Detection and characterization of pancreatic and biliary tract cancers using cell-free DNA fragmentomics.

BACKGROUND: Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection. METHODS: One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19-9 (CA19-9) was explored to improve model performance. RESULTS: The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved. CONCLUSIONS: Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.

Diagnostic and Prognostic Values of KLF5 and RUNX1 in Acute Kidney Injury in Septic Patients.

Diagnostic and prognostic values of Kruppel-like factor 5 (KLF5) and Runt-related transcription factor 1 (RUNX1) were determined in sepsis-induced acute kidney injury (SI-AKI). The study included 120 septic patients and set two groups: SI-AKI group (n = 60) or non-AKI group (n = 60). Fasting venous blood was drawn, and KLF5 and RUNX1 levels were measured. The receiver operating characteristic curve was plotted for diagnostic evaluation of KLF5 and RUNX1 in SI-AKI. The correlation between KLF5 and RUNX1 and serum creatinine (Scr), cystatin C (Cys-C), and kidney injury molecule 1 (KIM-1) were assessed by Pearson method. Predictive values of KLF5 and RUNX1 in 28-day survival of SI-AKI patients were considered by Kaplan-Meier survival curves and multivariate Cox regression analysis. Serum KLF5 and RUNX1 in SI-AKI patients were upregulated. Serum KLF5 and RUNX1 were of high diagnostic value in distinguishing SI-AKI patients from non-AKI patients. KLF5 and RUNX1 were in a positive correlation with Scr, Cys-C, and KIM-1, respectively. The 28-day survival of SI-AKI patients with high serum KLF5 or RUNX1 expression was poor, and serum KLF5 and RUNX1 expression were independently correlated with SI-AKI patients' survival. KLF5 and RUNX1 have diagnostic and prognostic values in SI-AKI patients.

A supramolecular photosensitizer based on triphenylamine and pyrazine with aggregation-induced emission properties for high-efficiency photooxidation reactions.

Recently, there has been a great interest in the study of photocatalysts (PCs) and photosensitizers (PSs) in the field of organic photocatalysis. In the present study, a pure organic thermally activated delayed fluorescence (TADF) molecule 4,4'-(12-(pyridin-4-yl)dibenzo[f,h]pyrido[2,3-b]quinoxaline-3,6-diyl)bis(N,N-diphenylaniline) (DPQ-TPA) was designed and synthesized, which not only have excellent TADF property and small energy splitting (ΔEST), but also can self-assembly in water to form cross-linked nanoparticles with exceptional aggregation-induced emission (AIE) characteristics. DPQ-TPA exhibits excellent remarkable selectivity and notably enhances the production capacity of reactive oxygen species (ROS), particularly 1O2, which was employed as a highly effective photocatalyst in the photooxidation reaction of phosphine and hydroazobenzenes under blue light irradiation with high yields up to 94% and 91%, respectively. This work expands the potential application of (donor-acceptor) D-A type AIE-TADF molecules in photocatalytic organic transformations through supramolecular self-assembly.

Hand-sewn gastrojejunal anastomosis reduces delayed gastric emptying after pancreaticoduodenectomy: A single-center retrospective clinical study of 1,077 consecutive patients.

BACKGROUND: Hand-sewn anastomosis and stapled anastomosis are the 2 main types of gastrojejunal anastomotic methods in pancreaticoduodenectomy. There is ongoing debate regarding the most effective anastomotic method for reducing delayed gastric emptying after pancreaticoduodenectomy. This study aims to identify factors that influence delayed gastric emptying after pancreaticoduodenectomy and assess the impact of different anastomotic methods on delayed gastric emptying. METHODS: The study included 1,077 patients who had undergone either hand-sewn anastomosis (n = 734) or stapled anastomosis (n = 343) during pancreaticoduodenectomy between December 2016 and November 2021 at our department. We retrospectively analyzed the clinical data, and a 1:1 propensity score matching was performed to balance confounding variables. RESULTS: After propensity score matching, 320 patients were included in each group. Compared with the stapled anastomosis group, the hand-sewn anastomosis group had a significantly lower incidence of delayed gastric emptying (28 [8.8%] vs 55 [17.2%], P = .001) and upper gastrointestinal tract bleeding (6 [1.9%] vs 17 [5.3%], P = .02). Additionally, the hand-sewn anastomosis group had a significantly reduced postoperative length of stay and lower hospitalization expenses. However, the hand-sewn anastomosis group had a significantly longer operative time, which was consistent with the analysis before propensity score matching. Logistic regression analysis showed that stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula were independent prognostic factors for delayed gastric emptying. CONCLUSION: Hand-sewn anastomosis was associated with a lower incidence rate of clinically relevant delayed gastric emptying after pancreaticoduodenectomy. Stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula could increase the incidence of postoperative clinically relevant delayed gastric emptying. Hand-sewn anastomosis should be considered by surgeons to reduce the occurrence of postoperative delayed gastric emptying and improve patient outcomes.

