Rapid summer Russian Arctic sea-ice loss enhances the risk of recent Eastern Siberian wildfires.

In recent decades boreal wildfires have occurred frequently over eastern Siberia, leading to increased emissions of carbon dioxide and pollutants. However, it is unclear what factors have contributed to recent increases in these wildfires. Here, using the data we show that background eastern Siberian Arctic warming (BAW) related to summer Russian Arctic sea-ice decline accounts for ~79% of the increase in summer vapor pressure deficit (VPD) that controls wildfires over eastern Siberia over 2004-2021 with the remaining ~21% related to internal atmospheric variability associated with changes in Siberian blocking events. We further demonstrate that Siberian blocking events are occurring at higher latitudes, are more persistent and have larger zonal scales and slower decay due to smaller meridional potential vorticity gradients caused by stronger BAW under lower sea-ice. These changes lead to more persistent, widespread and intense high-latitude warming and VPD, thus contributing to recent increases in eastern Siberian high-latitude wildfires.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

The role of mountains in shaping the global meridional overturning circulation.

The meridional overturning circulation (MOC) in the ocean is a key player in the global climate system, while continental topography provides an essential backdrop to the system. In this study, we design a series of coupled model sensitivity experiments to investigate the influence of various mountain ranges on the global thermohaline circulation. The results highlight the influence of the Tibetan Plateau (TP) on the global thermohaline circulation. It emerges as a requisite for establishing the Atlantic MOC (AMOC) and a determining factor for the cessation of the Pacific MOC (PMOC). Additionally, the Antarctic continent plays a vital role in facilitating the TP to form the AMOC. While the formation of the AMOC cannot be attributed to any single mountain range, the TP alone can inhibit the PMOC's development. By modifying the global hydrological cycle, the TP is likely to have been crucial in molding the global thermohaline circulation.

Epidemiological study of multi-site WMSDs in the footwear industry in China.

Objectives. This study aimed to identify the prevalence of multi-site work-related musculoskeletal disorders (WMSDs) in Chinese footwear industry workers from 2018 to 2020 and explore the possible influencing factors of WMSDs. Methods. 7106 subjects from 26 large shoe factories in China were investigated using the epidemiological cross-sectional survey method by using the Nordic musculoskeletal questionnaire (NMQ). Results. The total prevalence of WMSDs in the study subjects was 36.8% (2616/7106). Among them, the prevalence of multi-site WMSDs was 26.1% (1858/7106). The proportion of multi-site WMSDs involving two sites was the largest (31.38%). In addition, the results showed that the risk factors of multi-site WMSDs were gender, marital status, long current job experience, poor health, poor working posture, etc. Conclusions. The prevalence of WMSDs was high in the Chinese footwear industry. Based on the results, therefore, it seems necessary to improve work posture, work organization and workenvironment to prevent WMSDs.

Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography.

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

Infection with COVID-19 promotes the progression of pancreatic cancer through the PI3K-AKT signaling pathway.

OBJECTIVE: To investigate the effect of COVID-19 infection on pancreatic cancer. METHODS: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. RESULTS: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. CONCLUSION: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

A Large-Scale Sensor Layout Optimization Algorithm for Improving the Accuracy of Inverse Finite Element Method.

The inverse finite element method (iFEM) based on fiber grating sensors has been demonstrated as a shape sensing method for health monitoring of large and complex engineering structures. However, the existing optimization algorithms cause the local optima and low computational efficiency for high-dimensional strain sensor layout optimization problems of complex antenna truss models. This paper proposes the improved adaptive large-scale cooperative coevolution (IALSCC) algorithm to obtain the strain sensors deployment on iFEM, and the method includes the initialization strategy, adaptive region partitioning strategy, and gbest selection and particle updating strategies, enhancing the reconstruction accuracy of iFEM for antenna truss structure and algorithm efficiency. The strain sensors optimization deployment on the antenna truss model for different postures is achieved, and the numerical results show that the optimization algorithm IALSCC proposed in this paper can well handle the high-dimensional sensor layout optimization problem.

Controlled synthesis and photocatalytic hydrogen evolution activities of cobalt carbides with different phase compositions.

