Dissolving Microneedle-Based Cascade-Activation Nanoplatform for Enhanced Photodynamic Therapy of Skin Cancer.

Purpose: Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ). Methods: TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs). Results: Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process. Conclusion: The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.

Nanocarrier-Mediated Immunogenic Cell Death for Melanoma Treatment.

Melanoma, a highly aggressive skin tumor, exhibits notable features including heterogeneity, a high mutational load, and innate immune escape. Despite advancements in melanoma treatment, current immunotherapies fail to fully exploit the immune system's maximum potential. Activating immunogenic cell death (ICD) holds promise in enhancing tumor cell immunogenicity, stimulating immune amplification response, improving drug sensitivity, and eliminating tumors. Nanotechnology-enabled ICD has emerged as a compelling therapeutic strategy for augmenting cancer immunotherapy. Nanoparticles possess versatile attributes, such as prolonged blood circulation, stability, and tumor-targeting capabilities, rendering them ideal for drug delivery. In this review, we elucidate the mechanisms underlying ICD induction and associated therapeutic strategies. Additionally, we provide a concise overview of the immune stress response associated with ICD and explore the potential synergistic benefits of combining ICD induction methods with the utilization of nanocarriers.

Risk factors for the rupture of intracranial aneurysms: a systematic review and meta-analysis.

Purpose: The study aimed to identify potential risk factors for aneurysm rupture by performing a systematic review and meta-analysis. Materials and methods: We systematically searched the PubMed, Embase, and Cochrane Library electronic databases for eligible studies from their inception until June 2023. Results: Eighteen studies involving 17,069 patients with unruptured intracranial aneurysm (UIA) and 2,699 aneurysm ruptures were selected for the meta-analysis. Hyperlipidemia [odds ratio (OR): 0.47; 95% confidence interval (CI): 0.39-0.56; p < 0.001] and a family history of subarachnoid hemorrhage (SAH) (OR: 0.81; 95% CI: 0.71-0.91; p = 0.001) were associated with a reduced risk of aneurysm rupture. In contrast, a large-size aneurysm (OR: 4.49; 95% CI: 2.46-8.17; p < 0.001), ACA (OR: 3.34; 95% CI: 1.94-5.76; p < 0.001), MCA (OR: 2.16; 95% CI: 1.73-2.69; p < 0.001), and VABA (OR: 2.20; 95% CI: 1.24-3.91; p = 0.007) were associated with an increased risk of aneurysm rupture. Furthermore, the risk of aneurysm rupture was not affected by age, sex, current smoking, hypertension, diabetes mellitus, a history of SAH, and multiple aneurysms. Conclusion: This study identified the predictors of aneurysm rupture in patients with UIAs, including hyperlipidemia, a family history of SAH, a large-size aneurysm, ACA, MCA, and VABA; patients at high risk for aneurysm rupture should be carefully monitored. Systematic Review Registration: Our study was registered in the INPLASY platform (INPLASY202360062).

Giant Malignant Meningioma Penetrates the Skull.

Meningioma is a primary tumor of the central nervous system, most commonly found in the middle-aged and elderly. Most meningiomas are benign, whereas malignant meningiomas account for only 1% of all meningiomas. Meningiomas usually grow slowly, and patients often have headaches and epilepsy as the first symptoms. According to the location of the tumor, there can also be vision, visual field, olfactory, hearing impairment, and so on. Surgery is the main treatment. A case of giant malignant meningioma penetrating the skull is reported. The patient was a 67-year-old male with a left parietal scalp mass about 1 year ago, which gradually enlarged to the size of 6×6 cm and had no other symptoms. Imaging examination showed that the tumor eroded the skull, and the density was uneven. After surgical resection (Simpson grade I), poorly differentiated meningioma (World Health Organization Grade Ⅲ) was returned pathologically. After operation, the patient recovered well.

Lycorine transfersomes modified with cell-penetrating peptides for topical treatment of cutaneous squamous cell carcinoma.