Early oral feeding versus nasojejunal early enteral nutrition in patients following pancreaticoduodenectomy: a propensity score-weighted analysis of 428 consecutive patients.

BACKGROUND: Notwithstanding that significant medical progress has been achieved in recent years, the optimal nutritional support method following pancreaticoduodenectomy (PD) remains uncertain. This study compared the safety and feasibility of early oral feeding (EOF) with nasojejunal early enteral nutrition (NJEEN) after PD. METHODS: A retrospective cohort study was conducted on 428 consecutive patients who underwent PD between August 2018 and December 2020. During the first study phase, the routine postoperative feeding strategy was NJEEN, later replaced by EOF during the second study phase. The primary outcome was the incidence of delayed gastric emptying (DGE) following PD. Propensity score weighting was used to control for confounding factors. RESULTS: Four hundred forty patients underwent PD during the overall study period, with 438 patients aged 18 years and older. Ten patients experienced accidental tube dislodgement or migration and were excluded from the study based on the exclusion criteria. Finally, 211 patients and 217 patients underwent EOF and NJEEN, respectively. After propensity score weighting, it was observed that patients who underwent postoperative EOF experienced a significantly lower DGE (B/C) rate compared to those who underwent postoperative NJEEN [7.38% (31/424) vs. 14.97% (62/413), P =0.0005]. Subgroup analyses according to the presence of soft pancreatic texture yielded consistent results. The EOF group exhibited lower DGE grade, DGE (B/C) rate [5.90% (11/194) vs. 22.07% (43/193), P <0.0001], postoperative gastrointestinal endoscopic intervention rate, and Clavien-Dindo Grade III or higher rate. CONCLUSIONS: EOF is superior to NJEEN in reducing the incidence of grade B/C DGE after PD. The EOF procedure is safe and feasible and should be recommended as the optimal postoperative feeding method following PD.

CD147: an integral and potential molecule to abrogate hallmarks of cancer.

CD147 also known as EMMPRIN, basigin, and HAb18G, is a single-chain type I transmembrane protein shown to be overexpressed in aggressive human cancers of CNS, head and neck, breasts, lungs, gastrointestinal, genitourinary, skin, hematological, and musculoskeletal. In these malignancies, the molecule is integral to the diverse but complimentary hallmarks of cancer: it is pivotal in cancerous proliferative signaling, growth propagation, cellular survival, replicative immortality, angiogenesis, metabolic reprogramming, immune evasion, invasion, and metastasis. CD147 also has regulatory functions in cancer-enabling characteristics such as DNA damage response (DDR) and immune evasion. These neoplastic functions of CD147 are executed through numerous and sometimes overlapping molecular pathways: it transduces signals from upstream molecules or ligands such as cyclophilin A (CyPA), CD98, and S100A9; activates a repertoire of downstream molecules and pathways including matrix metalloproteinases (MMPs)-2,3,9, hypoxia-inducible factors (HIF)-1/2α, PI3K/Akt/mTOR/HIF-1α, and ATM/ATR/p53; and also functions as an indispensable chaperone or regulator to monocarboxylate, fatty acid, and amino acid transporters. Interestingly, induced loss of functions to CD147 prevents and reverses the acquired hallmarks of cancer in neoplastic diseases. Silencing of Cd147 also alleviates known resistance to chemoradiotherapy exhibited by malignant tumors like carcinomas of the breast, lung, pancreas, liver, gastric, colon, ovary, cervix, prostate, urinary bladder, glioblastoma, and melanoma. Targeting CD147 antigen in chimeric and induced-chimeric antigen T cell or antibody therapies is also shown to be safer and more effective. Moreover, incorporating anti-CD147 monoclonal antibodies in chemoradiotherapy, oncolytic viral therapy, and oncolytic virus-based-gene therapies increases effectiveness and reduces on and off-target toxicity. This study advocates the expedition and expansion by further exploiting the evidence acquired from the experimental studies that modulate CD147 functions in hallmarks of cancer and cancer-enabling features and strive to translate them into clinical practice to alleviate the emergency and propagation of cancer, as well as the associated clinical and social consequences.

