Search

Abstract Background To elucidate the relationship between the triglyceride-glycemic index (TyG) and clinical characteristics of pancreatic ductal adenocarcinoma (PDAC). Methods A total of 1,594 individuals diagnosed with pancreatic and periampullary neoplasms were categorized into four groups: PDAC-early (n = 403), locally advanced PDAC (LAPC, n = 315), PDAC-late with distant metastasis (n = 371), and other tumor types (n = 505). TyG-high was defined as a TyG index greater than 8.81 in males and 8.73 in females. Results The prevalence of TyG-high status was highest in PDAC-early (68.48%), followed by LAPC (53.33%), and lowest in PDAC-late (44.47%). TyG-high status significantly predicted worse PDAC prognosis (P = 0.0166), particularly in PDAC-late (P = 0.0420). Despite similar blood glucose levels across PDAC groups (P = 0.897), PDAC-early patients showed significantly higher rates of glycemic disturbances (56.33% vs. 32.28%) and TyG-high status (68.48% vs. 47.13%) compared to those with other tumors. Progressive increases in glycemic disturbances and TyG-high status were observed from benign to pre-malignant lesions and PDAC-early. PDAC-early patients at the pancreatic head exhibited higher rates of glycemic disturbances (58.12% vs. 33.33%, P

Receptor-like cytoplasmic kinase OsBSK1-2 was reported to play an important role in regulation of response to rice blast, but the signaling pathway remained unknown. In this study, we identified OsMAPKKK18 and previously uncharacterized MAPKKKs OsMAPKKK16 and OsMAPKKK19 that interact with OsBSK1-2. Expression of all three MAPKKKs was induced by Magnaporthe oryzae infection, and all three induced cell death when transiently expressed in Nicotiana benthamiana leaves. Knockout of OsMAPKKK16 and OsMAPKKK18 compromised blast resistance and overexpression of OsMAPKKK19 increased blast resistance, indicating that all three MAPKKKs are involved in regulation of rice blast response. Furthermore, both OsMAPKKK16 and OsMAPKKK19 interacted with and phosphorylated OsMKK4 and OsMKK5, and chitin-induced MAPK activation was suppressed in osmapkkk16 and osbsk1-2 mutants. OsMAPKKK18 was earlier reported to interact with and phosphorylate OsMKK4 and affect chitin-induced MAPK activation, suggesting that OsBSK1-2 is involved in regulation of immunity through multiple MAPK signaling pathways. Unlike BSK1 in Arabidopsis, OsBSK1-2 was not involved in response to avirulent M. oryzae strains. Taken together, our results revealed important roles of OsMAPKKK16/18/19 and a OsBSK1-2-OsMAPKKK16/18/19-OsMKK4/5 module in regulating response to rice blast.

Abstract Background Good food safety practices are essential to minimizing foodborne diseases. The present study explored the food safety-related practices of residents during the COVID-19 pandemic in Southwest China and identified the impacting factors. Methods Residents aged 18–75 years from Guizhou, Yunnan, Sichuan, and Chongqing, China, were included in our study. The convenience sampling method was used to select participants, and face-to-face surveys were conducted in households and communities to collect data. Descriptive statistics including sociodemographic characteristics of respondents and weighted percentages were obtained and the log-binomial regression was used to evaluate the influencing factors associated with food safety-related practices. Results Overall, 7,848 respondents were involved, with 97.5% efficacy. Disparities in food safety-related practices were observed between males and females, with the former performing poorer practices than the latter (70.5% vs. 68.0%, respectively). Notably, paying attention to nutrition labels when shopping for prepackaged foods was the worst practice. Age, ethnicity, region, occupation, education level, and income were identified as significant determinants of food safety-related practices. Moreover, in comparison to males, females were more likely to acquire pertinent knowledge from diverse sources, including social media, family members/ friends, books/ newspapers/ magazines, experts, and food sales staff (p

Abstract Objective The global epidemic of overweight/obesity in children and adolescents poses a significant public health threat. This longitudinal study aims to investigate the relationship between adolescents’ and their parents’ dietary knowledge and overweight/obesity among adolescents in China. Methods Data were collected from the China Health and Nutrition Survey (CHNS) in 2004, 2006, 2009, 2011 and 2015. Overweight/obesity was defined according to the International Obesity Task Force (IOTF) cut-off for body mass index (BMI). A set of questions were used to assess the dietary knowledge scores of both adolescents and their parents during face-to-face interviews. Mixed effect models were used to analyze the data. Results A total of 2035 adolescents aged 12–17 years were included in the data analysis. The mean BMI increased from 19.2 in 2004 to 20.5 in 2015, with a significant increase in the prevalence of overweight and obesity from 6.8% and 0.5% in 2004 to 15.1% and 7.8% in 2015, respectively. Adolescents with medium-score dietary knowledge were less likely to be overweight/obese compared to those with low-score dietary knowledge (OR (95% CI): 0.20 (0.05–0.80), P 0.05). Additionally, a significant interaction between adolescents’ dietary knowledge score and education in relation to adolescents’ BMI (P for interaction

Abstract Objective: We aimed to examine the association between dietary Se intake and CVD risk in Chinese adults. Design: This prospective cohort study included adults above 20 years old in the China Health and Nutrition Survey (CHNS), and they were followed up from 1997 to 2015 (n 16 030). Dietary data were retrieved from CHNS, and a 3-d, 24-h recall of food intake was used to assess the cumulative average intake of dietary Se, which was divided into quartiles. The Cox proportional hazards model was adopted to analyse the association between dietary Se intake and incident CVD risk. Setting: CHNS (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011 and 2015) Results: A total of 663 respondents developed CVD after being followed up for a mean of 9·9 years (median 9 years). The incidence of CVD was 4·3, 3·7, 4·6 and 4·0 per 1000 person-years across the quartiles of cumulative Se intake. After adjusting all potential factors, no significant associations were found between cumulative Se intake and CVD risk. No interactions were found between Se intake and income, urbanisation, sex, region, weight, hypertension and CVD risk. Conclusion: We found no association between dietary Se and CVD.

In clinical practice, pancreatic neuroendocrine neoplasms (pNENs) with a diameter smaller than 2 cm are commonly referred to as small pNENs. Due to their generally favorable biological characteristics, the diagnosis and treatment of small pNENs differ from other pNENs and are somewhat controversial. In response to this, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association have developed a consensus on the diagnosis and treatment of small pNENs, which is based on evidence-based medicine and expert opinions. This consensus covers various topics, including concepts, disease assessment, treatment selection, follow-up, and other relevant aspects.

