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Malignant insulinomas are rare neuroendocrine tumors that require management for both symptomatic control and tumor reduction. It is clinically challenging to optimize treatment strategies for refractory malignant insulinoma. We report a case of metastatic grade 3 insulinoma presented with recurrent hypoglycemia in a 23-year-old female with RAD51D p.Q192 germline mutation. During the disease course of 5 years, the tumor has continuously progressed despite locoregional therapy and multiple lines of systemic treatment. However, oxaliplatin-based chemotherapy achieved a partial response, which was maintained for 2 years. The hypoglycemic symptoms were controlled after the treatment response and did not recur. The platinum-based regimen could be a feasible therapeutic strategy for malignant insulinoma. The relationship between germline mutation in the DNA damage repair pathway and treatment response to platinum-based regimens in neuroendocrine tumors warrants further investigation.

Objective:. Real-world diagnostic and treatment data for pancreatic cancer in China are lacking. As such, the present study investigated the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer (including locally advanced and metastatic disease) in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database. Methods:. A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database. The entire course of real-world pancreatic cancer management was analyzed. Results:. The proportion of patients with advanced pancreatic cancer was higher among males than females (62.4% vs 37.6%, respectively). Patients typically had a history of hypertension (30.8%), diabetes (21.6%), and cholangitis (20.2%). Abdominal pain (51.6%), abdominal distension (27.1%), jaundice (20.1%), and weight loss (16.3%) were the main symptoms observed in patients with advanced pancreatic cancer in this cohort. Serum carbohydrate antigen (CA)19-9 is one of the most common tumor markers. In the present study, 2562 patients underwent first-line therapy. The median progression-free survival (PFS) for patients undergoing first-line therapy was 4.1 months. The major options for first-line therapy included gemcitabine (GEM) plus S-1 (GS/X) (23.4%), nab-paclitaxel plus GEM (AG) (18.1%), oxaliplatin, irinotecan, and leucovorin-modulated fluorouracil (FOLFIRINOX; 11.9%), nab-paclitaxel plus S-1 (AS) (8.9%), and GEM combined with oxaliplatin/cisplatin (GEMOX/GP) (7.6%). The AS and GS/X regimens were associated with the highest PFS rates. Conclusion:. This is the first study to report multicenter, real-world data regarding advanced pancreatic cancer in China. Results revealed that real-world treatment options differed from guideline recommendations, and PFS was shorter than that in previously reported data. Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

Abstract Objectives To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). Methods A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram’s performance, calibration, discrimination and clinical benefit. Results The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. Conclusions The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly progressive lethal malignancy, with chemotherapy being the primary treatment modality. This article provides a review of the initial chemotherapy options for PDAC patients with adequate performance status, comparing FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) or modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NabP) regimens. The availability of limited evidence from randomized trials restricts a direct comparison between the 2 regimens. Based on our review, (m)FOLFIRINOX yields superior survival outcomes compared to GEM-NabP in metastatic PDAC. For locally advanced PDAC, either (m)FOLFIRINOX or GEM-NabP can be considered initial chemotherapy. In the neoadjuvant setting for borderline resectable PDAC, both regimens have demonstrated promising results in achieving feasible resection rates. However, mFOLFIRINOX remains the preferred choice for adjuvant chemotherapy. The selection of initial chemotherapy for PDAC depends on the disease stage, patients’ performance status, and tumor molecular alterations. Further research and clinical trials are necessary to optimize treatment approaches for PDAC patients.

Objective: Gemcitabine plus nab-paclitaxel (GnP) is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC). S-1, an oral fluoropyrimidine derivative, as compared with gemcitabine, is non-inferior in terms of overall survival (OS) and is associated with lower hematologic toxicity. Accordingly, S-1 is a convenient oral alternative treatment for advanced PDAC. This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1 (GS) vs. GnP as first-line chemotherapy for advanced PDAC. Methods: Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated. Results: A total of 300 patients were assessed, of whom 84 received GS and 216 received GnP. The chemotherapy completion rate was higher with GS than GnP (50.0% vs. 30.3%, P = 0.0028). The objective response rate (ORR) was slightly higher (14.3% vs. 9.7%, P = 0.35), and the median OS was significantly longer (17.9 months vs. 13.3 months, P = 0.0078), in the GS group than the GnP group. However, the median progression-free survival (PFS) did not significantly differ between groups. Leukopenia risk was significantly lower in the GS group than the GnP group (14.9% vs. 28.1%, P = 0.049). Conclusions: As first-line chemotherapy for advanced PDAC, the GS regimen led to a significantly longer OS than the GnP regimen. The PFS, ORR, and incidence of severe adverse events were comparable between the GS and GnP groups.