A neoadjuvant therapy compatible prognostic staging for resected pancreatic ductal adenocarcinoma.

OBJECTIVE: To improve prediction, the AJCC staging system was revised to be consistent with upfront surgery (UFS) and neoadjuvant therapy (NAT) for PDAC. BACKGROUND: The AJCC staging system was designed for patients who have had UFS for PDAC, and it has limited predictive power for patients receiving NAT. METHODS: We examined 146 PDAC patients who had resection after NAT and 1771 who had UFS at Changhai Hospital between 2012 and 2021. The clinicopathological factors were identified using Cox proportional regression analysis, and the Neoadjuvant Therapy Compatible Prognostic (NATCP) staging was developed based on these variables. Validation was carried out in the prospective NAT cohort and the SEER database. The staging approach was compared to the AJCC staging system regarding predictive accuracy. RESULTS: The NAT cohort's multivariate analysis showed that tumor differentiation and the number of positive lymph nodes independently predicted OS. The NATCP staging simplified the AJCC stages, added tumor differentiation, and restaged the disease based on the Kaplan-Meier curve survival differences. The median OS for NATCP stages IA, IB, II, and III was 31.7 months, 25.0 months, and 15.8 months in the NAT cohort and 30.1 months, 22.8 months, 18.3 months, and 14.1 months in the UFS cohort. Compared to the AJCC staging method, the NATCP staging system performed better and was verified in the validation cohort. CONCLUSIONS: Regardless of the use of NAT, NATCP staging demonstrated greater predictive abilities than the existing AJCC staging approach for resected PDAC and may facilitate clinical decision-making based on accurate prediction of patients' OS.

Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer.

Metabolic reprogramming is known as an emerging mechanism of chemotherapy resistance, but the metabolic signatures of pancreatic ductal adenocarcinomas (PDACs) remain unclear. Here, we characterize the metabolomic profile of PDAC organoids and classify them into glucomet-PDAC (high glucose metabolism levels) and lipomet-PDAC (high lipid metabolism levels). Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression. Pharmacological inhibition of GLUT1 or G6PD enhances the chemotherapy response of glucomet-PDAC. Our findings uncover potential metabolic heterogeneity related to differences in chemotherapy sensitivity in PDAC and develop a promising pharmacological strategy for patients with chemotherapy-resistant glucomet-PDAC through the combination of chemotherapy and GLUT1/ALDOB/G6PD axis inhibitors.

Psychoneurological symptoms and inflammatory markers in patients with glioma in China: a network analysis.

PURPOSE: Anxiety, depression, sleep disorder, fatigue, and pain develop as common psychoneurological symptoms in patients with glioma, and their occurrence and development are potentially related to inflammatory factors. However, this theory has not been proven within the context of glioma. This study aimed to estimate interconnections among psychoneurological symptoms and inflammatory biomarkers by a network analysis. PATIENTS AND METHODS: We selected 203 patients with stage I-IV glioma from a tertiary hospital in China using convenient sampling method. Patients completed the self-made questionnaires, Hamilton Anxiety Scale-14 (HAMA-14), Hamilton Depression Scale-24 (HAMD-24), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory-20 (MFI-20), and pain Numerical Rating Scale (NRS). The plasma inflammatory cytokines were examined. Partial correlation network analysis was performed to illustrate interactions of symptoms and inflammatory biomarkers. RESULTS: Among the 203 included patients, all psychoneurological symptoms, except for depression and pain, exhibited significant connections with each other. Depression, anxiety, fatigue, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) with higher strength centrality indices were identified as the most central node within the symptom-biomarker network. CONCLUSIONS: Depression, anxiety, fatigue, IL-6, and TNF-α play a significant role in the symptom-biomarker network in patients with glioma. Medical staff should strengthen the dynamic evaluation of the involved symptoms and inflammatory cytokines and take effective measures to alleviate the burden of symptoms and improve the quality of life of patients.

Negative family body talk and negative emotional eating among Chinese adolescent girls and young adult women: The role of body dissatisfaction and feminism consciousness.