Rice (Oryza sativa) is one of the most important staple foods worldwide. However, rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, seriously affects the yield and quality of rice. Calmodulin-binding transcriptional activators (CAMTAs) play vital roles in the response to biotic stresses. In this study, we showed that OsCAMTA3 and CAMTA PROTEIN LIKE (OsCAMTAPL), an OsCAMTA3 homolog that lacks the DNA-binding domain, functioned together in negatively regulating disease resistance in rice. OsCAMTA3 associated with OsCAMTAPL. The oscamta3 and oscamtapl mutants showed enhanced resistance compared to wild-type plants, and oscamta3/pl double mutants showed more robust resistance to M. oryzae than oscamta3 or oscamtapl. An RNA-Seq analysis revealed that 59 and 73 genes, respectively, were differentially expressed in wild-type plants and oscamta3 before and after inoculation with M. oryzae, including OsALDH2B1, an acetaldehyde dehydrogenase that negatively regulates plant immunity. OsCAMTA3 could directly bind to the promoter of OsALDH2B1, and OsALDH2B1 expression was decreased in oscamta3, oscamtapl, and oscamta3/pl mutants. In conclusion, OsCAMTA3 associates with OsCAMTAPL to regulate disease resistance by binding and activating the expression of OsALDH2B1 in rice, which reveals a strategy by which rice controls rice blast disease and provides important genes for resistance breeding holding a certain positive impact on ensuring food security.

Background: Unhealthy lifestyles among adolescents are reaching alarming levels and have become a major public health problem. This study aimed to assess the relationship between sleep time, physical activity (PA) time, screen time (ST), and nutritional literacy (NL). Methods: This cross-sectional online study involving adolescents aged 10–18 years was conducted in September 2020 in 239 schools in Chongqing, China. NL was measured using the “Nutrition Literacy Scale for middle school students in Chongqing (CM-NLS)”. According to the recommended by the Chinese dietary guidelines (2022), we divided the sleep time of junior high school students into Results: A total of 18,660 adolescents (50.2% males) were included. The proportion of participants that were junior high school students and attended boarding schools was 57.2% and 65.3%, respectively. Compared with senior high school students, junior high school students had a higher level of NL. Whether on workdays or weekends, participants with sleep time ≥ 8/9 h, PA time ≥ 1 h, and ST < 2 h per day had higher levels of NL. On weekdays, participants who met the sleep time ≥ 8 h/9 h (OR = 1.48, 95% CI: 1.36, 1.62) and PA time ≥ 1 h (OR = 1.69, 95% CI: 1.59, 1.81) had higher reporting of NL levels. Conclusions: Sleep time, PA time, and ST were positively correlated with NL among adolescents, especially junior high school students.

Objective This study aimed to investigate the current status and influencing factors of healthy diet knowledge, attitude, and practice (KAP) among middle-aged and older adults aged 45–75 in Southwest China. Methods A questionnaire survey was conducted among 1822 middle-aged and older adults in Southwest China (including Guizhou, Sichuan, Yunnan, and Chongqing) from February to May 2021. Results The average score of healthy diet knowledge was (4.82 ± 2.98), with a passing rate of 7.6%. The mean score of healthy diet attitude was (21.26 ± 4.18), with a passing rate of 69.5%. The average score of healthy diet practice was (13.76 ± 2.84), with a passing rate of 55.5%. The score for healthy diet KAP was (39.85 ± 7.21), with a passing rate of 41.2%. Univariate analysis showed that the scores of healthy diet KAP were significantly different among participants of different ages, genders, ethnicities, residences, education levels, monthly household incomes, and regions, as well as varying according to whether several generations have lived in the same area (p < 0.05). The results of multiple linear regression showed that the healthy diet KAP of participants was influenced by age, gender, residence, education level, monthly household income, and region (p < 0.05). Conclusion The healthy diet KAP of middle-aged and older adults aged 45–75 in Southwest China shows room for improvement. The knowledge regarding healthy diet was relatively low, and certain specific healthy diet practices were not up to the standard. However, there was a positive trend in the attitude towards a healthy diet. Healthy diet education should be promoted for middle-aged and older adults.

Background: Modified fluorouracil/leucovorin/irinotecan/oxaliplatin (FOLFIRINOX) regimen (mFOLFIRINOX), comprised of fluorouracil, leucovorin, irinotecan and oxaliplatin, is the first-line standard chemotherapy in patients with advanced pancreatic cancer. The S-1/oxaliplatin/irinotecan (SOXIRI) regimen has also been studied recently under similar conditions. This study compared its efficacy and safety. Methods: All cases of locally advanced or metastatic pancreatic cancer treated with the SOXIRI or mFOLFIRINOX regimen in Sun Yat-sen University Cancer Centre from July 2012 to June 2021 were reviewed retrospectively. The data of patients who satisfied the inclusion criteria were compared between two cohorts, including overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate and safety. Results: A total of 198 patients were enrolled in the study, including 102 patients treated with SOXIRI and 96 patients treated with mFOLFIRINOX. There was no significant difference in OS [12.1 months versus 11.2 months, hazard ratio (HR) = 1.04, p = 0.81] or PFS (6.5 months versus 6.8 months, HR = 0.99, p = 0.96) between patients treated with SOXIRI and mFOLFIRINOX. In the subgroup analysis, patients with slightly elevated baseline total bilirubin (TBIL) or underweight patients before chemotherapy were more likely to have a longer OS or PFS from SOXIRI than from mFOLFIRINOX. In addition, the carbohydrate antigen (CA)19-9 decline was a good predictor for the efficacy and prognosis of both chemotherapy regimens. All grade adverse events were parallel in all kinds of toxicities except that anaemia was more common in the SOXIRI group than in the mFOLFIRINOX group (41.4% versus 24%, p = 0.03). The occurrence of any grade 3 to 4 toxicity was similar in the two groups. Conclusions: For locally advanced or metastatic pancreatic cancer patients, the SOXIRI regimen had similar efficacy and controllable safety compared with the mFOLFIRINOX regimen.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancy with poor prognosis. To improve patient outcomes, it is necessary to gain a better understanding of the oncogenesis and progression of this disease. Metabolic reprogramming, particularly the regulation of lactate metabolism, is known to have a significant impact on tumor microenvironment and could provide valuable insights for the management of PDAC patients. In this study, we aimed to investigate the prognostic potential of lactate metabolism-related genes (LMRGs).Methods: Transcriptomic data of patients with PDAC along with the clinical outcomes were retrieved from The Cancer Genome Atlas database, and the expression data in normal pancreas from Genotype-Tissue Expression dataset were adopted as the normal control. By using Cox and LASSO regression models, we identified key genes that are differentially expressed in cancerous tissues and related to prognosis. To determine the prognostic value of LMRGs in PDAC, we evaluated their clinical significance and model performance using both the area under the receiver operator characteristic curve (AUC) and calibration curves. In addition, we evaluated the drug sensitivity prediction and immune infiltration by using oncoPredict algorithm, single sample gene set enrichment analysis and Tumor Immune Estimation Resource.Results: A total of 123 LMRGs were identified through differential gene screening analysis, among which 7 LMRGs were identified to comprise a LMRGs signature that independently predict overall survival of these PDAC patient. The AUC values for the LMRGs signature were 0.786, 0.820, 0.837, and 0.816 for predicting 1-, 2-, 3- and 5-year overall survival respectively. Furthermore, this prognostic signature was used to stratify patients into high-risk and low-risk groups, with the former having worse clinical outcomes. This observation was further validated through analysis of the International Cancer Genome Consortium database. In addition, lower sensitivity to gemcitabine and infiltration of immune effector cells were observed in the cancer tissue of patients in the high-risk group.Conclusion: In conclusion, our data suggests that a genomic signature comprised of these LMRGs may be a novel predictor of overall clinical outcomes and present therapeutic potential for PDAC patients.

In general, a multiple robotic manipulator system (MRMS) with uncertainties can be considered a composition system with a robotic manipulator subsystem (RMS) and a communication strength subsystem (CSS), and both subsystems are coupled to each other. In this paper, a new position tracking control scheme is proposed for the MRMS while considering the communication strength dynamics between robotic manipulators. The control scheme designed in this paper consists of two parts: the first part is to design the control protocol in the RMS, and the second part is to design the coupling relationship in the CSS. Through these two parts, we can achieve the position tracking of an MRMS. Firstly, the dynamical mathematical model of the RMS and CSS in the MRMS is constructed, and the corresponding assumptions are given. Then, the corresponding stability analysis is proposed, which provides the basis for a theoretical understanding of the underlying problem. Finally, an illustrative example is presented to verify the effectiveness of the proposed control scheme.

The mean square synchronization problem of the complex dynamical network (CDN) with the stochastic link dynamics is investigated. In contrast to previous literature, the CDN considered in this paper can be viewed as consisting of two subsystems coupled to each other. One subsystem consists of all nodes, referred to as the nodes subsystem, and the other consists of all links, referred to as the network topology subsystem, where the weighted values can quantitatively reflect changes in the network’s topology. Based on the above understanding of CDN, two vector stochastic differential equations with Brownian motion are used to model the dynamic behaviors of nodes and links, respectively. The control strategy incorporates not only the controller in the nodes but also the coupling term in the links, through which the CDN is synchronized in the mean-square sense. Meanwhile, the dynamic stochastic signal is proposed in this paper, which is regarded as the auxiliary reference tracking target of links, such that the links can track the reference target asymptotically when synchronization occurs in nodes. This implies that the eventual topological structure of CDN is stochastic. Finally, a comparison simulation example confirms the superiority of the control strategy in this paper.

Abstract Background Ampullary adenocarcinoma (AAC) arises from the ampulla of Vater where the pancreatic duct and bile duct join and empty into the duodenum. It can be classified into intestinal and pancreatobiliary types based on histopathology or immunohistochemistry. However, there are no biomarkers for further classification of pancreatobiliary-type AAC which has important implications for its treatment. We aimed to identify the tumor origin of pancreatobiliary-type AAC by systematically analyzing whole-slide images (WSIs), survival data, and genome sequencing data collected from multiple centers. Methods This study involved three experiments. First, we extracted quantitative and highly interpretable features from the tumor region in WSIs and constructed a histologic classifier to differentiate between pancreatic adenocarcinoma (PAC) and cholangiocarcinoma. The histologic classifier was then applied to patients with pancreatobiliary-type AAC to infer the tumor origin. Secondly, we compared the overall survival of patients with pancreatobiliary-type AAC stratified by the adjuvant chemotherapy regimens designed for PAC or cholangiocarcinoma. Finally, we compared the mutation landscape of pancreatobiliary-type AAC with those of PAC and cholangiocarcinoma. Results The histologic classifier accurately classified PAC and cholangiocarcinoma in both the internal and external validation sets (AUC > 0.99). All pancreatobiliary-type AACs (n = 45) were classified as PAC. The patients with pancreatobiliary-type AAC receiving regimens designed for PAC showed more favorable overall survival than those receiving regimens designed for cholangiocarcinoma in a multivariable Cox regression (hazard ratio = 7.24, 95% confidence interval: 1.28–40.78, P = 0.025). The results of mutation analysis showed that the mutation landscape of AAC was very similar to that of PAC but distinct from that of cholangiocarcinoma. Conclusions This multi-center study provides compelling evidence that pancreatobiliary-type AAC resembles PAC instead of cholangiocarcinoma in different aspects, which can guide the treatment selection and clinical trials planning for pancreatobiliary-type AAC.

Objectives: This study aimed to compare the awareness of Chinese dietary guidelines (CDGs, 2016) between rural and urban areas in Southwest China and identify the factors that affect CDGs (2016) awareness.Methods: This cross-sectional survey included 8,320 individuals aged 18–75 years from Chongqing, Sichuan, Guizhou, and Yunnan, China. Convenience sampling method was adopted to select the survey subjects and face-to-face surveys in each region were conducted to collect data. Descriptive statistics and generalized linear model were used to evaluate differences in awareness of CDGs among urban and rural residents and its influencing factors.Results: Overall CDGs awareness was low in urban and rural areas, although the awareness rate was higher in the former than in the latter (29.1% vs. 19.9%, respectively). Region, education level, Body Mass Index (BMI), gender, income, and age are the influencing factors of CDGs awareness. Urban participants were likely to acquire relevant knowledge from social media, books/magazines, family/friends, and experts. However, rural participants were likely to acquire relevant knowledge from food sales staff (p < 0.05).Conclusion: Rural residents are less aware of CDGs than their urban counterparts in Southwest China. Future dietary education should adopt different strategies for different populations, with considerable focus on rural residents.

Abstract. Objective:. Irreversible electroporation (IRE) is emerging as a new therapy for locally advanced pancreatic cancer (LAPC). We aimed to conduct survival and safety analyses in LAPC patients after treatment with IRE combined with chemotherapy. Methods:. A total of 64 patients with LAPC who had received IRE and chemotherapy were retrospectively collected from August 2015 to March 2019 at Sun Yat-sen University Cancer Center. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier method and compared by the log-rank test. A multivariate Cox regression model was used to determine the prognostic factors of survival. The perioperative complications of IRE were also evaluated. The study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center (approval No. C2021-003). Results:. The median survival of all included patients were 24.63 (95% confidence interval: 21.78–27.49) for overall survival and 13.00 (95% confidence interval: 8.81–17.19) months for progression-free survival, with 96.8%, 51.9%, 18.3%; and 52.3%, 21.5%, 7.9% as the 1-, 2- and 3-year OS and PFS rates, respectively. Tumor size [OS, hazard ratio (HR)=1.768, P = 0.048; PFS, HR = 0.304, P = 0.010], neoadjuvant chemotherapy (OS, HR = 0.338, P = 0.030; PFS, HR = 0.358, P = 0.034), carbohydrate antigen 19-9 variation after IRE (OS, HR = 19.320, P = 0.003; PFS, HR = 14.591, P = 0.021) and tumor response after neoadjuvant chemotherapy (OS, HR = 8.779, P = 0.033; PFS, HR = 5.562, P = 0.008) were predictive factors of survival in patients with LAPC after IRE. Complications were observed in 20.3% of patients. Grade B pancreatic fistula was the most common complication. The complication rates of the late treatment group (6.1%) were significantly lower than those of the first 15 patients after IRE treatment (66.7%). The median length of hospital stay of late treatment group was 8.6 days, which was also shorter than that of the early treatment group (10.0 days). Conclusions:. IRE combined with chemotherapy could improve survival of LAPC patients with acceptable complication rates. Therefore, it may be a suitable method for LAPC but should be validated in prospective randomized trials.

ObjectivePuerperae’ dietary patterns (DPs) during the puerperium may be influenced by the mode of delivery, but population studies on this topic are scarce. This study aims to explore the relationship between DPs and different modes of delivery among puerperae.MethodsA cross-sectional study was conducted on 3,345 parturients in Lanzhou, China. The postpartum food intake was measured by a food frequency questionnaire (FFQ). Factor analysis was used to determine the DPs. Multiple linear regression was employed to examine the association between the mode of delivery and DP.ResultsIn this study, two DPs, i.e., traditional and modern DPs, were identified. Traditional DP was characterized by high energy-adjusted intake of tubers, coarse cereals, rice, whole grains, fishery products, and eggs. Modern DP included a high intake of coffee, non-sugary drinks, wine, tea, and fishery products. Compared with participants with vaginal delivery (reference category), cesarean section had an inverse association with modern DP (β: −0.11, 95% CI: −0.36, −0.09). A significant interaction was found between education level, monthly household income, alcohol drinking, and modes of delivery. The inverse association between cesarean section and modern DP or the intake of coffee was significant among puerperae with higher or lower monthly household income. However, the inverse association between cesarean section and traditional DP was only found among puerperae with higher monthly household income. Moreover, among the participants with high education, cesarean section was positively associated with intake of vegetables.ConclusionCesarean puerperae with higher levels of education and those with lower and higher monthly household income had less unhealthy foods intake than those who had vaginal delivery. They need to be accounted for in educational programs and interventions focused on healthy diet recommendations in puerperium.

As one of the largest carbon emitters worldwide, China has promised to peak its carbon emissions by 2030 and achieve national carbon neutrality by 2060. In order to achieve the carbon reduction goal, the low-carbon pilot (LCP) program has been implemented in China since 2010. It is particularly significant to recognise the effectiveness of the LCP program and learn valuable experience from these LCP provinces. Therefore, this study develops a systemic experience learning approach by analysing the evolution of carbon footprint (CF) and net carbon footprint (NCF) and investigating the impact factors in representative LCP provinces. The results demonstrated that the CF of nine LCP provinces showed an upward trend from 2006 to 2015, and the NCF of eight provinces was larger than 0 except for Yunnan province, with a negative NCF. The implementation of the LCP program is effective since the average annual growth rates of CF and NCF in pilot provinces were significantly lower after they were selected as LCP provinces. Based on the identified four impact factors of CF (i.e., population, GDP per capita, industrial structure, and technology), the low-carbon experience with regional characteristics can be summarised and shared with other regions throughout the country. Accordingly, targeted guidelines are put forward from the perspectives of policy, industry structure, population, and carbon uptake. This study not only develops a new experience learning approach incorporating the regional characteristics but also provides effective pathways towards carbon neutrality.

A large number of carbon fiber reinforced polymers have been applied to aircraft and automobiles, and many nondestructive testing methods have been studied to detect their defects. Eddy current magneto-optical imaging nondestructive testing technology has been widely used in the detection of metal materials such as aircraft skin, but it usually requires a large excitation current and, at present, can only detect metal materials with high conductivity. In order to take full advantage of the innate benefits and efficiency of eddy current magneto-optic imaging and enable it to detect defects in carbon fiber reinforced polymers with weak conductivity, it is necessary to improve the magnetic field response of the eddy current magneto-optic imaging system and explore suitable excitation and detection methods. The scanning eddy current magneto-optical imaging nondestructive testing device built in this study has improved the magnetic field response of the system, and the eddy current magneto-optical phase imaging testing method has been proposed to detect the crack defects of carbon fiber reinforced polymers. The effectiveness of the method has been verified by simulation and experiment.

Abstract. Acute pancreatitis (AP) is a common acute abdominal condition of the digestive system. In recent years, treatment concepts, methods, and strategies for the diagnosis of AP have advanced, and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients. On the basis of previous guidelines and expert consensus, this guideline adopts an evidence-based, problem-based expression; synthesizes important clinical research data at home and abroad in the most recent 5 years; and forms 29 recommendations through multidisciplinary expert discussion, including diagnosis, treatment, and follow-up. It is expected to provide evidence support for the treatment of AP in the clinical setting in China.

Abstract. The incidence of pancreatic cancer has been rising worldwide, and its clinical diagnosis and treatment remain a great challenge. To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years, Chinese Pancreatic Association, the Chinese Society of Surgery, Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China (2014) after reviewing evidence-based and problem-oriented literature published during 2015–2021, mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer, conversion strategies for locally advanced pancreatic cancer, treatment of pancreatic cancer with oligo metastasis, adjuvant and neoadjuvant therapy, standardized processing of surgical specimens and evaluation of surgical margin status, systemic treatment for unresectable pancreatic cancer, genetic testing, as well as postoperative follow up of patients with pancreatic cancer. Forty recommendation items were finally proposed based on the above issues, and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation, Assessment, Development, and Evaluation system. This guideline aims to standardize the clinical diagnosis and therapy, especially surgical treatment of pancreatic cancer in China, and further improve the prognosis of patients with pancreatic cancer.

Background: Desmoplasia or rich fibrotic stroma is a typical property of pancreatic cancer (PC), with a significant impact on tumor progression, metastasis, and chemotherapy response. Unusual inflammatory responses are considered to induce fibrosis of tissue, but the expression and clinical significance of inflammatory response-related genes in PC have not been clearly elucidated.Methods: Prognosis-related differentially expressed genes (DEGs) between tumor and normal tissues were identified by comparing the transcriptome data of PC samples based on The Cancer Genome Atlas (TCGA) portal and the Genotype Tissue Expression (GTEx) databases. Samples from the ArrayExpress database were used as an external validation cohort.Results: A total of 27 inflammatory response-related DEGs in PC were identified. Least absolute shrinkage and selection operator (LASSO) analysis revealed three core genes that served as an inflammatory response gene signature (IRGS), and a risk score was calculated. The diagnostic accuracy of the IRGS was validated in the training (n = 176) and validation (n = 288) cohorts, which reliably predicted the overall survival (OS) and disease-free survival (DFS) of patients with PC. Furthermore, multivariate analysis identified the risk score as an independent risk factor for OS and DFS. The comprehensive results suggested that a high IRGS score was correlated with decreased CD8+ T-cell infiltration, increased M2 macrophage infiltration, increased occurrence of stroma-activated molecular subtype and hypoxia, enriched myofibroblast-related signaling pathways, and greater benefit from gemcitabine.Conclusion: The IRGS was able to promisingly distinguish the prognosis, the tumor microenvironment characteristics, and the benefit from chemotherapy for PC.