BACKGROUND: Topical anticancer drugs offer a potential therapeutic modality with high compliance for treating cutaneous squamous cell carcinoma (cSCC). However, the existing topical treatments for cSCC are associated with limited penetrating ability to achieve the desired outcome. Therefore, there remains an urgent requirement to develop drugs with efficient anticancer activity suitable for treating cSCC and to overcome the skin physiological barrier to improve the efficiency of drug delivery to the tumor. RESULTS: We introduced lycorine (LR) into the topical treatment for cSCC and developed a cell-penetrating peptide (CPP)-modified cationic transfersome gel loaded with lycorine-oleic acid ionic complex (LR-OA) (LR@DTFs-CPP Gel) and investigated its topical therapeutic effects on cSCC. The anti-cSCC effects of LR and skin penetration of LR-OA transfersomes were confirmed. Simultaneously, cationic lipids and modification of R5H3 peptide of the transfersomes further enhanced the permeability of the skin and tumor as well as the effective delivery of LR to tumor cells. CONCLUSIONS: Topical treatment of cSCC-xenografted nude mice with LR@DTFs-CPP Gel showed effective anticancer properties with high safety. This novel formulation provides novel insights into the treatment and pathogenesis of cSCC.

Construction of Z-Scheme Ag2MoO4/ZnWO4 Heterojunctions for Photocatalytically Removing Pollutants.

Facilitation of the photocarrier separation is a crucial strategy for developing highly efficient photocatalysts in eliminating environmental pollutants. Herein we have developed a new kind of Ag2MoO4/ZnWO4 (AMO/ZWO) composite photocatalysts with a Z-scheme mechanism by anchoring AMO nanoparticles onto ZWO nanorods. Multiple characterization methodologies and density functional theory (DFT) calculations were employed to study the performances of the AMO/ZWO heterojunctions as well as the underlying photocatalytic mechanism. Simulated-sunlight-driven photodegradation experiments for removing methylene blue (MB) demonstrates that the 8%AMO/ZWO heterojunction can photocatalytically remove 99.8% of MB within 60 min, and the reaction rate constant is obtained as 0.10199 min-1, which is enhanced by 6.8 (or 4.9) times when compared with that of pure ZWO (or AMO). On the base of the experimental results and DFT calculations, the enhanced photocatalytic mechanism of the AMO/ZWO heterojunctions was revealed to be the efficient separation of photocarriers via a Z-scheme transfer process. In addition, photodegradion of various organic pollutants over 8%AMO/ZWO was further compared and aimed at incorporating it into industrial application in pollutant removal.

Target and Enhance Ethanol and Butyrate Production from Anaerobic Fermentation via the pH and Organic Loading Rate Combined Strategy.

The large capacity production and low utilization rate increase the difficulty of fruit and vegetable wastes (FVW) treatment. Efficient and targeted recovery strategies can solve these problems. This study investigated and proposed combined strategies via pH and organic loading rate (OLR) to target and enhance ethanol- and butyrate-dominant acidogenic production in the FVW mixed culture fermentation. Under pH 4.0, OLR 18 gCOD/(L∙d), and mesophilic (35 °C), ethanol-dominant fermentation was formed. The long-term operation (168 days) showed that the highest ethanol yield was 0.33 g/gCOD which was greater than that in other studies. Also, the hydrolysis rate of ethanol-type fermentation reached 74.5%. Besides, butyrate-type fermentation was stable at yield 0.39 g/gCOD following conditions: pH 6.0, OLR 28 gCOD/(L∙d), and 35 °C, of which hydrolysis and acidogenic rate were 78.0% and 62.0%, respectively. The high relative abundance of Lactobacillus, Olsenella, and Bifidobacterium played positive role in achieving ethanol, butyrate, and lactate production among various metabolic pathways. The results revealed the pH value together with OLR was the valid parameter to affect product formation and composition during FVW fermentation.

Evaluation of pH regulation in carbohydrate-type municipal waste anaerobic co-fermentation: Roles of pH at acidic, neutral and alkaline conditions.

