target for treating CRC patients with liver metastasis. Graphical abstract

As the main technology of CBM development in the Qinshui CBM field, single-branch fractured horizontal wells have supported the breakthrough of 2 billion m3/year production of gas field. However, in the process of its large-scale application, there have been a series of problems, such as large difference in production among wells and poor adaptability in local areas, which seriously restrict the further improvement of CBM production in gas fields. On the one hand, although many key elements affecting the production of single-branch fractured horizontal wells have been identified, the core key elements are not clear. On the other hand, the understanding of the change rule of key elements on the plane is generally simple mathematical extrapolation or pure mathematical inversion, which lacks geological constraints and corrections, and has low reliability and resolution. Therefore, it is urgent to clear the core key elements that affect the production, and then establish targeted technical countermeasures on this basis. First of all, based on the objective geological conditions and the understanding of development and production practice in the Zhengzhuang block, the preliminary screening principle of the core key elements affecting the production of single−branch fractured horizontal wells was proposed, and nine elements were selected, including drilling length in pure coal seam, horizontal section inclination, total hydrocarbon, GR, number of fracturing stages, average sand gradient, average displacement gradient, average fluid volume gradient and desorption pressure gradient. Then, grey correlation analysis and single element analysis were used to determine the correlation degree between the nine elements of the preliminary screening and the production of single−branch fractured horizontal wells, and determine the internal mechanism of the elements' influence on the production. Secondly, from the three perspectives of resource base, reserve control and reconstruction, combined with the specific process of a single-branch fractured horizontal well deployment, reconstruction design and operation, nine elements were classified, and targeted technical countermeasures for production enhancement were established. In the stage of well location deployment, extrapolation data based on evaluation wells were used to initially identify the relatively enriched area, and the seismic data were processed by structure-oriented filtering + high−frequency coherence technology to delineate the local area for clearing hidden destructive structures in the area, and then straight/inclined wells were drilled to obtain GR and total hydrocarbons in the coal seam segment to determine the resource base of the well location deployment area. In the stage of well trajectory design and drilling, the waveform clustering technology was used to predict the distribution law of strongly deformed coal in the well location deployment area. The pre−stack depth migration of seismic data was processed to predict the thickness and fluctuation change law of coal seam in the well location deployment area, the well group mode was used to drill in batches, and the near−bit geological guidance technology was combined with the real drilling data to correct the local coal seam understanding in real time, to increase drilling length in pure coal seam, optimize well trajectory, ensure more high−quality fracturing stages, and improve reservoir control. In the reservoir reconstruction stage, GR (Gamma Ray), total hydrocarbon, well trajectory conditions and real drilling data were used to select fracturing stages, and the joint operation techniques of bridge plug setting, shooting and fracturing was used as a new fracturing technology to increase the displacement, sand and fluid volume, increase the reconstruction scale and strengthen the reconstruction, and improve resource utilization. Finally, relevant tests were carried out in the Zhengzhuang block by using the above countermeasures. A well group with 7 wells was deployed in the north of Zhengzhuang. Compared with the early single-branch fractured horizontal wells around the well group, the desorption pressure of the test wells is about 1-1.5 MPa higher than before, and the stable gas production is increased by nearly 5 000-10 000 m3/d. According to field practice tests, the core key elements affecting the production of single-branch fractured horizontal wells and the targeted production technical countermeasures established on this basis can greatly improve the stable gas production and desorption pressure of coalbed methane, which can help improve the production of the Qinshui coalbed methane field and provide important production practice experience and successful cases that can be learned from for peers who adopt the same main development technology.

Abstract Cancer is the leading cause of death worldwide, accounting for nearly 10 million deaths every year. Immune checkpoint blockade approaches have changed the therapeutic landscape for many tumor types. However, current immune checkpoint inhibitors PD-1 or CTLA-4 are far from satisfactory, due to high immune-related adverse event incident (up to 60%) and the inefficiency in cases of “cold” tumor microenvironment. TNFR2, a novel hopeful tumor immune target, was initially proposed in 2017. It not only promotes tumor cell proliferation, but also correlates with the suppressive function of Treg cells, implicating in the development of an immunosuppressive tumor microenvironment. In preclinical studies, TNFR2 antibody therapy has demonstrated efficacy alone or a potential synergistic effect when combined with classical PD-1/ CTLA-4 antibodies. The focus of this review is on the characteristics, functions, and recent advancements in TNFR2 therapy, providing a new direction for the next generation of anti-tumor alternative therapy.

BackgroundPituitary adenomas (PAs) present with clinical features such as neuroendocrine abnormalities and mass effects, common in the general morbidity population. However, in elderly patients, the disease progression renders some clinical features difficult to detect and identify in time. Consequently, elderly patients with PAs are often not identified and receive sufficient intervention on time to achieve a satisfactory outcome.MethodsClinical data were collected from 114 consecutive patients older than 70 years with PAs who had undergone surgery. Based on the average age, the patients were categorized into a younger group and an elder group, and were statistically analyzed and compared.ResultsSixty-five males (57.0%) and 49 females (43.0%) were included in the study, with an average age of 73.2 years. Their common preoperative symptoms included vision impairment, followed by headache and vomiting, and visual field defect. The milder the preoperative visual impairment, the greater the possibility of post-operative visual improvement (P=0.001). The tumors were primarily non-functional pituitary adenomas (NFPAs, 73.7%), with a high degree of suprasellar invasion but a low degree of parasellar invasion (P

Abstract Efficient seawater desalination is an effective way to solve the shortages of fresh water and energy but with limitations of the low fresh water production rate and high cost. Here, a hollow carbon fiber (HCF) wrapped by regular reduced graphene oxide (rGO) wave-like folds (rGO@HCF) is prepared on account of the differences in thermal shrinkage performance between graphene oxide (GO) and willow catkins fiber. Under one sun irradiation (1 kW m−2), the dry and wet surface temperature of the resulting evaporator reached up to 119.1 °C and 61.7 °C, respectively, and the water steam production rate reached 3.42 kg m−2 h−1. Also, for the outdoor experiment, the rGO@HCF exhibits good evaporator performance which reach up 27.8 kg m−2 day−1. Additionally, rGO@HCF also shows good seawater desalination performance and excellent durability for longtime work. DSC results indicate that the evaporation enthalpy of bulk water and adsorbed water decreased from 2503.92 to 1020.54 J g−1. The excellent evaporating performance is mainly attributed to the regular wave-like microstructure surface of the HCF, which can enhance the light absorption, reduced the vaporization enthalpy of the adsorption water. The findings not only introduce a novel approach for agricultural utilization, but also establish a crucial theoretical foundation for the design of regular wave-like microstructures.

