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BACKGROUND To evaluate the event rate of major adverse kidney events within 30 days (MAKE30) in acute pancreatitis (AP) and its potential risk factors. METHODS A retrospective analysis of a tertiary center data on all AP patients admitted within 72 h after onset of abdominal pain between June 2015 and June 2019 was conducted. MAKE30 - a composite of death, new renal replacement therapy (RRT), or persistent renal dysfunction (PRD) - and its individual components were retrieved at discharge or 30 days. Logistic regression analysis was used to assess the risk factors for MAKE30. RESULTS 295 patients were enrolled and 16% experienced MAKE30. For individual components, the incidence was 3% for death, 15% for new RRT, and 5% for PRD. In multivariate logistic regression analysis, hyperchloremia at admission [OR = 8.38 (1.07-65.64); P = 0.043] and SOFA score [OR 1.63 (1.18-2.26); P = 0.003] were independent risk factors in predicting MAKE30. Further analysis showed that patients with hyperchloremia had more requirements of RRT (57% vs. 10%, P

Background Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide with continuous rise. Limited studies indicate that COPD was associated with major storms and related power outages (PO). However, significant gaps remain in understanding what PO’s role is on the pathway of major storms-COPD. This study aimed to examine how PO mediates the major storms-COPD associations. Methods In this time-series study, we extracted all hospital admissions with COPD as the principal diagnosis in New York, 2001–2013. Using distributed lag nonlinear models, the hospitalization rate during major storms and PO was compared to non-major storms and non-PO periods to determine the risk ratios (RRs) for COPD at each of 0–6 lag days respectively after controlling for time-varying confounders and concentration of fine particulate matter (PM2.5). We then used Granger mediation analysis for time series to assess the mediation effect of PO on the major storms-COPD associations. Results The RRs of COPD hospitalization following major storms, which mainly included flooding, thunder, hurricane, snow, ice, and wind, were 1.23 to 1.49 across lag 0–6 days. The risk was strongest at lag3 and lasted significantly for 4 days. Compared with non-outage periods, the PO period was associated with 1.23 to 1.61 higher risk of COPD admissions across lag 0–6 days. The risk lasted significantly for 2 days and was strongest at lag2. Snow, hurricane and wind were the top three contributors of PO among the major storms. PO mediated as much as 49.6 to 65.0% of the major storms-COPD associations. Conclusions Both major storms and PO were associated with increased hospital admission of COPD. PO mediated almost half of the major storms-COPD hospitalization associations. Preparation of surrogate electric system before major storms is essential to reduce major storms-COPD hospitalization.

Yihong Sun,1 Xia Tang,1 Bo Ye,1 Keyue Ding1,2 1Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, 410006, People’s Republic of China; 2Medical Genetic Institute of Henan Province, Henan Provincial People’s Hospital, Henan Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defect Prevention, Henan Provincial People’s Hospital of Henan University, People’s Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450003, People’s Republic of ChinaCorrespondence: Keyue DingDepartment of Bioinformatics, School of Basic Medicine, Chongqing Medical University, #1 Road Yixueyuan, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 23 6389 2759Email ding.keyue@igenetics.org.cnAim: Metabolic reprogramming has recently attracted extensive attention for understanding cancer development. We aimed to demonstrate a genomic and transcriptomic landscape of metabolic reprogramming underlying liver cancer cell lines.Methods: We investigated metabolic aberrant at both the transcriptome and genome levels using transcriptome and whole-exome sequencing data from 12 human liver cancer cell lines (hLCCLs) and one normal liver cell line.Results: Three subgroups of hLCCLs characterized from transcriptome sequencing data exhibit significantly different aberrations in various metabolic processes, including amino acid, lipid, energy, and carbohydrate metabolism. Furthermore, whole-exome sequencing revealed distinct mutational signatures among different subgroups of hLCCLs and identified a total of 19 known driver genes implicated in metabolism.Conclusion: Our findings highlighted differential metabolic mechanisms in the development of liver cancer and provided a resource for further investigating its metabolic mechanisms.Keywords: human liver cancer cell lines (hLCCLs), transcriptome, whole-exome, sequencing, tumor metabolism

Background/purpose The current standard care for acute pancreatitis with acute necrotic collections (ANC) is to postpone invasive intervention for 4 weeks when indicated. However, in patients with persistent organ failure (POF), this delayed approach may prolong organ failure. In this study, we aimed to assess the feasibility and safety of earlier drainage for acute pancreatitis patients with ANC and POF. Methods A single-center, randomized controlled trial was conducted. Eligible patients were randomly assigned to either the early on-demand (EOD) group or the standard management (SM) group. Within 21 days of randomization, early drainage was triggered by unremitted or worsening organ failure in the EOD group. The primary endpoint was a composite of major complications/death during 90-days follow-up. Results Thirty patients were randomized. Within 21 days of randomization, eight of the 15 patients (53%) in the EOD group underwent percutaneous drainage compared to four of the 15 patients (27%) in the SM group (P = 0.26). The primary outcome occurred in three of the 15 (20%) patients in the EOD group and seven of the 15(46.7%) in the controls (P = 0.25, relative risk 0.43, 95%CI 0.14 to 1.35). Conclusions Although the EOD approach did not result in significant differences between groups, the primary outcome assessed in this trial demonstrated the potential for clinical benefits favoring early drainage.