This study investigated and evaluated the roles of acidic (pH 4.0), neutral (pH 7.0) and alkaline (pH 10.0) in anaerobic co-fermentation of sewage sludge and carbohydrate-type municipal waste. CO2, CH4 and H2 are produced in acidic, neutral and alkaline fermentation, respectively. The neutral co-fermentation contained the vast number of aqueous metabolites as total of 22.12 g/L, with the advantage of over 50 % biodegradable components in extracellular polymeric substance and over 80 % hydrolysis rate. Acidic and alkaline pH facilitated ammonia release, with the max concentration of 0.46 g/L and 0.44 g/L, respectively. Microbial analysis indicated that pH is the key parameter to impact microbial activity and drive microbial community transition. The high abundance of Lactobacillus, Bifidobacterium and Clostridium was associated with harvest of ethanol, lactic acid and acetate in acidic, neutral and alkaline fermentation. Meanwhile, the floc feature showed better dewaterability (zeta potential -8.48 mV) and poor nutrient convey (distribution spread index 1.03) in acidic fermentation. In summary, acidic and alkaline fermentation were prioritised for targeted spectrum. Neutral fermentation was prioritised for high production. This study presented an upgraded understanding of the pH role in fermentation performance, microbial structure and sludge behaviour, which benefits the development of fermentation processing unit.

Disseminated Kaposi Sarcoma.

AIDS-associated Kaposi sarcoma (KS) is the most common HIV-associated neoplasm. Disseminated Kaposi sarcoma became rare with the application of antiretroviral therapy. Oral AIDS-associated KS has prognostic relevance, indicating higher mortality than those with cutaneous lesions only. In this study, we reported a 40-year-old man presented with ulcerated violaceous plaques on his hard palate. Similar lesion can be observed on his left groin and anus, as well as on esophagus and gastric fundus under upper gastrointestinal endoscopy. Histological examination accorded with KS. After five cycles of doxorubicin, his oral, skin and esophagus lesions regressed considerably.

Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis.

BACKGROUND: Although anti-programmed cell death protein 1 (PD-1) immunotherapy is greatly effective in melanoma treatment, low response rate and treatment resistance significantly hinder its efficacy. Tumor cell ferroptosis triggered by interferon (IFN)-γ that is derived from tumor-infiltrating CD8+ T cells greatly contributes to the effect of immunotherapy. However, the molecular mechanism underlying IFN-γ-mediated ferroptosis and related potentially promising therapeutic strategy warrant further clarification. MicroRNAs (miRNAs) participate in ferroptosis execution and can be delivered systemically by multiple carriers, which have manifested obvious therapeutic effects on cancer. METHODS: MiRNAs expression profile in IFN-γ-driven ferroptosis was obtained by RNA sequencing. Biochemical assays were used to clarify the role of miR-21-3p in IFN-γ-driven ferroptosis and the underlying mechanism. MiR-21-3p-loaded gold nanoparticles were constructed and systemically applied to analyze the role of miR-21-3p in anti-PD-1 immunotherapy in preclinical transplanted tumor model. RESULTS: MiRNAs expression profile of melanoma cells in IFN-γ-driven ferroptosis was first obtained. Then, upregulated miR-21-3p was proved to facilitate IFN-γ-mediated ferroptosis by potentiating lipid peroxidation. miR-21-3p increased the ferroptosis sensitivity by directly targeting thioredoxin reductase 1 (TXNRD1) to enhance lipid reactive oxygen species (ROS) generation. Furthermore, miR-21-3p overexpression in tumor synergized with anti-PD-1 antibody by promoting tumor cell ferroptosis. More importantly, miR-21-3p-loaded gold nanoparticles were constructed, and the systemic delivery of them increased the efficacy of anti-PD-1 antibody without prominent side effects in preclinical mice model. Ultimately, ATF3 was found to promote miR-21-3p transcription in IFN-γ-driven ferroptosis. CONCLUSIONS: MiR-21-3 p upregulation contributes to IFN-γ-driven ferroptosis and synergizes with anti-PD-1 antibody. Nanoparticle delivery of miR-21-3 p is a promising therapeutic approach to increase immunotherapy efficacy without obvious systemic side effects.

Morphological and Spatial Heterogeneity of Microbial Communities in Pilot-Scale Autotrophic Integrated Fixed-Film Activated Sludge System Treating Coal to Ethylene Glycol Wastewater.