ObjectiveTo investigate the knowledge, attitude, and practice (KAP) of adult Atopic Dermatitis patients and parents of pediatric atopic dermatitis patients toward the disease.MethodsA cross-sectional study was conducted from January to February 2022, involving 1,193 Asian Atopic Dermatitis patients from the Atopic Dermatitis patient organization “Atopic Dermatitis Home.” The study included 594 adult patients and 599 parents of pediatric atopic dermatitis patients, with self-designed questionnaires assessing general demographics and continuous variables KAP.ResultsAdult patients demonstrated higher knowledge scores, particularly in areas of bathing and skincare (3.64 ± 0.68 vs. 3.35 ± 0.93, p

Abstract Previous deep multi-agent reinforcement learning (MARL) algorithms have achieved impressive results, typically in symmetric and homogeneous scenarios. However, asymmetric heterogeneous scenarios are prevalent and usually harder to solve. In this paper, the main discussion is about the cooperative heterogeneous MARL problem in asymmetric heterogeneous maps of the Starcraft Multi-Agent Challenges (SMAC) environment. Recent mainstream approaches use policy-based actor-critic algorithms to solve the heterogeneous MARL problem with various individual agent policies. However, these approaches lack formal definition and further analysis of the heterogeneity problem. Therefore, a formal definition of the Local Transition Heterogeneity (LTH) problem is first given. Then, the LTH problem in SMAC environment can be studied. To comprehensively reveal and study the LTH problem, some new asymmetric heterogeneous maps in SMAC are designed. It has been observed that baseline algorithms fail to perform well in the new maps. Then, the authors propose the Grouped Individual-Global-Max (GIGM) consistency and a novel MARL algorithm, Grouped Hybrid Q-Learning (GHQ). GHQ separates agents into several groups and keeps individual parameters for each group. To enhance cooperation between groups, GHQ maximizes the mutual information between trajectories of different groups. A novel hybrid structure for value factorization in GHQ is also proposed. Finally, experiments on the original and the new maps show the fabulous performance of GHQ compared to other state-of-the-art algorithms.

BackgroundPatients with Chronic Obstructive Pulmonary Disease (COPD) frequently face substantial medication burdens. Follow-up care on medication management is critical in achieving disease control. This study aimed to analyze the complexity of COPD-specific medication and determine how it impacted patients’ attendance on follow-up care.MethodsThis multicenter study includes patients with COPD from 1,223 hospitals across 29 provinces in China from January 2021 to November 2022. The medication Regimen Complexity Index (MRCI) score was used to measure COPD-specific medication complexity. The association between medication complexity and follow-up care attendance was evaluated using the Cox Proportional Hazard Model.ResultsAmong 16,684 patients, only 2,306 (13.8%) returned for follow-up medication management. 20.3% of the patients had high complex medication regimen (MRCI score >15.0). The analysis revealed that compared to those with less complex regimens, patients with more complex medication regimens were significantly less likely to attend the follow-up medication care, with a Hazard Ratio (HR) of 0.82 (95% Confidence Interval [CI], 0.74–0.91). Specifically, patients with more complex dosage forms were 51% less likely to attend the follow-up care (95% CI, 0.43–0.57). This pattern was especially marked among male patients, patients younger than 65 years, and those without comorbid conditions.ConclusionHigher medication complexity was associated with a decreased likelihood of attending follow-up care. To promote care continuity in chronic disease management, individuals with complex medication regimens should be prioritized for enhanced education. Furthermore, pharmacists collaborating with respiratory physicians to deprescribe and simplify dosage forms should be considered in the disease management process.

PurposeMetastatic non-small cell lung cancer (mNSCLC) has a high incidence rate, and economic burdens to patients, healthcare systems, and societies. Durvalumab plus tremelimumab and chemotherapy (T+D+CT) is a novel therapeutic strategy for mNSCLC, which demonstrated promising efficacy in a phase-3 randomized clinical trial, but its economic value remains unclear.MethodsThis economic evaluation used a hypothetical cohort of patients with mNSCLC, with characteristics mirroring those of the participants in the POSEIDON trial. Several partitioned survival models were constructed to estimate 15-year costs and health outcomes associated with the T+D+CT, durvalumab plus chemotherapy (D+CT) and chemotherapy alone (CT) strategies, discounting costs and effectiveness at 3% annually. Costs were in 2023 US dollars. Data were derived from the POSEIDON trial and published literature. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of input parameters and study generalizability. The analysis was designed and conducted from September 2022 to March 2023. To evaluate the cost-effectiveness of T+D+CT, compared with CT and D+CT, for mNSCLC from the perspectives of the US healthcare sector and society.FindingsFrom the healthcare sector’s perspective, the T+D+CT yielded an additional 0.09 QALYs at an increased cost of $7,108 compared with CT, which resulted in an ICER of $82,501/QALY. The T+D+CT strategy yielded an additional 0.02 QALYs at an increased cost of $27,779 compared with the D+CT, which resulted in an ICER of $1,243,868/QALY. The economic results of T+D+CT vs. CT were most sensitive to the annual discount rate, subsequent immunotherapy cost, tremelimumab cost, palliative care and death cost, pemetrexed cost, and durvalumab cost. The T+D+CT strategy was considered cost-effective relative to CT in 59%–82% of model iterations against willingness-to-pay. thresholds of $100,000/QALY gained to $150,000/QALY gained. From the societal perspective, the T+D+CT can be considered as cost-effective as compared with CT or D+CT, independent of histology.ImplicationsIn this cost-effectiveness analysis, the T+D+CT strategy represented good value compared with CT for patients with mNSCLC from the perspectives of the healthcare sector and the society. This treatment strategy may be prioritized for mNSCLC patients at high risks of disease progression.

Background & Aims: Hepatic ischemia-reperfusion injury is a significant complication of partial hepatic resection and liver transplantation, impacting the prognosis of patients undergoing liver surgery. The protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily synthesized by hepatocytes and has been implicated in myocardial ischemic diseases. However, the role of PCSK9 in hepatic ischemia-reperfusion injury remains unclear. This study aims to investigate the role and mechanism of PCSK9 in hepatic ischemia-reperfusion injury. Methods: We first examined the expression of PCSK9 in mouse warm ischemia-reperfusion models and AML12 cells subjected to hypoxia/reoxygenation. Subsequently, we explored the impact of PCSK9 on liver ischemia-reperfusion injury by assessing mitochondrial damage and the resulting inflammatory response. Results: Our findings reveal that PCSK9 is up-regulated in response to ischemia-reperfusion injury and exacerbates hepatic ischemia-reperfusion injury. Blocking PCSK9 can alleviate hepatocyte mitochondrial damage and the consequent inflammatory response mediated by ischemia-reperfusion. Mechanistically, this protective effect is dependent on mitophagy. Conclusions: Inhibiting PCSK9 in hepatocytes attenuates the inflammatory responses triggered by reactive oxygen species and mitochondrial DNA by promoting PINK1-Parkin–mediated mitophagy. This, in turn, ameliorates hepatic ischemia-reperfusion injury.