ObjectiveThe burden of overweight and obesity in adolescents is increasing rapidly. This study aimed to assess the association between nutrition literacy and overweight/obesity among adolescents in China.MethodsThis cross–sectional online study involving adolescents aged 10–18 years was conducted in September 2020 in 239 schools in Chongqing China. Overweight and obese adolescents were determined based on the International Obesity Task Force's recommended age–sex specific body mass index cutoff points. Nutrition literacy was measured using the “Nutrition literacy scale for middle school students in Chongqing (CM–NLS).” The CM–NLS included three subdomains (functional nutritional literacy, interactive nutrition literacy, and critical nutrition literacy). Multinomial logistic regression model was used to examine the association.ResultsA total of 18,176 adolescents (49.8% girls) were included. The prevalence of overweight and obesity was 9.6% and 17.0%, respectively. Compared with those having a low nutrition literacy score (below median), those with a high score were less likely to be overweight and obese. The odds ratio (95% CI) for overweight was 0.87 (0.79–0.97) (nutrition literacy) and 0.81 (0.73–0.90) (functional nutritional literacy). The corresponding figures for obesity were 0.84 (0.77–0.91) and 0.73 (0.67–0.80), respectively. Significant interaction existed between grade and nutrition literacy. The inverse association between nutrition literacy and overweight/obesity was significant among those in senior school but not among those in junior high school.ConclusionNutrition literacy was inversely associated with overweight/obesity among adolescents, especially those attending senior high schools.

Lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC) is shown to be related with poor prognosis. To construct an immune-related gene prognostic risk model for PDAC and clarify the molecular and immune characteristics and the benefit of immune checkpoint inhibitor (ICI) therapy in prognostic risk model-defined subgroups of PDAC, we analyze the association between the density of immune cell infiltration and lymph node metastatic status and further study the potential role of immune cells, immune cell–related genes, and immunotherapy outcomes in PDAC patients using bioinformatics models and machine learning methods. Based on The Cancer Genome Atlas (TCGA), PACA-AU and PACA-CA data sets, 62 immune-related hub genes were identified by weighted gene co-expression network analysis (WGCNA). Four genes were selected to construct a molecular subtype identification based on the type 1 T helper cell–related hub genes by using the Cox regression method. We found that lower type 1 T helper cell abundance was correlated with prolonged survival in PDAC patients. Further, prognostic risk score model constructed with the type 1 T helper cell-related signature showed high accuracy in predicting overall survival and response to immunotherapy. This study might improve the understanding of the role of type 1 T helper cells in PDAC patients and aid in the development of immunotherapy and personalized treatments for these patients.

Antibiotics were the main fishery drugs for treating Aeromonas hydrophila (A. hydrophila) infection, which would generate selective pressure and result in the appearance of antibiotic-resistant bacteria. The bacterial quorum sensing (QS) system provides a new alternative strategy against A. hydrophila infection. QS inhibitors can reduce bacterial virulence behaviors by disrupting QS, which has no effect on bacterial growth. Therefore, we studied the effect of cinnamaldehyde from a natural plant extract on the QS of A. hydrophila aiming to reduce its pathogenicity. The efficacy of cinnamaldehyde against A. hydrophila was evaluated from various aspects, including the effects on aerolysin, lipase, protease, swarming motility, biofilm formation, acyl-homoserine lactones (AHLs), and QS-related genes. Moreover, the therapeutic effect of cinnamaldehyde in vitro and in vivo was studied. The results showed that cinnamaldehyde could decrease the virulence phenotypes of A. hydrophila regulated by QS. Moreover, the transcriptions of related genes (aerA, ahyR, and ahyI) were downregulated following the addition of cinnamaldehyde. The in vitro and in vivo therapeutic assays show that cinnamaldehyde could reduce the aerolysin-mediated A549 cell injury and increase the survival rate of crucian carp infected with A. hydrophila. These results indicate that cinnamaldehyde would be a candidate QS inhibitor against A. hydrophila infection.

Rice false smut (RFS), which is caused by Ustilaginoidea virens (U. virens), has become one of the most devastating diseases in rice-growing regions worldwide. The disease results in a significant yield loss and poses health threats to humans and animals due to producing mycotoxins. In this review, we update the understanding of the symptoms and resistance genes of RFS, as well as the genomics and effectors in U. virens. We also highlight the genetic mechanism of the immune response to RFS. Finally, we analyse and explore the identification method for RFS, breeding for resistance against the disease, and interactions between the effector proteins and resistance (R) proteins, which would be involved in the development of rice disease resistance materials for breeding programmes.

Inconsistent findings have been discovered in studies examining the link between dietary selenium (Se) and sleep. Data were obtained from 17,176 people aged 20 and over who participated in the China Health and Nutrition Survey (CHNS) from 2004 to 2011. Face-to-face interviews were used to measure sleep duration in 2004, 2006, 2009, and 2011. To track dietary Se consumption, a 3-day, 24-h recall was undertaken. In the analysis, multilevel mixed-effects logistic regression was employed. The odds ratios (95% confidence intervals) of optimal sleep duration (7–9 h/day) in the regression of Model 4 were 1.00, 1.01 (0.89–1.15) and 1.19 (1.02–1.38) for the three tertiles of selenium consumption, respectively. Only overweight patients displayed a substantial positive connection between Se intake and the optimal sleep duration in the subgroup analysis. In summary, Se intake was significantly associated with optimal sleep duration.

This paper formulates and solves a new problem of the double model following adaptive control (MFAC) of nodes and links in a complex dynamical network (CDN). This is different from most existing studies on CDN and MFAC. Inspired by the concept of composite systems, the CDN with dynamic links is regarded as an interconnected system composed of an interconnected node group (NG) and link group (LG). Guided by the above-mentioned new idea of viewing a CDN from the perspective of composite systems, by means of Lyapunov theory and proposed related mathematical preliminaries, a new adaptive control scheme is proposed for NG. In addition, to remove the restriction that the states of links in a CDN are unavailable due to physical constraints, technical restraints, and expensive measurement costs, we synthesize the coupling term in LG with the proposed adaptive control scheme for NG, such that the problem of double MFAC of nodes and links in CDN is solved. Finally, a simulation example is presented to verify the theoretical results.

The Magnetic Flux Leakage (MFL) visualization technique is widely used in the surface defect inspection of ferromagnetic materials. However, the information of the images detected through the MFL method is incomplete when the defect (especially for the cracks) is complex, and some information would be lost when magnetized unidirectionally. Then, the multidirectional magnetization method is proposed to fuse the images detected under different magnetization orientations. It causes a critical problem: the existing image registration methods cannot be applied to align the images because the images are different when detected under different magnetization orientations. This study presents a novel image registration method for MFL visualization to solve this problem. In order to evaluate the registration, and to fuse the information detected in different directions, the mutual information between the reference image and the MFL image calculated by the forward model is designed as a measure. Furthermore, Particle Swarm Optimization (PSO) is used to optimize the registration process. The comparative experimental results demonstrate that this method has a higher registration accuracy for the MFL images of complex cracks than the existing methods.