Negative emotional eating has been increasingly a prominent disordered eating and public health problem among young women, especially during COVID-19. Although previous studies have attempted to explain the relationship between body talk and negative emotional eating, limited studies focused on examining the potential mechanisms, especially the potential protective mechanism. Thus, the current study aimed to examine the relationship between negative family body talk (NFBT) and negative emotional eating, as well as its underlying mechanism - the mediating role of body dissatisfaction (BDIS) and the moderating role of feminism consciousness (FC). A cross-sectional study was employed among a sample of Chinese girls and young women (n = 813, Mage = 19.4 years) from a junior college in central China. Participants completed surveys assessing NFBT (Adapted Body Talk Scale), BDIS (Body Image State Scale), negative emotional eating (Dutch Eating Behavior Questionnaire), and FC (Synthesis Subscale from Feminist Identity Composite). A moderated mediation analysis was conducted. The results showed that: (1) after controlling for age and BMI, NFBT was positively associated with negative emotional eating, and BDIS could significantly mediate this relationship (mediating effect = 0.03, 95% CI [0.02, 0.06]); (2) FC significantly moderated both the direct relationship between NFBT and negative emotional eating and the relationship between NFBT and BDIS. Specifically, these two associations were not significant for participants with higher FC (+1SD above average). This study deepens our understanding of the relationship between NFBT and negative emotional eating, as well as the protective role of FC. If future studies demonstrate causal relationships, this evidence could point to a need for programs to prevent negative emotional eating in young women by increasing their level of feminism consciousness.

Parental Phubbing and Adolescent Depressive Symptoms during COVID-19: A Serial Meditating Model.

BACKGROUND: During the COVID-19 pandemic, depressive symptoms, a common emotional problem among adolescents, have become more prominent. Regarding the influencing factors of adolescent depressive symptoms, it is widely accepted that parents' problematic cellphone use around the family (specifically parental phubbing) is a strong predictive factor for the development of depressive symptoms among adolescents. Notably, the COVID-19 pandemic caused a sharp increase in the number of individuals with depressive symptoms, and the negative consequences of parental phubbing and depressive symptoms might have been exacerbated. Accordingly, this study aimed to examine the association between parental phubbing and adolescent depressive symptoms as well as their underlying mechanism. METHOD: To test our hypotheses, we conducted an offline/online survey with 614 adolescents in Central China from May to June 2022, which corresponded to a period of strict lockdowns in some areas due to the outbreak of the Omicron variant. The participants completed a set of measures, including a technology interference questionnaire, a parent-child relationship scale, a self-concept clarity scale, and the depressive symptoms scale. RESULTS: Parental phubbing was positively associated with adolescent depressive symptoms; the parent-child relationship and self-concept clarity could independently mediate this relationship; and the parent-child relationship and self-concept clarity were also serial mediators in this association. These findings extend previous research by highlighting the impact of parental technology use on their children and the underlying mechanism explaining adolescent depressive symptoms. They provide practical recommendations for parents to prioritize fostering a positive family environment and minimizing phubbing behaviors to enhance adolescent development, particularly in the context of the COVID-19 pandemic.

Modified artery-first approach for distal pancreatectomy with celiac axis resection.

BACKGROUND: The superior mesenteric artery-first approach has been proved superior in pancreatoduodenectomy compared with the standard procedure. It is unclear whether similar benefits could be obtained in distal pancreatectomy with celiac axis resection. METHODS: Perioperative and survival outcomes of patients who underwent distal pancreatectomy with celiac axis resection with the modified artery-first approach or traditional approach between January 2012 and September 2021 were compared. RESULTS: The entire cohort comprised 106 patients (modified artery-first approach, n = 35; traditional approach, n = 71). The most common complication was postoperative pancreatic fistula (n = 18, 17.0 per cent), followed by ischaemic complications (n = 17, 16.0 per cent) and surgical site infection (n = 15, 14.0 per cent). Intraoperative blood loss (400 versus 600 ml, P = 0.017) and intraoperative transfusion rate (8.6 versus 29.6 per cent, P = 0.015) were lower in the modified artery-first approach group compared with the traditional approach group. A higher number of harvested lymph nodes (18 versus 13, P = 0.030) and R0 resection rate (88.6 versus 70.4 per cent, P = 0.038) and a lower incidence of ischaemic complications (5.7 versus 21.1 per cent, P = 0.042) was observed in the modified artery-first approach group compared with the traditional approach group. In multivariable analysis, the modified artery-first approach (OR 0.006, 95 per cent c.i., 0 to 0.447; P = 0.020) was protective against ischaemic complications. CONCLUSIONS: Compared with the traditional approach, the modified artery-first approach was associated with lower blood loss and fewer ischaemic complications, and a higher number of harvested lymph nodes and R0 resection rate. Thus, it might improve the safety, staging and prognosis of distal pancreatectomy with celiac axis resection for pancreatic cancer.

