Efficacy, safety, and cost-effectiveness of pegylated PEG-rhg-CSF in pediatric patients receiving high-intensity chemotherapy: results from a phase II study.

Background: High-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy. Methods: Treatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3-4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®). Results: Here, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3-4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF. Conclusion: Our findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

Pegylated liposomal doxorubicin combined with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory solid tumor: a single-arm, open-label, phase I study.

Background: The combined vincristine, pegylated liposomal doxorubicin (PLD), and cyclophosphamide (VPC) regimen has never been studied in pediatric patients. Methods: This open-label, single-center, single-arm phase I study utilizing a "3 + 3" design enrolled children with relapsed/refractory (R/R) solid tumors. Three dose levels of PLD (Duomeisu®) were studied (30, 40, or 50 mg/m2) in combination with cyclophosphamide (1500 mg/m2), mesna (1500 mg/m2), and vincristine (1.5 mg/m2, maximum 2 mg) once every 3 weeks. The primary endpoints included safety, the maximum tolerated dose (MTD) of PLD (Duomeisu®), and the recommended phase 2 dose (RP2D) of PLD (Duomeisu®) for further phase 2 investigation. The secondary endpoints were objective response rate (ORR) and disease control rate (DCR). This study is registered with ClinicalTrials.gov, NCT04213612. Findings: Between January 7, 2020, and November 18, 2021, 34 patients were eligible and evaluable for toxicity, while 26 patients were evaluable for response. The MTD of PLD (Duomeisu®) was 30 mg/m2. The most common adverse event (AE) was grade 3 or 4 neutropenia (61.8%). The most common grade 1 or 2 non-hematologic AE and cardiotoxicity effects were vomiting (35.3%) and abnormal electrocardiogram T waves (20.6%), respectively. ORR and DCR to VPC regimen after two cycles were 50.0% and 92.3%, respectively. Targeted gene panel sequencing revealed the activation of TP53 mutation may be an adverse prognostic factor. Interpretation: The VPC regimen showed a promising safety profile and had preliminary efficacy in children with R/R solid tumors. The RP2D for PLD (Duomeisu®) combined with cyclophosphamide and vincristine is 30 mg/m2 once every 3 weeks. Funding: CSPC Ouyi Pharmaceutical Co., Ltd., Shijiazhuang, the National Key Research and Development Program of China [No. 2022YFC2705005], the National Natural Science Foundation of China [No. 82203303], and the Basic and Applied Basic Research Foundation of Guangdong Province [No. 2021A1515110234].

Influence of male's facial attractiveness, vocal attractiveness and social interest on female's decisions of fairness.

The present study employed dictator game and ultimatum game to investigate the effect of facial attractiveness, vocal attractiveness and social interest in expressing positive ("I like you") versus negative signals ("I don't like you") on decision making. Female participants played against male recipients in dictator game and ultimatum game while played against male proposers in ultimatum game. Results showed that participants offered recipients with attractive faces more money than recipients with unattractive faces. Participants also offered recipients with attractive voices more money than recipients with unattractive voices, especially under the positive social interest condition. Moreover, participants allocated more money to recipients who expressed positive social interest than those who expressed negative social interest, whereas they would also expect proposers who expressed positive social interest to offer them more money than proposers who expressed negative social interest. Overall, the results inform beauty premium for faces and voices on opposite-sex economic bargaining. Social interest also affects decision outcomes. However, the beauty premium and effect of social interest varies with participants' roles.

Efficient Near-Infrared Spectrum Detection in Nondestructive Wood Testing via Transfer Network Redesign.