Background A prescribing monitoring policy (PMP) was implemented in November 2015 in Anhui province, China, the first province to pilot this policy to manage the use and costs of select drugs based on their large prescription volumes and/or costs in hospitals. This study evaluated the impact of PMP on the use and expenditures of different drugs in three tertiaryhospitals in Anhui.Methods We obtained monthly drug use and expenditures data from three tertiary hospitals in Anhui (November 2014 through September 2017). An interrupted time series (ITS) design was used to estimate changes in defined daily doses (DDDs per month) and drug expenditures (dollars per month) of policy-targeted and non-targeted drugs after PMP implementation. Drugs were grouped based on whether they were recommended (recommended drugs) by any clinical guidelines or not (non-recommended drugs), or if they were potentially over-used (proton pump inhibitors, PPIs).Results After PMP, DDDs and costs of the targeted PPIs (omeprazole) declined while use of non-targeted PPIs increased correspondingly with overall sustained declines in total PPIs. The policy impact on recommended drugs varied based on whether the targeted drugs have appropriate alternatives. The DDDs and costs of recommended drugs that have readily accessible appropriate alternatives (atorvastatin) declined, which offset increases in its alternative non-target drugs (rosuvastatin), while there was no significant change in those recommended drugs that did not have appropriate alternative drugs (clopidogrel and ticagrelor). Finally, the DDDs and costs of non-recommended drugs decreased significantly.Conclusion PMP policy impact was not the same across different drug groups. PMP did help contain the use and costs of potentially over-used drugs and non-recommended drugs. PMP did not seem to reduce the use of first-line therapeutic drugs recommended by clinical treatment guidelines, especially those lacking alternatives; such drugs are unlikely appropriate candidates for PMP.

Bacterial fruit blotch (BFB) is a devastating disease caused by Acidovorax citrulli, severely impacting the watermelon and melon industries and leading to significant economic losses. Currently, researchers have not identified any commercial melon varieties with high resistance to BFB, and farmers primarily rely on chemical agents for prevention and control. However, the extensive use of these agents contributes to increased drug resistance among pathogenic bacteria, making it essential to develop environmentally friendly control methods. To explore the feasibility of combining the Bacillus velezensis ZY1 strain with chemical agents for BFB management, we assessed the efficacy of 10 bactericides and the ZY1 strain against Acidovorax citrulli. The results show that Prothioconazole, Zhongsheng Tetramycin Solution, Streptomycin Sesquisulfate, Tetramycin, Zhongshengmycin, and ZY1 exhibited significant inhibitory effects on the growth of Acidovorax citrulli. We determined the biocompatibility of the bactericides with the ZY1 strain using the plate confrontation method and the flat counting method. Zhongsheng Tetramycin Solution, Zhongshengmycin, and Kasugamycin exhibited good compatibility with the ZY1 strain. Additionally, we established the optimal compounding ratio of the bactericide and ZY1 using the Horsfall method. Among these, Zhongshengmycin demonstrated the best performance when combining its efficacy against Acidovorax citrulli with its biocompatibility with the ZY1 strain. The combination of Zhongshengmycin and ZY1 at a volume ratio of 5:5 significantly inhibited Acidovorax citrulli, exhibiting a clear synergistic effect with a synergy index (IR) value of 1.542. Field tests conducted over 21 days in Beijing greenhouses, Hainan Field facility greenhouses, and Xinjiang showed that the control efficacy of the Zhongshengmycin and ZY1 combination (89.23%) significantly surpassed that of the single agent Zhongshengmycin (80.35%) and the biocontrol bacterium ZY1 (72.12%). Notably, the application rate of Zhongshengmycin in the mixture was only half that of the single agent, resulting in a significant reduction in chemical usage. The combination of Bacillus velezensis ZY1 and Zhongshengmycin not only decreases chemical usage but also significantly enhances control efficacy compared to using Zhongshengmycin alone.

This study presents a one-step multiplex reverse transcription polymerase chain reaction (RT-PCR) method for the simultaneous detection of multiple viruses affecting melon crops. Viruses such as Watermelon mosaic virus (WMV), Cucumber mosaic virus (CMV), Zucchini yellow mosaic virus (ZYMV), Squash mosaic virus (SqMV), Tobacco mosaic virus (TMV), Papaya ring spot virus (PRSV), and Melon yellow spot virus (MYSV) pose a great threat to melons. The mixed infection of these viruses is the most common observation in the melon-growing fields. In this study, we surveyed northern Xingjiang (Altay, Changji, Wujiaqu, Urumqi, Turpan, and Hami) and southern Xingjiang (Aksu, Bayingolin, Kashgar, and Hotan) locations in Xinjiang province and developed a one-step multiplex RT-PCR to detect these melon viruses. The detection limits of this multiplex PCR were 103 copies/μL for ZYMV and MYSV and 102 copies/μL for WMV, SqMV, PRSV, CMV, and TMV. The detection results in the field showed 242 samples were infected by one or more viruses. The multiplex RT-PCR protocol demonstrated rapid, simultaneous, and relatively effective detection of viruses such as WMV, CMV, ZYMV, SqMV, TMV, PRSV, and MYSV. The technique is designed to identify these melon viruses in a single reaction, enhancing diagnostic efficiency and reducing costs, thus serving as a reference for muskmelon anti-virus breeding in Xinjiang.

The geomagnetic observation data of FHD-2B at Datong seismic station in Shanxi is mainly affected by the interference of the instrument’s own observation system and the surrounding environment. Since the performance of the instrument is nearly stable after delivery, we can improve the quality of observation data by improving the environment. In this paper, the quality of observation data from 2017 to 2021 was evaluated from three aspects: continuity rate, integrity rate and background noise, and it is found that the background noise level of the instrument has been significantly reduced since the instrument was updated in June 2019. By analyzing the data curves of different interferences such as construction interference, vehicle interference, high-voltage direct current transmission interference and power failure, it is found that the construction interference is generally manifested in the same period of time when each component is interfered, and the interference amplitude is different; the interference of high-voltage direct current transmission is usually serious in Z component, which can be processed through the interference period given by the National Geomagnetic Network Center and combined with the data of surrounding geomagnetic stations; vehicle interference interferes with each component of data, corresponding to vehicle activity period; the power failure interference shows that the observed data curves of D, H and Z components become thicker, burrs increase, and even wrong data appear, which can be solved by modifying the parameters of the instrument home page. The characteristics of different interference curves are summarized, which is convenient for workers to use FHD-2B geomagnetic data correctly for seismic research.

A convenient and efficient strategy for the preparation of 2-sulfonylindoles has been achieved through iodophor-/H2O2-mediated 2-sulfonylation of indoles with readily available sulfonyl hydrazides in the aqueous phase. Iodophor is commercially available and serves as the green catalyst and aqueous phase. A series of 2-sulfonylated products from indoles and N-methylpyrrole were synthesized in moderate yields in only 10 min. Control experiments were also conducted to reveal the mechanism of action. This method is environment friendly, easy to operate and suitable for a wide range of substrates.