The understanding of microbial compositions in different dimensions is essential to achieve the successful design and operation of the partial nitritation/anammox (PN/A) process. This study investigated the microbial communities of different sludge morphologies and spatial distribution in the one-stage PN/A process of treating real coal to ethylene glycol (CtEG) wastewater at a pilot-scale integrated fixed-film activated sludge (IFAS) reactor. The results showed that ammonia-oxidizing bacteria (AOB) was mainly distributed in flocs (13.56 ± 3.16%), whereas anammox bacteria (AnAOB) was dominated in the biofilms (17.88 ± 8.05%). Furthermore, the dominant AnAOB genus in biofilms among the first three chambers was Candidatus Brocadia (6.46 ± 2.14% to 11.82 ± 6.33%), whereas it was unexpectedly transformed to Candidatus Kuenenia (9.47 ± 1.70%) and Candidatus Anammoxoglobus (8.56 ± 4.69%) in the last chamber. This demonstrated that the niche differentiation resulting from morphological (dissolved oxygen) and spatial heterogeneity (gradient distribution of nutrients and toxins) was the main reason for dominant bacterial distribution. Overall, this study presents more comprehensive information on the heterogeneous distribution and transformation of communities in PN/A processes, providing a theoretical basis for targeted culture and selection of microbial communities in practical engineering.

Potential Therapeutic Targets of Rehmannia Formulations on Diabetic Nephropathy: A Comparative Network Pharmacology Analysis.

Background: Previous retrospective cohorts showed that Rehmannia-6 (R-6, Liu-wei-di-huang-wan) formulations were associated with significant kidney function preservation and mortality reduction among chronic kidney disease patients with diabetes. This study aimed to investigate the potential mechanism of action of common R-6 variations in a clinical protocol for diabetic nephropathy (DN) from a system pharmacology approach. Study Design and Methods: Disease-related genes were retrieved from GeneCards and OMIM by searching "Diabetic Nephropathy" and "Macroalbuminuria". Variations of R-6 were identified from a published existing clinical practice guideline developed from expert consensus and pilot clinical service program. The chemical compound IDs of each herb were retrieved from TCM-Mesh and PubChem. Drug targets were subsequently revealed via PharmaMapper and UniProtKB. The disease gene interactions were assessed through STRING, and disease-drug protein-protein interaction network was integrated and visualized by Cytoscape. Clusters of disease-drug protein-protein interaction were constructed by Molecular Complex Detection (MCODE) extension. Functional annotation of clusters was analyzed by DAVID and KEGG pathway enrichment. Differences among variations of R-6 were compared. Binding was verified by molecular docking with AutoDock. Results: Three hundred fifty-eight genes related to DN were identified, forming 11 clusters which corresponded to complement and coagulation cascades and signaling pathways of adipocytokine, TNF, HIF-1, and AMPK. Five variations of R-6 were analyzed. Common putative targets of the R-6 variations on DN included ACE, APOE, CCL2, CRP, EDN1, FN1, HGF, ICAM1, IL10, IL1B, IL6, INS, LEP, MMP9, PTGS2, SERPINE1, and TNF, which are related to regulation of nitric oxide biosynthesis, lipid storage, cellular response to lipopolysaccharide, inflammatory response, NF-kappa B transcription factor activity, smooth muscle cell proliferation, blood pressure, cellular response to interleukin-1, angiogenesis, cell proliferation, peptidyl-tyrosine phosphorylation, and protein kinase B signaling. TNF was identified as the seed for the most significant cluster of all R-6 variations. Targets specific to each formulation were identified. The key chemical compounds of R-6 have good binding ability to the putative protein targets. Conclusion: The mechanism of action of R-6 on DN is mostly related to the TNF signaling pathway as a core mechanism, involving amelioration of angiogenesis, fibrosis, inflammation, disease susceptibility, and oxidative stress. The putative targets identified could be validated through clinical trials.

Performance and microbial community evaluation of full-scale two-phase anaerobic digestion of waste activated sludge.