Background: Renal biopsy plays an important role in the establishment of the diagnosis and the management of patients with lupus nephritis. Immunoglobulin A (IgA) nephropathy rarely has been reported in kidney biopsy of lupus patients. Lupus nephritis and IgA nephropathy can be readily diagnosed on renal biopsy when the classic patterns are present. However, atypical patterns can become a diagnostic challenge. Galactose-deficient IgA1 (Gd-IgA1) is a key element in the pathogenesis of primary IgA nephropathy. Glomerular Gd-IgA1 deposits, detected by immunofluorescent staining of KM-55 (a Gd-IgA1-specific monoclonal antibody), are consistently identified in the mesangium of IgA nephropathy but are significantly less or absent in lupus nephritis accompanied by significant IgA deposition. Case Presentation: Here we report the case of an 11-year-old girl who was recently diagnosed with systemic lupus erythematosus (SLE) and was found to have hematuria and proteinuria. Renal biopsy showed focal mesangial hypercellularity with IgA dominant, “full house” like pattern of mesangial deposition. The biopsy findings present a diagnostic dilemma with the differential diagnosis of IgA nephropathy versus lupus nephritis with atypical immunofluorescence, and IgA nephropathy is favored, in the absence of strong straining of C1q or C3, extraglomerular deposits, tissue antinuclear antibodies, and endothelial tubuloreticular inclusions. However, no detectable glomerular KM-55 staining was seen in the kidney biopsy. Conclusions: We demonstrate the unique diagnostic utility of immunostaining for KM-55 in a challenging kidney biopsy of an SLE patient with features suggestive of IgA nephropathy. The absence of KM-55 staining excludes IgA nephropathy, supporting a diagnosis of lupus nephritis with atypical immunofluorescence in this patient with SLE.

Objectives All patients who undergo cardiopulmonary bypass (CPB) experience some degree of ischemia reperfusion injury (IRI). Severe IRI-induced acute kidney injury (AKI) occurs in approximately 1–2% of patients undergoing CPB. Previous studies using activity-based protein profiling of urine identified group XV phospholipase A2, PLA2G15/LPLA2, as potentially associated with patients who develop AKI post CPB. The present study examined urinary PLA2G15/LPLA2 activity during CPB and in the near postoperative period for associations with subsequent AKI development. Design & methods Samples were collected in a nested case controlled cohort of 21 patients per group who either did (AKI) or did not (non-AKI) develop AKI post-operatively. Serum and urine samples from each patient before, during and after CPB were assayed for PLA2G15/LPLA2 activity. Results Urine activity significantly increased during the intra operative period. In contrast the activities in paired sera were markedly decreased during CPB. There was no correlation between the serum and urine activity levels of patients. There were no significant differences in activity levels of PLA2G15/LPLA2 in the urine or sera from patients that did and did not develop AKI. Conclusions The lack of correlation between serum and urine activity levels suggests that the rapid intraoperative increases in PLA2G15/LPLA2 activity may originate from the kidney and as such offer an intraoperative indicator of early renal response to CPB associated stressors.

T-cadherin functions as a suppressor gene, which is frequently inactivated by aberrant promoter methylation in several human cancers, but its methylation status in oral squamous cell carcinoma (OSCC) has been scarcely studied. Thus this study aimed at exploring the clinical significance and prognostic value of T-cadherin methylation in sera of patients with OSCC. Methylation-specific PCR (MSP) and bisulfate sequencing PCR (BSP) was performed to examine the methylation status of T-cadherin. Then, the associations between methylation status of T-cadherin and various clinicopathological variables or patient survival were investigated in 202 patients with OSCC and 68 controls. T-cadherin methylation was detected in 62 out of 202 (30.7%) patients with OSCC, and the methylation status of T-cadherin in corresponding tissues was confirmed by BSP. Methylation of T-cadherin was significantly associated with advanced tumor T-stage (P < 0.001) and N-stage (P = 0.003), positive lymphatic metastasis (P = 0.004) and tumor recurrence (P = 0.001). In addition, patients with methylation of T-cadherin had worse overall survival (P = 0.018) and progression-free survival (P < 0.001) than patients without, and methylation of T-cadherin in sera was an independent prognostic factor for worse overall survival (HR: 3.626, 95% CI: 1.112-9.624, P = 0.007) and progression-free survival (HR: 4.201, 95% CI: 1.562-10.038, P < 0.001) of patients with OSCC. These results demonstrated that methylation of T-cadherin was frequently detected in sera of patients with OSCC, which was associated with risk factors of poor outcomes, and may act as a potential independent prognostic marker for patients with OSCC.

