Celiac Axis Stenosis as an Independent Risk Factor for Bile Leakage in Laparoscopic Pancreaticoduodenectomy: A Retrospective Study.

Background: Celiac axis stenosis can potentially lead to insufficient blood supply to vital organs, such as the liver, spleen, pancreas, and stomach. This condition result in the development of collateral circulation between the superior mesenteric artery and the hepatic artery. However, these collateral circulations are often disrupted during pancreaticoduodenectomy (PD), which may increase the risk of postoperative complications. Methods: A retrospective analysis was conducted on patients who underwent laparoscopic pancreaticoduodenectomy (LPD) from April 2015 to April 2023. Celiac trunk stenosis is classified according to the degree of stenosis: no stenosis (<30%), grade A (30%-<50%), grade B (50%-≤80%), and grade C (>80%). The incidence of postoperative complications was evaluated, and both univariate and multivariate risk analyses were conducted. Results: A total of 997 patients were included in the study, with mild celiac axis stenosis present in 23 (2.3%) patients, moderate stenosis in 18 (1.8%) patients, and severe stenosis in 10 (1.0%) patients. Independent risk factors for the development of bile leakage, as identified by both univariate and multivariate analyses, included body mass index (BMI) (HR = 1.108, 95% CI = 1.008-1.218, P = .033), intra-abdominal infection (HR = 2.607, 95% CI = 1.308-5.196, P = .006), postoperative hemorrhage (HR = 4.510, 95% CI = 2.048-9.930, P = <0.001), and celiac axis stenosis (50%-≤80%, HR = 4.235, 95% CI = 1.153-15.558, P = .030), and (>80%, HR = 4.728, 95% CI = .882-25.341, P = .047). Celiac axis stenosis, however, was not determined to be an independent risk factor for pancreatic fistula (P > 0.05). Additionally, the presence of an aberrant hepatic artery did not significantly increase the risk of postoperative complications when compared with celiac axis stenosis alone. Conclusion: Severe celiac axis stenosis is an independent risk factor for postoperative bile leakage following LPD.

The Inflammatory Response and Long-Term Outcomes Between Open and Laparoscopic Pancreatoduodenectomy:A Propensity-Matched Single-Institution Study.

Background: In recent years, although laparoscopic pancreatoduodenectomy (LPD) has experienced rapid development both domestically and internationally, however, there are still varying opinions toward LPD. Methods: From January 2020 to July 2022, the data were collected. We compared the inflammatory response at various postoperative time points and evaluated long-term outcomes between the two groups. Results: In the early stage, the LPD group exhibited lower values of white blood cells, C-reactive protein, neutrophils, and platelets after surgery compared with open pancreatoduodenectomy (OPD) (P all<0.05). However, no statistically significant differences were observed in terms of procalcitonin, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Before propensity score matching, no statistical significance was observed between two groups, whether in terms of disease-free survival (DFS) (P = .406) or overall survival (OS) (P = .851). However, to further control for confounding factors, propensity score matching was used. The analysis revealed that DFS still showed no significant difference (P = .928), but, in the term of OS, a statistical significance was observed between the two groups. Conclusion: LPD demonstrates a comparable long-term outcomes to OPD and even slightly superior OS. Moreover, the LPD group exhibits a lower inflammatory response during early postoperative period.

Screening of colorectal cancer: Methods and strategies.

Colorectal cancer (CRC) has high incidence and mortality rates, and the emergence and application of CRC screening have helped us effectively control the occurrence and development of CRC. Currently, common international screening methods include tests based on feces and blood, and examination methods that allow for visualization, such as sigmoidoscopy and colonoscopy. Some methods have been widely used, whereas others such as multi-target stool RNA test are still being explored and developed, and are expected to become front-line screening methods for CRC in the future. The choice of screening method is affected by external conditions and the patients' situation, and the clinician must choose an appropriate strategy according to the actual situation and the patient's wishes. This article introduces various CRC screening methods and analyzes the factors relevant to the screening strategy.