This study systematically developed a deep transfer network for near-infrared spectrum detection using convolutional neural network modules as key components. Through meticulous evaluation, specific modules and structures suitable for constructing the near-infrared spectrum detection model were identified, ensuring its effectiveness. This study extensively analyzed the basic network components and explored three unsupervised domain adaptation structures, highlighting their applications in the nondestructive testing of wood. Additionally, five transfer networks were strategically redesigned to substantially enhance their performance. The experimental results showed that the Conditional Domain Adversarial Network and Globalized Loss Optimization Transfer network outperformed the Direct Standardization, Piecewise Direct Standardization, and Spectral Space Transformation models. The coefficients of determination for the Conditional Domain Adversarial Network and Globalized Loss Optimization Transfer network are 82.11% and 83.59%, respectively, with root mean square error prediction values of 12.237 and 11.582, respectively. These achievements represent considerable advancements toward the practical implementation of an efficient and reliable near-infrared spectrum detection system using a deep transfer network.

MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.

MYCN amplification is an independent poor prognostic factor in patients with high-risk neuroblastoma (NB). Further exploring the molecular regulatory mechanisms in MYCN-amplified NB will help to develop novel therapy targets. In this study, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) was identified as the differentially expressed gene (DEG) highly expressed in MYCN-amplified NB, and it showed a positive correlation with MYCN and was associated with a poor prognosis of NB patients. Knockdown of MTHFD1 inhibited proliferation and migration, and induced apoptosis of NB cells in vitro. Mouse model experiments validated the tumorigenic effect of MTHFD1 in NB in vivo. In terms of the mechanism, ChIP-qPCR and dual-luciferase reporter assays demonstrated that MTHFD1 was directly activated by MYCN at the transcriptional level. As an important enzyme in the folic acid metabolism pathway, MTHFD1 maintained the NADPH redox homeostasis in MYCN-amplified NB. Knockdown of MTHFD1 reduced cellular NADPH/NADP+ and GSH/GSSG ratios, increased cellular reactive oxygen species (ROS) and triggered the apoptosis of NB cells. Moreover, genetic knockdown of MTHFD1 or application of the anti-folic acid metabolism drug methotrexate (MTX) potentiated the anti-tumor effect of JQ1 both in vitro and in vivo. Taken together, MTHFD1 as an oncogene is a potential therapeutic target for MYCN-amplified NB. The combination of MTX with JQ1 is of important clinical translational significance for the treatment of patients with MYCN-amplified NB.

DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma.

Neutrophil extracellular traps (NET), formed by the extracellular release of decondensed chromatin and granules, have been shown to promote tumor progression and metastasis. Tumor-associated neutrophils in hepatocellular carcinoma (HCC) are prone to NET formation, highlighting the need for a more comprehensive understanding of the mechanisms of action of NETs in liver cancer. Here, we showed that DNA of NETs (NET-DNA) binds transmembrane and coiled-coil domains 6 (TMCO6) on CD8+ T cells to impair antitumor immunity and thereby promote HCC progression. TGFß1 induced NET formation, which recruited CD8+ T cells. Binding to NET-DNA inhibited CD8+ T cells function while increasing apoptosis and TGFß1 secretion, forming a positive feedback loop to further stimulate NET formation and immunosuppression. Mechanistically, the N-terminus of TMCO6 interacted with NET-DNA and suppressed T-cell receptor signaling and NFκB p65 nuclear translocation. Blocking NET formation by inhibiting PAD4 induced potent antitumor effects in wild-type mice but not TMCO6-/- mice. In clinical samples, CD8+ T cells expressing TMCO6 had an exhausted phenotype. TGFß1 signaling inhibition or TMCO6 deficiency combined with anti-PD-1 abolished NET-driven HCC progression in vivo. Collectively, this study unveils the role of NET-DNA in impairing CD8+ T-cell immunity by binding TMCO6 and identifies targeting this axis as an immunotherapeutic strategy for blocking HCC progression. SIGNIFICANCE: TMCO6 is a receptor for DNA of NETs that mediates CD8+ T-cell dysfunction in HCC, indicating that the NET-TMCO6 axis is a promising target for overcoming immunosuppression in liver cancer.

Activation of cGAS-STING suppresses coxsackievirus replication via interferon-dependent signaling.