BACKGROUND Hemorrhoidal prolapse is a common benign disease with a high incidence. The treatment procedure for prolapse and hemorrhoids (PPH) remains an operative method used for internal hemorrhoid prolapse. Although it is related to less pos-operative pain, faster recovery and shorter hospital stays, the postoperative recurrence rate is higher than that of the Milligan-Morgan hemorrhoidectomy (MMH). We have considered that recurrence could be due to shortage of the pulling-up effect. This issue may be overcome by using lower purse-string sutures [modified-PPH (M-PPH)]. AIM To compare the therapeutic effects and the patients' satisfaction after M-PPH, PPH and MMH. METHODS This retrospective cohort study included 1163 patients (M-PPH, 461; original PPH, 321; MMH, 381) with severe hemorrhoids (stage III/IV) who were admitted to The 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from 2012 to 2014. Early postoperative complications, efficacy, postoperative anal dysfunction and patient satisfaction were compared among the three groups. Established criteria were used to assess short- and long-term postoperative complications. A visual analog scale was used to evaluate postoperative pain. Follow-up was conducted 5 years postoperatively. RESULT Length of hospital stay and operating time were significantly longer in the MMH group (8.05 ± 2.50 d, 19.98 ± 4.21 min; P < 0.0001) than in other groups. The incidence of postoperative anastomotic bleeding was significantly lower after M-PPH than after PPH or MMH (1.9%, 5.1% and 3.7%; n = 9, 16 and 14; respectively). There was a significantly higher rate of sensation of rectal tenesmus after M-PPH than after MMH or PPH (15%, 8% and 10%; n = 69, 30 and 32; respectively). There was a significantly lower rate of recurrence after M-PPH than after PPH (8.7% and 18.8%, n = 40 and 61; P < 0.0001). The incidence of postoperative anal incontinence differed significantly only between the MMH and M-PPH groups (1.3% and 4.3%, n = 5 and 20; P = 0.04). Patient satisfaction was significantly greater after M-PPH than after other surgeries. CONCLUSION M-PPH has many advantages for severe hemorrhoids (Goligher stage III/IV), with a low rate of anastomotic bleeding and recurrence and a very high rate of patient satisfaction. M-PPH

Background COPD is the third leading cause of death in the United States, with 16 million Americans currently experiencing difficulty with breathing. Power outages could be life-threatening for those relying on electricity. However, significant gaps remain in understanding the potential impact of power outages on COPD exacerbations. Research Question The goal of this study was to determine how power outages affect COPD exacerbations. Study Design and Methods Using distributed lag nonlinear models controlling for time-varying confounders, the hospitalization rate during a power outage was compared vs non-outage periods to determine the rate ratio (RR) for COPD and its subtypes at each of 0 to 6 lag days in New York State from 2001 to 2013. Stratified analyses were conducted according to sociodemographic characteristics, season, and clinical severity; changes were investigated in numerous critical medical indicators, including length of stay, hospital cost, the number of comorbidities, and therapeutic procedures between the two periods. Results The RR of COPD hospitalization following power outages ranged from 1.03 to 1.39 across lag days. The risk was strongest at lag0 and lag1 days and lasted significantly for 7 days. Associations were stronger for the subgroup with acute bronchitis (RR, 1.08-1.69) than for cases of acute exacerbation (RR, 1.03-1.40). Compared with non-outage periods, the outage period was observed to be $4.67 thousand greater in hospital cost and 1.38 greater in the number of comorbidities per case. The average cost (or number of comorbidities) was elevated in all groups stratified according to cost (or number of comorbidities). In contrast, changes in the average length of stay (–0.43 day) and the average number of therapeutic procedures (–0.09) were subtle. Interpretation Power outages were associated with a significantly elevated rate of COPD hospitalization, as well as greater costs and number of comorbidities. The average cost and number of comorbidities were elevated in all clinical severity groups.