Laparoscopic Pancreaticoduodenectomy Combined With Portal-Superior Mesenteric Vein Resection and Reconstruction: Inferior-Posterior "Superior Mesenteric Artery-First" Approach.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) with portal-superior mesenteric vein (PV/SMV) resection and reconstruction is increasingly performed. We aimed to introduce a safe and effective surgical approach and share our clinical experience with LPD with PV/SMV resection and reconstruction. METHODS: We reviewed data for the patients undergoing LPD and open pancreaticoduodenectomy (OPD) combined with PV/SMV resection and reconstruction at the First Hospital of Jilin University between April 2021 and May 2023. The inferior-posterior "superior mesenteric artery-first" approach was used. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the 2 groups to conduct a comprehensive evaluation of LPD with major vascular resection. RESULTS: A cohort of 37 patients with periampullary and pancreatic tumors underwent pancreaticoduodenectomy (PD) with major vascular resection and reconstruction, consisting of 21 LPDs and 16 OPDs. The LPD group had a longer operation time (322 vs. 235 min, P =0.039), reduced intraoperative bleeding (152 vs. 325 mL, P =0.026), and lower intraoperative blood transfusion rates (19.0% vs. 50.0%, P =0.046) compared with the OPD group. The LPD group had significantly shorter operation times in end-to-end anastomosis (26 vs. 15 min, P =0.001) and artificial grafts vascular reconstruction (44 vs. 22 min, P =0.000) compared with the OPD group. There was no significant difference in the rate of R0 resection (100% vs. 87.5%, P =0.096). The length of hospital stay and ICU stay did not show significant differences between the 2 groups (15 vs. 18 d, P =0.636 and 2.5 vs. 4.5 d, P =0.726, respectively). However, the postoperative hospital stay in the LPD group was notably shorter compared with the OPD group (11 vs. 16 d, P =0.007). Postoperative complication rates, including postoperative pancreatic fistula (POPF) Grade A/B, biliary leakage, and delayed gastric emptying (DGE), were similar between the two groups (38.1% vs. 43.8%, P =0.729). In addition, 1 patient in each group developed thrombosis, with vascular patency improving after anticoagulation treatment. CONCLUSION: LPD combined with PV/SMV resection and reconstruction can be easily and safely performed using the inferior-posterior "superior mesenteric artery-first" approach in cases of venous invasion. Further studies are required to evaluate the procedure's long-term outcomes.

Analysis of the Short-Term Complications of Laparoscopic Pancreaticoduodenectomy in Patients with Metabolic Syndrome.

Objective: To investigate the impact of metabolic syndrome (MetS) on short-term complications of laparoscopic pancreaticoduodenectomy (LPD). Materials and Methods: We retrospectively analyzed perioperative data of patients who underwent LPD in our department from January 2020 to January 2022. The patients were divided into the MetS group and non-MetS group based on whether they had MetS. The incidence of postoperative complications and mortality rate was compared between the two groups. Results: The study involved 279 patients, with 30 having MetS and 249 without. However, the MetS and non-MetS groups differed significantly in terms of postoperative pancreatic fistula rate (26.6% versus 8.4%), abdominal infection rate (33.3% versus 10.0%), pulmonary complications rate (16.7% versus 6.42%), Clavien-Dindo ≥3 rate (20% versus 8.0%), multiple complications rate (23.3% versus 9.6%), percutaneous drainage rate (33.3% versus 10.0%), 90-day mortality rate (6.7% versus 1.2%), and length of postoperative hospital stay (15.00 ± 12.78 versus 10.63 ± 5.23 days). However, the two groups differed no significantly with respect to age, gender, American Society of Anesthesiologists score, preoperative CA125/CA199 levels, surgery time, specimen removal time, and intraoperative blood loss. Conclusion: MetS increases the incidence of postoperative complications and perioperative mortality rate in LPD.

The Impact of Body Mass Index on Multiple Complications, Respiratory Complications, Failure to Rescue and In-hospital Mortality After Laparoscopic Pancreaticoduodenectomy: A Single-Center Retrospective Study.

Background: Pancreaticoduodenectomy serves as the standard surgical treatment for periampullary tumors. Previous studies have suggested that high body mass index (BMI) is associated with an unfavorable prognosis following laparoscopic pancreaticoduodenectomy (LPD). However, the relationship between low BMI and postoperative complications remains unclear. Materials and Methods: A retrospective analysis of clinical data from 1130 patients who underwent LPD between April 2014 and December 2022 was conducted. Multivariate regression and restricted cubic spline analyses were utilized to explore the correlations between BMI and short-term outcomes, with adjustments for potential confounders. Results: Multivariable logistic regression revealed that overweight, obese, or severely underweight patients had an elevated risk of postoperative pancreatic fistula (POPF) compared to those with a normal BMI. Moreover, obesity was significantly correlated with a higher proportion of "failure to rescue." BMI exhibited a J-shaped relationship with respiratory complications and in-hospital mortality, a W-shaped relationship with multiple complications and anastomotic leakage (pancreatic fistula), and a U-shaped association with "failure to rescue" rates. The lowest risk was observed at BMI levels of 20 and 25 kg/m2 for multiple complications and pancreatic fistula, respectively. Conclusion: Both high and low BMI are identified as risk factors for the occurrence of postoperative POPF and in-hospital mortality following LPD. Notably, patients with higher BMI and severe underweight conditions are associated with an increased likelihood of "failure to rescue."