Coxsackievirus B3 (CVB3) is a non-enveloped, single-stranded, positive RNA virus known for its role in provoking inflammatory diseases that affect the heart, pancreas, and brain, leading to conditions such as myocarditis, pancreatitis, and meningitis. Currently, there are no FDA-approved drugs treating CVB3 infection; therefore, identifying potential molecular targets for antiviral drug development is imperative. In this study, we examined the possibility of activating the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that triggers a type-I interferon (IFN) response, in inhibiting CVB3 infection. We found that activation of the cGAS-STING pathway through the application of cGAS (poly dA:dT and herring testes DNA) or STING agonists (2'3'-cGAMP and diamidobenzimidazole), or the overexpression of STING, significantly suppresses CVB3 replication. Conversely, gene-silencing of STING enhances viral replication. Mechanistically, we demonstrated that cGAS-STING activation combats CVB3 infection by inducing IFN response. Notably, we discovered that knockdown of IFN-α/ß receptor, a key membrane receptor in type-I IFN signaling, or inhibition of the downstream JAK1/2 signaling with ruxolitinib, mitigates the effects of STING activation, resulting in increased viral protein production. Furthermore, we investigated the interplay between CVB3 and the cGAS-STING pathway. We showed that CVB3 does not trigger cGAS-STING activation; instead, it antagonizes STING and the downstream TBK1 activation induced by cGAMP. In summary, our results provide insights into the interaction of an RNA virus and the DNA-sensing pathway, highlighting the potential for agonist activation of the cGAS-STING pathway in the development of anti-CVB3 drugs.

A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB/c mice with acute toxoplasmosis.

IMPORTANCE: Toxoplasma gondii, an obligate intracellular eukaryotic parasite, can infect about one-third of the world's population. One vaccine, Toxovax, has been developed and licensed commercially; however, it is only used in the sheep industry to reduce the losses caused by congenital toxoplasmosis. Various other vaccine approaches have been explored, including excretory secretion antigen vaccines, subunit vaccines, epitope vaccines, and DNA vaccines. However, current research has not yet developed a safe and effective vaccine for T. gondii. Here, we generated an mRNA vaccine candidate against T. gondii. We investigated the efficacy of vaccination with a novel identified candidate, TGGT1_278620, in a mouse infection model. We screened T. gondii-derived protective antigens at the genome-wide level, combined them with mRNA-lipid nanoparticle vaccine technology against T. gondii, and investigated immune-related factors and mechanisms. Our findings might contribute to developing vaccines for immunizing humans and animals against T. gondii.

The dual HDAC and PI3K inhibitor, CUDC­907, inhibits tumor growth and stem­like properties by suppressing PTX3 in neuroblastoma.

Neuroblastoma (NB) is one of the common solid tumors in childhood and poses a threat to the lives of children. Patients with advanced­stage or recurrent NB have a poor prognosis. CUDC­907, as a novel dual­target inhibitor of histone deacetylase (HDAC) and phosphatidylinositol­3­kinase (PI3K), has been proven to play an antitumor role in several types of tumors. However, the exact role of CUDC­907 in NB remains unclear. In the present study, in vivo and in vitro assays were performed to investigate the anti­NB activity of CUDC­907. Pentraxin 3 (PTX3) small interfering RNA (siRNA) and PTX3 overexpression plasmid were transfected into cells to define the underlying mechanisms of CUDC­907. Tumor tissues and clinical information were collected and immunohistochemistry (IHC) was conducted to analyze the association between the expression of HDAC1, HDAC2, HDAC3 and CD44, and the prognosis of patients with NB. The results indicated that CUDC­907 significantly inhibited the proliferation and migration, and induced the apoptosis of NB cells, downregulating the expression level of MYCN, and suppressing the PI3K/AKT and MAPK/ERK pathways. Furthermore, CUDC­907 suppressed the stem­like properties of NB cells by inhibiting PTX3, a ligand and upstream protein of CD44. IHC revealed that the high expression of HDAC1, 2, 3 and CD44 was associated with a poor prognosis of patients with NB. On the whole, these findings indicate that CUDC­907 may be developed into a possible therapeutic approach for patients with NB.

PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma.