Background Colonic fistula is a potentially fatal complication in acute necrotizing pancreatitis (ANP), especially in patients with infected pancreatic necrosis (IPN). The aim of this study was to evaluate the feasibility of a step-up approach including percutaneous catheter drainage (PCD) and continuous negative pressure irrigation (CNPI) in a group of patients with colonic fistula. Methods A retrospective review of a prospectively collected data was performed. Data were extracted for patients complicated by colonic fistula from January 2010 to January 2017. Results A total of 1750 patients were admitted with ANP during the study period. Of these patients, 711 (41%) developed IPN and colonic fistula was present in 132 (19%). A step-up approach was adopted for all patients, with 47% avoiding surgery. The mortality in patients requiring surgery (37%) was higher than that in patients managed non-surgically (19%) constituting an overall mortality rate of 29%. In patients managed conservatively, 92% had spontaneous closure of the fistula. Conclusion Colonic fistula is not a rare complication in ANP occurring in 19% of patients with IPN in the current study. A step-up approach was effective and safe in managing colonic fistula and surgery could be obviated in nearly half of the patients.

Introduction/aim Pancreatic necrosis occurs in a quarter of patients with acute pancreatitis, many of whom form an acute necrotic collection (ANC). The current standard treatment is to defer percutaneous catheter drainage (PCD) until the latter becomes “walled off,” which takes approximately four weeks. The majority of patients that develop persistent organ failure (POF), the primary determinant of mortality, do so within four weeks. To defer PCD until after four weeks may result in a worse outcome because of a missed opportunity to treat early infection and thereby reduce the severity and/or duration of POF. This study is aimed to compare the clinical outcome of the current standard approach with early on-demand PCD in acute necrotizing pancreatitis (ANP) patients with ANC and POF. Methods/design This is an open-label, multi-center, parallel, randomized, controlled trial. All patients with ANP who develop POF during the first week of onset will be screened for eligibility. In total, 120 study subjects will be randomized to either early on-demand PCD or standard care. Patients assigned to the former will receive PCD when they show signs of decompensation like new-onset OF, aggravation of pre-existent OF, and persistent OF for more than a week. The primary composite endpoint is major complication and/or death. Patients will be followed until discharge or death with an additional follow-up 90 days after randomization. Discussion This study challenges the standard 4-week delay before PCD and will answer the question whether early on-demand PCD is associated with a lower incidence of major complications and/or death.

OBJECTIVES The efficacy of pulse index contour continuous cardiac output (PiCCO) monitoring in patients with constrictive pericarditis undergoing pericardiectomy remains unclear. The goal of this study was to explore whether PiCCO monitoring could improve clinical outcomes in these patients. METHODS We retrospectively studied 74 patients with constrictive pericarditis undergoing pericardiectomy and assigned them to a PiCCO group and a control group. Postoperative and survival outcomes were compared between the 2 groups. RESULTS There were 33 (44.6%) cases in the PiCCO group and 41 (55.4%) cases in the control group. The baseline characteristics were comparable between the 2 groups. In comparison to the control group, the PiCCO group showed more intraoperative fluid infusion (P = 0.003), higher postoperative central venous pressure (P = 0.007) and lower levels of postoperative brain natriuretic peptide (P = 0.021). The incidence of postoperative complications (P = 0.004) including cardiac complications (P = 0.033) was also lower in the PiCCO group. Despite no difference in survival outcomes, duration of chest drainage (P = 0.032), length of stay in the intensive care unit (P CONCLUSIONS This study confirmed the clinical significance of PiCCO monitoring in the enhanced recovery of patients with constrictive pericarditis undergoing pericardiectomy and provided new evidence for applying PiCCO monitoring in these patients.

A 6-week growth trial was conducted to evaluate the influences of dietary valine (Val) levels on growth, protein utilisation, immunity, antioxidant status and gut micromorphology of juvenile hybrid groupers. Seven isoenergetic, isoproteic and isolipidic diets were formulated to contain graded Val levels (1·21, 1·32, 1·45, 1·58, 1·69, 1·82 and 1·94 %, DM basis). Each experimental diet was hand-fed to triplicate groups of twelve hybrid grouper juveniles. Results showed that weight gain percentage (WG%), protein productive value, protein efficiency ratio, and feed efficiency were increased as dietary Val level increased, reaching a peak value at 1·58 % dietary Val. The quadratic regression analysis of WG% against dietary Val levels indicated that the optimum dietary Val requirement for hybrid groupers was estimated to be 1·56 %. Gut micromorphology and expression of growth hormone in pituitary, insulin-like growth factor 1, target of rapamycin and S6 kinase 1 in liver were significantly affected by dietary Val levels. In serum, fish fed 1·58 % dietary Val had higher superoxide dismutase, catalase, lysozyme activities and IgM concentrations than fish fed other dietary Val levels. Fish fed 1·58 % dietary Val had higher expression of NF-E2-related factor 2 in head kidney than fish fed other dietary Val levels. Generally, the optimum dietary Val requirement for maximal growth of hybrid groupers was estimated to be 1·56 % of DM, corresponding to 3·16 % of dietary protein, and dietary Val levels affected growth, protein utilisation, immunity and antioxidant status in hybrid groupers.