Abstract Noble and commoner in the medieval China capital of Chang’an (modern-day Xi’an) engaged in an intricately intertwined agricultural and pastoral economy. The period represents the peak of the integration of nomadic and agricultural populations in early China. Here we firstly reported human collagen δ 13C and δ 15N values for eight middle age nobles whose lifespans cover roughly a century (AD 503–604) and who include a Northern Zhou, Emperor Wu (北周武帝) and his consort, Empress A’shina (阿史那皇后). We also consider stable isotopic evidence from nine individuals in commoner burials in the Chang’an region, likewise dating to the sixth century. This century-long dietary profile provides direct archeological evidence for dietary variability at this core metropolitan population. Constructing a comparative model using existing historical human isotopic data (n = 1233) from northern China and its northern Steppe, we find a marked regional divergence in noble and commoner dietary patterns. We trace this back to the considerable variety of agricultural and pastoral dietary practices, likely pointing to different economic and geographic backgrounds of the individuals under study. We argue that a two-way relationship between shifting pastoral and agricultural practices was reflected to separate degrees at the elite and commoner level. This study offers an improved understanding of the multiplicity of dietary patterns and associated lifeways for the metropolitan societies of medieval northern China.

Multi-criteria decision analysis has been widely used in health decision making. Measuring attractiveness by a categorical based evaluation technique (MACBETH) is a multi-criteria decision analysis approach. Its key distinction from other value-measurement methods is that MACBETH uses qualitative judgments of differences in attractiveness in order to generate value scores for the options. The MACBETH analysis process can be implemented by the M-MACBETH software, which is capable of structuring the value trees, developing the value functions, scoring each criterion of alternatives, assigning weights to criteria, consistency testing and sensitivity analysis. This article mainly introduces the basic principle of MACBETH and demonstrates how to use M-MACBETH software to realize multi-criteria decision analysis.

Abstract Background Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Surgical resection of the liver metastases increases the incidence of long-term survival in patients with colorectal liver metastasis (CRLM). However, many patients experience CRLM recurrence after the initial liver resection. As an unavoidable pathophysiological process in liver surgery, liver ischemia-reperfusion (IR) injury increases the risk of tumor recurrence and metastasis. Methods Colorectal liver metastasis (CRLM) mouse models and mouse liver partial warm ischemia models were constructed. The levels of lipid peroxidation were detected in cells or tissues. Western Blot, qPCR, elisa, immunofluorescence, immunohistochemistry, scanning electron microscope, flow cytometry analysis were conducted to evaluate the changes of multiple signaling pathways during CRLM recurrence under liver ischemia-reperfusion (IR) background, including SGK1/IL-6/STAT3, neutrophil extracellular traps (NETs) formation, polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) infiltration. Results Hepatocyte serum/glucocorticoid regulated kinase 1 (SGK1) was activated in response to hepatic ischemia-reperfusion injury to pass hepatocyte STAT3 phosphorylation and serum amyloid A (SAA) hyperactivation signals in CRLM-IR mice, such regulation is dependent on SGK-activated IL-6 autocrine. Administration of the SGK1 inhibitor GSK-650394 further reduced ERK-related neutrophil extracellular traps (NETs) formation and polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) infiltration compared with targeting hepatocyte SGK1 alone, thereby alleviating CRLM in the context of IR. Conclusions Our study demonstrates that hepatocyte and immune cell SGK1 synergistically promote postoperative CRLM recurrence in response to hepatic IR stress, and identifies SGK1 as a translational target that may improve postoperative CRLM recurrence.

Background China’s National Reimbursement Drug List (NRDL) has become the primary route for drug reimbursement in China. More recently, the authority has made pharmacoeconomic evaluation an integral part of the application for NRDL inclusion. The underlying financial conflict of interests (FCOI) of pharmacoeconomic evaluations, however, has the potential to influence evidence generated and thus subsequent decision-making yet remains poorly understood.Methods We searched for studies published between January 2012 and January 2022 on the 174 drugs added to the 2017–2020 NRDLs after successful negotiation. We categorised the study’s FCOI status into no funding, industry funding, non-profit funding and multiple fundings based on authors’ disclosure and assessed the reporting quality of included studies using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. We compiled descriptive statistics of funding types and study outcomes using t-tests and χ2 tests and conducted multivariate regression analysis.Results We identified 378 records and our final sample included 92 pharmacoeconomic evaluations, among which 69.6% were conducted with at least one funding source. More than half (57.6%) of the evaluations reached favourable conclusions towards the intervention drug and 12.6% reached a dominant result of the intervention drug over the comparison from model simulation. The reporting quality of included studies ranged from 19 to 25 (on a scale of 28), with an average of 22.3. The statistical tests indicated that industry-funded studies were significantly more likely to conclude that the intervention therapy was economical (p

In order to cope with the shortage of non-renewable energy and the increasingly environmental pollution, sustainable vegetable oils, as competitive alternatives, have widely been held in the good graces of the researchers. Vegetable oils are suitable for a wide range of applications such as biofuels and biodiesel. However, the development of vegetable oils is limited due to the characteristics of unsatisfactory oxidation stability and poor cold-flow properties. Chemical modification is considered as an effective solution to enhance the performance. The research progress of the chemical modification methods and applications of vegetable oils in recent years are summarized in this review. Reducing the content of carbon–carbon double bonds and increasing the degree of saturation are the keys to improve the physicochemical properties of vegetable oils. The prospects for the development direction and challenges of vegetable oils are proposed. Future research may focus on the use of multifunctional catalysts to optimize reaction conditions or to introduce active groups with lubricating properties in epoxidation reactions and explore the combination of chemical and auxiliary methods.

An iodophor-catalyzed direct disulfenylation of amino naphthalenes with aryl sulfonyl hydrazines in water was developed. A series of aryl sulfides were obtained in moderate to excellent yields. The advantages of this green protocol were the simple reaction conditions (metal-free, water as the solvent, under air), the odorless and easily available sulfur reagent, the broad substrate scope, and gram-scale synthesis. Moreover, the potential application of aryl sulfides was exemplified by further transformations.

Lubricating oils play an important role in friction-reducing and anti-wear, as well as enhancing mechanical efficiency. To improve the oxidation stability and service life of lubricating oils, the composition and structure of antioxidants should be strategically designed, and these parameters have significantly affected the performance of antioxidants in lubricating oils. Antioxidants are classified into two types based on the substrates they act on: peroxide decomposers and radical scavengers. In this review, the effects of peroxide decomposers (including sulfur compounds, phosphorus compounds, sulfur–phosphorus compounds, and sulfur–nitrogen compounds) and radical scavengers, such as hindered phenols and aromatic amines, have been discussed as additives in the antioxidant properties of lubricating oils. The results indicate that peroxide decomposers have excellent performances in lubricating oils, but high pollution of S and P is not conducive to their widespread use. On the contrary, radical scavengers also have superior antioxidant properties and no pollution, possessing the potential to replace traditional antioxidants. In addition, molecular structures with (multiple) synergistic antioxidant properties have been extensively designed and reported. This review serves as a reference for researchers to design and develop high-end new antioxidants.

