A flavonoid metabolon: cytochrome b5 enhances B-ring trihydroxylated flavan-3-ols synthesis in tea plants.

Flavan-3-ols are prominent phenolic compounds found abundantly in the young leaves of tea plants. The enzymes involved in flavan-3-ol biosynthesis in tea plants have been extensively investigated. However, the localization and associations of these numerous functional enzymes within cells have been largely neglected. In this study, we aimed to investigate the synthesis of flavan-3-ols in tea plants, particularly focusing on epigallocatechin gallate. Our analysis involving the DESI-MSI method to reveal a distinct distribution pattern of B-ring trihydroxylated flavonoids, primarily concentrated in the outer layer of buds. Subcellular localization showed that CsC4H, CsF3'H, and CsF3'5'H localizes endoplasmic reticulum. Protein-protein interaction studies demonstrated direct associations between CsC4H, CsF3'H, and cytoplasmic enzymes (CHS, CHI, F3H, DFR, FLS, and ANR), highlighting their interactions within the biosynthetic pathway. Notably, CsF3'5'H, the enzyme for B-ring trihydroxylation, did not directly interact with other enzymes. We identified cytochrome b5 isoform C serving as an essential redox partner, ensuring the proper functioning of CsF3'5'H. Our findings suggest the existence of distinct modules governing the synthesis of different B-ring hydroxylation compounds. This study provides valuable insights into the mechanisms underlying flavonoid diversity and efficient synthesis and enhances our understanding of the substantial accumulation of B-ring trihydroxylated flavan-3-ols in tea plants.

The role of glycosylation in non-productive adsorption of cellulase to lignin isolated from pretreated corn stover.

Glycosylation, a general post-translational modification for fungal cellulase, has been shown to affect cellulase binding to its substrate. However, the exact impact of glycosylation on cellulase-lignin interaction remain unclear. Here, we demonstrated that the lignin isolated from tetrahydrofuran-pretreated corn stover exhibits strong adsorption capability to cellulase due to its negatively charged and porous structure. For the cellulases with varying glycosylation levels, the less-glycosylated protein showed high adsorption capability to lignin, and that trend was observed for the main cellulase components secreted by Penicillium oxilicum, including endoglucanase PoCel5B, cellobiohydrolase PoCel7A-2, and ß-glucosidase PoBgl1. Additionally, N-glycan sites and motifs were examined using mass spectrometry, and protein structures with N-glycans were constructed, where PoBgl1 and PoCel7A-2 contained 13 and 1 glycosylated sites respectively. The results of molecular dynamics simulations indicated that the N-glycans impacted on the solvent-accessible surface area and secondary structure of protein, and the binding conformation of lignin fragment on cellulase, resulting in a decrease in binding energy (14 kcal/mol for PoBgl1 and 13 kcal/mol for PoCel7A-2), particularly for van der Waals and electrostatic interaction. Those findings suggested that glycosylation negatively impacted the lignin-cellulase interaction, providing a theoretical basis for the rational engineering of enzymes to reduce lignin-enzyme interaction.

Spin-degree manipulation for one-dimensional room-temperature ferromagnetism in a haldane system.

The intricate correlation between lattice geometry, topological behavior and charge degrees of freedom plays a key role in determining the physical and chemical properties of a quantum-magnetic system. Herein, we investigate the introduction of the unusual oxidation state as an alternative pathway to modulate the magnetic ground state in the well-known S = 1 Haldane system nickelate Y2BaNiO5 (YBNO). YBNO is topologically reduced to incorporate d9-Ni+ (S = 1/2) in the one-dimensional Haldane chain system. The random distribution of Ni+ for the first time results in the emergence of a one-dimensional ferromagnetic phase with a transition temperature far above room temperature. Theoretical calculations reveal that the antiferromagnetic interplay can evolve into ferromagnetic interactions with the presence of oxygen vacancies, which promotes the formation of ferromagnetic order within one-dimensional nickel chains. The unusual electronic instabilities in the nickel-based Haldane system may offer new possibilities towards unconventional physical and chemical properties from quantum interactions.

The role of mTORC1/TFEB axis mediated lysosomal biogenesis and autophagy impairment in fluoride neurotoxicity and the intervention effects of resveratrol.