Cobalt carbides are emerging as promising materials for various magnetic and catalytic applications. However, exploring dedicated cobalt carbides with optimal catalytic properties via adjusting phase compositions remains a significant challenge. Herein, three different cobalt carbides, CoxC (Co2C-Co3C), Co2C-Co, and Co3C, were successfully prepared using a facile one-pot green method. The phase compositions of cobalt carbides could be easily controlled by varying the cobalt-based precursors and carbon sources. More remarkably, three different cobalt carbides could serve as reduction cocatalysts decorated CdS for improved hydrogen production under visible light. Intriguingly, the obtained Co3C/CdS nanocomposite displayed the highest photocatalytic hydrogen evolution activity among the three composites and superior photocatalytic stability. This work provides a fundamental approach to tuning the photocatalytic properties of cobalt carbides for energy conversion fields.

An algorithm for discovering vital nodes in regional networks based on stable path analysis.

Vital node discovery is a hotspot in network topology research. The key is using the Internet's routing characteristics to remove noisy paths and accurately describe the network topology. In this manuscript, a vital regional routing nodes discovery algorithm based on routing characteristics is proposed. We analyze the stability of multiple rounds of measurement results to overcome the single vantage point's path deviation. The unstable paths are eliminated from the regional network which is constructed through probing for target area, and the pruned topology is more in line with real routing rules. Finally, we weight the edge based on the actual network's routing characteristics and discover vital nodes in combination with the weighting degree. Unlike existing algorithms, the proposed algorithm reconstructs the network topology based on communication and transforms unweighted network connections into weighted connections. We can evaluate the node importance in a more realistic network structure. Experiments on the Internet measurement data (275 million probing results collected in 107 days) demonstrate that: the proposed algorithm outperforms four existing typical algorithms. Among 15 groups of comparison in 3 cities, our algorithm found more (or the same number) backbone nodes in 10 groups and found more (or the same number) national backbone nodes in 13 groups.

Noise-aware infrared polarization image fusion based on salient prior with attention-guided filtering network.

Infrared polarization image fusion integrates intensity and polarization information, producing a fused image that enhances visibility and captures crucial details. However, in complex environments, polarization imaging is susceptible to noise interference. Existing fusion methods typically use the infrared intensity (S0) and degree of linear polarization (DoLP) images for fusion but fail to consider the noise interference, leading to reduced performance. To cope with this problem, we propose a fusion method based on polarization salient prior, which extends DoLP by angle of polarization (AoP) and introduces polarization distance (PD) to obtain salient target features. Moreover, according to the distribution difference between S0 and DoLP features, we construct a fusion network based on attention-guided filtering, utilizing cross-attention to generate filter kernels for fusion. The quantitative and qualitative experimental results validate the effectiveness of our approach. Compared with other fusion methods, our method can effectively suppress noise interference and preserve salient target features.

A quantum dot aptamer fluorescent sensor based on magnetic graphene oxide for the detection of zearalenone.

As an estrogenic mycotoxin found in a wide range of agricultural crops, the toxicity of zearalenone (ZEN) poses a serious risk to human health. Accordingly, to achieve rapid detection of zearalenone in complex samples, an aptamer fluorescence sensor based on magnetic graphene oxide was developed. Compared with traditional methods, this technique has the virtues of simple operation, low cost, and reliable performance. Magnetic graphene oxide (MGO) was synthesized as a fluorescent bursting agent, using a chemical precipitation approach by depositing Fe3O4 on the surface of graphene oxide. As a fluorescent probe, an aptamer coupling with CdTe quantum dots and zearalenone was used. Following the specific binding of zearalenone and the aptamer, the affinity interaction between the fluorescent probe and MGO was weakened, resulting in the recovery of fluorescence and making the qualitative and quantitative analysis of zearalenone available via fluorescence intensity determination. The results indicated that the method's linear range was 5-120 µg L-1 and its detection limit was 2.9 µg L-1. In addition, the recoveries varied from 76.4 to 118.8% for crop samples, with relative standard deviations (RSDs) between 0.8 and 9.5%, which suggests an effective method for the separation and detection of mycotoxins in actual environmental samples.

Anti-Parity-Time Symmetry in a Su-Schrieffer-Heeger Sonic Lattice.

The Su-Schrieffer-Heeger (SSH) model is an important cornerstone in modern condensed-matter topology, yet it is the simplest one-dimensional (1D) tight binding approach to dwell into the characteristics of spinless electrons in chains of staggered bonds. Moreover, the chiral symmetry assures that its surface-confining states pin to zero energy, i.e., they reside midgap in the energy dispersion. Symmetry is also an attribute related to artificial media that are subject to parity P and time-reversal T operations. This non-Hermitian family has been thoroughly nourished in a wave-based context, where anti-PT (APT) symmetric systems are the youngest belonging members, permitting refractionless optics, inverse PT-symmetry breaking transition, and asymmetric mode switching. Here, we report the first extension of APT symmetry in an acoustic setting by endowing a SSH lattice with gain and loss components. We show that the in-gap topological defect state hinges on the non-Hermitian phase, in that the broken symmetry suppresses it, yet when PT or APT symmetry is intact, it is observed with either damped or evanescent decay, respectively. Our experiments showcase how the non-Hermitian SSH lattice serves as a utile platform to investigate topological properties across various PT symmetric phases using sound.