Background The risk factors of postoperative outcomes after pericardiectomy in tuberculous constrictive pericarditis have still been unclear. This study aimed to investigate the predictors of postoperative complication and prolonged intensive care unit (ICU) stay in the patients with tuberculous constrictive pericarditis undergoing pericardiectomy. Methods A total of 88 patients with tuberculous constrictive pericarditis undergoing pericardiectomy were retrospectively enrolled. Logistic regression and Cox regression analysis were performed to identify the predictors of postoperative complication and prolonged ICU stay, respectively. Results All patients underwent complete pericardiectomy and 35 (39.8%) had postoperative complication with no mortality within 30 days after surgery and no in-hospital deaths. Postoperative complication prolonged postoperative ICU stay (P P P P = 0.004, OR 4.051, 95%CI 1.558–10.533) and preoperative central venous pressure (CVP) (P = 0.031, OR 1.151, 95%CI 1.013–1.309) were independent risk factors of postoperative complication. Postoperative complication (P Conclusion Complete pericardiectomy was associated with high risk of postoperative complication in tuberculous constrictive pericarditis. Poor preoperative NYHA functional class and high preoperative CVP were shown to predict postoperative complication which was the predictor of prolonged ICU stay.

Objective: This study aimed to investigate the value of elastic strain rate ratio (SR) in the differential diagnosis of benign and malignant thyroid imaging reporting and data system (TI-RADS) 4 nodules under the influence of various factors. Method: This study included 180 patients with type 4 unifocal thyroid nodules diagnosed by ultrasound examination in the Xiangyang No. 1 People's Hospital from March 2016 to March 2019. All patients underwent elasticity imaging and surgical operations. The pathological results were used as the gold standard to perform logistic regression analyses and identify the factors influencing the differential diagnosis of benign and malignant thyroid nodules. Then, the receiver operating characteristic (ROC) curve was drawn. Results: The ROC curve suggested a cutoff value of 0.52 in differentiating between benign and malignant TI-RADS 4 nodules using the SR value. The nodule size, calcification, border, and thyroid gland with diffuse lesions were factors influencing the differential diagnosis of benign and malignant TI-RADS 4 nodules with the SR value. SR had a high accuracy identifying benign and malignant TI-RADS 4 nodules with a diameter of less than 0.8 cm (but >0.4 cm), no or granular calcification, nodules with blurred borders, and no thyroid gland with diffuse lesions. Conclusion: The diagnostic accuracy was improved by combining the two-dimensional ultrasound with SR determination in the differential diagnosis of benign or malignant TI-RADS 4 nodules.

Background We analyzed the pathological characteristics and recurrence pattern of cN0 submucosal esophageal cancer after esophagectomy and conducted risk stratification to determine the feasibility of performing endoscopic resection for cN0pT1b esophageal squamous cell malignancies. Methods We retrospectively enrolled 167 patients who underwent right-sided transthoracic esophagectomy and extended thoracic/abdominal two-field lymphadenectomy. Patients with pathologically confirmed lymph node metastasis or tumor recurrence constituted the high-risk group for endoscopic submucosal resection, and the remainder were defined as low risk. Factors affecting lymphatic metastasis and long-term recurrence were identified by univariate and multivariate analyses. Results Postoperative pathology showed that five patients (5/167; 3%) had lymph node metastases. Follow-up ranged from 12–60 months, with a median of 29 months. A total of 17 patients (10.2%) had recurrences during follow-up, including three patients with pathologic nodal metastasis (pN +) found at surgery. Invasion depth, differentiation, and tumor size differed significantly in high-risk patients. Overall 3-year survival rates were 94.2% (low-risk) and 40.9% (high-risk) (p Conclusions Endoscopic submucosal resection alone may be feasible for patients with small (≤ 2 cm) clinically N0 submucosal esophageal squamous cell carcinoma with low invasion depth (sm1) and higher differentiation, but prospective studies are required for confirmation. Other patients require surgical resection with extended two-field thoracic/abdominal lymphadenectomy.

Background The gut microbiome plays an important role in various cardiovascular diseases, such as atherosclerosis and hypertension, which are associated with abdominal aortic aneurysms (AAAs). Methods Here, we used 16S rRNA sequencing to explore gut microbiota in C57BL ApoE−/− mice with AAAs. A mouse model of abdominal aortic aneurysms was induced with angiotensin II (Ang II) (1000 ng/min per kg). On day 28 after the operation, fecal samples were collected and stored at − 80 °C until DNA extraction. We determined the relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding, and sequences were analyzed using a combination of mother software and UPARSE. Results We found that the gut microbiome was different between control and AAA mice. The results of correlation analysis between AAA diameter and the gut microbiome as well as LEfSe of the genera Akkermansia, Odoribacter, Helicobacter and Ruminococcus might be important in the progression of AAAs. Conclusions AAA mice is subjected to gut microbial dysbiosis, and gut microbiota might be a potential target for further investigation.