Abstract Background There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or CDK4/6 inhibitors for pancreatic adenocarcinoma showed promising efficacy in preclinical studies. However, the regimens have not been well examined in patients with mPDAC. Methods Patients with mPDAC who received the combination of trametinib and HCQ or CDK4/6 inhibitors as third- or later-line therapy were reviewed. The efficacy and prognosis were further analyzed. Results A total of 13 mPDAC patients were enrolled, of whom 8 and 5 patients were treated with trametinib plus HCQ or a CDK4/6 inhibitor (palbociclib or abemaciclib), respectively. All enrolled patients had either KRAS G12D or G12V mutations and had received a median of 3 prior lines of therapy (range, 2–6). The median trametinib treatment duration was 1.4 months. Of the 10 patients with measurable disease, only 1 patient achieved stable disease, and the remaining patients had progressive disease. Moreover, in patients treated with trametinib plus HCQ and a CDK4/6 inhibitor, the median progression-free survival was 2.0 and 2.8 months, respectively, and the median overall survival was 4.2 and 4.7 months, respectively. Moreover, 5 (50%) patients experienced grade 3–4 adverse events in 10 patients with available safety data. Conclusions The combination of trametinib and HCQ or CDK4/6 inhibitors may not be an effective later-line treatment for mPDAC, and the current preliminary findings need to be confirmed by other studies with larger sample sizes.

Grass Carp Reovirus (GCRV) and Aeromonas hydrophila (Ah) are the causative agents of haemorrhagic disease in grass carp. This study aimed to investigate the molecular mechanisms and immune responses at the miRNA, mRNA, and protein levels in grass carp kidney cells (CIK) infected by Grass Carp Reovirus (GCRV, NV) and Aeromonas hydrophilus (Bacteria, NB) to gain insight into their pathogenesis. Within 48 h of infection with Grass Carp Reovirus (GCRV), 99 differentially expressed microRNA (DEMs), 2132 differentially expressed genes (DEGs), and 627 differentially expressed proteins (DEPs) were identified by sequencing; a total of 92 DEMs, 3162 DEGs, and 712 DEPs were identified within 48 h of infection with Aeromonas hydrophila. It is worth noting that most of the DEGs in the NV group were primarily involved in cellular processes, while most of the DEGs in the NB group were associated with metabolic pathways based on KEGG enrichment analysis. This study revealed that the mechanism of a grass carp haemorrhage caused by GCRV infection differs from that caused by the Aeromonas hydrophila infection. An important miRNA–mRNA–protein regulatory network was established based on comprehensive transcriptome and proteome analysis. Furthermore, 14 DEGs and 6 DEMs were randomly selected for the verification of RNA/small RNA-seq data by RT-qPCR. Our study not only contributes to the understanding of the pathogenesis of grass carp CIK cells infected with GCRV and Aeromonas hydrophila, but also serves as a significant reference value for other aquatic animal haemorrhagic diseases.

Objective:. Different SSTR2 antagonists have been developed. This study aims to evaluate the impact of different peptides and chelators on the diagnostic performance of SSTR2 antagonists in well-differentiated NETs. Methods:. In this prospective study, participants were equally randomized into 2 arms: arm A, participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the first day and 68Ga-DOTA-LM3 PET/CT scan on the second day; arm B, participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the first day and 68Ga-NODAGA-JR11 PET/CT scan on the second day. Biodistribution in normal organs, lesion detection ability, and tumor uptakes were compared within each arm. Results:. A total of 40 participants (age, 49.5 ± 13.4, 21 men), 20 in each arm, were recruited in the study. In arm A, 68Ga-DOTA-LM3 showed lower background. However, the lesion detection ability (overall lesion detected, 445 vs 548; P = .005) and the lesion uptake (overall lesions SUVmax, 19.8 ± 17.2 vs 35.3 ± 28.8; P < .001) was significantly lower than those of 68Ga-NODAGA-LM3. In arm B, both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 showed similar biodistribution and lesion uptake (SUVmax, 28.5 ± 23.8 vs 25.0 ± 20.0; P < .001) despite minor differences. The lesion detection ability was the same between these 2 tracers (overall lesion detected, 503 vs 503). Conclusions:. The diagnostic performance of SSTR2 antagonists was sensitive to chelators. Both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 outperformed 68Ga-DOTA-LM3 with higher lesion uptake and detection ability, of which 68Ga-NODAGA-LM3 had marginally but significantly higher lesion uptake.

Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogenous malignancies that require well-designed trials to develop effective management strategies. This cross-sectional study aimed to illustrate the current landscape of clinical trials in GEP-NENs to provide insights for future research. Materials and methods: We reviewed all clinical trials registered on ClinicalTrials.gov between 1 January 2000 and 31 December 2021 with GEP-NEN in the ‘condition or disease’ field. Results: We included 206 eligible trials. Most trials enrolled less than 50 patients (59.8%) and were sponsored by institutions other than government or industry (67.0%). Most trials were conducted in high-income countries (86.6%) and countries located in Europe (30.1%) or Northern America (29.6%). The overall result reporting rates of GEP-NEN trials was 41.4%, and the median time from primary completion to result reporting was 101 months. Characteristics that improved the reporting of results included larger sample size, tumor differentiation specification for inclusion, p rogression-free survival as primary endpoint, industry sponsorship, and multicenter or multinational participation (all P < 0.05). Compared with trials registered between 2000 and 2011 (n = 28), trials registered between 2012 and 2021 (n = 178) were more likely to specify the Ki-67 index for inclusion (68.0% vs 35.7%, P = 0.002) and to be conducted outside Europe or Northern America (16.4% vs 3.7%, P = 0.02), while the sample size and the sponsorship did not change significantly. Conclusions: Novel management options have been explored for GEP-NENs with more specific inclusion criteria during the past two decades. More eff orts are needed to promote international collaborations in clinical trials and enhance timely result dissemination.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous collection of tumors derived from various neuroendocrine cells and are divided into functioning NEN and non-functioning NEN. Some NENs present with mild symptoms and can secrete somatostatin. These neoplasms are known as somatostatin-producing oligosymptomatic NENs. In this report, we describe a case of metastatic somatostatin-producing oligosymptomatic NEN with peritumoral hepatic steatosis and review the relevant literature. The patient was a 45-year-old woman who presented with mild steatorrhea and melena. A computed tomography scan revealed an enlarged pancreas protruding into the duodenum. Pathology after total pancreatectomy showed a grade 2 pancreatic NEN with positive somatostatin immunostaining. Enlarging masses on the liver were observed after the operation. Ultrasound examination revealed several lesions in the liver, with inner hypoechoic areas that showed rapid enhancement and fast washout on contrast-enhanced ultrasonography and with outer hyperechoic areas with continuous iso-enhancement. Therefore, the inner hypoechoic areas seen on contrast-enhanced ultrasonography were suspected to be true metastases. A biopsy confirmed this suspicion and indicated that the outer areas were peritumoral liver steatosis. This case highlights the importance of the imaging pattern described in this report for accurate diagnosis of metastatic NEN to avoid incorrect estimation of tumor size or a missed diagnosis on biopsy.

Background: S-1 has been recognized as one of the standard adjuvant chemotherapies for pancreatic ductal adenocarcinoma (PDAC) in East Asia, but the optimal adjuvant chemotherapy regimen has not been determined. We aimed to compare the efficacy and safety of adjuvant gemcitabine plus S-1 (GS) with S-1 monotherapy for PDAC. Methods: Patients with resected PDAC who received adjuvant GS or S-1 chemotherapy in Peking Union Medical College Hospital between May 2014 and May 2022 were reviewed. Data retrieved from medical records were used to evaluate efficacy and toxicity. Results: A total of 241 patients were included, with 167 receiving GS and 74 receiving S-1. The patients who received GS were generally younger (median [range] age: 62 [36-78] versus 64 [44-87] years, p = 0.004), but chemotherapy began later (median [range] interval between chemotherapy and surgery: 49 [17-125] versus 40 [16-100] days, p < 0.001). The median disease-free survival (DFS, 15.1 versus 15.9 months, p = 0.52) and overall survival (OS, 34.8 versus 27.1 months, p = 0.34) did not differ significantly between the GS and S-1 groups, even after adjustment for the biases. However, the chemotherapy completion rate was higher in the patients treated with S-1 (52.4% versus 75.7%, p = 0.006), while grade 3-4 neutropenia occurred more frequently in the GS group (49.5% versus 18.2%, p = 0.015). Conclusions: Adjuvant S-1 monotherapy demonstrated noninferiority to the GS regimen in DFS and OS with better tolerability for PDAC following surgery.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