Establishment of a prognostic model toward lung squamous cell carcinoma based on m7G-related genes in the cancer genome atlas.

Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (m7G) modifications, a tRNA modification, are common in eubacteria, eukaryotes, and a few archaea. These modifications promote the turnover and stability of some mRNAs to prevent mRNA decay, improve translation efficiency, and reduce ribosomal pausing but are associated with poor survival in human cancer cells. However, expression of m7G-related genes in LUSC and their association with prognosis remain unclear. In the present study, we identified nine differentially expressed genes related to prognosis by comparing the expression profiles of tumor tissues (502 LUSC reports) with normal tissues (49 adjacent nontumor lung tissue reports). The genes included six upregulated genes (KLK7, LCE3E, AREG, KLK6, ZBED2, and MAPK4) and three downregulated genes (ADH1C, NTS, and ERLIN2). Based on these nine genes, patients with LUSC were classified into low- and high-risk groups to analyze the trends in prognosis. We found that the nine m7G-related genes play important roles in immune regulation, hormone regulation, and drug sensitivity through pathways including antigen processing and presentation, adherent plaques, extracellular matrix receptor interactions, drug metabolism of cytochrome P-450, and metabolism of cytochrome P-450 to xenobiotics; the functions of these genes are likely accomplished in part by m6A modifications. The effect of m7G-related genes on the diagnosis and prognosis of LUSC was further indicated by population analysis.NEW & NOTEWORTHY Based on the differential expression of 7-methylguanosine (m7G) modification-associated genes between normal and lung squamous cell carcinoma (LUSC) tissues, and considering the performance of our m7G-related gene risk profiles as independent risk factors in predicting overall survival, we conclude that m7G modification is closely linked to the development of LUSC. In addition, this study offers a new genetic marker for predicting the prognosis of patients with LUSC and presents a crucial theoretical foundation for future investigations on the relationship between m7G modification-related genes, immunity, and drug sensitivity in LUSC.

Oceanic repeaters boost the global climatic impact of the Tibetan Plateau.

The topography of the Tibetan Plateau (TP) has shaped the paleoclimatic evolution of the Asian monsoon. However, the influence of the TP on the global climate, beyond the domain of the Asian monsoon, remains unclear. Here we show that the Pacific and Atlantic Oceans act as efficient repeaters that boost the global climatic impact of the TP. The simulations demonstrate that oceanic repeaters enable TP heating to induce a wide-ranging climate response across the globe. A 1 °C TP warming can result in a 0.73 °C temperature increase over North America. Oceanic repeaters exert their influence by enhancing the air-sea interaction-mediated horizontal heat and moisture transport, as well as relevant atmospheric circulation pathways including westerlies, stationary waves, and zonal-vertical cells. Air-sea interactions were further tied to local feedbacks, mainly the decreased air-sea latent heat flux from the weakening air-sea humidity difference and the increased shortwave radiation from sinking motion-induced cloud reduction over the North Pacific and Atlantic Oceans. Our findings highlight the crucial influence of TP heating variation on the current climate under a quasi-fixed topography, in contrast to topography change previously studied in paleoclimate evolution. Therefore, TP heating should be considered in research on global climate change.