Background: Acute pancreatitis in pregnancy is a rare but highly life-threatening gestational and perinatal disease.Objective: This study aimed to identify the risk factors for fetal death and acute pancreatitis severity.Methods: This retrospective cohort study enrolled patients with acute pancreatitis in pregnancy in our center from January 1, 2012, to August 1, 2020, and classified them according to two clinical endpoints, fetal outcome and disease severity. The groups were examined and compared according to gestational week, etiology, gravidity and parity, complications in pre- and post-delivery, and medical history. Logistic regression analysis was performed to identify the independent risk factors for fetal death and acute pancreatitis severity.Results: Of the 90 enrolled patients, 28 (31.1%) had fetal death and 43 (47.8%) had severe acute pancreatitis. Logistic regression analysis showed that pre-delivery acute respiratory distress syndrome (OR, 5.8; 95% CI, 1.5–22.4; p = 0.010) and gestational week (OR, 0.9; 95% CI, 0.8–1.0; p = 0.011) were risk factors for fetal death. Gestation week (OR, 1.2; 95% CI, 1.1–1.3; p = 0.003) and fetal intrauterine death (OR, 5.9; 95% CI, 1.8–19.4; p = 0.003) were risk factors for severe acute pancreatitis.Conclusions: Pre-delivery acute respiratory distress syndrome and gestational week were independent risk factors for fetal death. Fetal intrauterine death and gestational week were independent risk factors for severe acute pancreatitis.

BACKGROUND Feeding intolerance (FI) is common in critically ill patients fed with enteral nutrition. Although there is increasing evidence showing the association between FI and mortality, no reliable quantitative assessment was available in clinical practice. In this study, we proposed a FI scoring system based on gastrointestinal (GI) symptoms to assist the implementation of enteral nutrition and assessed its association with 28-day mortality. METHODS This is a post hoc analysis based on data collected in a previous cross-sectional study. All adult patients who were enterally fed were included. Various definitions of FI were compared. The area under the receiver operating characteristic (AUROC) was used to assess the predictive performance for 28-day mortality. Pearson correlation coefficient and the variance inflation factor were applied to detect collinearity among variables. Multiple logistic regression analysis was used to determine the risk factors for 28-day mortality. RESULTS Of the 1098 patients included, 200 (18.2%) were nonsurvivors. The incidence of GI symptoms was higher in nonsurvivors on the study day. The multiple logistic regression analysis showed that the proposed FI score was an independent risk factor for 28-day mortality (odds ratio [OR]: 1.37; 95% CI, 1.25-1.51; P < .001). Moreover, the FI score showed better predictive accuracy for 28-day mortality than the other definitions (AUROC: 0.633 [95% CI, 0.591-0.675] for the FI score vs 0.595 (95% CI, 0.557-0.633] for the best-performing FI definition [P = 0.001]). CONCLUSIONS FI score is independently associated with 28-day mortality in critically ill patients with acceptable predictive accuracy.

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration.Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment.Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy.Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

BACKGROUND Junctional adhesion molecule-like protein (JAML) is a member of the junctional adhesion molecule family and mediates migration of immune cells, but its function in cancers remains unclear. This study aimed to evaluate the role of JAML in the prognosis and immune infiltrates of lung adenocarcinoma (LUAD). MATERIAL AND METHODS JAML expressions in LUAD tissues and normal tissues were compared using The Cancer Genome Atlas (TCGA) database and datasets from the Gene Expression Omnibus (GEO) database. The influence of JAML expression on prognosis was analyzed by Kaplan-Meier curve and Cox regression model. Interactive and functional analyses of JAML were performed by LinkedOmics and GeneMANIA databases. TIMER2.0, TISIDB, and GEPIA2 databases were used to investigate the correlation between JAML expression and immune infiltrates. RESULTS JAML expression was decreased in LUAD (P0.001), and lower JAML expression was associated with worse outcomes of LUAD patients. High JAML expression was the protective factor for overall survival (OS) (HR 0.706, 95% CI 0.500-0.997, P=0.048). Interactive and functional analyses suggested that co-expressed genes with JAML have an obvious link to immune-related pathways. In addition, JAML expression was positively associated with infiltrating levels of CD8+ T cells, CD4+ T cells, B cells, dendritic cells, macrophages, and neutrophils, and had significant correlations with diverse immune marker sets in LUAD. CONCLUSIONS JAML expression was significantly correlated with prognosis and immune infiltrates. These preliminary findings suggested JAML could be considered as a potential prognostic biomarker and therapeutic target for LUAD.