"Temperature Staging and Biological Phasing" (TSBP) is an improved two-phase anaerobic digestion (AD) technology. This technology hydrolyzes waste activated sludge (WAS) at 45 °C and converts methane at mesophilic temperature (35-38 °C), with hydraulic retention times of 3-5 d and 14-17 d, respectively. In this study, the performance and microbial community dynamics of full-scale TSBP-based sludge anaerobic digestion system were studied, and the technology was evaluated by energy balance and ecological benefit analysis. The stable operation for 390 d showed that the cumulative biogas yield was about 349,041 m3, the maximum biogas yield rate was 563.68 L/kg VS, and the VS degradation rate of organic matters in the sludge was 47.19%. Proteobacteria and Firmicutes were found to be the dominant bacteria in both thermophilic and mesophilic reactors. Methanobacterium and Methanosarcina were the two most abundant methanogenic genera in the AD samples. The aceticlastic methanogenesis was likely the predominant production pathway of methane in AD processes based on metagenomics. The TSBP system operated stably, and the recovered energy could achieve energy self-sufficiency, which provided technical reference for the anaerobic treatment of sludge.

Hydrogenotrophic methanogenic granular sludge formation for highly efficient transforming hydrogen to CH4.

This paper presents a potential process that can enhance H2 transformation to CH4 and simultaneously upgrading biogas by using hydrogenotrophic methanogens. For the first time, anaerobic granules were developed in upflow anaerobic sludge blanket (UASB) reactor feeding H2/CO2 syngas as the sole substrate and the granule characterization was thoroughly investigated. The results from experiment revealed that the H2 consumption rates of UASB reactor increased from 32.2 mmol L-1·d-1 at H2 feeding rate 0.08 g L-1·d-1 to 132.0 mmol L-1·d-1 at 0.37 g L-1·d-1, indicating that the hydrogenotrophic methanogenesis pathway was stimulated by injection of H2. Abundant cavities and cracks were observed on the surface and cross-section of granules, which greatly facilitated internally transferring H2/CO2 synthesis gas and biogas escape. The abundance of hydrogenotrophic Methanobacterium increased, while Methanosaeta, Methanosarcina, and Methanomassiliicoccus decreased with increasing H2 feeding rate. In general, this paper offers a feasible solution in terms of energy transformation and connecting power to fuel.

A novel anammox aggregate nourished sustainably internal heterotrophic nitrate removal pathway with endogenous carbon source.

Anaerobic ammonium oxidation (anammox) is a cost-effective nitrogen removal pathway but instinctively generated nitrate limits its application. A novel anammox aggregate reduced the production of nitrate significantly with efficient removal of ammonia and nitrite in this work. The results demonstrated that the internal heterotrophic nitrate removal (IHNAR) pathway exists stably at inner of anammox aggregates, which eliminated 42.31 ± 3.85 % nitrate generated in anammox at without consuming external carbon source. The observed volatile fatty acids (VFAs) and adequate protein, polysaccharide and humic acids in the aggregates verified that the in-situ fermentation supplied sustainably endogenous carbon sources for the IHNAR. The efficient interspecies cooperation between anammox bacteria, heterotrophic denitrifiers and fermentative bacteria was identified, as the intrinsic justification for the obtained sustainability of IHNAR pathway. The findings were expected to provide theoretical guidance for promotions and applications of the anammox process with high-efficiency total nitrogen removal capabilities.

Erythrocyte membrane bioengineered nanoprobes via indocyanine green-directed assembly for single NIR laser-induced efficient photodynamic/photothermal theranostics.

Traditional combinational photodynamic therapy (PDT) and photothermal therapy (PTT) were limited in clinical therapy of cancer due to exceptionally low drug payload and activation by light with separate wavelengths. We have accidentally discovered that zinc phthalocyanine (ZNPC, a typical hydrophobic photosensitizer) and indocyanine green (ICG, a clinically approved fluorescence probe) could be co-assembled into carrier-free nanodrugs (almost 100 wt%) for single NIR laser-induced efficient PDT/PTT. Interestingly, ICG could act as "transformers" for modulating the geometric shape of ZNPC/ICG co-assembling structures from needle-like/spindle-like structure via cubic structure finally to spherical structure. Unfortunately, the nanodrugs suffered from rapid immune clearance. The ZNPC-ICG nanoprobes were further embedded into the erythrocyte membrane (RBC)-camouflaged framework. The designed ZNPC-ICG@RBC could be efficiently accumulated within the tumor sites (continue for ~60 h) and rapidly internalized into cancer cells upon laser irradiation rather than macrophage RAW264.7 cells. Compared with the free ZnPC or ICG, the biomimetic ZNPC-ICG@RBC nanoprobes exhibited amplified therapeutic effects by simultaneously producing ROS and hyperthermia, thereby synergistically improving antitumor efficiency and eliminating the tumors without any regrowth under the guidance of fluorescence imaging. The co-delivery of ZnPC and ICG via a biomimetic carrier-free system might be a promising strategy for bimodal phototherapy of cancer.

