Floquet Engineering Hz-Level Rabi Spectra in Shallow Optical Lattice Clock.

Quantum metrology with ultrahigh precision usually requires atoms prepared in an ultrastable environment with well-defined quantum states. Thus, in optical lattice clock systems deep lattice potentials are used to trap ultracold atoms. However, decoherence, induced by Raman scattering and higher order light shifts, can significantly be reduced if atomic clocks are realized in shallow optical lattices. On the other hand, in such lattices, tunneling among different sites can cause additional dephasing and strongly broadening of the Rabi spectrum. Here, in our experiment, we periodically drive a shallow ^{87}Sr optical lattice clock. Counterintuitively, shaking the system can deform the wide broad spectral line into a sharp peak with 5.4 Hz linewidth. With careful comparison between the theory and experiment, we demonstrate that the Rabi frequency and the Bloch bands can be tuned, simultaneously and independently. Our work not only provides a different idea for quantum metrology, such as building shallow optical lattice clock in outer space, but also paves the way for quantum simulation of new phases of matter by engineering exotic spin orbit couplings.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.

BACKGROUND: SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown. METHODS: We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020. RESULTS: In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases. CONCLUSIONS: Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the "first wave" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.

Doubly Modulated Optical Lattice Clock: Interference and Topology.

The quantum system under periodical modulation is the simplest path to understand the quantum nonequilibrium system because it can be well described by the effective static Floquet Hamiltonian. Under the stroboscopic measurement, the initial phase is usually irrelevant. However, if two uncorrelated parameters are modulated, their relative phase cannot be gauged out so that the physics can be dramatically changed. Here, we simultaneously modulate the frequency of the lattice laser and the Rabi frequency in an optical lattice clock (OLC) system. Thanks to the ultrahigh precision and ultrastability of the OLC, the relative phase could be fine-tuned. As a smoking gun, we observed the interference between two Floquet channels. Finally, by experimentally detecting the eigenenergies, we demonstrate the relation between the effective Floquet Hamiltonian and the one-dimensional topological insulator with a high winding number. Our experiment not only provides a direction for detecting the phase effect but also paves a way in simulating the quantum topological phase in the OLC platform.

High mobility group AT-hook 2 promotes tumorigenicity of pancreatic cancer cells via upregulating ANLN.

HMGA2 is associated with the regulation of cellular biological processes in various human disorders and cancer progression, yet little is known about how HMGA2 controls tumorigenesis. This study uncovered the mechanism of HMGA2-mediated regulation of tumorigenicity in pancreatic cancer. We showed that HMGA2 was highly expressed in pancreatic cancer cells and correlated with poor prognosis. HMGA2 expression knockdown inhibited the tumorigenicity of pancreatic cancer cells. Conversely, overexpression of HMGA2 promoted tumorigenicity. Combination of ChIP-Seq, RNA-Seq and dual-luciferase reporter assays revealed HMGA2 could directly regulate ANLN expression. Furthermore, we found ANLN could mediate the HMGA2-induced effects on pancreatic cancer cells. The identification of the regulatory mechanism of HMGA2 and ANLN will provide insights into the progression for human pancreatic cancer.

Optimising trial designs to identify appropriate antibiotic treatment durations.

BACKGROUND: For many infectious conditions, the optimal antibiotic course length remains unclear. The estimation of course length must consider the important trade-off between maximising short- and long-term efficacy and minimising antibiotic resistance and toxicity. MAIN BODY: Evidence on optimal treatment durations should come from randomised controlled trials. However, most antibiotic randomised controlled trials compare two arbitrarily chosen durations. We argue that alternative trial designs, which allow allocation of patients to multiple different treatment durations, are needed to better identify optimal antibiotic durations. There are important considerations when deciding which design is most useful in identifying optimal treatment durations, including the ability to model the duration-response relationship (or duration-response 'curve'), the risk of allocation concealment bias, statistical efficiency, the possibility to rapidly drop arms that are clearly inferior, and the possibility of modelling the trade-off between multiple competing outcomes. CONCLUSION: Multi-arm designs modelling duration-response curves with the possibility to drop inferior arms during the trial could provide more information about the optimal duration of antibiotic therapies than traditional head-to-head comparisons of limited numbers of durations, while minimising the probability of assigning trial participants to an ineffective treatment regimen.

Whole genome analysis of cephalosporin-resistant Escherichia coli from bloodstream infections in Australia, New Zealand and Singapore: high prevalence of CMY-2 producers and ST131 carrying blaCTX-M-15 and blaCTX-M-27.