Abstract Objective To investigate the expression of programmed death ligand-1 (PD-L1) and the levels of CD8+ tumor-infiltrating lymphocytes (TILs) in meningioma as well as determine the association between their levels and the clinical outcomes. Methods We performed a retrospective case-control study on 93 patients with meningioma. The patients showed tumor recurrence and were matched with the control patients without recurrence in their age, gender, admission time, tumor sites, tumor volume, peritumoral brain edema (PTBE), Simpson grade resection, WHO grade, postoperative radiotherapy, and the follow-up duration. We reviewed the clinical data of patients and performed immunohistochemistry analysis to investigate the PD-L1 expression and the levels of CD8+ TILs. Multivariate logistic regression was performed to analyze the association between clinical features and immune markers. The conditional logistic regression models were used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and Kaplan–Meier analysis was performed to analyze tumor recurrence. Results Tumor volume was correlated with the PD-L1 expression (P = 0.003, HR = 5.288, 95%CI, 1.786–15.651). PTBE served as an independent predictor of CD8+ TIL levels (P = 0.001, HR = 0.176, 95%CI 0.065–0.477). The levels of CD8+ TILs were associated with tumor recurrence (P = 0.020, OR = 0.325, 95%CI, 0.125–0.840). Conclusion Tumor volume was associated with PD-L1 expression, and PTBE was an independent predictor of CD8+ TIL levels in meningioma. CD8+ TIL levels correlated with tumor recurrence in meningioma.

Background: Diabetic nephropathy is a major microvascular complication and the main cause of end-stage renal disease in diabetic patients. The therapeutic effects of Bailing capsules for diabetic nephropathy have already been demonstrated; however, the cost-effectiveness of Bailing capsules remains controversial. This study aimed to evaluate the cost-effectiveness of Bailing capsules combined with Western medicine compared with Western medicine alone in diabetic nephropathy from a Chinese healthcare system perspective.Methods: A Markov model was established to simulate the disease process of patients over a 20-year period. Clinical efficacy data were obtained from a meta-analysis, and transition probability was estimated based on microsimulation. Direct costs and utility values were collected from the Chinese Drug Bidding Database (https://www.shuju.menet.com.cn) and published literature. The incremental cost-effectiveness ratio (ICER) was measured, and one-way and probabilistic sensitivity analyses were performed to observe model stability.Results: A total of 34 randomized controlled trials involving 3,444 patients with diabetic nephropathy were selected for the meta-analysis. Compared to Western medicine alone, the addition of Bailing capsules resulted in an increase of 0.39 quality-adjusted life-years (QALYs) and additional costs of Chinese Yuan (CNY) 24,721, yielding an ICER of CNY 63,001 per QALY gained. The ICER was lower than the threshold of willingness-to-pay of CNY 80,976 (The GDP per Capita in China). The reliability and stability of the results were confirmed by the sensitivity analysis.Conclusion: We found that Bailing capsules may be a cost-effective treatment choice for patients with diabetic nephropathy in the Chinese population.

Purpose: The aim of this study was to evaluate the cost-effectiveness of a recently approved first-line therapy (adebrelimab plus chemotherapy vs. chemotherapy alone) for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the US and China, and to estimate the reasonable range of adebrelimab price from the decision-makers.Methods: Several partitioned survival models were built to compare the cost and effectiveness of adebrelimab plus chemotherapy vs. chemotherapy alone over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CAPSTONE-1 trial. Costs and utilities were obtained from previously published studies. Sensitivity, scenario and subgroup analyses were performed to explore the uncertainty of the model outcomes. Price simulation was conducted at three thresholds of willingness-to-pay (WTP), including WTP of $100,000 in the US and of $37,422 in China, 0.5WTP of $50,000 in the US and of $18,711 in China, and 1.5WTP of 150,000 in the US and of $56,133 in China.Findings: Base-case analysis at $1382.82/600 mg of adebrelimab price indicated that adebrelimab plus chemotherapy would be cost-effective in the US at the WTP threshold of $100,000, but not in China at the WTP threshold of $37,422. If PAP was taken into account, the regimen would be cost-effective in China at the given WTP. The results of price simulation indicated that adebrelimab plus chemotherapy was completely favored in the US if adebrelimab price was less than $8894.98/600 mg (total quality-adjusted life years [QALYs] were calculated with progression-based utility [PB-utility]) or $8912.51/600 mg (total QALYs were calculated with time-to-death utility [TTD-utility]) at the WTP threshold of $100,000; if adebrelimab price was reduced by at least $202.03/600 mg (total QALYs were calculated with PB-utility) or $103.06/600 mg (total QALYs were calculated with TTD-utility), the regimen was also cost-effective in China without PAP at the WTP threshold of $37,422. The above results were stable in the sensitivity analyses. Subgroup analysis found that the subgroup with better survival benefits tended to have a higher probability of cost-effectiveness, which was also associated with adebrelimab price.Implications: First-line adebrelimab plus chemotherapy represented a dominant treatment strategy comparing with chemotherapy alone in the US and also did in China with PAP at $1382.82/600 mg of adebrelimab price. Decision-makers could benefit from pricing strategy provided by this study in making optimal decisions. More evidences were needed to verify and improve the results.

ObjectiveTo investigate the levels of tumor-infiltrating CD8+ lymphocytes (CD8+ TILs) and the expression of programmed cell death receptor ligand 1 (PD-L1) in the tumor microenvironment (TME) of pediatric and adolescent pituitary adenomas (PAPAs) and analyze the correlation between their levels and the clinical characteristics.MethodsA series of 43 PAPAs cases were enrolled over a period of 5 years. To compare the TME of PAPAs and adult PAs, 43 PAPAs cases were matched with 60 adult PAs cases (30 cases were between 20 and 40 years old, and 30 cases were older than 40 years) for main clinical characteristics. The expression of immune markers in PAPAs was detected by immunohistochemistry, and their correlation with the clinical outcomes was analyzed using statistical methods.ResultsIn the PAPAs group, CD8+ TILs level was significantly lower (3.4 (5.7) vs. 6.1 (8.5), p = 0.001), and PD-L1 expression (0.040 (0.022) vs. 0.024 (0.024), p < 0.0001) was significantly higher as compared with the older group. The level of CD8+ TILs was negatively correlated with the expression of PD-L1 (r = −0.312, p = 0.042). Moreover, CD8+ TILs and PD-L1 levels were associated with Hardy (CD8, p = 0.014; PD-L1, p = 0.018) and Knosp (CD8, p = 0.02; PD-L1, p = 0.017) classification. CD8+ TILs level was associated with high-risk adenomas (p = 0.015), and it was associated with the recurrence of PAPAs (HR = 0.047, 95% CI 0.003–0.632, p = 0.021).ConclusionCompared with the TME in adult PAs, the TME in PAPAs was found to express a significantly altered level of CD8+ TILs and PD-L1. In PAPAs, CD8+ TILs and PD-L1 levels were associated with clinical characteristics.

Cholangiocarcinoma is a heterogenous group of cancers, with large genetic variation seen within subtypes. Here, the authors find 12 significantly mutated genes and 5 focal CNA regions were found in perihilar cholangiocarcinoma, and identified METTL14 to have a potential tumour suppressive role.