Elevated exposures to fluoride have been linked to neurological diseases. Identifying mechanisms of fluoride neurotoxicity and finding ways for prevention and treatment of epidemic fluorosis are important issues of public health. In this study, fluoride inhibited TFEB nuclear translocation by activating p-mTORC1/p-p70S6K, thus inhibiting lysosomal biogenesis, leading to dysfunctional lysosome accumulation, which further negatively affected autophagosome and lysosome fusion, thus impairing autophagy degradation, evidenced by the blocked conversion of LC3II to LC3I, and the increased p62 levels. Interestingly, RSV alleviated rats' cognition by improving fluoride-induced nerve damage and promoted lysosomal biogenesis demonstrated by the increased nucleus translocation of TFEB via inhibiting p-mTORC1 and p-p70S6K, the decreased expression of LC3II and p62. Collectively, we clarified the correlation between fluoride neurotoxicity and mTORC1/TFEB-mediated lysosomal biogenesis and autophagy. Meanwhile, RSV appeared to be a promising drug for the prevention and treatment of epidemic fluorosis.

Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells.

Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) to sensitize it to anti-PD-1 antibody (a-PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a-PD-1, and stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected PDACs following different neoadjuvant therapies as comparisons, effector cells in PDACs were found to skew toward a more exhausted status in LAPCs following chemotherapy. The combination of GVAX/a-PD-1/SBRT drives TME to favor antitumor immune response including increased densities of GZMB+CD8+ T cells, TH1, and TH17, which are associated with longer survival, however increases immunosuppressive M2-like tumor-associated macrophages (TAMs). Adding SBRT to GVAX/a-PD-1 shortens the distances from PD-1+CD8+ T cells to tumor cells and to PD-L1+ myeloid cells, which portends prolonged survival. These findings have guided the design of next radioimmunotherapy studies by targeting M2-like TAM in PDACs.

Cucumber (Cucumis sativus L.) with heterologous poly-γ-glutamic acid has skin moisturizing, whitening and anti-wrinkle effects.

Three genes involved in poly-γ-glutamic acid(γ-PGA)synthesis cloned from Bacillus licheniformis were transformed into cucumber for the first time. Compared with control, its water content increased by 6-14 % and water loss rate decreased by 11-12 %. In zebrafish and human skin experiments, the moisturizing effect of transgenic cucumber was significantly higher than that of CK, γ-PGA and hyaluronic acid group. Transgenic cucumber reduced facial wrinkles and roughness by 19.58 % and 24.97 %, reduced skin melanin content by 5.27 %, increased skin topological angle and L-value by 5.89 % and 2.49 %, and increased the R2 and Q1 values of facial elasticity by 7.67 % and 5.64 %, respectively. The expressions of aqp3, Tyr, silv and OCA2 were down-regulated, eln1, eln2, col1a1a and col1a1b were up-regulated in zebrafish after treated with transgenic cucumber. This study provides an important reference for the endogenous synthesis of important skin care functional molecules in plants.

Overexpression of ZmSUS1 increased drought resistance of maize (Zea mays L.) by regulating sucrose metabolism and soluble sugar content.

MAIN CONCLUSION: ZmSUS1 improved drought tolerance of maize by regulating sucrose metabolism and increasing soluble sugar content, and endowing transgenic maize with higher relative water content and photosynthesis levels. Sucrose synthase (SUS), a key enzyme of sugar metabolism, plays an important role in the regulation of carbon partitioning in plant, and affects important agronomic traits and abiotic responses to adversity. However, the function of ZmSUS1 in plant drought tolerance is still unknown. In this study, the expression patterns of ZmSUS1 in different tissues and under drought stress were analyzed in maize (Zea mays L.). It was found that ZmSUS1 was highly expressed during kernel development but also in leaves and roots of maize, and ZmSUS1 was induced by drought stress. Homozygous transgenic maize lines overexpressing ZmSUS1 increased the content and activity of SUS under drought stress and exhibited higher relative water content, proline and abscisic acid content in leaves. Specifically, the net photosynthetic rate and the soluble sugar contents including sucrose, glucose, fructose and SUS decomposition products including UDP-glucose (UDP-G) and ADP-glucose (ADP-G) in transgenic plants were significantly improved after drought stress. RNA-seq analysis showed that overexpressing of ZmSUS1 mainly affected the expression level of carbon metabolism-related genes. Especially the expression level of sucrose metabolism-related genes including sucrose phosphatase gene (SPP), sucrose phosphate synthase gene (SPS) and invertase gene (INV) were significantly up-regulated in transgenic maize. Overall, these results suggested that ZmSUS1 improved drought tolerance by regulating sucrose metabolism and increasing the soluble sugar content, and endowing transgenic maize with higher relative water content and photosynthesis levels, which can serve as a new gene candidate for cultivating drought-resistant maize varieties.