T/NK cell-based immunotherapy has achieved remarkable success in adult cancers but has limited efficacy in pediatric malignancies including high-risk neuroblastoma (NB). Immune defects of NB tumor microenvironment are poorly understood compared with adults. Here, we described the unique characteristics of NB immune contexture and determined the phenotype signatures of PD-L1-expressing CD8+ T and NK cells in NB tumors by systemically analyzing the spatial distribution of T and NK cells and the distinct expression of programmed death 1 (PD-1) and its ligand (PD-L1) in patients with NB. We found that PD-L1-expressing CD8+ T and NK cells in NB tumors were highly activated and functionally competent and associated with better clinical outcomes. Intratumoral NK cells were a favorable prognostic biomarker independent of CD8+ T cells, PD-1/PD-L1 expression, tumor stage, MYCN amplification, and risk classification. NK cells combined with anti-PD-1/PD-L1 antibodies showed potent antitumor activity against both MYCN-amplified and non-amplified NBs in vitro and in vivo, and PD-L1-expressing NK cells associated with improved antitumor efficacy. Collectively, we raise novel insights into the role of PD-L1 expression on CD8+ T-cell and NK-cell activation. We highlight the great potential of intratumoral NK cells in better defining risk stratification, and predicting survival and response to anti-PD-1/PD-L1 therapy in NB. These findings explain why single anti-PD-1/PD-L1 therapy may not be successful in NB, suggesting its combination with NK cell-adoptive cellular therapy as a promising strategy for relapsing/refractory NB. This study provides a potential prospect that patients with PD-L1-expressing NK cells may respond to anti-PD-1/PD-L1 therapy.

Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study.

The aim of this phase I study is to evaluate, for the first time, the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies. During the dose escalation phase, patients received a single intravenous infusion of sintilimab at varying doses of 1, 3, and 10 mg/kg. The primary endpoints included the identification of dose-limiting toxicities (DLTs) as well as the evaluation of safety and tolerance. Secondary endpoints focused on assessing objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 29 patients were enrolled, including 10 individuals diagnosed with Hodgkin lymphoma (HL) and 19 patients with various other tumor categories. Notably, diverse pathological types such as thymoma, choroid plexus carcinoma, and NK/T-cell lymphoma were also included in the study cohort. By the safety data cutoff, most adverse events were grade 1 or 2, with grade 3 or higher treatment-related adverse events (TRAE) occurring in 10% of patients. Among the 27 evaluated subjects, four achieved confirmed complete response (CR) while seven patients exhibited confirmed partial response (PR). Additionally, seven patients maintained disease (SD) during the study period. Notably, sintilimab demonstrated remarkable tolerability without DLTs and exhibited promising anti-tumor effects in pediatric HL. Whole-exome sequencing (WES) was conducted in 15 patients to assess the mutational landscape and copy number variation (CNV) status. The completion of this phase I study establishes the foundation for potential combination regimens involving sintilimab in childhood cancer treatment. The trial is registered on ClinicalTrials.gov with the identifier NCT04400851.

Comparative proteomics in captive giant pandas to identify proteins involved in age-related cataract formation.

Approximately 20% of aged captive giant pandas (Ailuropoda melanoleuca) have cataracts that impair their quality of life. To identify potential biomarkers of cataract formation, we carried out a quantitative proteomics analysis of 10 giant pandas to find proteins differing in abundance between healthy and cataract-bearing animals. We identified almost 150 proteins exceeding our threshold for differential abundance, most of which were associated with GO categories related to extracellular localization. The most significant differential abundance was associated with components of the proteasome and other proteins with a role in proteolysis or its regulation, most of which were depleted in pandas with cataracts. Other modulated proteins included components of the extracellular matrix or cytoskeleton, as well as associated signaling proteins and regulators, but we did not find any differentially expressed transcription factors. These results indicate that the formation of cataracts involves a complex post-transcriptional network of signaling inside and outside lens cells to drive stress responses as a means to address the accumulation of protein aggregates triggered by oxidative damage. The modulated proteins also indicate that it should be possible to predict the onset of cataracts in captive pandas by taking blood samples and testing them for the presence or absence of specific protein markers.