In this work, ball-on-disk wear experiments were carried out on different wear parameters such as sliding speed, sliding distance, normal load, temperature, and oil film thickness. In total, 81 different sets of wear depth data were obtained. Four different machine learning (ML) algorithms, namely Random Forest (RF), K-neighborhood (KNN), Extreme Gradient Boosting (XGB), and Support Vector Machine (SVM) were applied to predict wear depth. By analyzing the performance of several ML algorithms, it is demonstrated that ball bearing wear depth can be estimated by ML models by inputting different parameter variables. A comparative analysis of the performance of the different models revealed that XGB was more accurate than the other ML models at anticipating wear depth. Further analysis of the attribute of feature importance and correlation heatmap of the Pearson correlation reveals that each input feature has an effect on wear.

Robust and precise visual localization over extended periods of time poses a formidable challenge in the current domain of spatial vision. The primary difficulty lies in effectively addressing significant variations in appearance caused by seasonal changes (summer, winter, spring, autumn) and diverse lighting conditions (dawn, day, sunset, night). With the rapid development of related technologies, more and more relevant datasets have emerged, which has also promoted the progress of 6-DOF visual localization in both directions of autonomous vehicles and handheld devices.This manuscript endeavors to rectify the existing limitations of the current public benchmark for long-term visual localization, especially in the part on the autonomous vehicle challenge. Taking into account that autonomous vehicle datasets are primarily captured by multi-camera rigs with fixed extrinsic camera calibration and consist of serialized image sequences, we present several proposed modifications designed to enhance the rationality and comprehensiveness of the evaluation algorithm. We advocate for standardized preprocessing procedures to minimize the possibility of human intervention influencing evaluation results. These procedures involve aligning the positions of multiple cameras on the vehicle with a predetermined canonical reference system, replacing the individual camera positions with uniform vehicle poses, and incorporating sequence information to compensate for any failed localized poses. These steps are crucial in ensuring a just and accurate evaluation of algorithmic performance. Lastly, we introduce a novel indicator to resolve potential ties in the Schulze ranking among submitted methods. The inadequacies highlighted in this study are substantiated through simulations and actual experiments, which unequivocally demonstrate the necessity and effectiveness of our proposed amendments.

Abstract Background Dizziness and vertigo are common clinical symptoms. Gastrodin injection has shown clinical effects on dizziness or vertigo. However, little is known about the effectiveness and costs of combining Gastrodin injection with conventional treatment on dizziness or vertigo in daily practice. This study aimed to analyze the clinical and economic effects of Gastrodin injection for patients with dizziness or vertigo in comparison to Extract of Ginkgo Biloba Leaves injection in real-world practice. Methods Data was collected from the Hospital Information System of 131 hospitals across China from January to December 2018. Patients whose primary discharge diagnosis was dizziness or vertigo according to ICD-10 diagnostic coding were included and divided into two samples: sample of dizziness or vertigo; sample of dizziness or vertigo, with the complication of cerebral infarction. Comparative analysis of the medical cost per hospitalization, hospitalization duration, effective rates, and cure rates between the group of Gastrodin injection and the group of Extract of Ginkgo Biloba Leaves injection was conducted. Propensity Score Matching was used to control potential confounding factors. Results In the sample of dizziness or vertigo, although there was no significant differences on hospitalization duration (P = 0.080), the group of Gastrodin injection was significantly better than the group of Extract of Ginkgo Biloba Leaves injection (P

Abstract Liver fibrosis is a danger signal indicating a huge risk of liver cancer occurrence, but there is still no effective clinical means to regulate the progress of liver fibrosis. Although a variety of drugs targeting SYK have been developed for tumors and autoimmune diseases, the mechanism and specific efficacy of SYK’s role in liver fibrosis are not yet clear. Our studies based on chronic CCL4, bile duct ligation, and subacute TAA mouse models show that SYK in monocyte-derived macrophages (MoMFs) is fully dependent on phosphorylation of Erk to up-regulate the expression of Hif1α, thereby forming the crosstalk with SYK to drive liver fibrosis progress. We have evaluated the ability of the small molecule SYK inhibitor GS9973 in a variety of models. Contrary to previous impressions, high-frequency administration of GS9973 will aggravate CCL4-induced liver fibrosis, which is especially unsuitable for patients with cholestasis whose clinical features are bile duct obstruction. In addition, we found that inhibition of MoMFs SYK impairs the expression of CXCL1, on one hand, it reduces the recruitment of CD11bhiLy6Chi inflammatory cells, and on the other hand, it promotes the phenotype cross-dress process of pro-resolution MoMFs, thereby remodeling the chronic inflammatory environment of the fibrotic liver. Our further findings indicate that on the basis of the administration of CCR2/CCR5 dual inhibitor Cenicriviroc, further inhibiting MoMFs SYK may give patients with fibrosis additional benefits.

Summary: A high point of Tibetan Plateau (TP) civilization, the expansive Tubo Empire (618–842 AD) wielded great influence across ancient western China. However, whether the Tubo expansion was cultural or demic remains unclear due to sparse ancient DNA sampling. Here, we reported ten ancient genomes at 0.017- to 0.867-fold coverages from the Dulan site with typical Tubo archaeological culture dating to 1308–1130 BP. Nine individuals from three different grave types have close relationship with previously reported ancient highlanders from the southwestern Himalayas and modern core-Tibetan populations. A Dulan-related Tubo ancestry contributed overwhelmingly (95%–100%) to the formation of modern Tibetans. A genetic outlier with dominant Eurasian steppe-related ancestry suggesting a potential population movement into the Tubo-controlled regions from Central Asia. Together with archeological evidence from burial styles and customs, our study suggested the impact of the Tubo empire on the northeast edge of the TP involved both cultural and demic diffusion.

It is essential to develop infrared (IR) thermogram identification technologies to establish automatic diagnosis systems in power substations. The convolutional neural network (CNN) based methods show the highest accuracy in this field. The IR thermograms of electrical equipment are very different from general digital images, which means the present methods need further improvements. For data-driven CNN methods, it is necessary to study the characteristics of the IR data. This paper collected 11817 thermograms from substations and structured the dataset according to equipment types. The statistical features of mean, variance, skewness, kurtosis and contrast are analyzed and compared with other five image datasets. Several tricks are revealed from the analysis and tested on CNN models. Firstly, greycaling the Iron pseudo-color images extracts the temperature information and makes it possible to design models with fewer channels. The test shows it could reduce over 35% computational costs. Secondly, the sparse information of color and edges of thermograms makes it necessary to keep the original aspect ratio. The image preprocessing method of cropping shows better performance than padding and rescaling. Thirdly, the 0–1 normalization can boost the training process for about 100 epochs, which is related to the particular background of thermograms.