Background WD repeat domain 76 (WDR76) is a predicted member of the WD40-repeat-containing domain superfamily and possibly involves in various biological processes, but its function in cancers is poorly characterized. This study aimed to evaluate the role of WDR76 in the prognosis and immune infiltrates of lung adenocarcinoma (LUAD). Methods WDR76 expressions in LUAD tissues and normal tissues were primarily compared by The Cancer Genome Atlas (TCGA) database, and were validated in cohorts from Gene Expression Omnibus (GEO) database. The associations between WDR76 expression and clinicopathologic characteristics were analyzed. Kaplan–Meier and Cox regression analyses were performed to determine the impact of WDR76 expression on survival outcomes. The protein interaction network of WDR76 was built using STRING website. TIMER and GEPIA databases were used to investigate the correlation between WDR76 expression and immune infiltrates. Results WDR76 expression was elevated in LUAD (P P = 0.033) and disease specific survival (DSS) (HR 1.764, 95% CI [1.095–2.842], P = 0.020). DDB1 and LSH were the important proteins interacting with WDR76. WDR76 expression correlated with CD8+ T cells presence and was also positively associated with levels of inhibitory receptors. Conclusion WDR76 expression was involved in the regulation of immune infiltrates and had predictive value for prognosis in LUAD.

BackgroundLINC00346 has recently been reported to regulate the development of several cancer types, but its biological functions and underlying mechanisms in lung adenocarcinoma (LUAD) have not been elucidated. The purpose of this study was to investigate the molecular mechanism of LINC00346 in the progression of LUAD.MethodsBioinformatics was performed to find the target lncRNA, miRNA and mRNA, and the binding relationship between the target genes was verified by dual luciferase reporter gene and RIP assays. Fluorescence in situ hybridization was used to detect the location of LINC00346 in LUAD tissues. The expressions of LINC00346, miR-30c-2-3p and MYBL2 in each group were detected by qRT-PCR, and western blot was performed to detect expressions of MYBL2 and CELL CYCLE related proteins. Proliferation, metastasis, apoptosis and cell cycle of LUAD cells were detected by CCK-8, colony formation, Transwell and flow cytometry assays, respectively. Mouse xenograft models were established to further determine the effects of LINC00346 on LUAD tumor growth in vivo.ResultsLINC00346 was upregulated in LUAD tissues and cells and was mainly localized in the cytoplasm. Knockdown of LINC00346 inhibited tumor growth in vivo, proliferation, metastasis and cell cycle progression, while induced apoptosis. LINC00346 sponged miR-30c-2-3 by targeting MYBL2 and regulating CELL CYCLE signaling pathway. Inhibiting miR-30c-2-3p or overexpressing MYBL2 could reverse the inhibitory effect of LINC00346 knockdown on LUAD process.ConclusionsLINC00346 as a ceRNA played a carcinogenic role in the development of LUAD via miR-30c-2-3p/MYBL2 axis regulating the CELL CYCLE signaling pathway. The study generally elucidated the mechanism by which LINC00346 regulated the development of LUAD, providing new ideas for the diagnosis and treatment of LUAD guided by lncRNA.

Introduction Infected pancreatic necrosis (IPN) is an important complication of acute pancreatitis (AP). Absolute lymphocyte count (ALC) was reported to be associated with immunosuppression and the development of IPN. The aim of this study was to describe the trajectory of ALC during the early phase of AP and assess its association with IPN. Methods We retrospectively screened patients with AP admitted to our center between January 2016 and July 2019. The ALC levels for the first 7 days after admission were collected. Group-based trajectory modeling was performed to detect the trajectories. Cox proportional hazards regression model was adopted to identify potential risk factors of IPN. Results Overall, 292 patients were enrolled for analysis. A triple-group trajectory model was developed, assigning 116 patients to the low-level ALC group, 133 to the medium-level ALC group, and 43 to the high-level ALC group. There was no overall significant difference regarding the incidence of IPN among the 3 groups (P = 0.066). In pairwise comparison, patients in the low-level ALC group had significantly higher incidence of IPN than those in the high-level ALC group (hazard ratio: 3.50; 95% confidence interval: 1.22-10.00, P = 0.020). Length of hospital stay and intensive care unit stay differed significantly among patients with different trajectories (P = 0.042 and 0.033, respectively). Discussion Despite the fact that the trajectories of ALC is overall insignificant for the development of IPN, patients with persistent low ALC trajectories during the early phase of AP are more likely to develop IPN when compared with patients with high ALC trajectories.

Background: Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with multiple etiologies. The prevalence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has been increasing in recent years. It is reported that early triglyceride (TG) levels were associated with the severity of the disease, and TG- lowering therapies, including medical treatment and blood purification, may impact the clinical outcomes. However, there is no consensus regarding the optimal TG-lowering therapy, and clinical practice varies greatly among different centers. Our objective is to evaluate the TG-lowering effects of different therapies and their impact on clinical outcomes in HTG-AP patients with worrisome features.Methods: This is a multicenter, observational, prospective cohort study. A total of approximately 300 patients with HTG-AP with worrisome features are planned to be enrolled. The primary objective of the study is to evaluate the relationship between TG decline and the evolution of organ failure, and patients will be dichotomized depending on the rate of TG decline. The primary outcome is organ failure (OF) free days to 14 days after enrollment. Secondary outcomes include new-onset organ failure, new-onset multiple-organ failure (MOF), new-onset persistent organ failure (POF), new receipt of organ support, requirement of ICU admission, ICU free days to day 14, hospital free days to day 14, 60-day mortality, AP severity grade (Based on the Revised Atlanta Classification), and incidence of systemic and local complications. Generalized linear model (GLM), Fine and Gray competing risk regression, and propensity score matching will be used for statistical analysis.Discussion: Results of this study will reveal the current practice of TG-lowering therapy in HTG-AP and provide necessary data for future trials.

Background The effects of matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expressions on the patients with constrictive pericarditis undergoing pericardiectomy remain unclear. This study explored the associations of MMPs and TIMPs expressions with postoperative outcomes in these patients. Methods Pericardial specimens were obtained during pericardiectomy from the patients with constrictive pericarditis. The levels of MMP1, MMP2, MMP9 and TIMP1 in pericardium were analyzed by quantitative real-time polymerase chain reaction. The enrolled patients were divided into two groups according to the optimal cutoff value of gene expression predicting postoperative complications. Postoperative outcomes were compared between the two groups. Binary logistic regression analysis was performed to determine the degree of contribution of gene expression on postoperative outcomes. Results A total of 22 patients and their pericardial specimens were included. The level of MMP9 was significantly associated with postoperative complications and the optimal cutoff value predicting postoperative complications was 3.67. The patients with low level of MMP9 (P = 0.002), shorter postoperative intensive care unit (P = 0.040) and hospital stay (P = 0.043) in comparison to those with high level of MMP9 (≥ 3.67). Binary logistic regression analysis showed that high level of MMP9 increased the risk of postoperative complications (OR 27.096, 95% CI 1.166–629.886, P = 0.040). Conclusions High level of MMP9 in the pericardium was associated with poor postoperative outcomes and was the independent risk factor of postoperative complications. The level of MMP9 could be used as a potential marker for prediction of surgical outcomes.

The role of cis-elements and their aberrations remains unclear in esophageal squamous cell carcinoma (ESCC, further abbreviated EC). Here we survey 28 H3K27ac-marked active enhancer profiles and 50 transcriptomes in primary EC, metastatic lymph node cancer (LNC), and adjacent normal (Nor) esophageal tissues. Thousands of gained or lost enhancers and hundreds of altered putative super-enhancers are identified in EC and LNC samples respectively relative to Nor, with a large number of common gained or lost enhancers. Moreover, these differential enhancers contribute to the transcriptomic aberrations in ECs and LNCs. We also reveal putative driver onco-transcription factors, depletion of which diminishes cell proliferation and migration. The administration of chemical inhibitors to suppress the predicted targets of gained super-enhances reveals HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Thus, our epigenomic profiling reveals a compendium of reprogrammed cis-regulatory elements during ESCC carcinogenesis and metastasis for uncovering promising targets for cancer treatment., The role of regulatory cis-elements in carcinogenesis and metastasis in esophageal squamous cell carcinoma remains crucial. Here the authors investigate H3K27ac-marked active enhancer profiles and transcriptomes in different types of esophageal tissues and identify oncogenic events and potential therapeutic targets.

PurposeT-cadherin is an immunoglobulin-like adhesion molecule which acts as a tumor suppressor gene, programmed cell death ligand 1 (PD-L1) is a cell surface protein that involves in the suppression of the immune system. This study aimed at exploring the correlation between T-cadherin and PD-L1, as well as their prognostic value in patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). MethodsIn this study, immunohistochemical staining was used to determine the protein expression of T-cadherin and PD-L1 in 104 tissue specimens of HPV-negative HNSCC. Spearman linear correlation analysis was used to determine the association between protein expression of T-cadherin and PD-L1. Kaplan-Meier analysis was used to plot overall survival (OS) and disease-free survival (DFS) curves. Cox proportional hazards regression analysis was used to conduct univariate and multivariate analysis. ResultsThe results showed a large negative association between protein expression of T-cadherin and PD-L1 (r=-0.775, P