Objectives: To characterize MDR Escherichia coli from bloodstream infections (BSIs) in Australia, New Zealand and Singapore. Methods: We collected third-generation cephalosporin-resistant (3GC-R) E. coli from blood cultures in patients enrolled in a randomized controlled trial from February 2014 to August 2015. WGS was used to characterize antibiotic resistance genes, MLST, plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disc diffusion and Etest. Results: A total of 70 3GC-R E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community associated (62.9%) and in older patients (median age 71 years). The median Pitt score was 1 and ICU admission was infrequent (3.1%). ST131 possessed more acquired resistance genes than non-ST131 (P = 0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of ST131, respectively) and these were all ciprofloxacin resistant. All clade A ST131 (n = 6) were community associated. The predominant ESBL types were blaCTX-M (80.0%) and were strongly associated with ST131 (95% carried blaCTX-M), with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC genes (mainly blaCMY-2) were frequent (17.1%) but were more common in non-ST131 (P < 0.001) isolates from Singapore and Brisbane. Two strains carried both blaCMY-2 and blaCTX-M. The majority of plasmid replicon types were IncF. Conclusions: In a prospective collection of 3GC-R E. coli causing BSI, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.

Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study.

Introduction: Malnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors. Methods: Two-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations. Results: Three phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60-1.90; P = 3.95 × 10-39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60-1.80; P = 1.35 × 10-73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44-1.65; P = 4.82 × 10-37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27-3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27-0.60; P = 8.41 × 10-6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67-0.79; P = 2.27 × 10-13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84-0.96; P = 4.22 × 10-3). There was a bidirectional causality between HF and UWP (Effect estimate = -0.03; 95%CI, -0.05 to -0.01; P = 1.95 × 10-3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05). Conclusions: BMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

[Individualized surgical treatment and prognosis of intraductal papillary mucinous neoplasms of the pancreas].

OBJECTIVE: To investigate the clinical manifestation, individualized surgical treatment, and prognosis of intraductal papillary mucinous neoplasms (IPMN) of pancreas. METHODS: The clinical data of 56 IPMN cases treated between January 2007 and December 2011 was retrospectively analyzed. Among the 56 patients (38 male and 18 female, mean age (61 ± 7) years), 26 were main-duct type, 18 were branch-duct type, 12 were mixed type. Pancreatectomy was performed on 48 cases, including pancreaticoduodenectomy on 29 patients, distal pancreatectomy on 17 patients, and total pancreatectomy on 2 patients. RESULTS: The overall postoperative morbidity rate was 27.1% (13/48), there was no perioperative mortality. Pathology showed 31 cases of noninvasive IPMN, 17 cases of invasive IPMN, and 7 cases of lymph node metastasis. The rate of invasive tumors was 46.2% (12/26) in main duct type, 3/12 in mixed type, and 2/18 in branch duct type IPMN, the difference was statistically significant (χ(2) = 6.385, P = 0.041). The five-year survival rate for patients with noninvasive and invasive neoplasms was 100% and 24.6%, respectively. The prognosis of invasive cases with lymph node metastasis was significantly worse than those without lymph node metastasis (P = 0.017). A regular follow-up without surgical treatment was performed on 8 cases with asymptomatic side branch IPMN less than 3 cm in diameter, and no progression was found during the follow-up. CONCLUSIONS: IPMN has a relative good prognosis. Main duct type and mixed type IPMN have a higher malignant potential, and should receive a surgical treatment. Patients of branch duct type IPMN with a <3 cm diameter lesion and no clinical manifestations can be managed with close follow-up only.

[The diagnosis and management strategies for gastrointestinal hemorrhage following pancreaticoduodenectomy].