Background and Objectives: The modification of histone acetylation plays a vital role in regulating tumor occurrence and development, but the interaction between histone acetylation modulator genes and the liver hepatocellular carcinoma (LIHC) microenvironment, as well as immunotherapy, has not been investigated. Materials and Methods: Analysis of all statistical data was carried out using R software (Version 4.2.0) and the online tool Sangerbox. Comprehensive bioinformatics analysis, including signature construction and validation, functional analyses, immune and genomic features analyses, and immunotherapy prediction analyses, were performed to explore the prognostic and therapeutic role of histone acetylation modulator genes in LIHC development and progression. Results: The LIHC cohort from The Cancer Genome Atlas (TCGA) database was selected as the training cohort; the GSE76427 cohort from the Gene Expression Omnibus (GEO) database and the LIRI-JP cohort from the International Cancer Genome Consortium (ICGC) database were selected as the validation cohorts. The histone acetylation modulator gene-based prognostic signature was constructed and validated successfully. Immune infiltration analysis showed that most immune cells and immune functions were enriched in patients with high histone acetylation risk scores (HARS). Additionally, high levels of checkpoint inhibitors (ICIs) and human leukocyte antigens (HLAs) were also observed in high HARS patients. Meanwhile, TIDE algorithm analysis was conducted to explore the relationship between HARS and immunotherapy response, and submap algorithm analysis was used for the verification of the results, from which we found that high HAPS patients were more likely to respond to immunotherapy. Conclusions: Our findings revealed that the histone acetylation modulator genes, particularly for KAT21, SIRT6, and HAT1, may have the potential to function as a new prognostic marker and therapeutic target for LIHC.

Background and purpose: The latest RATIONALE-302 trial (NCT03430843) showed that tislelizumab therapy significantly improved overall survival benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with traditional chemotherapy. This study aimed to compare the cost-effectiveness of tislelizumab versus chemotherapy as a second-line treatment for advanced or metastatic ESCC in China.Methods: A partitioned survival model was developed to predict patients’ lifetime quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) from the Chinese healthcare payers’ perspective. We extracted efficacy and safety data from the RATIONALE-302 trial and the local cost and resource use data from online databases and published studies. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to explore model uncertainty.Results: Compared with chemotherapy, tislelizumab generated a higher cost (US$ 10211.78 vs. US$ 7294.72) but yielded more QALY (0.78 vs. 0.51 QALYs). The ICER for tislelizumab was US$11073.85 per QALY gained. The PSA results indicated that the probability of tislelizumab being economical was 76% under a willingness-to-pay (WTP) threshold of 1.5 times per capita GDP ($17915) in China.Conclusion: Tislelizumab could be a promising cost-effective strategy as the second-line treatment for patients with ESCC compared with chemotherapy in the Chinese setting.

Background and purpose: The TASTE trial indicated that patients with acute ischemic stroke (AIS) using edaravone dexborneol have a significantly higher proportion of 90-day good functional outcomes (mRS 0–1) than those using edaravone. This study compared the cost-effectiveness of the aforementioned interventions in treating AIS in the Chinese setting, aiming to inform treatment decisions in clinical practice.Methods: A model combining a decision tree and a Markov model was developed to assess the cost-effectiveness of edaravone dexborneol versus edaravone for AIS over a 30-year time horizon from the Chinese healthcare system’s perspective. Both efficacy and safety data were extracted from the TASTE study. Local costs and utilities were derived from publications and open-access databases; both cost and effectiveness were discounted at a rate of 5% per year. Sensitivity analyses were conducted to ensure robustness and identify the main drivers of the result.Results: Compared with edaravone, edaravone dexborneol for AIS was found to be cost-effective in the first year and highly cost-effective as the study time horizons extended. In the long term (30 years), edaravone dexborneol yielded a lifetime gain of 0.25 (0.07–0.45) quality-adjusted life years (QALYs) at an additional cost of CNY 2201.07 (-3,445.24–6,637.23), yielding an ICER of CNY 8823.41 per QALY gained under the willingness-to-pay (WTP) of 1.5 times per capita GDP (121,464 CNY). The result is robust in both deterministic and probabilistic sensitivity analysis (PSA) methods, with the advantage of the edaravone dexborneol strategy increasing over time. Specifically, the probability of edaravone dexborneol dominant dexborneol is 76.30%, 98.90%, and 99.50% over 1-, 5-, and 30-year time horizons.Conclusion: Both short- and long-term economic analyses suggest that edaravone dexborneol is highly likely to be a cost-effective alternative to treat AIS compared with edaravone in China.

Objective To understand the current situation of a patient management service and evaluate its effect in direct-to-patient (DTP) pharmacies. Method This is a retrospective cohort study using real-world data routinely collected from DTP pharmacies. A cohort of lung cancer patients using PD-1/L1 was retrospectively established using sales and follow-up data which were collected from 79 Medbanks DTP pharmacies during their daily business activities. Cox regression analysis was used to explore the factors associated with the durations of drug purchase and follow-up. Result A total of 12,226 subjects were included in this study, 76.4% of them were male, with a median age of 62 years. Across the total study population, 1,902 (15.56%) were described as low follow-up response rate group, 1,448 (11.84%) were described as middle follow-up response rate group and 8,876 (72.60%) as high follow-up response rate group. Statistically significant differences were observed in both median drug purchase duration and follow-up duration across the three groups. Findings from Cox regression analysis indicated that factors associated with longer duration of drug purchase included participating a patient access program (HR=0.873, P

Background: Glioma is the most prevalent malignant intracranial tumor. Many studies have shown that angiogenesis plays a crucial role in glioma tumorigenesis, metastasis, and prognosis. In this study, we conducted a comprehensive analysis of angiogenesis-related genes (ARGs) in glioma.Methods: RNA-sequencing data of glioma patients were obtained from TCGA and CGGA databases. Via consensus clustering analysis, ARGs in the sequencing data were distinctly classified into two subgroups. We performed univariate Cox regression analysis to determine prognostic differentially expressed ARGs and least absolute shrinkage and selection operator Cox regression to construct a 14-ARG risk signature. The CIBERSORT algorithm was used to explore immune cell infiltration, and the ESTIMATE algorithm was applied to calculate immune and stromal scores.Results: We found that the 14-ARG signature reflected the infiltration characteristics of different immune cells in the tumor immune microenvironment. Additionally, total tumor mutational burden increased significantly in the high-risk group. We combined the 14-ARG signature with patient clinicopathological data to construct a nomogram for predicting 1-, 3-, and 5-year overall survival with good accuracy. The predictive value of the prognostic model was verified in the CGGA cohort. SPP1 was a potential biomarker of glioma risk and was involved in the proliferation, invasion, and angiogenesis of glioma cells.Conclusion: In conclusion, we established and validated a novel ARG risk signature that independently predicted the clinical outcomes of glioma patients and was associated with the tumor immune microenvironment.

Introduction: Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is widely used and often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China. In recent years, an elevated risk of allergic reactions has been observed following XYP, but whether concomitant medication use contributes to this risk is still unknown.Objective: This study aims to investigate the association between the concomitant use of XYP and the 25 most frequently co-applied medications with suspected allergic reactions for China’s patients receiving XYP.Methods: A nested case–control study was conducted using the sampling data from 2015 China’s Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with a 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day.Results: Out of 57,612 participants with XYP prescription, we obtained 949 matched case–control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin [OR = 4.29; 95% CI (2.52, 7.30)], cefoperazone-sulbactam [OR = 4.26; 95% CI (1.40, 13.01)], lidocaine [OR = 2.76; 95% CI (1.79, 4.25)], aminophylline [OR = 1.73; 95% CI (1.05, 2.85)], ribavirin [OR = 1.54; 95% CI (1.13, 2.10)], potassium chloride [OR = 1.45; 95% CI (1.10, 1.91)], and vitamin C [OR = 1.32; 95% CI (1.03, 1.70)] were associated with increased risk, while cefathiamidine [OR = 0.29; 95% CI (0.16, 0.51)] was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings.Conclusion: Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine, and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.