Comparison of Complications between Anterior Cervical Diskectomy and Fusion versus Anterior Cervical Corpectomy and Fusion in Two- and Three-Level Cervical Spondylotic Myelopathy: A Meta-analysis.

BACKGROUND: In this study, we systematically analyze the differences in complications between anterior cervical diskectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) in two- and three-level cervical spondylotic myelopathy (CSM). METHODS: We performed a systematic search in MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases, Chinese Biomedical Literature Database, CNKI, and Wan Fang Data for all relevant studies. All statistical analyses were performed using Review Manager version 5.3. RESULTS: A total of 11 articles with 849 study subjects were included, with 474 patients in the ACDF group and 375 patients in the ACCF group. The results of the meta-analysis showed that in C5 palsy (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.16-1.06), pseudarthrosis (OR: 1.07; 95% CI: 0.23-5.07), dysphagia (OR: 1.06; 95% CI: 0.60-1.86), infection (OR: 0.41; 95% CI: 0.16-1.09), cerebrospinal fluid leakage (OR: 1.21; 95% CI: 0.39-3.73), graft dislodgment (OR: 0.28; 95% CI: 0.06-1.37), and hematoma (OR: 0.32; 95% CI: 0.06-1.83), there are no significant differences between the ACDF and ACCF groups, whereas total complication (OR: 0.50; 95% CI: 0.31-0.80) showed that the ACDF group had a significantly lower morbidity than the ACCF group. Furthermore, the three-level subgroup of ACDF had significantly better results in C5 palsy (OR: 0.31; 95% CI: 0.11-0.88), infection (OR: 0.22; 95% CI: 0.05-0.94), graft dislodgment (OR: 0.07; 95% CI: 0.01-0.40), and total complication (OR: 0.37; 95% CI: 0.23-0.60) compared with the ACCF subgroup. CONCLUSION: In general, postoperative pseudarthrosis, dysphagia, cerebrospinal fluid leakage, hematoma, C5 palsy, infection, and graft dislodgment did not differ significantly between the two groups. Total complication was significantly less in the ACDF group compared to the ACCF group. In the three-level subgroup, the morbidity of C5 palsy, infection, and graft dislodgment was significantly lower in ACDF than in ACCF.

Resistance to Powdery Mildew Is Conferred by Different Genetic Loci at the Adult-Plant and Seedling Stages in Winter Wheat Line Tianmin 668.

Winter wheat line Tianmin 668 was crossed with susceptible cultivar Jingshuang 16 to develop 216 recombinant inbred lines (RILs) for dissecting its adult-plant resistance (APR) and all-stage resistance (ASR) against powdery mildew. The RIL population was genotyped on a 16K genotyping by target sequencing single-nucleotide polymorphism array and phenotyped in six field trials and in the greenhouse. Three loci-QPmtj.caas-2BL, QPmtj.caas-2AS, and QPmtj.caas-5AL-conferring APR to powdery mildew were detected on chromosomes 2BL, 2AS, and 5AL, respectively, of Tianmin 668. The effect of resistance to powdery mildew for QPmtj.caas-2BL was greater than that of the other two loci. A Kompetitive allele-specific PCR marker specific for QPmtj.caas-2BL was developed and verified on 402 wheat cultivars or breeding lines. Results of virulence and avirulence patterns to 17 Blumeria graminis f. sp. tritici isolates, bulked segregant analysis-RNA-sequencing, and a genetic linkage mapping identified a resistance allele at locus Pm4 in Tianmin 668 based on the seedling phenotypes of the RIL population. The PCR-based DNA sequence alignment and cosegregation of the functional marker with the phenotypes of the RIL population demonstrated that Pm4d was responsible for the ASR to isolate Bgt1 in Tianmin 668. The dissection of genetic loci for APR and ASR may facilitate the application of Tianmin 668 in developing powdery mildew-resistant wheat cultivars.