Healthy plant-based diet might be inversely associated with gastric precancerous lesions: new evidence from a case-control study based on dietary pattern and fecal metabolic profiling.

Preventing the progression of gastric precancerous lesions (GPLs) can reduce the morbidity and mortality of gastric cancer (GC). The preventive effect of a plant-based diet on cancers has been widely recognised. In this case-control study, 1,130 subjects were included using 1:1 propensity score matching for age and sex. Dietary habits, anthropometry and sample collection were conducted using standard and effective methods. Plant-based diet indices (PDIs) were calculated using a previously reported method. Faecal samples were analysed by untargeted metabolomics. Our study found that adherence to a healthy plant-based diet was inversely associated with the occurrence of GPLs. Metabolomic analysis identified six different metabolites correlated with GPLs, among which luteolin-related metabolites may be used as biomarkers of the association between PDIs and GPLs. In addition, the difference in N-acyl amides found in PDIs needs further verification. Our findings suggest that a healthy plant-based diet may have a protective effect against GPLs.

Deep learning and targeted metabolomics-based monitoring of chewing insects in tea plants and screening defense compounds.

Tea is an important cash crop that is often consumed by chewing pests, resulting in reduced yields and economic losses. It is important to establish a method to quickly identify the degree of damage to tea plants caused by leaf-eating insects and screen green control compounds. This study was performed through the combination of deep learning and targeted metabolomics, in vitro feeding experiment, enzymic analysis and transient genetic transformation. A small target damage detection model based on YOLOv5 with Transformer Prediction Head (TPH-YOLOv5) algorithm for the tea canopy level was established. Orthogonal partial least squares (OPLS) was used to analyze the correlation between the degree of damage and the phenolic metabolites. A potential defensive compound, (-)-epicatechin-3-O-caffeoate (EC-CA), was screened. In vitro feeding experiments showed that compared with EC and epicatechin gallate, Ectropis grisescens exhibited more significant antifeeding against EC-CA. In vitro enzymatic experiments showed that the hydroxycinnamoyl transferase (CsHCTs) recombinant protein has substrate promiscuity and can catalyze the synthesis of EC-CA. Transient overexpression of CsHCTs in tea leaves effectively reduced the degree of damage to tea leaves. This study provides important reference values and application prospects for the effective monitoring of pests in tea gardens and screening of green chemical control substances.

Phosphate deficiency induced by infection promotes synthesis of anthracnose-resistant anthocyanin-3-O-galactoside phytoalexins in the Camellia sinensis plant.

Tea (Camellia sinensis) is a well-known beverage crop rich in polyphenols with health benefits for humans. Understanding how tea polyphenols participate in plant resistance is beneficial to breeding resistant varieties and uncovering the resistance mechanisms. Here, we report that a Colletotrichum infection-induced 'pink ring' symptom appeared outside the lesion, which is highly likely to occur in resistant cultivars. By identifying morphological feature-specific metabolites in the pink ring and their association with disease resistance, and analysis of the association between metabolite and gene expression, the study revealed that the accumulation of anthocyanin-3-O-galactosides, red phytotoxin compounds resistant to anthracnose, plays a pivotal role in the hypersensitive response surrounding infection sites in tea plants. The results of genetic manipulation showed that the expression of CsF3Ha, CsANSa, CsUGT78A15, CsUGT75L43, and CsMYB113, which are involved in anthocyanin biosynthesis, is positively correlated with anthracnose-resistance and the formation of the pink ring. Further phosphorus quantification and fertilization experiments confirmed that phosphate deficiency caused by anthracnose is involved in the occurrence of the pink ring. Genetic manipulation studies indicated that altering the expression levels of Pi transporter proteins (CsPHT2-1, CsPHT4;4) and phosphate deprivation response transcription factors (CsWRKY75-1, CsWRKY75-2, CsMYB62-1) enhances resistance to anthracnose and the formation of the pink ring symptom in tea plants. This article provides the first evidence that anthocyanin-3-O-galactosides are the anthracnose-resistant phytoalexins among various polyphenols in tea plants, and this presents an approach for identifying resistance genes in tea plants, where genetic transformation is challenging.