CircRNAs have been reported to be related to hepatocellular carcinoma (HCC) development. Limited studies have revealed the expression profile of circRNAs in tumor and para-tumor normal samples in HCC patients. We found that circASPH was significantly increased in HCC tumor samples and that the level of circASPH was closely related to the overall survival of HCC patients. Mechanistically, circASPH could regulate the methylation of the promoter and expression of hydrocyanic oxidase 2 (HAO2) to promote HCC progression by acting as a sponge for miR-370-3p, and miR-370-3p could target DNMT3b and increase the 5mC level. In summary, our study determined that circASPH could regulate the methylation and expression of HAO2 and it could be considered an important epigenetic regulator in HCC progression.

BackgroundLung cancer is imposing significant pressure on the national health insurance system worldwide, especially under the COVID-19 pandemic. However, the cost-effectiveness of all available first-line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) is still uncertain. The aim of this study was to evaluate the cost-effectiveness of 12 first-line treatments for patients with advanced EGFR mutated NSCLC from the perspective of the United Kingdom (UK) National Health Service and Chinese health care system.MethodsWe used a Markov model to estimate the cost-effectiveness of 12 treatments, including 6 EGFR tyrosine kinase inhibitors, 4 combination treatments and 2 chemotherapies. The key clinical efficacy and safety data were from a network meta-analysis. The cost and health preference were mainly collected from the literature. The most cost-effective treatment was inferred through a sequential analysis. Uncertainty was tested with one-way sensitivity analyses, scenario analyses, and probabilistic sensitivity analyses. Quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated, at willingness-to-pay thresholds of £20000 to £50000 and £8000 to £24000 per QALY in the UK and China respectively.ResultsFor clinical effectiveness, osimertinib and gefitinib plus pemetrexed based chemotherapy (PbCT) yielded the highest QALYs, while two chemotherapy treatments gained the lowest QALYs. For costs, gefitinib treatment was the cheapest option in both countries (£24529 in the UK and £12961 in China). For cost-effectiveness, 4 treatments including gefitinib, gefitinib plus pemetrexed, gefitinib plus PbCT, and osimertinib formed the cost-effectiveness frontier in both countries. Gefitinib alone (70.7% and 80.0% under the threshold of £20000 and £8000 per QALY in the UK and China, respectively) and gefitinib plus PbCT (62.3% and 71.2% under the threshold of £50000 and £24000 per QALY in the UK and China, respectively) were most likely to be cost-effective compared with other first-line treatments.ConclusionsGefitinib and gefitinib plus PbCT were likely to be cost-effective for patients with advanced EGFR mutated NSCLC in both countries.

Abstract Currently, the controversy regarding the expression profile and function of BUB1B in different malignancies still exist. In this project, we aimed to explore the role and molecular mechanism of BUB1B in the progression of extrahepatic cholangiocarcinoma (ECC). The expression levels of BUB1B in human ECC were evaluated by immunohistochemistry, western blot, and real-time PCR. The role and mechanism of BUB1B in CCA cell proliferation and invasion were investigated in both in vitro and in vivo functional studies. To indicate the clinical significance, a tissue microarray was performed on 113 ECC patients, followed by univariate and multivariate analyses. The expression of BUB1B was increased in both human CCA tissues and CCA cells. Results from loss-of-function and gain-of-function experiments suggested that the inhibition of BUB1B decreased the proliferation and invasiveness of CCA cells in vitro and in vivo, while overexpression of BUB1B achieved the opposite effect. Furthermore, the activation of c-Jun N-terminal kinase-c-Jun (JNK)-c-Jun pathway was regulated by BUB1B. BUB1B regulated the proliferation and invasiveness of CAA cells in a JNK-c-Jun-dependent manner. Clinically, ECC patients with BUB1B high expression had worse overall survival and recurrence-free survival than those with BUB1B low expression. Multivariate analysis identified that BUB1B was an independent predictor for postoperative recurrence and overall survival of ECC patients. In conclusion, BUB1B promoted ECC progression via JNK/c-Jun pathways. These findings suggested that BUB1B could be a potential therapeutic target and a biomarker for predicting prognosis for ECC patients.

PurposePatients with intraventricular tumors are more susceptible to postoperative meningitis (POM) than other intracranial tumors. In this study, we explored the risk factors of POM in lateral ventricular trigone meningiomas (LVTMs).MethodsClinical features of 64 patients with LVTMs were analyzed. Age, gender, body mass index, medical history, intraoperative blood loss (IBL), intraventricular drainage placement, surgical duration, tumor grade, postoperative tumor cavity hemorrhage, and tumor size were included in univariate and multivariate analyses of POM.ResultsOf the 64 patients, 14 patients (21.9%) received diagnosis of POM. The univariate analysis revealed IBL ≥400 mL (odds ratio [OR], 9.012; p = 0.003), tumor size ≥50 cm3 (OR, 3.071; p = 0.080), and surgical duration ≥5 h (OR, 2.970; p = 0.085) were considered possible risk factors for POM (p

In vehicle re-identification, identifying a specific vehicle from a large image dataset is challenging due to occlusion and complex backgrounds. Deep models struggle to identify vehicles accurately when critical details are occluded or the background is distracting. To mitigate the impact of these noisy factors, we propose Identity-guided Spatial Attention (ISA) to extract more beneficial details for vehicle re-identification. Our approach begins by visualizing the high activation regions of a strong baseline method and identifying noisy objects involved during training. ISA generates an attention map to mask most discriminative areas, without the need for manual annotation. Finally, the ISA map refines the embedding feature in an end-to-end manner to improve vehicle re-identification accuracy. Visualization experiments demonstrate ISA’s ability to capture nearly all vehicle details, while results on three vehicle re-identification datasets show that our method outperforms state-of-the-art approaches.

In this work, a chemical modification method was used to prepare silicone grease with high thermal conductivity. We report two preparation methods for thermal conductive fillers, which are hydroxylated boron nitride-grafted carboxylic silicone oil (h-BN-OH@CS) and amino boron nitride-grafted carboxylic silicone oil (h-BN-NH2@CS). When h-BN-OH@CS and h-BN-NH2@CS were filled with 30 wt% in the base grease, the thermal conductivity was 1.324 W m−1 K−1 and 0.982 W m−1 K−1, which is 6.04 and 4.48 times that of the base grease (0.219 W m−1 K−1), respectively. The interfacial thermal resistance is reduced from 11.699 °C W−1 to 1.889 °C W−1 and 2.514 °C W−1, respectively. Inorganic filler h-BN and organic filler carboxylic silicone oil were chemically grafted to improve the compatibility between h-BN and the base grease. The covalent bond between functionalized h-BN and carboxylic silicone oil is stronger than the van der Waals force, which can reduce the viscosity of the silicone grease.