Noninvasive detection of pancreatic ductal adenocarcinoma using the methylation signature of circulating tumour DNA.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the lowest overall survival rate primarily due to the late onset of symptoms and rapid progression. Reliable and accurate tests for early detection are lacking. We aimed to develop a noninvasive test for early PDAC detection by capturing the circulating tumour DNA (ctDNA) methylation signature in blood. METHODS: Genome-wide methylation profiles were generated from PDAC and nonmalignant tissues and plasma. Methylation haplotype blocks (MHBs) were examined to discover de novo PDAC markers. They were combined with multiple cancer markers and screened for PDAC classification accuracy. The most accurate markers were used to develop PDACatch, a targeted methylation sequencing assay. PDACatch was applied to additional PDAC and healthy plasma cohorts to train, validate and independently test a PDAC-discriminating classifier. Finally, the classifier was compared and integrated with carbohydrate antigen 19-9 (CA19-9) to evaluate and maximize its accuracy and utility. RESULTS: In total, 90 tissues and 546 plasma samples were collected from 232 PDAC patients, 25 chronic pancreatitis (CP) patients and 323 healthy controls. Among 223 PDAC cases with known stage information, 43/119/38/23 cases were of Stage I/II/III/IV. A total of 171 de novo PDAC-specific markers and 595 multicancer markers were screened for PDAC classification accuracy. The top 185 markers were included in PDACatch, from which a 56-marker classifier for PDAC plasma was trained, validated and independently tested. It achieved an area under the curve (AUC) of 0.91 in both the validation (31 PDAC, 26 healthy; sensitivity = 84%, specificity = 89%) and independent tests (74 PDAC, 65 healthy; sensitivity = 82%, specificity = 88%). Importantly, the PDACatch classifier detected CA19-9-negative PDAC plasma at sensitivities of 75 and 100% during the validation and independent tests, respectively. It was more sensitive than CA19-9 in detecting Stage I (sensitivity = 80 and 68%, respectively) and early-stage (Stage I-IIa) PDAC (sensitivity = 76 and 70%, respectively). A combinatorial classifier integrating PDACatch and CA19-9 outperformed (AUC=0.94) either PDACatch (0.91) or CA19-9 (0.89) alone (p < 0.001). CONCLUSIONS: The PDACatch assay demonstrated high sensitivity for early PDAC plasma, providing potential utility for noninvasive detection of early PDAC and indicating the effectiveness of methylation haplotype analyses in discovering robust cancer markers.

Investigation of the Neutralizing Behaviors of Cement-Based Materials Using a New pH Indicator Formulated from February Orchid Petals.

Investigation of the neutralizing behavior of concrete is essential, as it can help reveal the durability properties of concrete structures. In this paper, anthocyanin extracted from February orchid (F. orchid) petals was used to characterize the neutralized (carbonated, leached, and sulfate-attacked) regions of cement-based materials. The durability of F. orchid indicator was evaluated through comparison between discoloring behaviors of fresh and aged F. orchid indicators, and the capability of the new indicator in neutralization characterization was then verified by combining indicator (phenolphthalein, malachite green, indigo carmine, or thymolphthalein) spray, X-ray computed tomography (CT), and the X-ray attenuation method (XRAM). The result in the present study showed that, with a lower color intensity as compared to phenolphthalein/thymolphthalein, F. orchid indicator was less preferable in studying carbonation but a better choice in characterizing leaching and sulfate attack of cement-based materials. In addition, a sharp carbonation front was revealed in the present study, suggesting that the carbonation process in this study was controlled mainly by diffusion. For leaching and sulfate attack, the broader fronts revealed suggested that both processes were co-controlled by diffusion and reaction. The current work serves as a 'leap' toward the application of natural pigments in analyzing the durability of concrete structures.

Design, synthesis and antitumor activity of potent and safe para-quinone methides derivatives in vitro and in vivo.