The XBP1‒MARCH5‒MFN2 Axis Confers Endoplasmic Reticulum Stress Resistance by Coordinating Mitochondrial Fission and Mitophagy in Melanoma.

Melanoma cells are relatively resistant to endoplasmic reticulum (ER) stress, which contributes to tumor progression under stressful conditions and renders tolerance to ER stress‒inducing therapeutic agents. Mitochondria are tightly interconnected with ER. However, whether mitochondria play a role in regulating ER stress resistance in melanoma remains elusive. In this study, we reported that the XBP1‒MARCH5‒MFN2 axis conferred ER stress resistance by coordinating mitochondrial fission and mitophagy in melanoma. Our integrative bioinformatics first revealed that the downregulation of mitochondrial genes was highly correlated with unfolded protein response activation in melanoma. Then we proved that mitochondrial fission and mitophagy were prominently induced to contribute to ER stress resistance both in vitro and in vivo by maintaining mitochondrial function. Mechanistically, the activation of IRE1α/ATF6-XBP1 branches of unfolded protein response promoted the transcription of E3 ligase MARCH5 to facilitate the ubiquitination and degradation of MFN2, which thereby triggered mitochondrial fission and mitophagy under ER stress. Together, our findings show a regulatory axis that links mitochondrial fission and mitophagy to the resistance to ER stress. Targeting mitochondrial quality control machinery can be exploited as an approach to reinforce the efficacy of ER stress‒inducing agents against cancer.

Prognosis prediction model for a special entity of gastric cancer, linitis plastica.

BACKGROUND: Gastric linitis plastica (GLP) is characteristic by its poor prognosis and highly aggressive characteristics compared with other types of gastric cancer (GC). However, the guidelines have not yet been distinguished between GLP and non-GLP. METHODS: A total of 342 eligible patients with GLP identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training set (n=298) and validation set (n=153). A nomogram would be developed with the constructed predicting model based on the training cohort's data, and the validation cohort would be used to validate the model. Principal component analysis (PCA) was used to evaluate the differences between groups. Cox regression and LASSO (least absolute shrinkage and selection operator) were used to construct the models. Calibration curve, time-dependent receiver operating characteristic (ROC) curve, concordance index (C-index) and decision curve analysis (DCA) were used to evaluate the predicting performance. Restricted mean survival time (RMST) was used to analyze the curative effect of adjuvant therapy. RESULTS: For patients in training cohort, univariable and multivariable Cox analyses showed that age, examined lymph nodes (LN.E), positive lymph nodes (LN.P), lesion size, combined resection, and radiotherapy are independent prognostic factors for overall survival (OS), while chemotherapy can not meet the proportional hazards (PHs) assumption; age, race, lesion size, LN.E, LN.P, combined resection and marital status are independent prognostic factors for cancer-specific survival (CSS). The C-index of the nomogram was 0.678 [95% confidence interval (CI), 0.660-0.696] and 0.673 (95% CI, 0.630-0.716) in the training and validation cohort, respectively. Meanwhile, the C-index of the CSS nomogram was 0.671 (95% CI, 0.653-0.699) and 0.650 (95% CI, 0.601-0.691) in the training and validation cohort for CSS, respectively. Furthermore, the nomogram was well calibrated with satisfactory consistency. RMST analysis further determined that chemotherapy and radiotherapy might be beneficial for improving 1- and 3-year OS and CSS, but not the 5-year CSS. CONCLUSIONS: We developed nomograms to help predict individualized prognosis for GLP patients. The new model might help guide treatment strategies for patients with GLP.