Glycosylation of Secondary Metabolites: A Multifunctional UDP-Glycosyltransferase, CsUGT74Y1, Promotes the Growth of Plants.

Camellia sinensis contains numerous glycosylated secondary metabolites that provide various benefits to plants and humans. However, the genes that catalyze the glycosylation of multitype metabolites in tea plants remain unclear. Here, 180 uridine diphosphate-dependent glycosyltransferases that may be involved in the biosynthesis of glycosylated secondary metabolites were identified from the National Center for Biotechnology Information public databases. Subsequently, CsUGT74Y1 was screened through phylogenetic analysis and gene expression profiling. Compositional and induced expression analyses revealed that CsUGT74Y1 was highly expressed in tea tender shoots and was induced under biotic and abiotic stress conditions. In vitro enzymatic assays revealed that rCsUGT74Y1 encoded a multifunctional UGT that catalyzed the glycosylation of flavonoids, phenolic acids, lignins, and auxins. Furthermore, CsUGT74Y1-overexpressing Arabidopsis thaliana exhibited enhanced growth and accumulation of flavonol and auxin glucosides. Our findings provide insights into identifying specific UGTs and demonstrate that CsUGT74Y1 is a multifunctional UGT that promotes plant development.

Item-specific neural representations during human sleep support long-term memory.

Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Here, we employed the targeted memory reactivation (TMR) paradigm to unobtrusively replaying auditory memory cues during human participants' slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found temporally segregated and functionally distinct item-specific neural representations: the early post-cue EEG activity (within 0 to 2,000 ms) contained comparable item-specific representations for memory cues and control cues, signifying effective processing of auditory cues. Critically, the later EEG activity (2,500 to 2,960 ms) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, indicating memory reprocessing. Moreover, these later item-specific neural representations were supported by concurrently increased spindles, particularly for items that had not been tested prior to sleep. These findings elucidated how external memory cues triggered item-specific neural representations during SWS and how such representations were linked to successful long-term memory. These results will benefit future research aiming to perturb specific memory episodes during sleep.

SIRT1, a target of miR-708-3p, alleviates fluoride-induced neuronal damage via remodeling mitochondrial network dynamics.

INTRODUCTION: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. OBJECTIVES: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. METHODS: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. RESULTS: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. CONCLUSION: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study.

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Natural Coumarin Shows Toxicity to Spodoptera litura by Inhibiting Detoxification Enzymes and Glycometabolism.

Coumarin and its derivatives are plant-derived compounds that exhibit potent insecticidal properties. In this study, we found that natural coumarin significantly inhibited the growth and development of Spodoptera litura larvae through toxicological assay. By transcriptomic sequencing, 80 and 45 differentially expressed genes (DEGs) related to detoxification were identified from 0 to 24 h and 24 to 48 h in S. litura after coumarin treatment, respectively. Enzyme activity analysis showed that CYP450 and acetylcholinesterase (AChE) activities significantly decreased at 48 h after coumarin treatment, while glutathione S-transferases (GST) activity increased at 24 h. Silencing of SlCYP324A16 gene by RNA interference significantly increased S. litura larval mortality and decreased individual weight after treatment with coumarin. Additionally, the expression levels of DEGs involved in glycolysis and tricarboxylic acid (TCA) cycle were inhibited at 24 h after coumarin treatment, while their expression levels were upregulated at 48 h. Furthermore, metabonomics analysis identified 391 differential metabolites involved in purine metabolism, amino acid metabolism, and TCA cycle from 0 to 24 h after treated with coumarin and 352 differential metabolites associated with ATP-binding cassette (ABC) transporters and amino acid metabolism. These results provide an in-depth understanding of the toxicological mechanism of coumarin on S. litura.

Thermosensitive black phosphorus hydrogel loaded with silver sulfadiazine promotes skin wound healing.

Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.

Functional diversity of subgroup 5 R2R3-MYBs promoting proanthocyanidin biosynthesis and their key residues and motifs in tea plant.