Compounds containing Michael acceptor units display a wide variety of biological effects, and have attracted much attention in medicinal chemistry. In this paper, we designed and synthesized a panel of para-quinone methides (p-QMs) derivatives, classified as electron-deficient alkenes, and evaluated their cytotoxicity against cancer cells. These results revealed that drawing substituents into the ortho-position of the phenyl ring could obviously strengthen the cytotoxicity of p-QMs derivatives compared with that of meta- and para-substituents. Further biological studies demonstrated that the cytotoxicity of p-QMs derivatives originated from their ROS-generation abilities, which could further disrupt the redox balance, lipid peroxidation, the loss of MMP, cell cycle arrest at G0/G1 phase and apoptosis. 1h also exhibited potent antitumor activity through inhibiting TrxR and activating Bax and caspase 3 expression in vitro and in vivo, and 1h had certain safety in vivo. Moreover, the electrophilicity of the Michael acceptor, which could covalently modify with the TrxR, play a potent role in the ROS generation. From the perspective of chemistry, we affirmed that p-QMs derivatives could rapidly covalent binding with cysteamine, and the addition product was characterized by 1H NMR. Together, these new p-QMs derivatives may possess potential as leads for development of effective antitumor agents.

Social Exclusion and Depression among undergraduate students: the mediating roles of rejection sensitivity and social self-efficacy.

Nowadays, depression has been a prominent mental health problem throughout the world. A common but negative social experience, social exclusion (also known as ostracism) is a great risk factor for individuals' health and adaptation. Undergraduate students are in a development period of challenges and transitions, so they are vulnerable to suffering from depression and negative social experiences. Against this background, the present study aimed to examine the association between social exclusion and undergraduate students' depression as well as the underlying mechanism - the mediating roles of rejection sensitivity and social self-efficacy. Seven hundred sixty-two undergraduate students were recruited to participate in this study, who were asked to complete a set of questionnaires measuring social exclusion, depression, rejection sensitivity, and social self-efficacy. After controlling for gender, social exclusion was positively associated with undergraduate students' depression. And rejection sensitivity and social self-efficacy could significantly mediate this relation through three mediating paths - the separate mediating effects of rejection sensitivity and social self-efficacy, as well as the serial mediating effect of rejection sensitivity and social self-efficacy. These results could not only deepen our understanding of this theme, but also have several practical implications for the intervention of depression, for example, relevant social skill training and cognitive therapy could be adopted to intervene the rejection sensitivity and social self-efficacy.

Systemic therapy and perioperative management improve the prognosis of pancreatic ductal adenocarcinoma: A retrospective cohort study of 2000 consecutive cases.

OBJECTIVE: This study aimed to explore patterns of the treatment strategies of pancreatic ductal adenocarcinoma based on 2000 consecutive cases of a prospective database since 2012 to obtain new insights for future directions. METHODS: Among 2000 patients enrolled in this study, 210 patients were excluded, and 710, 521, and 559 patients were treated between 2012 and 2015 (group 1), between 2016 and 2017 (group 2), and between 2018 and 2019 (group 3), respectively. Patient clinicopathologic and biological factors, and perioperative outcomes were used to assess the prognostic factors. RESULTS: The median survival for all patients with pancreatic ductal adenocarcinoma was 21.7 months (1-year survival, 75.0%; 2-year survival, 43.7%; 5-year survival, 19.7%). Group 3 had a better survival outcome than groups 1 and 2 (median survival time: 23 versus 20.5 and 21.1 months). The proportion of patients younger than 65 gradually increased over time, as did the use of systemic chemotherapy and postoperative adjuvant radiotherapy. The tendency for early diagnosis (lower CA19-9 and CEA levels, smaller size, and earlier N stage), use of chemotherapy and radiotherapy, early recovery (lesser hospital stay and Clavien-Dindo grade <3), absence of abdominal pain, younger age, length of operation ≤3 h, and pathological factors (absence of lymphovascular invasion, peripancreatic fat infiltration and neural invasion, higher differentiation) were related to patients' survival. Multivariable analysis for prognosis revealed that tumor biological factors (increased preoperative serum CA19-9 level, tumor size, tumor differentiation, N stage, and presence of lymphovascular invasion and neural invasion), chemotherapy, radiotherapy, abdomen pain, operation period, length of stay, and length of operation correlated with patients' survival. CONCLUSIONS: Systemic therapy, including chemotherapy and radiotherapy, has gradually improved the prognosis after operative resection for pancreatic ductal adenocarcinoma. Neoadjuvant therapy is also beneficial to improve the prognosis to a certain extent. The enhanced recovery after surgery (ERAS) policies and the specific assessment of postoperative pancreatic fistula (POPF) risk may be related to reduced hospital stays and the reduction of serious complications. These advancements show that the concept of systemic therapy has been accepted and actively applied by Chinese medical institutions.