Abstract Background The understanding of molecular changes in mCRC during treatment could be used to personalise therapeutic strategies. The aim of our study was to explore the association of circulating tumour DNA (ctDNA) with clinical outcome in metastatic colorectal cancer (mCRC). Methods Sequential patients with mCRC receiving standard first-line chemotherapy were included prospectively. Both plasma ctDNA and serum CEA were assessed in samples obtained before treatment and after 4 cycles of chemotherapy (C4). Computed tomography (CT) scans were carried out at baseline and post-C4 (8–10 weeks) and were assessed using Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1). Target-capture deep sequencing with a panel covering 1021 genes was performed to detected somatic mutations in ctDNA. Results A total of 20 patients were prospectively included and treated with either leucovorin, fluorouracil, and oxaliplatin (FOLFOX) (15/20) or leucovorin, fluorouracil, and irinotecan (FOLFIRI) (5/20). Median follow-up was 6.9 months (range 1.6–26.6). Somatic mutations for baseline ctDNA analysis were identified in 85% (17/20) of the patients. Mutation variations of ctDNA after chemotherapy were tested in 16/20 (80.0%) of the patients. In multivariate analyses, a high baseline molecular tumour burden index (mTBI) in ctDNA was associated with a higher risk of disease progression, as well as emergence of new mutations in ctDNA during chemotherapy. Patients with newly detected mutations had shorter progression-free survival (PFS) compared to those without (median 3.0 versus 7.3 months; hazard ratio (HR), 5.97; 95% confidence interval (CI), 0.70–50.69; P = 0.0003). Fold changes in mTBI from baseline to post-C4 were obtained in 80.0% (16/20) of the patients, which were also related to PFS. Patients with fold reduction in mTBI above 0.8-fold had longer PFS compared to those below (median 9.3 versus 4.1 months; HR, 4.51; 95% CI, 1.29–15.70; P = 0.0008). Conclusions Newly detected mutations in ctDNA during treatment might potentially be associated with clinical outcome in mCRC and may provide important clinical information.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor prognosis. In resectable PDAC, the recurrence rate is still high even when surgery and adjuvant chemotherapy (CT) are applied. Regional lymph node metastasis and positive margins are associated with higher recurrence risk and worse survival. Adjuvant radiotherapy has been explored, but its efficacy remains controversial. In recent years, some characteristics have been reported to stratify patients who may benefit from adjuvant chemoradiation (CRT), such as lymph node metastasis and margin status. Adjuvant chemotherapy followed by chemoradiation (CT-CRT) was also proposed. A total of 266 patients with resectable PDAC who have lymph node metastasis or R1 resection after surgery were enrolled. In multivariate Cox regression analyses, pancreatic body or tail tumor location (HR 0.433, p

PDE6H is a cone cell-specific inhibitory subunit that plays a critical role in the adaptation of the photosensitive system to bright and dark phases of the light environment. Thyroid hormone (TH) is one of the most important factors that control development and metabolism in animals, composed mainly of triiodothyronine (T3), and thyroxine (T4). TH also plays a key role in the metamorphosis of the flounder (Paralichthys olivaceus), wherein exogenous TH can accelerate the behavioral changes of larvae from the pelagic to benthic type accompanying changes in the light environment from bright to dark. In this study, transcriptional analysis showed that pde6h is expressed in adult eye, that its expression peaks at the climax of metamorphosis, and that it can be significantly up-regulated to the highest level by exogenous T4 in the early stages of metamorphosis but is inhibited by thiourea (TU). The rescue experiment showed that metamorphic inhibition of larvae and expression inhibition of pde6h gene in TU groups can be rescued by removing TU. Further, dual-luciferase reporter assay indicated the putative regulatory effect of TH on pde6h expression, mediated directly on the gene promoter by the TRαA gene. Together, we speculated that TH may control physiological adaptation of the photosensitive system to light changes during metamorphosis by acting directly on pde6h. This study can help us further study the physiological function of pde6h during flounder metamorphosis in the future.

Digestive system neuroendocrine carcinomas (NECs) are rare neoplasms originating from neuroendocrine cells with a poor prognosis and limited effective treatments. Programmed cell death protein 1/ligand 1 (PD-1/PD-L1) blockade has been used in the management of more than 10 solid tumors and has achieved promising clinical outcomes. PD-L1 expression, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) are all verified biomarkers that can predict the response to anti-PD-1/PD-L1 therapy. Here, we investigated PD-L1 expression and immune cell infiltration density by immunohistochemical (IHC) staining of tumor samples from 33 patients with digestive system NECs. Tumor and paratumor normal samples from 31 of these patients underwent whole-exome sequencing to evaluate TMB and the MSI-high (MSI-H) status. In total, 29.0% of digestive system NECs had positive PD-L1 expression according to the tumor proportion score (TPS). Infiltration of CD3+, CD8+, and CD68+ cells was observed in 69.7, 27.3, and 54.5% of patients, respectively. The TMB value for patients sequenced ranged from 0.57 to 11.75 mutations/Mb, with a median of 5.68 mutations/Mb. mSINGS, MSIsensor, and MSIseq were used to analyze the MSI status according to the sequencing data, and in our evaluation, no MSI-H status was detected. Our data might indicate a limited potential of anti-PD-1/PD-L1 monotherapy in digestive system NECs, although clinical trials are warranted.