The tea plant (Camellia sinensis) is rich in polyphenolic compounds. Particularly, flavan-3-ols and proanthocyanidins (PAs) are essential for the flavor and disease-resistance property of tea leaves. The fifth subgroup of R2R3-MYB transcription factors comprises the primary activators of PA biosynthesis. This study showed that subgroup 5 R2R3-MYBs in tea plants contained at least nine genes belonging to the TT2, MYB5, and MYBPA types. Tannin-rich plants showed an expansion in the number of subgroup 5 R2R3-MYB genes compared with other dicotyledonous and monocot plants. The MYBPA-type genes of tea plant were slightly expanded. qRT-PCR analysis and GUS staining analysis of promoter activity under a series of treatments revealed the differential responses of CsMYB5s to biotic and abiotic stresses. In particular, CsMYB5a, CsMYB5b, and CsMYB5e responded to high-intensity light, high temperature, MeJA, and mechanical wounding, whereas CsMYB5f and CsMYB5g were only induced by wounding. Three genetic transformation systems (C. sinensis, Nicotiana tabacum, and Arabidopsis thaliana) were used to verify the biological function of CsMYB5s. The results show that CsMYB5a, CsMYB5b, and CsMYB5e could promote the gene expression of CsLAR and CsANR. However, CsMYB5f and CsMYB5g could only upregulate the gene expression of CsLAR but not CsANR. A series of site-directed mutation and domain-swapping experiments were used to verify functional domains and key amino acids of CsMYB5s responsible for the regulation of PA biosynthesis. This study aimed to provide insight into the induced expression and functional diversity model of PA biosynthesis regulation in tea plants.

Alternative splicing of chitin deacetylase 2 regulates chitin and fatty acid metabolism in Asian citrus psyllid, Diaphorina citri.

Chitin plays an important role in the development and molting of insects. The key genes involved in chitin metabolism were considered promising targets for pest control. In this study, two splice variants of chitin deacetylase 2 (CDA2) from Diaphorina citri were identified, including DcCDA2a and DcCDA2b. Bioinformatics analysis revealed that DcCDA2a and DcCDA2b encoded 550 and 544 amino acid residues with a signal peptide, respectively. Spatio-temporal expression patterns analysis showed that DcCDA2a and DcCDA2b were highly expressed in D. citri wing and nymph stages. Moreover, DcCDA2a and DcCDA2b expression levels were induced by 20-hydroxyecdysone (20E). Silencing DcCDA2a by RNA interference (RNAi) significantly disrupted the D. citri molting and increased D. citri mortality and malformation rate, whereas inhibition of DcCDA2b resulted in a semimolting phenotype. Furthermore, silencing DcCDA2a and DcCDA2b significantly suppressed D. citri chitin and fatty acid metabolism. Our results indicated that DcCDA2 might play crucial roles in regulating D. citri chitin and fatty acid metabolism, and it could be used as a potential target for controlling D. citri.

Reoperation for heterochronic intraductal papillary mucinous neoplasm of the pancreas after bile duct neoplasm resection: A case report.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) and intraductal papillary mucinous neoplasm (IPMN) of the pancreas have similar pathological manifestations. However, they often develop separately and it is rare for both to occur together. Patients presenting with heterochronic IPMN after IPNB are prone to be misdiagnosed with tumor recurrence. CASE SUMMARY: A 67-year-old male patient was admitted 8.5 years after IPNB carcinoma and 4 years after the discovery of a pancreatic tumor. A left hepatic bile duct tumor with distal bile duct dilatation was found 8.5 years ago by the computed tomography; therefore, a left hepatectomy was performed. The postoperative pathological diagnosis was malignant IPNB with negative cutting edge and pathological stage T1N0M0. Magnetic resonance imaging 4 years ago showed cystic lesions in the pancreatic head with pancreatic duct dilatation, and carcinoembryonic antigen continued to increase. Positron emission tomography showed a maximum standard uptake value of 11.8 in the soft tissue mass in the pancreatic head, and a malignant tumor was considered. Radical pancreatoduodenectomy was performed. Postoperative pathological diagnosis was pancreatic head IPMN with negative cutting edge, pancreaticobiliary type, stage T3N0M0. He was discharged 15 d after the operation. Follow-up for 6 mo showed no tumor recurrence, and quality of life was good. CONCLUSION: IPNB and IPMN are precancerous lesions with similar pathological characteristics and require active surgery and long-term follow-up.

Factors predicting recurrence after left­sided pancreatectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately. METHODS: Patients with PDAC after left­sided pancreatectomy between May 2015 and August 2021 were retrospectively identified. RESULTS: One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019). CONCLUSIONS: Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery.