Effect of isavuconazole on the pharmacokinetics of sunitinib and its mechanism.

BACKGROUND: Sunitinib, a newly developed multi-targeted tyrosine kinase inhibitor (TKI), has become a common therapeutic option for managing advanced renal cell carcinoma (RCC). Examining the mechanism underlying the interaction between sunitinib and isavuconazole was the aim of this effort. METHODS: The concentrations of sunitinib and its primary metabolite, N-desethyl sunitinib, were analyzed and quantified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Our study evaluated the potential interaction between isavuconazole and sunitinib using rat liver microsomes (RLM), human liver microsomes (HLM), and in vivo rat models. For the in vivo study, two groups (n = 5) of Sprague-Dawley (SD) rats were randomly allocated to receive sunitinib either with or without co-administration of isavuconazole. Additionally, the effects of isavuconazole on the metabolic stability of sunitinib and N-desethyl sunitinib were studied in RLM in vitro. RESULTS: Our findings demonstrated that in RLM, isavuconazole exhibited a mixed non-competitive and competitive inhibition mechanism, with an IC50 (half maximal inhibitory concentration) value of 1.33 µM. Meanwhile, in HLM, isavuconazole demonstrated a competitive inhibition mechanism, with an IC50 of 5.30 µM. In vivo studies showed that the presence of isavuconazole significantly increased the pharmacokinetic characteristics of sunitinib, with the AUC(0→t), AUC(0→∞), and Tmax rising to approximately 211.38%, 203.92%, and 288.89%, respectively, in contrast to the control group (5 mg/kg sunitinib alone). The pharmacokinetic characteristics of the metabolite N-desethyl sunitinib in the presence of isavuconazole remained largely unchanged compared to the control group. Furthermore, in vitro metabolic stability experiments revealed that isavuconazole inhibited the metabolic processing of both sunitinib and N-desethyl sunitinib. CONCLUSIONS: Isavuconazole had a major impact on sunitinib metabolism, providing fundamental information for the precise therapeutic administration of sunitinib.

Effects of Different Straw Return Modes on Soil Carbon, Nitrogen, and Greenhouse Gas Emissions in the Semiarid Maize Field.

Returning straw to the field is a crucial practice for enhancing soil quality and increasing efficient use of secondary crop products. However, maize straw has a higher carbon-to-nitrogen ratio compared to other crops. This can result in crop nitrogen loss when the straw is returned to the field. Therefore, it is crucial to explore how different methods of straw return affect maize (Zea mays L.) farmland. In this study, a field experiment was performed with three treatments (I, no straw returned, CK; II, direct straw return, SR; and III, straw returned in deep furrows, ISR) to explore the effects of the different straw return modes on soil carbon and nitrogen content and greenhouse gas emissions. The results indicated that the SR and ISR treatments increased the dissolved organic carbon (DOC) content in the topsoil (0-15 cm). Additionally, the ISR treatment boosted the contents of total nitrogen (TN), nitrate nitrogen (NO3--N), ammonium nitrogen (NH4+-N), dissolved organic nitrogen (DON), and DOC in the subsurface soil (15-30 cm) compared with CK. When it comes to greenhouse gas emissions, the ISR treatment led to an increase in CO2 emissions. However, SR and ISR reduced N2O emissions, with ISR showing a more pronounced reduction. The ISR treatment significantly increased leaf and grain biomass compared to CK and SR. The correlation analyses showed that the yield was positively correlated with soil DOC, and soil greenhouse gas emission was correlated with soil NO3--N. The ISR technology has great potential in sequestering soil organic matter, improving soil fertility, and realizing sustainable agricultural development.

The safety and feasibility assessment of overlap esophagojejunostomy with self-pulling and latter transection technique in totally laparoscopic total gastrectomy.

BACKGROUND: This study presented an innovative technique in totally laparoscopic total gastrectomy (TLTG) for overlap esophagojejunostomy (E-J), termed self-pulling and latter transection (SPLT) (overlap SPLT). It evaluated the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end (FETE) E-J incorporating SPLT. METHODS: From September 2018 to September 2023, this study enrolled 68 patients with gastric cancer who underwent TLTG with overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathologic characteristics and surgical and postoperative outcomes data for overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for overlap SPLT was 25.3 ± 7.4 minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0 minutes, P = .031). Perioperatively, 1 anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = .682). No statistically significant differences were found between the 2 groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs 5.8%, P = .676). CONCLUSION: The overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between overlap SPLT and FETE SPLT, but overlap SPLT costed 1 additional stapler cartridge and required a longer duration.

A hemodynamic model of artery bypass graft considering microcirculation function.

BACKGROUND: The incidence of arterial stenosis is increasing year by year. In order to better diagnose and treat arterial stenosis, numerical simulation technology has become a popular method. OBJECTIVE: A novel model is constructed to investigate the influence of microcirculation on the hemodynamics of artery bypass graft. METHODS: In this paper, a severely narrow artery bypass graft model is considered. The geometric shape includes a narrow artery tube and a bypass graft of the same diameter with a 45° suture angle. The fluid-structure interaction model is considered by finite element numerical calculation, and the flow is simulated with microcirculation as the outlet boundary condition. The changes of blood flow velocity, pressure and wall shear stress are analyzed. RESULTS: The results show that blood almost entirely flows into the graft tube and there is no recirculation area at the anastomosis. CONCLUSION: The artery bypass graft model considering microcirculation function could simulate the physiological characteristics of blood flow more reasonably, and it provide helps for clinicians to diagnose and treat arterial stenosis.

Development of an UPLC-MS/MS method for quantitative analysis of abexinostat levels in rat plasma and application of pharmacokinetics.

Broad-spectrum histone deacetylase inhibitors (HDACi) have excellent anti-tumor effects, such as abexinostat, which was a novel oral HDACi that was widely used in clinical treatment. The purpose of this study was to establish a rapid and reliable method for the detection of abexinostat concentrations in rat plasma using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The mobile phase we used was acetonitrile and 0.1% formic acid, and the internal standard (IS) was givinostat. Selective reaction monitoring (SRM) was used for detection with ion transitions at m/z 397.93 → 200.19 for abexinostat and m/z 422.01 → 186.11 for givinostat, respectively. The intra-day and inter-day precision of abexinostat were less than 11.5% and the intra-day and inter-day accuracy ranged from - 10.7% to 9.7% using this method. During the analysis process, the stability of the test sample was reliable. In addition, the recovery and matrix effects of this method were within acceptable limits. Finally, the method presented in this paper enabled accurate and quick determination of abexinostat levels in rat plasma from the pharmacokinetic study following gavage at a dose of 8.0 mg/kg abexinostat.

Caregiving burdens of family members of patients living with hepatocellular carcinoma.

BACKGROUND: Caregiving burden is common among family caregivers (FCs). In Taiwan, no reports have compared caregiving burden according to disease stage, or explored the comprehensive factors of caregiving burden in the FCs of patients with hepatocellular carcinoma (HCC). AIM: The aim of the study was to investigate caregiving burden at different diagnosis stages and its potential predictors in the FCs of patients with hepatocellular carcinoma. METHODS: This descriptive, cross-sectional study included 192 FCs. Caregiving burden was measured using the Caregiver Reaction Assessment tool. The predictive factors of caregiving burden in the FCs of patients with HCC were identified using a linear regression model. RESULTS: The global caregiving burden had no significant differences between the four disease stages. The lack of family support and impact on schedule were significantly higher at the terminal stage than at the earlier stage. The risk factors of caregiving burden were high depression, high financial demand, heavy caregiving tasks, advanced age and frequent patient contact, which obtained a variance of 47.8% in the regression model. CONCLUSION: Healthcare providers need to proactively identify and assess FCs with risk factors of caregiving burden and provide appropriate interventions specific to individual needs at different disease stages.

Nucleolus and Nucleolar Stress: From Cell Fate Decision to Disease Development.

Besides the canonical function in ribosome biogenesis, there have been significant recent advances towards the fascinating roles of the nucleolus in stress response, cell destiny decision and disease progression. Nucleolar stress, an emerging concept describing aberrant nucleolar structure and function as a result of impaired rRNA synthesis and ribosome biogenesis under stress conditions, has been linked to a variety of signaling transductions, including but not limited to Mdm2-p53, NF-κB and HIF-1α pathways. Studies have uncovered that nucleolus is a stress sensor and signaling hub when cells encounter various stress conditions, such as nutrient deprivation, DNA damage and oxidative and thermal stress. Consequently, nucleolar stress plays a pivotal role in the determination of cell fate, such as apoptosis, senescence, autophagy and differentiation, in response to stress-induced damage. Nucleolar homeostasis has been involved in the pathogenesis of various chronic diseases, particularly tumorigenesis, neurodegenerative diseases and metabolic disorders. Mechanistic insights have revealed the indispensable role of nucleolus-initiated signaling in the progression of these diseases. Accordingly, the intervention of nucleolar stress may pave the path for developing novel therapies against these diseases. In this review, we systemically summarize recent findings linking the nucleolus to stress responses, signaling transduction and cell-fate decision, set the spotlight on the mechanisms by which nucleolar stress drives disease progression, and highlight the merit of the intervening nucleolus in disease treatment.

Safety of chronic high-dose calcium channel blockers exposure in children with pulmonary arterial hypertension.

Background: Chronic calcium channel blockers (CCBs) are indicated in children with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) and positive response to acute vasodilator challenge. However, minimal safety data are available on the long-term high-dose exposure to CCBs in this population. Methods: Patients aged 3 months to 18 years who were diagnosed with IPAH/HPAH and treated with CCB in the past 15 years were retrospectively reviewed. The maximum tolerated dose and the long-term safety of high-dose CCBs on the cardiovascular and noncardiovascular systems were assessed. Results: Thirty-two eligible children were enrolled in the study, with a median age of 9 (6-11) years old. Thirty-one patients were treated with diltiazem after diagnosis. The median maximum tolerated dose was 12.9 (9.8-16.8) mg/kg/day. Children younger than 7 years used higher doses than children in the older age group, 16.4 (10.5-28.5) mg/kg/day vs. 12.7 (6.6-14.4) mg/kg/day, P < 0.05. Patients were followed up for a median period of 6.2 (2.6-10.8) years. One patient died from a traffic accident, and others showed a stable or improved WHO functional class status. Thirteen (40.6%) and 10 (31.3%) patients developed arrhythmias and hypotension. Nine (28.1%) patients had sinus bradycardia, five (21.9%) had first-degree or second-degree type II atrial-ventricular blocks, and two (6.3%) had second-degree type II atrial-ventricular blocks. Most of these arrhythmias were transient and relieved after CCB dose adjustment. The most reported noncardiovascular adverse effect was gingival hyperplasia (13, 40.6%), accompanied by different degrees of dental dysplasia. No liver or kidney dysfunction was reported. Conclusion: Diltiazem was used in a very high dose for eligible children with IPAH/HPAH. The toxicity of long-term CCB use on the cardiovascular system is mild and controllable. Clinicians should also monitor the noncardiovascular adverse effects associated with drug therapy.

Relationship between multimorbidity and composite lifestyle status in Shenzhen, China.

Objective: The study aimed to understand multimorbidity among adults in a high-tech city in southern coastal China that has undergone rapid economic development and to investigate its relationship with lifestyle status. Methods: A population-based survey was conducted among 24 community centers in the Nanshan District of Shenzhen from February to December of 2018. Participants were recruited using a stratified random sampling approach. A self-administered questionnaire on typical chronic diseases, lifestyle factors, body composition, and social demographics was used to collect data. Multimorbidity was defined as two or more chronic diseases coexisting in a single person. An algorithm on body mass index, physical activity, drinking, smoking, and sleep quality was used to calculate lifestyle scores (0-9), with higher scores predicting a healthier lifestyle. Results: A total of 2,905 participants were included in the analysis, with men accounting for 52.4%, and single for 25%. The prevalence of multimorbidity was 4.8%, and the mean lifestyle score was 4.79 ± 1.55. People who were old, retired, married, and had less education were more likely to have multimorbidity (all P < .05). A higher prevalence of multimorbidity was found among those who were obese, less engaged in physical activity, consumed more alcohol, and had poorer sleep quality (all p < .05). After adjusting for age, employment, education, and marital status, one unit increase in lifestyle score was associated with 0.74 times lower to have multimorbidity (OR: 0.74; 95% CI: 0.63-0.87, p < .05). Conclusion: The prevalence of multimorbidity was relatively low in economically developed Shenzhen. Keeping a healthy lifestyle was related to the lower possibility of suffering from multiple chronic diseases.

ß2-adrenergic receptor drives the metastasis and invasion of pancreatic ductal adenocarcinoma through activating Cdc42 signaling pathway.

Recent investigations indicate that ß2-adrenergic receptor (ß2-AR) signaling may facilitate the progression of various tumors, whose underlying mechanisms remain largely elusive. In the present study, we showed that ß2-AR recruited Cdc42 in response to isoproterenol (ISO, a ß-AR selective agonist) exposure in pancreatic ductal adenocarcinoma (PDAC) cells. The association of ß2-AR and Cdc42 promoted the activation of Cdc42, as revealed by increased levels of Cdc42-GTP, and co-incubation with ß2-AR antagonist abrogated ISO-induced activation of Cdc42. ß2-AR-mediated Cdc42 activation further led to the phosphorylation of downstream PAK1, LIMK1 and Merlin. Furthermore, we showed that the activation of ß2-AR/Cdc42 signaling facilitated the migration and invasion of PDAC cells. In addition, ß2-AR and Cdc42 were overexpressed in PDAC specimens, compared with adjacent non-tumor tissues. High expression of ß2-AR and Cdc42 were correlated with lymph node metastasis and TNM stage in PDAC patients. Finally, we showed that overexpression of ß2-AR and Cdc42 were indicative of unfavorable prognosis in PDAC patients. Taken together, our findings suggested that ß2-AR might facilitate Cdc42 signaling to drive the migration and invasion of PDAC cells, consequently resulting in the metastasis and dismal prognosis of PDAC. These studies highlight targeting ß2-AR/Cdc42 signaling as a therapeutic strategy against PDAC.

Assessment of On-Board and Laboratory Gas Measurement Systems for Future Heavy-Duty Emissions Regulations.

Road transport contributes significantly to air pollution in cities. Regulations across the globe continuously reduce the limits that vehicles need to respect during their lifetimes. Furthermore, more pollutants are being subject to control with new regulations and, most important, testing tends to be done under real-world conditions on the road. In this study, various portable systems were compared with laboratory-grade equipment with a wide range of emissions, focusing on the lower end, where the measurement uncertainty of the instruments is crucial for the determination of emission limits. The engines were diesel- and compressed natural gas (CNG)-fueled. The results were promising, with relatively small differences between portable emissions measurement systems (PEMSs), portable Fourier transform infrared (FTIR) and quantum cascade laser infrared (QCL-IR) spectrometers, and the respective laboratory-grade analyzers based on chemiluminescence detection (CLD), non-dispersive infrared (NDIR), and FTIR principles. The results also highlighted the need for strict technical regulations regarding accuracy and drift for low emission limits in future.

Effect of different oesophagojejunostomy methods on the quality of life of gastric cancer patients after totally laparoscopic total gastrectomy with self-pulling and latter transected technique: study protocol for a randomised trial.

INTRODUCTION: Gastric cancer is the fifth most common cancer worldwide and the detection rate of proximal gastric cancer has been increasing. Currently, surgical resection using gastrectomy and proper perigastric lymphadenectomy is the only treatment option to enhance the survival rate of patients with gastric cancer. Laparoscopic total gastrectomy (LTG) is increasingly performed for adenocarcinoma of the oesophagogastric junction. However, totally LTG (TLTG) is only performed by a few surgeons due to difficulty associated with oesophagojejunostomy (OJ), in which there is no consensus on a standardised anastomosis technique. We propose a randomised trial to compare functional end-to-end anastomosis (FETE) and side-to-side anastomosis (Overlap) for OJ. METHODS AND ANALYSIS: A prospective, randomised, open-label, single-centre, interventional trial has been designed to evaluate the quality of life (QoL) outcomes and safety of FETE and Overlap, with a 1-year follow-up as the primary endpoint. The trial began in 2020 and is scheduled to enrol 96 patients according to a previous sample size calculation. Patients were randomly allocated to the FETE or Overlap groups with a follow-up of 1 year to assess QoL after the procedure. All relevant clinical data including biological markers were collected. The primary indicator is the D-value between the postoperative and preoperative QoL. Student's t-tests will be used to compare continuous variables, while χ2 tests or Fisher's exact tests will be used to compare categorical variables. Statistical analysis will be performed with SPSS V.23.0 statistical software. A p<0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: This study has been approved by the Hospital Institutional Review Board of Huashan Hospital, Fudan University (2020-1055). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000035583.

Evaluating behavioral economic interventions for promoting cancer screening uptake and adherence in targeted populations: a systematic review protocol.

OBJECTIVE: The objective of this review is to determine the effectiveness of behavioral economic interventions for promoting uptake of and adherence to cancer screening recommended by guidelines. INTRODUCTION: Cancer screening has been found to help reduce incidence of and mortality from advanced cancer. However, adherence to recommended cancer screening services is low in asymptomatic adults with average risk, possibly due to systematic decision biases. The findings of this review will demonstrate whether interventions informed by behavioral economic insights can help improve uptake of and adherence to cancer screening. INCLUSION CRITERIA: This review will consider experimental, quasi-experimental, and analytical observational studies that i) evaluate the effects of behavioral economic interventions in adults eligible for guideline-recommended cancer screening; and ii) report the number/percentage of individuals who used screening services; number/percentage of individuals who completed screening recommended by guidelines; participant self-reported intentions, choice, and satisfaction regarding the use of screening services; detection rates of early-stage cancers; use of early intervention for cancers; and cancer-related mortality. METHODS: A systematic literature search will be performed by one reviewer. After removing duplicates, two reviewers will independently screen and appraise eligible studies according to the JBI methodology for systematic reviews of effectiveness. Five databases will be searched: CINAHL, the Cochrane Library, PsyclNFO, PubMed, and Web of Science. Sources of gray literature and registered clinical trials will also be searched for potential studies. There will be no limits on publication date or language. Data synthesis will be conducted using meta-analysis and narrative synthesis where appropriate. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021258370.

PFOS facilitates liver inflammation and steatosis: An involvement of NLRP3 inflammasome-mediated hepatocyte pyroptosis.

Perfluorooctane sulfonate (PFOS) is a fluorinated organic pollutant with substantial accumulation in mammalian liver tissues. However, the impact of chronic PFOS exposure on liver disease progression and the underlying molecular mechanisms remain elusive. Herein, we for the first time revealed that micromolar range of PFOS exposure initiates the activation of NLR pyrin domain containing 3 (NLRP3) inflammasome to drive hepatocyte pyroptosis. We showed that 5 mg/kg/day PFOS exposure may exacerbated liver inflammation and steatosis in high-fat diet (HFD)-fed mice with concurrently elevated expression of NLRP3 and caspase-1. PFOS exposure resulted in viability impairment and LDH release in BRL-3A rat liver cells. 25-100 µM concentrations of PFOS exposure activated the NLRP3 inflammasome, leading to consequent GSDMD cleavage, IL-1ß release and the initiation of pyroptosis in a dose-dependent manner, whereas treatment with 10 µM NLRP3 inhibitor MCC950 abrogated this effect. Moreover, pretreatment of 5 mM ROS scavenger N-acetyl-L-cysteine (NAC) ameliorated PFOS-induced NLRP3 inflammasome activation and pyroptosis. Collectively, our data highlight a pivotal role of pyroptotic death in PFOS-mediated liver inflammation and metabolic disorder.

Plasma metabolomics in the perioperative period of defect repair in patients with pulmonary arterial hypertension associated with congenital heart disease.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD-PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO3), bicarbonate in superior vena cava (svcHCO3), and the partial pressure of dissolved CO2 gas in radial artery (aPCO2) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO3, svcHCO3, and aPCO2, would be of great value in disease monitoring and evaluating future therapeutic interventions.

Structure-guided engineering of a flavin-containing monooxygenase for the efficient production of indirubin.

Indirubin is a bisindole compound for the treatment of chronic myelocytic leukemia. Here, we presented a structure-guided method to improve the activity of a flavin-containing monooxygenase (bFMO) for the efficient production of indirubin in Escherichia coli. A flexible loop interlocked with the active pocket through a helix and the substrate tunnel rather than the active pocket in bFMO were identified to be two reconfigurable structures to improve its activity, resulting in K223R and N291T mutants with enhanced catalytic activity by 2.5- and 2.0-fold, respectively. A combined modification at the two regions (K223R/D317S) achieved a 6.6-fold improvement in catalytic efficiency (kcat/Km) due to enhancing π-π stacking interactions stabilization. Finally, an engineered E. coli strain was constructed by metabolic engineering, which could produce 860.7 mg/L (18 mg/L/h) indirubin, the highest yield ever reported. This work provides new insight into the redesign of FMOs to boost their activities and an efficient approach to produce indirubin.

Improving the functionality of chitosan-based packaging films by crosslinking with nanoencapsulated clove essential oil.

The study aimed to obtain chitosan composite films with gratifying physical and functional properties. First, we developed a Pickering emulsion containing clove essential oil (CEO)-loaded nanoparticles with 1:2 (w/w) zein and sodium caseinate (NaCas). We found that in this ratio, the CEO-loaded zein-NaCas (C/ZN) nanoparticles had smaller particle size, proper polydispersity index (PDI) and zeta potential as well as higher encapsulation efficiency. Then, the acquired C/ZN nanoparticles were incorporated into chitosan film at three levels (0.2%, 0.4% and 0.6%), reducing the water vapor permeability to 4.62 × 10-6 g·s-1·m-1·Pa. Also, the tensile strength and break elongation of chitosan films were increased, reaching 38.67 MPa and 1.56%, respectively. The infrared spectroscopy verified that the intermolecular hydrogen bonds exist between chitosan and C/ZN nanoparticles. The chitosan composite films showed a controlled-release property of CEO in 96 h. Finally, the chitosan composite films showed the improved antibacterial property by creating larger inhibition zones against Escherichia coli (3.29 mm) and Staphylococcus aureus (6.15 mm). In general, we improved the water resistance, light blocking, mechanical strength, controlled-release and antibacterial properties of chitosan film with C/ZN nanoparticles. The current edible antibacterial films have great potential on applications for food preservation and food delivery system.

The safety and feasibility of intra-corporeal gastroduodenostomy using a self-pulling and latter transected method (Delta SPLT) in totally laparoscopic distal gastrectomy.

BACKGROUND AND OBJECTIVES: In 2016, the self-pulling and latter transection method (named "Delta SPLT"), a modified delta-shaped gastroduodenostomy (DA) technique for totally laparoscopic distal gastrectomy, was described. Delta SPLT reduced the technical difficulty of the surgery and the quantity of cartridges required with a manageable initial safety profile. Here, the safety and feasibility of this technique are analyzed at 1 year's follow-up. METHODS: The demographic and clinicopathologic profiles, perioperative details, and postoperative outcomes of 45 consecutive patients who underwent Delta SPLT from March 2016 to March 2019 were retrospectively analyzed. The Delta SPLT technique, which consisted of one endoscopic linear stapler and four cartridges each, was used for reconstruction in every case. RESULTS: The mean operative time was 127.1 ± 38.2 min, including a reconstruction duration of 22.6 ± 7.2 min. There were no surgical or anastomotic complications. The mean postoperative stay duration was 5.8 ± 1.2 days, and the morbidity rate was 2.2% with one case of postoperative pneumonia. CONCLUSIONS: The results at the one-year follow-up suggest that Delta SPLT is a safe and feasible procedure. Delta SPLT is characterized by fewer difficulties experienced during surgery, lower surgical costs, it is easy to practice, and it is beneficial for patients who are undergoing gastroduodenostomy.

Clinicopathological Characteristics and Prognostic Factors of Patients with Gastric Cancer Accompanying Neuroendocrine Differentiation (NEDGC).

AIM: Gastric carcinoma with neuroendocrine differentiation (NEDGC) is a relatively rare pathologic diagnosis in clinical practice, which has no specific guidelines or treatment recommendations yet. In this study, we aim to investigate the clinicopathological characteristics and prognostic factors of this disease. PATIENTS AND METHODS: We retrospectively analyzed clinicopathological data from a series of 82 NEDGC patients who underwent surgery for gastrectomy at Huashan Hospital Fudan University between January 2007 and December 2018. Furthermore, a series of 50 cases were used to analyze 3-year overall survival (OS). RESULTS: Ages of the patients ranged from 26 to 83 years (M:F, 4.8:1). The majority of patients suffered from some symptoms (97.6%), as the most common one was abdominal pain (48.8%). Most of the tumors were ≥5 cm (53.7%), in the lower part of the stomach (47.5%), and with advanced T (87.8% ≥T3) and N (67.1% ≥N1) stage. As to the neuroendocrine markers, Syn showed a slight advantage on sensitivity than CgA (79.3 and 75.6%, respectively). The 3-year OS was 54%. Advanced T stage (≥T3) of the primary tumor, positive lymphovascular invasion (LVI), large tumor size (5.5cm), high neutrophil-to-lymphocyte ratio (NLR, 2.51), and low prealbumin level (173.87 mg/L) were associated with inferior OS based on the univariate analysis. Low preoperative hemoglobin level (113.87g/L), laparoscopic-assisted gastrectomy, and advanced N stage (N3) were three independent risk factors for 3-year OS of NEDGC patients in both univariate and multivariate analysis. CONCLUSION: The TN staging system for gastric adenocarcinoma also has a prognostic value for NEDGC patients, while N3 stage works as an independent predictor of patients' survival. Since most of the NEDGC patients were in advanced stage, proper indications to perform operative laparoscopy should be selected.