OBJECTIVE: To analyze the causes and clinical features of gastrointestinal hemorrhage following pancreaticoduodenectomy (PD), and to provide the management strategies for this complication. METHODS: The clinic data of 412 patients who underwent PD from January 2000 to April 2010 was retrospectively reviewed. There were 232 male and 180 female patients, average age was (60 ± 12) years. The mode of procedure was standard PD and the Child's reconstruction of digestive tract, whose anastomosic steps encluded gastroenterostomy following chlangioenterostomy and pancreaticoenterostomy, was employed. Etiology of gastrointestinal haemorrhage, diagnostic methods and treatment strategy was recorded and analyzed. RESULTS: The postoperative mobidity was 37.1% (153/412), the rate of haemorrhagic complications was 6.6% (27/412), and gastrointestinal hemorrhage was recorded in 11 patients (2.7%). The bleeding rate of pancreaticointestinal anastomosis and gastricointestinal anastomosis were 5/11 and 4/11, respectively. Among these 11 patients, early hemorrhage occurred in 6 patients, 7 patients were due to technical failure. In order to control this kind of complication, open abdominal operation alone was performed on 4 patients, endoscopic management was performed on 3 patients and succeeded in 2 patients, vascular interventional therapy was performed on 5 patients and succeeded in 2 patients, and Re-laparotomy following vascular interventional therapy was performed on 2 patients successfully. CONCLUSIONS: Gastrointestinal hemorrhage following PD always occurred in early stage and reliable hemostasis during operation is the key points for prevention. Angiography is minimally invasive and holds the diagnostic value. Timely and decisive reoperation is an important method to management of postoperative gastrointestinal hemorrhage.

Typical clinical presentation of acute myocardial infarction and confusing coronary angiography: A case report and literature review of coronary embolism.

RATIONALE: The purpose of this article is to discuss the characteristics, diagnosis, treatment, and outcomes of cases of multiple coronary embolism (CE) highly suspected to be caused by a dislodged aneurysm of the ventricular membranous septum (AVMS) thrombus. PATIENT CONCERNS: A 35-year-old man was rushed to the Chest Pain Center of Taicang TCM Hospital Affiliated to Nanjing University of Chinese Medicine for sudden onset of chest pain. The patient had severe and persistent chest pain without relief, accompanied by sweating throughout the body. DIAGNOSIS: An electrocardiogram showed ST-segment elevation in the inferior wall leads, and blood tests suggested elevated troponin I levels. The initial diagnosis was acute ST-segment elevation myocardial infarction. Emergency coronary angiography revealed complete occlusion of the first diagonal branch, thrombolysis in myocardial infarction grade 0 flow, and smooth remaining vessels. Complete occlusion of the left anterior descending artery unexpectedly occurred during interventional treatment. Postoperative cardiac ultrasonography revealed the presence of a thrombus within the AVMS and in the apical portion of the heart. The final diagnosis was a CE. INTERVENTIONS: Intraoperatively, the diagonal branch occluded segment was dilated with a balloon and intracoronary administration of tirofiban and nitroglycerin. Postoperatively, antithrombotic therapy (aspirin, clopidogrel, and rivaroxaban) was administered. OUTCOMES: Ten days after admission, a repeat coronary angiography showed complete restoration of left anterior descending artery flow on its own, balloon dilation was again performed on the diagonal branch, and flow was restored to thrombolysis in myocardial infarction grade 1. Six months later, the intracardiac thrombus disappeared on repeat cardiac ultrasound. LESSONS: AVMS is a potential source of embolism in patients with CE. CE has features that distinguish it from atherosclerosis, and a timely and correct diagnosis can help improve patient clinical outcomes.

Bibliometric analysis of traditional Chinese medicine research on heart failure in the 21st century based on the WOS database.

Introduction: Heart Failure (HF) is a key area of research in human medicine, and traditional Chinese medicine (TCM) is an important branch of this field. This study aimed to use bibliometric methods to sort out the trajectory of TCM research on HF in this century (2000-2022) from a high dimension and to analyze its characteristics, hotspots and frontiers. Methods: In this study, the search formula "TS=(("traditional Chinese medicine") OR ("Chinese medicine")) AND TS=("heart failure")" was used to find relevant studies included in the Web of Science Core Collection from 2000 to 2022. Targeted literature records were analyzed and mapped using CiteSpace and VOSviewer. Results: The authors and collaborators of this study were still in the formation process, but several well-known scholars were included: YONG WANG, WEI WANG, etc. The main research institutions in this research area were Beijing Univ Chinese Med, China Acad Chinese Med Sc, etc. The main country of study was China. Current research hotspots and frontiers were Qili Qiangxin capsules, extracts (Tanshinone ⅡA, Panax ginseng, etc.), cardiac hypertrophy, ventricular remodeling, oxidative stress, signaling pathways, network pharmacology, etc. Influential journals that publish papers in this field were the Journal of Ethnopharmacology, Scientific Reports, Biomedicine & Pharmacotherapy, etc. The top 3 co-cited journals were Circulation, J ethnopharmacol, and J am coll cardiol. Conclusions: We analyzed valuable details in TCM research on HF in the 21st century, which may help researchers identify potential collaborators and partner institutions, hotspots, and frontiers in the field.

Risk factors for SARS-CoV-2 infection among health workers in India: a case control study.

Background: COVID-19 was declared as a Public Health Emergency of International Concern on 30th January 2020. Compared to the general population, healthcare workers and their families have been identified to be at a higher risk of getting infected with COVID-19. Therefore, it is crucial to understand the risk factors responsible for the transmission of SARS-CoV-2 infection among health workers in different hospital settings and to describe the range of clinical presentations of SARS-CoV-2 infection among them. Methodology: A nested case-control study was conducted among healthcare workers who were involved in the care of COVID-19 cases for assessing the risk factors associated with it. To get a holistic perspective, the study was conducted in 19 different hospitals from across 7 states (Kerala, Tamil Nadu, Andhra Pradesh, Karnataka, Maharashtra, Gujarat, and Rajasthan) of India covering the major government and private hospitals that were actively involved in COVID-19 patient care. The study participants who were not vaccinated were enrolled using the incidence density sampling technique from December 2020 to December 2021. Results: A total of 973 health workers consisting of 345 cases and 628 controls were recruited for the study. The mean age of the participants was observed to be 31.17 ± 8.5 years, with 56.3% of them being females. On multivariate analysis, the factors that were found to be significantly associated with SARS-CoV-2 were age of more than 31 years (adjusted odds ratio [aOR] 1.407 [95% CI 1.53-1.880]; p = 0.021), male gender (aOR 1.342 [95% CI 1.019-1.768]; p = 0.036), practical mode of IPC training on personal protective equipment (aOR 1. 1.935 [95% CI 1.148-3.260]; p = 0.013), direct exposure to COVID-19 patient (aOR 1.413 [95% CI 1.006-1.985]; p = 0.046), presence of diabetes mellitus (aOR 2.895 [95% CI 1.079-7.770]; p = 0.035) and those received prophylactic treatment for COVID-19 in the last 14 days (aOR 1.866 [95% CI 0.201-2.901]; p = 0.006). Conclusion: The study was able to highlight the need for having a separate hospital infection control department that implements IPC programs regularly. The study also emphasizes the need for developing policies that address the occupational hazards faced by health workers.

Suppression of the epidermal growth factor receptor inhibits epithelial-mesenchymal transition in human pancreatic cancer PANC-1 cells.

BACKGROUND: Aberrant expression of epidermal growth factor receptor (EGFR) has been detected in pancreatic cancer; however, the mechanisms of EGFR in inducing pancreatic cancer development have not been adequately elucidated. The objective of this study was to determine the role of EGFR in mediating epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. METHODS: Pancreatic cancer cell line PANC-1 was transfected with small interfering RNA of EGFR by use of a lentiviral expression vector to establish an EGFR-knockdown cell line (si-PANC-1). PANC-1 cells transfected with lentiviral vector expressing negative control sequence were used as negative control (NC-PANC-1). Scratch assay and transwell study were used to analyze cell migration and invasion. Real-time PCR and Western blotting were used to detect the expression of EMT markers E-cadherin, N-cadherin, vimentin, and fibronectin and transcription factors snail, slug, twist1, and sip1 in PANC-1, NC-PANC-1, and si-PANC-1 cells. Immunofluorescent staining with these antibodies and confocal microscopy were used to observe their cellular location and morphologic changes. RESULTS: After RNA interference of EGFR, the migration and invasion ability of si-PANC-1 cells decreased significantly. The expression of epithelial phenotype marker E-cadherin increased and the expression of mesenchymal phenotype markers N-cadherin, vimentin, and fibronectin decreased, indicating reversion of EMT. We also observed intracellular translocation of E-cadherin. Expression of transcription factors snail and slug in si-PANC-1 cells decreased significantly. CONCLUSION: Suppression of EGFR expression can significantly inhibit EMT of pancreatic cancer PANC-1 cells. The mechanism may be related with the down-regulation of the expression of transcription factors snail and slug.

[Effects and mechanisms of combined suppression of epidermal growth factor receptor and hedgehog signaling on proliferation in pancreatic cancer cells].

OBJECTIVE: To explore the synergistic effects on proliferation and apoptosis by targeted suppression of epidermal growth factor receptor (EGFR) in combination with blockade of Hedgehog signaling pathways in pancreatic cancer cells and examine the synergistic mechanism of Hedgehog and EGFR signaling pathways. METHODS: The sequences of RNA interference targeting EGFR gene were designed, synthesized and cloned into the pFU-GW-RNAi vector. And a stable transfection cell line was obtained by transfecting the human Panc-1 cells with lentivirus. The expressions of Shh and Gli1 were tested by real-time polymerase chain reaction (PCR). The antiproliferative effect was examined by the assays of colony formation and methyl thiazolyl tetrazolium (MTT). Fluorescence activated cell sorter (FACS) was applied to assay the apoptotic rate in all experimental groups. Western blot was applied to detect the phosphorylation levels of ERK and AKT.In vivo nude mice tumorigenicity model was used to test the effect of growth inhibition. RESULTS: The RNAi technology with lentivirus could restrain the expression of EGFR gene. After the blocking of EGFR and Hedgehog signaling pathways by RNAi silencing, the chemosensitivity to cyclopamine significantly increased in human pancreatic cancer cells. The half-inhibitory concentration (IC 50) of cyclopamine declined from (2.978 ± 0.336) to (1.698 ± 0.057) µmol/L (P < 0.05). The prophase apoptotic rate of co-treated group was as high as 38.75% and it was significantly higher than the RNAi silencing EGFR (17.65%) and control groups (3.02%) (P < 0.05). The results of tumor xenografts assay showed that the tumor volume of co-treated group (394.8 ± 87.5 mm(3)) was significantly lower than that of simple EGFR RNAi (594.7 ± 86.1 mm(3)) and single cyclopamine treated group (771.3 ± 82.9 mm(3)); the combination treatment could also produce obviously synergistic antiproliferative effect in colony formation assays. After RNAi silencing EGFR, the phosphorylation levels of ERK and AKT decreased significantly versus the control group. Further reduction was obtained with the combined use of cyclopamine in the co-treated group. CONCLUSION: The blocking of EGFR and Hedgehog signaling pathways by RNAi silencing may further inhibit cell proliferation and increase apoptosis in vivo and in vitro in human pancreatic cancer cells. The synergism of Hh and EGFR signaling pathways may be correlated with the phosphorylation levels of ERK and AKT.

The potential impact of intensified community hand hygiene interventions on respiratory tract infections: a modelling study.

Hand hygiene is among the most fundamental and widely used behavioural measures to reduce the person-to-person spread of human pathogens and its effectiveness as a community intervention is supported by evidence from randomized trials. However, a theoretical understanding of the relationship between hand hygiene frequency and change in risk of infection is lacking. Using a simple model-based framework for understanding the determinants of hand hygiene effectiveness in preventing viral respiratory tract infections, we show that a crucial, but overlooked, determinant of the relationship between hand hygiene frequency and risk of infection via indirect transmission is persistence of viable virus on hands. If persistence is short, as has been reported for influenza, hand-washing needs to be performed very frequently or immediately after hand contamination to substantially reduce the probability of infection. When viable virus survival is longer (e.g. in the presence of mucus or for some enveloped viruses) less frequent hand washing can substantially reduce the infection probability. Immediate hand washing after contamination is consistently more effective than at fixed-time intervals. Our study highlights that recommendations on hand hygiene should be tailored to persistence of viable virus on hands and that more detailed empirical investigations are needed to help optimize this key intervention.

Emerging Role of Exosomal-Derived Long Noncoding RNAs in Human PDAC.

Background: The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are increasing recently. Most patients with PDAC are diagnosed at advanced stage because of the high invasiveness of cancer cells and the lack of typical early symptoms. Therefore, early diagnosis of PDAC is very important to improve the prognosis. Exosomes play crucial role in intercellular communication and deliver the contents to recipient cells to regulate their biological behaviors. Recent evidence suggests emerging role of exosomes in the carcinogenesis of a variety of cancers including PDAC. Long noncoding RNAs (LncRNAs) have been reported to be involved in the development of PDAC. It has been proved that LncRNAs have the potential to be biomarkers and therapeutic targets for PDAC. Moreover, increasing number of studies focus on the role of exosomal LncRNAs in PDAC. Summary: In this review, we summarize the current status on our understanding of the role of exosomal-derived LncRNAs in the progression and metastasis of PDAC. Key Messages: We focus on challenges in the potential of exosomal-derived LncRNAs as novel diagnostic and prognostic markers and therapeutic targets of PDAC. In addition, we provide an overview about the demonstrated important role of exosomal LncRNAs in the progression of PDAC.

Preoperative Anemia Is a Predictor of Worse Postoperative Outcomes Following Open Pancreatoduodenectomy: A Propensity Score-Based Analysis.

Background: Preoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias. Methods: We analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia. Results: The unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206-2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178-2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481-5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597-11.395), p = 0.004] were predictors of postoperative severe complications. Conclusion: Preoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.