Abstract Background Growing evidence indicates that the systemic inflammatory response plays an important role in cancer development and progression. Several inflammatory markers have been reported to be associated with clinical outcomes in patients with various types of cancer. This study was designed to evaluate the prognostic value of inflammatory indexes in patients with ampullary cancer (AC) who underwent pancreaticoduodenectomy (PD). Methods We retrospectively reviewed the data of 358 patients with AC who underwent PD between 2009 and 2018. R software was used to compare the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) of the inflammation-based indexes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI) and prognostic index (PI), in terms of their predictive value for survival. The survival differences of these indexes were compared by the Kaplan-Meier method and univariate and multivariate analyses were performed to determine the prognostic factors of disease-free survival (DFS) and overall survival (OS). Results The estimated 1-, 2-, and 3-year OS and DFS rates were 83.9, 65.8, and 55.2% and 58.0, 42.8, and 37.8%, respectively, for the entire cohort. The survival differences were significant in terms of OS and DFS when patients were stratified by these inflammation-based indexes. The comparisons of the AUROCs of these inflammation-based indexes illustrated that NLR and PI displayed the highest prognostic value, compared to the other indexes. When NLR and PI were combined, NLR-PI showed even higher AUROC values and was identified as a significant prognostic factor for OS and DFS. Conclusion Specific inflammatory indexes, such as NLR, PLR and dNLR, were found to be able to predict the OS or DFS of patients. As a novel inflammatory index, the level of NLR-PI, which can be regarded as a more useful prognostic index, exhibited strong predictive power for predicting the prognosis of patients with AC after the PD procedure.

BackgroundAnti-programmed cell death protein 1 and its ligand (anti-PD1/PDL1) have been proposed as a promising therapeutic option for advanced biliary tract cancer (aBTC). Given the scarce quantitative analyses of anti-PD1/PDL1 in aBTC, we thus did a meta-analysis to assess the benefits and risks of this emerging treatment strategy in patients with aBTC.MethodsPubMed, Embase, the Cochrane Library, Web of Science, and meeting resources were searched for relevant studies. The main endpoints were median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), any-grade adverse events (AEs), and grade 3–4 AEs.ResultsTwenty-eight studies with 1,338 participants were included. The best curative effect was found in the anti-PD1/PDL1 combined with anti-CTLA4 and chemotherapy group (mPFS: 12.4 months; mOS: 16.0 months; ORR: 45.1%; DCR: 95.0%), followed by the anti-PD1/PDL1 plus chemotherapy group (mPFS: 8.2 months; mOS: 14.8 months; ORR: 36.3%; DCR: 84.6%), the anti-PD1/PDL1 plus antiangiogenesis group (mPFS: 4.9 months; mOS: 10.2 months; ORR: 17.5%; DCR: 68.7%), the anti-PD1/PDL1 plus anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA4) group (mPFS: 2.9 months; mOS: 8.3 months; ORR: 9.9%; DCR: 36.8%), and the anti-PD1/PDL1 monotherapy group (mPFS: 2.5 months; mOS: 7.6 months; ORR: 6.8%; DCR: 34.7%). Compared with anti-PD1-containing regimens, anti-PDL1-containing regimens achieved preferable mPFS (11.1 vs. 3.8 months), mOS (12.2 vs. 9.8 months), and ORR (23.7% vs. 17.4%), despite a similar DCR (61.1% vs. 61.3%). The mPFS, mOS, ORR, and DCR were 10.6 months, 15.8 months, 42.3%, and 88.6% of first-line anti-PD1/PDL1 and 3.0 months, 9.1 months, 11.6%, and 51.1% of second-line therapy or beyond, respectively. There were 80.6% and 34.0% of the patients suffering any-grade AEs and grade 3–4 AEs. Anti-PD1/PDL1 monotherapy might be considered as a safer alternative than combination regimens. Meanwhile, obvious toxicities in the first-line setting could not be neglected.ConclusionsAnti-PD1/PDL1 showed encouraging efficacy and acceptable safety profile in aBTC and, thus, could be an alternative treatment.

Nutrition literacy plays an important role in children's dietary habits and nutrition. This study aimed to analyse the status of nutrition literacy and its influencing factors amongst middle school students in Chongqing, China. “Nutrition literacy scale for middle school students in Chongqing” was used in 29 districts of Chongqing in September 2020. The scores of nutrition literacy and its' three sub-domains (functional, interactive and critical nutrition literacy) were divided into low and high groups based on their median scores. Binary logistic regression was used to measure the influencing factors of nutrition literacy. A total of 18,660 middle school students were included in this study. The median of nutrition literacy of middle school students was 61.68 (IQR = 14.37). Interactive nutrition literacy had the highest score (median = 70.00, IQR = 20.00), followed by functional nutrition literacy (median = 68.69, IQR = 14.14) and critical nutrition literacy (median = 45.83, IQR = 25.00). Students who were the minority (OR = 0.71, 95% CI = 0.637–0.785), in senior high school (OR = 0.51, 95% CI = 0.477–0.548), in rural areas (OR = 0.85, 95% CI = 0.790–0.911), receiving school meal support from the government (OR = 0.63, 95% CI = 0.591–0.664), with other caregivers' parenting (OR = 0.86, 95% CI = 0.805–0.914), with parents having a low level of education and with an abnormal BMI [thin (OR = 0.91, 95% CI = 0.837–0.990), overweight (OR = 0.87, 95% CI = 0.785–0.968), and obese (OR = 0.83, 95% CI = 0.767–0.902)] presented less probability of being a high level of nutrition literacy. Our results could assist public health authorities in developing strategies of nutrition literacy promotion for references and theoretical foundations.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Objective Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor. This study aims to examine the clinicopathological features and surgical treatments of SPN and compare the clinical behavior and prognosis between men and women with SPN. Methods We collected the population data of patients with SPN diagnosed between 2004 and 2017 from the SEER database. The Kaplan‐Meier method was used to analyze overall survival (OS) and disease‐specific survival (DSS), and log‐rank tests were used to evaluate the differences between subgroups. Univariate and multivariate Cox regression analyses were performed to screen out prognostic risk factors of SPN. Results A total of 378 patients with SPN were included, with 246 (65.1%) female patients. 1‐, 3‐, and 5‐year overall survival rates were 98.9%, 95.7%, and 93.7%, respectively. Survival analysis revealed that regardless of stage, patients with SPN who underwent surgical interventions still had a significantly better prognosis than those without surgical interventions (P

Abstract Background Locally advanced pancreatic cancer (LAPC) remains a challenge for current treatments. Local destructive therapies, such as irreversible electroporation (IRE) and radiofrequency ablation (RFA), were used more and more frequently in the treatment of LAPC. Objective This study aimed to compare the efficacy of IRE with RFA in patients with LAPC. Methods From August 2015 to August 2017, 58 LAPC patients after IRE or RFA therapy, which was performed through open approach, were retrospectively reviewed. The survival outcomes after IRE (36 patients) and RFA (18 patients) were compared after propensity score matching (PSM) analysis. Results Before PSM analysis, IRE after the induction chemotherapy resulted in significant higher overall survival (OS) rates and progression‐free survival (PFS) rates to RFA (2‐year OS, 53.5% vs 30.8%, P = .013; 2‐year PFS, 28.4% vs 12.1%, P = .043). After PSM analysis, compared with RFA, the survival benefit of IRE was even more obvious, (2‐year OS, 53.5% vs 27.0%, P = .010; 2‐year PFS, 28.4% vs 6.4%, P = .018). For patients with tumor larger than 4 cm, IRE resulted in comparable OS and PFS between RFA and IRE while IRE also achieved better long‐term OS to RFA for those with tumor smaller than 4 cm. Multivariate analysis illustrated that IRE was a favorable prognostic factor in terms of OS and PFS in patients with LAPC. Conclusions IRE after induction chemotherapy is superior to RFA after induction chemotherapy for treating LAPC patients while these two therapies have comparable efficacy for tumors which were larger than 4 cm.