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a rare cause of Cushing syndrome. If routine imaging examinations cannot identify the source of ACTH production, long-term follow-up observation is necessary to determine the etiology. We present the case of a middle-aged male with gradual weight gain and a Cushingoid appearance over 4 years; he provided written informed consent. Laboratory and endocrine tests strongly suggested EAS, although the origin was not detected by multiple imaging methods. Bilateral adrenalectomy was performed to prevent severe complications in the patient. Two and a half years later, a cardiac mass 18 × 23 × 27 mm in size at the junction between the anterior wall of the left ventricle and the middle septum was found together with multiple bone metastases by 18F-FDG PET/CT, while the 68Ga-DOTATE PET/CT findings were negative. Biopsy of the lumbar vertebrae revealed a neuroendocrine tumor (NET) with positive ACTH staining. The patient underwent chemotherapy by CAPTEM, resulting in shrinkage of the cardiac mass and a significant decrease in the ACTH level. In the case of EAS with an unusual cause, long-term follow-up observation is necessary to determine the source of ACTH production. Cardiac NETs are quite rare in EAS, so treatment selection was also challenging. CAPTEM chemotherapy proved effective in controlling the progression of tumor growth and decreasing the ACTH level in this patient.

Early biomarkers of therapeutic responses can help optimize the treatment of metastatic colorectal cancers (mCRC). In this prospective exploratory study, we examined serial changes of plasma-circulating tumor DNA (ctDNA) in 41 mCRC patients receiving first-line chemotherapies and tested its association with treatment outcomes according to radiological assessments. Using next-generation sequencing technologies, we profiled somatic mutations in 50 cancer-related genes in ctDNA before each of the first four treatment cycles. We observed mutations in 95.7% of pre-treatment ctDNA samples. Using mutations of the maximal frequency in each pre-treatment plasma ctDNA sample as the candidate targets, we computed log2 fold changes of ctDNA levels between adjacent treatment cycles. We found that ctDNA reductions as early as prior to cycle 2 predicted responses after cycle 4. Log2 fold changes of ctDNA after cycle 1 (ctDNA log2 (C1/C0)) > −0.126 predicted progressive disease, with an accuracy of 94.6%. These patients also showed significantly worse progression-free survival than those with ctDNA log2 (C1/C0) ≤ −0.126 (median 2.0 vs. 9.0 months; P = 0.007). Together, the present exploratory study suggests that early changes in ctDNA levels detected via targeted sequencing are potential biomarkers of future treatment responses in mCRCs.

Paenibacillus polymyxa (formerly known as Bacillus polymyxa) has been extensively studied for agricultural applications as a plant-growth-promoting rhizobacterium and is also an important biocontrol agent. Our team has developed the P. polymyxa strain HY96-2 from the tomato rhizosphere as the first microbial biopesticide based on P. polymyxa for controlling plant diseases around the world, leading to the commercialization of this microbial biopesticide in China. However, further research is essential for understanding its precise biocontrol mechanisms. In this paper, we report the complete genome sequence of HY96-2 and the results of a comparative genomic analysis between different P. polymyxa strains. The complete genome size of HY96-2 was found to be 5.75 Mb and 5207 coding sequences were predicted. HY96-2 was compared with seven other P. polymyxa strains for which complete genome sequences have been published, using phylogenetic tree, pan-genome, and nucleic acid co-linearity analysis. In addition, the genes and gene clusters involved in biofilm formation, antibiotic synthesis, and systemic resistance inducer production were compared between strain HY96-2 and two other strains, namely, SC2 and E681. The results revealed that all three of the P. polymyxa strains have the ability to control plant diseases via the mechanisms of colonization (biofilm formation), antagonism (antibiotic production), and induced resistance (systemic resistance inducer production). However, the variation of the corresponding genes or gene clusters between the three strains may lead to different antimicrobial spectra and biocontrol efficacies. Two possible pathways of biofilm formation in P. polymyxa were reported for the first time after searching the KEGG database. This study provides a scientific basis for the further optimization of the field applications and quality standards of industrial microbial biopesticides based on HY96-2. It may also serve as a reference for studying the differences in antimicrobial spectra and biocontrol capability between different biocontrol agents.