Comparative analysis of the fecal microbiota of healthy and injured common kestrel (Falco tinnunculus) from the Beijing Raptor Rescue Center.

The gut microbiota is a complex ecosystem that interacts with many other factors to affect the health and disease states of the host. The common kestrel (Falco tinnunculus) is protected at the national level in China. However, the available sequencing data of the gut microbiota from the feces of wild common kestrels, especially for being rescued individuals by professional organization, remains limited. In the present study, we characterized the fecal bacterial communities of healthy and injured common kestrels, and compared the structure of their fecal microbiota by analyzing the V3-V4 region of the 16S rRNA gene using high-throughput sequencing technology with the Illumina MiSeq platform. We found that Firmicutes, Proteobacteria and Actinobacteria were the most predominant phyla in common kestrels. Further, the beta diversity analysis showed that changes in gut microbes were associated with injuries to the common kestrel. The Bacteroides/Firmicutes ratio was significantly lower in the injured group. At the genus level, Glutamicibacter showed significant difference in the two groups. The aim of our current study was to characterize the basic bacterial composition and community structure in the feces of healthy common kestrels, and then compare the differences in the fecal microbiota between healthy and injured individuals. Patescibacteria, Spirochaetes, and Glutamicibacter may be studied as potential biomarkers for certain diseases in raptors. The results could provide the basic data for additional research on the fecal microbiota of common kestrels and contribute to the rescue of wild raptors in the future.

The Synergy of Gene Targeting Drug Icaritin Soft Capsule with Immunomodulator and TACE Brings New Hope for Drug Combination in Patients with Advanced Liver Cancer: A Case Report and Literature Review.

At present, the average five-year survival rate of liver cancer in China is only 12.1%. The reason for this association lies in the diagnosis at its middle or/and advanced stage of liver cancer for lacking special clinical symptoms in almost 70% of patients without the chance of effective surgical resection. Epidemiological studies have shown that there are only 30% of patients with an initial diagnosis of liver cancer have the opportunity to undergo radical surgery. Therefore, systematic and comprehensive treatment would play an important role in liver cancer treatment at its middle or/and advanced stage, and the related therapeutic schedule still needs further improvement and optimization. We applied a gene-targeted drug of Icaritin soft capsule in the treatment of a liver cancer patient at its advanced stage. And the level of AFP was found to decrease to 6.4ng/mL from 10.86ng/mL; meanwhile, MRI showed that the primary tumor significantly reduced in size, with shrinking of the hepatogastric space, hepatic aortic side, and renal artery side lymph nodes. After treatment with TACE and Icaritin, the patient had no discomfort and no longer experienced abdominal pain and bloating and gained three kilograms of weight. The therapeutic effect of Icaritin-targeted drugs was completely demonstrated during the later treatment follow-up. That is to say, the multiple anti-tumor characteristics of Icaritin with good safety were fully displayed in this case, and it can be used in combination with other drugs to treat hepatocellular carcinoma in the clinical setting. The results show that Icaritin can put some effects on the combined treatment of patients with liver cancer.

Efficacy and safety of programmed cell death receptor 1 inhibition-based regimens in patients with pediatric malignancies: the real-world study in China.