RGLG1 is an E3 ubiquitin ligase in Arabidopsis thaliana that participates in ABA signaling and regulates apical dominance. Here, we present crystal structures of RGLG1 VWA domain, revealing two novel calcium ions binding sites (NCBS1 and NCBS2). Furthermore, the structures with guided mutagenesis in NCBS1 prove that Ca2+ ions play important roles in controlling conformational change of VWA, which is stabilized in open state with Ca2+ bound and converted to closed state after Ca2+ removal. This allosteric regulation mechanism is distinct from the ever reported one involving the C-terminal helix in integrin α and β I domains. The mutation of a key residue in NCBS2 do not abolish its Ca2+-binding potential, with no conformational change. MD simulations reveals that open state of RGLG1 VWA has higher ligand affinity than its closed state, consisting with integrin. Structural comparison of ion-free-MIDAS with Mg2+-MIDAS reveals that Mg2+ binding to MIDAS does not induce conformational change. With acquisition of first structure of plant VWA domain in both open state and closed state, we carefully analyze the conformational change and propose a totally new paradigm for its transition of open-closed states, which will be of great value for guiding future researches on VWA proteins and their important biological significance.

As a natural phenomenon, people with disabilities were not stigmatized from the very beginning. In antiquity, some parts of their body being “different from those of normal persons,” they were considered to have a special ability to communicate with heaven, earth, and the Gods. As a result, people with disabilities were able to hold the position of “wizard,” which had a high status and important influence. However, with the division of labor in the human society, people with disabilities gradually lost the prerogative in labor production due to the limitation of their ability to work, which affected their social status and led to the social discrimination and “stigmatization” toward them gradually. Before this transformation happened, people's envision on people with disabilities, including a variety of images, was indicative of the social consciousness at that time.

Background: Hepatitis B virus (HBV) infection has been well established as a high-risk factor for the carcinogenesis of hepatocellular carcinoma (HCC). Cellular microRNA (miRNA) is involved in tumorigenesis by accelerating the malignant phenotype in HCC. However, whether HBV can encode miRNAs that contribute to HCC is not entirely clear. Methods: In this study, an miRNA encoded by HBV (HBV-miR-2) was identified by Solexa sequencing in HBV-positive HCC specimens and further verified in serum samples from HCC patients with HBV infection and in HBV-positive HCC cell lines. To evaluate the roles of HBV-miR-2 in liver cancer cells, we determined cell viability and migration/invasion ability by gain-of-function experiment in HBV(−) liver cancer cells (HepG2 and Huh7) and loss-of-function experiments in Huh7 cells stably expressing HBV-miR-2 (Huh7/HBV-miR-2 cells) and HepG2.2.15 cells. Furthermore, to elucidate the mechanism by which HBV-miR-2 work on cell malignancy, we identified and studied the effect of two target genes (TRIM35 and RAN) of HBV-miR-2 in liver cancer cells. Findings: We revealed that HBV-miR-2 promoted HCC cell growth ability by suppressing apoptosis and promoting migration and invasion by enhancing the epithelial-mesenchymal transition (EMT), functioning as an oncogene in the development of HBV-related HCC. Furthermore, we demonstrated that HBV-miR-2 suppresses the expression of TRIM35 but enhances RAN expression by targeting their 3′-untranslated regions (3’UTR) and that the ectopic expression of TRIM35 or knockdown of RAN counteracted the malignant phenotypes induced by HBV-miR-2. Interpretation: Our findings indicate that an HBV-encoded miRNA, HBV-miR-2, promotes oncogenic activity by downregulating TRIM35 expression and upregulating RAN expression in liver cancer cells, likely providing insight into tumorigenesis in HBV-related liver cancer. Fund: This work was supported in part by the National Natural Science Foundation of China (No: 81830094; 91629302; 31270818) and the Natural Science Foundation of Tianjin (No: 12JCZDJC25100). Keywords: HBV, miRNA, Liver cancer, Proliferation, Invasion

Abstract Background To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-018-0681-y.

Abstract Background The prognostic benefits and safety of extended lymphadenectomy for hilar cholangiocarcinoma remain uncertain. The available evidence is still insufficient concerning its retrospective aspect. The aim of this study is to explore the clinical effect and safety of extended lymphadenectomy compared to regional lymphadenectomy in patients with hilar cholangiocarcinoma. Methods The Relay-HC trial is a prospective, multicenter, and randomized controlled trial. Seven hundred and thirty-four eligible patients with resectable perihilar cholangiocarcinoma across 15 tertiary hospitals in China will be randomly assigned (1:1) to receive either regional lymphadenectomy or extended lymphadenectomy. The primary objective is to determine the overall survival after the two approaches. Secondary objectives of the study include the evaluation of perioperative mortality, postoperative complication, and disease-free survival. This study has been approved by the ethics committee of each participating hospital. Discussion The Relay-HC trial is designed to investigate the prognostic benefits and safety of expanded lymphadenectomy for hilar cholangiocarcinoma. Currently, it has never been investigated in a prospective randomized controlled clinical trial. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR1800015688. Registered on 15 April 2018.

Cigarette smoke induces microRNA dysregulation in cancers. Here, the authors show that cigarette smoke promotes the maturation of oncogenic primary miR-25 due to METTL3 hypomethylation, and mature miR-25 suppresses PH domain leucine-rich repeat protein phosphatase 2, resulting in oncogenic AKT activation in pancreatic cancer.

Abstract Background Locally advanced pancreatic cancer (LAPC) represents more than one third of pancreatic cancers and owns poor survival after the standard chemotherapy. Irreversible electroporation (IRE) is a novel method and has been recently used in LAPC. The aim of this study was to compare the efficacy of IRE and radiotherapy after induction chemotherapy for patients with LAPC. Methods From August 2015 to August 2017, a total of 76 patients with biopsy proven LAPC and who had received IRE or radiotherapy after chemotherapy were included. Thirty-two pairs of patients were selected through propensity score matching (PSM) analysis and the efficacy of two treatments was compared. Results Before PSM analysis, after induction chemotherapy, patients with LAPC benefited more in terms of overall survival (OS) and progression free survival (PFS) from IRE, compared with radiotherapy (2-year OS rates, 53.5% vs 26.9%, p = 0.039; 2-year PFS rates, 28.4% vs 13.3%, p = 0.045). After PSM analysis, the survival benefits of OS and PFS of patients after induction chemotherapy followed by IRE were more obvious than those of patients treated with radiotherapy (2-year OS rates, 53.5% vs 20.7%, p = 0.011; 2-year PFS rates, 28.4% vs 5.6%, p = 0.004). Multivariate Cox regression analysis indicated that IRE after induction chemotherapy was identified as a significant favourable factor for both OS and PFS in both the whole and matched cohort. Conclusions Induction chemotherapy followed by IRE is superior to induction chemotherapy followed by radiotherapy for treating LAPC. A randomized clinical trial comparing the efficacy of IRE and radiotherapy after the induction chemotherapy is therefore considerable.

Background: The association between selenium and chronic kidney disease (CKD) remains controversial. Population studies with large samples facilitate the reliability of conclusions. Objective: In this study, we aimed to describe the prevalence of a CKD association with selenium intake in middle-aged and older Chinese. Methods: Data for this study were obtained from the China Health and Nutrition Survey (CHNS). A total of 5381 participants (aged ≥ 45) with biochemical test data were included in the study. Logistic regression models were used to examine the association between diet selenium intake (quartile) and the prevalence of CKD. Results: A total of 942 (17.01%) participants had CKD. The prevalence of CKD was 23.33%, 20.32%, 14.98%, and 9.25% among participants with average selenium intakes of 21.5 ± 4.82, 33.1 ± 2.79, 43.8 ± 3.70, and 67.0 ± 13.97 µg/day, respectively. In the fully adjusted model (Model 3), across the quartiles of selenium intake, the ORs for the prevalence of CKD were 1.00, 1.09 (95% CI 0.69–1.73), 0.82 (95% CI 0.49–1.38), and 0.43 (95% CI 0.22–0.85). The protein intake had a certain diagnostic significance for the selenium intake. Conclusions: An adequate selenium intake may have a positive effect on CKD. The influence of individual weight and location on the effect of selenium on CKD needs to be further explored.

Pancreatic cancer is a highly fatal disease and an increasing common cause of cancer mortality. Mounting evidence now indicates that molecular heterogeneity in pancreatic cancer significantly impacts its clinical features. However, the dynamic nature of gene expression pattern makes it difficult to rely solely on gene expression alterations to estimate disease status. By contrast, biological networks tend to be more stable over time under different situations. In this study, we used a gene interaction network from a new point of view to explore the subtypes of pancreatic cancer based on individual-specific edge perturbations calculated by relative gene expression value. Our study shows that pancreatic cancer patients from the TCGA database could be separated into four subtypes based on gene interaction perturbations at the individual level. The new network-based subtypes of pancreatic cancer exhibited substantial heterogeneity in many aspects, including prognosis, phenotypic traits, genetic mutations, the abundance of infiltrating immune cell, and predictive therapeutic efficacy (chemosensitivity and immunotherapy efficacy). The new network-based subtypes were closely related to previous reported molecular subtypes of pancreatic cancer. This work helps us to better understand the heterogeneity and mechanisms of pancreatic cancer from a network perspective.

Locally advanced pancreatic cancer (LAPC) is a lethal disease and neoadjuvant chemotherapy and conversional resection is shown to provide the best survival for LAPC patients. Irreversible electroporation (IRE) is a new and effective method for the treatment of LAPC. This study aimed to compare the long-term survival of LAPC patients after neoadjuvant chemotherapy followed by conversional resection and IRE. A total of 140 LAPC patients were included from August 2015 to March 2020. The survival outcomes of patients after treatment with chemotherapy, chemotherapy combined with conversional resection or IRE were analyzed and compared. Patients in these three groups had similar clinical and pathological characteristics. Patients in the resection and IRE groups had similar median OS time (resection group vs. IRE group: 25.3 months vs. 26.0 months, P>0.050), which was significantly longer than that of the chemotherapy group (8.7 months, P

Irreversible electroporation (IRE) is an effective method for treating pancreatic ductal adenocarcinoma (PDAC). It remains unclear whether IRE can induce a specific immune response by stimulating macrophages. Here, the associated markers of macrophages were analyzed after exposure to tumor culture supernatant (TSN) of tumor cells treated with electroporation. Subcutaneous and orthotopic PDAC models were also used to evaluate the effect of macrophage polarization induced by IRE. Aside from its direct killing effect, IRE could induce the immunogenic cell death of tumor cells by increasing the synthesis and secretion of damage associated molecular patterns. Moreover, IRE could increase the release of HMGB1, which activates the MAPK-p38 pathway and leads to the increased expression of M1 markers in macrophages, through binding to the receptor of the advanced glycation end-product (RAGE) receptor. M1 polarization was inhibited by the inhibitors of HMGB1 release, the RAGE receptor, and the MAPK-p38 signaling pathway, but it was activated by rHMGB1 or the stimulator of MAPK-p38. In addition, the promotion of M1 macrophage polarization was enhanced by the positive-feedback release or expression of HMGB1 and RAGE through the MAPK-ERK pathway in macrophages. The promotion of M1 macrophage polarization induced by IRE provided a specific rationale for the combination of IRE and immune therapy in treating PDAC.

Synaptophysin-like 1 (SYPL1) is a neuroendocrine-related protein. The role of SYPL1 in pancreatic ductal adenocarcinoma (PDAC) and the underlying molecular mechanism remain unclarified. Here, after analyzing five datasets (GSE15471, GSE16515, GSE28735, TCGA, and PACA-AU) and 78 PDAC patients from Sun Yat-sen University Cancer Center, we demonstrated that SYPL1 was upregulated in PDAC and that a high level of SYPL1 indicated poor prognosis. Bioinformatics analysis implied that SYPL1 was related to cell proliferation and cell death. To validate these findings, gain-of-function and loss-of-function experiments were carried out, and we found that SYPL1 promoted cell proliferation in vitro and in vivo and that it protected cells from apoptosis. Mechanistic studies revealed that sustained extracellular-regulated protein kinase (ERK) activation was responsible for the cell death resulting from knockdown of SYPL1. In addition, bioinformatics analysis showed that the expression of SYPL1 positively correlated with antioxidant activity. Reactive oxygen species (ROS) were upregulated in cells with SYPL1 knockdown and vice versa. Upregulated ROS led to ERK activation and cell death. These results suggest that SYPL1 plays a vital role in PDAC and promotes cancer cell survival by suppressing ROS-induced ERK activation.

The post-progression survival (PPS) of patients with pancreatic ductal adenocarcinoma (PDAC) after radical resection is varied and influenced by the characteristics of tumor progression. We aimed to establish and validate a nomogram to predict PPS for PDAC patients after surgery. A total of 302 PDAC patients who had undergone curative resection from 2008 to 2018 were enrolled in this study and randomly divided into training and validation cohorts at a ratio of 3:1. The nomogram was established based on independent prognostic factors selected by LASSO and Cox regression and measured by the area under the receiver operating characteristic curve (AUC) and the concordance index (C-index). Significant prognostic factors included carbohydrate antigen 19-9 (CA19-9), lymph node (LN)9 metastasis, LN14 metastasis, LN16 metastasis, tumor differentiation, imaging-detected tumor size, local progression, liver-only metastasis, lung-only metastasis, and multiple metastases. The nomogram built on these factors showed powerful efficacy in PPS prediction, with C-index values of 0.751 (95% CI 0.692–0.0.810) and 0.710 (95% CI 0.645–0.755) for the training and validation cohorts, respectively. The AUC values for the 1-year and 2-year PSS rates were 0.745, 0.747, and 0.783, 0.748, respectively; these values were higher than those of the 8th tumor–node–metastasis (TNM) stage system. The exploration of risk factors and the establishment of a nomogram can provide new versions of personalized recurrence management for PDAC patients after surgery.