Uncovering the key pharmacodynamic material basis and possible molecular mechanism of extract of Epimedium against liver cancer through a comprehensive investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver cancer is a worldwide malignant tumor, and currently lacks effective treatments. Clinical studies have shown that epimedium (YYH) has therapeutic effects on liver cancer, and some of its prenylflavonoids have demonstrated anti-liver cancer activity through multiple mechanisms. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of YYH. AIM OF THE STUDY: This study aimed to screen the anti-cancer material basis of YYH via integrating spectrum-effect analysis with serum pharmacochemistry, and explore the multi-target mechanisms of YYH against liver cancer by combining network pharmacology with metabolomics. MATERIALS AND METHODS: The anti-cancer effect of the extract of YYH (E-YYH) was first evaluated in mice with xenotransplantation H22 tumor cells burden and cultured hepatic cells. Then, the interaction between E-YYH compounds and the cytotoxic effects was revealed through spectrum-effect relationship analysis. And the cytotoxic effects of screened compounds were verified in hepatic cells. Next, UHPLC-Q-TOF-MS/MS was employed to identify the absorbed components of E-YYH in rat plasma to distinguish anti-cancer components. Subsequently, network pharmacology based on anti-cancer materials and metabolomics were used to discover the potential anti-tumor mechanisms of YYH. Key targets and biomarkers were identified and pathway enrichment analysis was performed. RESULTS: The anti-cancer effect of E-YYH was verified through in vitro and in vivo experiments. Six anti-cancer compounds in plasma (icariin, baohuoside Ⅰ, epimedin C, 2″-O-rhamnosyl icariside Ⅱ, epimedin B and sagittatoside B) were screened out by spectrum-effect analysis. Forty-five liver-cancer-related targets were connected with these compounds. Among these targets, PTGS2, TNF, NOS3 and PPARG were considered to be the potential key targets preliminarily verified by molecular docking. Meanwhile, PI3K/AKT signaling pathway and arachidonic acid metabolism were found to be associated with E-YYH's efficacy in network pharmacology and metabolomics analysis. CONCLUSIONS: Our research revealed the characteristics of multi-component, multi-target and multi-pathway mechanism of E-YYH. This study also provided an experimental basis and scientific evidence for the clinical application and rational development of YYH.

An updated patent review of histone deacetylase (HDAC) inhibitors in cancer (2020 - present).

INTRODUCTION: Histone deacetylase (HDAC) inhibitors have been considered as an attractive strategy to reverse aberrant epigenetic changes associated with cancer treatments. The use of HDAC inhibitors in various cancer types has continued to develop for decades, bringing several novel HDAC inhibitors successfully into clinical trials. The combination use of HDAC inhibitors with other agents have also been developed and have demonstrated superior efficacy compared to that of monotherapy in recent studies. Hence, development of new anticancer treatment and therapeutic regimen is necessary. AREAS COVERED: This review summarizes a comprehensive review of the patent literature from 2020 to 2022 including HDAC inhibitors and their use as anticancer agents (searched from European Patent Office, 2020-2022). The approved and developing HDAC inhibitors are described. It also provides perspectives on the challenges and future opportunities. EXPERT OPINION: Although hundreds of clinical trials of HDAC inhibitors are still going on, the application for HDAC inhibitors has been limited at present . Not only in the anticancer treatment, but also non-oncology disease therapies are being investigated eagerly. Recently, applications of HDAC inhibitors in non-oncology diseases have also been revealed and proceeded to clinical trials. New indications for HDAC inhibitors are needed urgently in the future.

The effect of SMAD4 on the prognosis and immune response in hypopharyngeal carcinoma.

Objectives: In malignant tumors, elevated infiltration of intratumoral CD8+ cytotoxic T cells predicts a beneficial prognosis, whereas high levels of CD15+ neutrophils in peritumor tissues indicate poor prognosis. It is unclear how SMAD4, which promotes favorable clinical outcomes and antitumor immunoregulation, along with CD8+ cytotoxic T cells and CD15+ neutrophils exert an influence on hypopharyngeal carcinoma (HPC). Materials and methods: Specimens were collected from 97 patients with HPC. Immunohistological analyses of SMAD4, CD8+ cytotoxic T cell and CD15+ neutrophil expression were performed. SMAD4 nuclear intensity was measured, meanwhile, CD8+ cytotoxic T cells and CD15+ neutrophils were counted under a microscope. The prognostic role of SMAD4 was determined using the log-rank test and univariate and multivariate analyses. The relationship among SMAD4, CD8+ cytotoxic T cells, and CD15+ neutrophils was estimated by Mann-Whitney U test. Results: High levels of SMAD4 were associated with favorable overall survival (OS) and disease-free survival (DFS) in HPC. Multivariate analysis suggested that SMAD4 is an independent predictor of OS and DFS. A high density of intratumoral CD8+ cytotoxic T cells and low accumulation of CD15+ neutrophils in the peritumor area were associated with longer OS and DFS. Furthermore, SMAD4 was linked to the levels of intratumoral CD8+ cytotoxic T cells and peritumoral CD15+ neutrophils. Patients with high SMAD4/high intratumoral CD8+ cytotoxic T cells or high SMAD4/low peritumoral CD15+ neutrophils showed the best prognosis. Conclusion: SMAD4, CD8+ cytotoxic T cell level, and CD15+ neutrophil level have prognostic value in HPC. SMAD4 is a promising prognostic marker reflecting immune response in HPC.