Background: Programmed death receptor 1 (PD-1) inhibition has shown durable response and mild adverse events (AEs) in adult malignancies. However, data on the clinical activity of PD-1 inhibition in pediatric patients are lacking. We comprehensively assessed the efficacy and safety of PD-1 inhibitor-based regimens for pediatric malignancies. Methods: We conducted a real-world, multi-institutional, retrospective analysis of pediatric malignancies treated with PD-1 inhibitor-based regimens. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints included disease control rate (DCR), duration of response (DOR), and AEs. The Kaplan-Meier method was used to calculate PFS and DOR. The National Cancer Institute Common Toxicity Criteria for AEs (version 5.0) were used to grade toxicity. Results: A total of 93 and 109 patients were evaluated for efficacy and safety, respectively. For all efficacy-evaluable patients, PD-1 inhibitor monotherapy, combined chemotherapy, combined histone deacetylase inhibitor, and combined vascular endothelial growth factor receptor tyrosine kinase inhibitor cohorts, the ORR and DCR were 53.76%/81.72%, 56.67%/83.33%, 54.00%/80.00%, 100.00%/100.00%, and 12.50%/75.00%, respectively; the median PFS and DOR were 17.6/31.2 months, not achieved/not achieved, 14.9/31.2 months, 17.6/14.9 months, and 3.7/1.8 months, respectively; the incidence rate of AEs were 83.49%, 55.26%, 100.00%, 80.00%, and 100.00%, respectively. One patient in the PD-1 inhibitor-combined chemotherapy cohort discontinued treatment due to diabetic ketoacidosis. Conclusions: This largest retrospective analysis demonstrate that PD-1 inhibitor-based regimens are potentially effective and tolerable in pediatric malignancies. Our findings provide references for future clinical trials and practice of PD-1 inhibitors in pediatric cancer patients.

A Pan-Cancer Analysis of Prognostic and Immunological Roles for Cell Death Genes.

The dysregulation of cell death is closely associated with the development, progression, tumor microenvironment (TME), and prognosis of cancer. However, there is no study that comprehensively explores the prognostic and immunological role of cell death in human pan-cancer. We used published human pan-cancer RNA-sequencing and clinical data to explore the prognostic and immunological roles of programmed cell death, which included apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis. A total of 9925 patients were included for bioinformatic analysis, with 6949 and 2976 patients in the training cohort and validation cohort, respectively. Five-hundred and ninety-nine genes were defined as programmed-cell-death-related genes. In the training cohort, 75 genes were identified to define PAGscore by survival analysis. According to the median value of PAGscore, patients were divided into high- and low-risk groups, and subsequent analyses demonstrated that the high-risk group had a higher level of genomic mutation frequency, hypoxia score, immuneScore, expression of immune genes, activity of malignant signaling pathways, and cancer immunity cycle. Most anti-tumor and pro-tumor components of the TME showed greater activity in high-risk patients. Scores of malignant cell properties were also higher in high-risk patients. These findings were confirmed in the validation cohort and external cohort. Our study constructed a reliable gene signature to distinguish prognosis-favorable and prognosis-unfavorable patients and demonstrated that cell death was significantly associated with cancer prognosis and the TME.

Case report: A case study on the treatment using icaritin soft capsules in combination with lenvatinib achieving impressive PR and stage reduction in unresectable locally progressive pancreatic cancer and a literature review.

Background: Pancreatic cancer is one of the most deadly malignancies in the world. It is characterized by rapid progression and a very poor prognosis. The five-year survival rate of pancreatic cancer in China is only 7.2%, which is the lowest among all cancers and the use of combined paclitaxel albumin, capecitabine, and digital has been the clinical standard treatment for advanced pancreatic cancer since 1997. Also, the application of multidrug combinations is often limited by the toxicity of chemotherapy. Therefore, there is an urgent need for a more appropriate and less toxic treatment modality for pancreatic cancer. Case presentation: The patient was a 79-year-old woman, admitted to the hospital with a diagnosis of unresectable locally advanced pancreatic cancer (T3N0M0, stage IIA), with its imaging showing overgrowth of SMV involvement and unresectable reconstruction of the posterior vein after evaluation. As the patient refused chemotherapy, lenvatinib (8 mg/time, qd) and icaritin soft capsules (three tablets/time, bid) were recommended according to our past experience and a few clinical research cases. The tumor lesion was greatly reduced by 57.5% after the treatment, and the extent of vascular involvement also decreased. The aforementioned medication resulted in a significant downstaging of the patient's tumor. Conclusion: Better results were achieved in the treatment with icaritin soft capsules and lenvatinib in this case. Because of its less toxic effect on the liver and kidney and bone marrow suppression, it was suitable to combine icaritin soft capsules with targeted drugs for treating intermediate and advanced malignancies, which brings hope to patients who cannot or refuse to take chemotherapy.