Laparoscopic Duodenum-Preserving Pancreatic Head Resection: A Technique for the Treatment of Benign or Low-Grade Malignant Tumors (10 Cases Report).

Background: Laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) is a surgical procedure that involves the removal of the pancreatic head while aiming to preserve the integrity of the digestive and biliary tracts. With advancements in laparoscopic techniques, the utilization of LDPPHR has been increasing. Methods: We retrospectively analyzed the clinical data of 10 patients who underwent laparoscopic duodenum-preserving total pancreatic head resection (LDPPHR-t) at our center from June 2019 to October 2021. Additionally, we analyzed the use of indocyanine green (ICG) in the initial stage of LDPPHR, based on current reports. Results: LDPPHR-t was successfully performed in all patients. After surgery, 3 patients experienced pancreatic fistula (Grade B), 2 patients experienced bile leakage, and 2 patients experienced postoperative hemorrhage. However, no patient exhibited recurrence or required secondary surgery. Conclusion: LDPPHR-t is a new method for treating benign and low-grade malignant tumors in the pancreatic head. However, it is associated with a high incidence of postoperative complications. In the initial stage, the use of ICG can assist surgeons in identifying the biliary duct and pancreaticoduodenal artery arcade.

Prevalence of Malnutrition and the Value of Predicting Pancreatic Fistula in Patients with Laparoscopic Pancreatoduodenectomy.

Background: Pancreatoduodenectomy is a standard surgical procedure for periampullary tumors. With recent improvements in perioperative management, postoperative mortality has decreased significantly in recent years; however, postoperative pancreatic fistula (POPF) is still one of the most prevalent and dangerous complications. The purpose of this study was to analyze the prevalence of malnutrition and the value of predicting POPF in patients with laparoscopic pancreatoduodenectomy (LPD). Methods: We retrospectively analyzed the perioperative data of 747 patients undergoing LPD in the Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, China. Simultaneously, we analyzed the prevalence rate of malnutrition with three different nutritional assessment scores and explored the independent risk variables for POPF to identify potential predictive value. Results: Malnutrition was observed in 20.1% of patients with the prognostic nutritional index (PNI), 85.0% of patients with the controlling nutritional status (CONUT) score, and 73.1% of patients with the NRI score. Univariate and multivariate analyses all showed that the risk factors for POPF were pancreatic texture, pancreatic duct diameter, abdominal infection, body mass index (BMI), nomogram-revised risk index (NRI), and PNI. The receiver operating characteristic curve indicated that the BMI/PNI ratio was capable of predicting the occurrence of clinical POPF following LPD, with an area under the curve of 0.708. Conclusions: Compared with no malnourished patients, malnutrition is associated with a higher risk of POPF among patients with LPD. In addition, the BMI/PNI ratio has some predictive value in the development of POPF following LPD.

A Short-Term Outcomes Comparison of Laparoscopic Pancreaticoduodenectomy and Open Pancreaticoduodenectomy at Different Stages of Learning Curves: A Single Center Report.

Background: With the development of surgical instruments and the growth of professional expertise over the past decades, laparoscopic pancreatoduodenectomy (LPD) is widely applied in different centers. However, there are still some controversies about the safety of this procedure. Meanwhile, perioperative outcomes are affected by hospital size, surgeon experience, and the learning curve. The purpose of this study is to compare the short-term outcomes of LPD with open pancreatoduodenectomy (OPD) at different stages of the learning curve. Methods: We retrospectively analyzed the clinical data of 911 patients who had received pancreatoduodenectomy (PD) at a single institution. Among them, 208 patients underwent OPD, and 703 cases received LPD successfully. We divided those patients into three phases based on the key point of the learning curve for LPD and compared the perioperative outcomes with OPD at each stage. Result: Morbidity and mortality rates associated with LPD were significantly higher in the initial stage than in the OPD group, whereas the number of harvested lymph nodes and R0 resection rate for pancreatic cancer were comparable to the OPD group. As surgical experience increased, postoperative complications, operating time, and intraoperative blood loss all are greatly decreased. At the mature stage of the learning curve, the rate of postoperative complications in LPD was lower than in the OPD group. Meanwhile, the length of hospital stay was significantly shortened compared to the OPD group. Conclusion: After a long period of training and learning, LPD can be performed safely. And LPD can produce comparable oncological results, with faster postoperative recovery and lower incidence of postoperative complications, after the surgeons successfully surmounted the learning curve.

Application of Retrocolic Approach with Uncinate Process Priority in Laparoscopic Pancreaticoduodenectomy.

Background: Pancreaticoduodenectomy (PD) is a complex operative procedure, which remains the primary curative treatment for pancreatic, distal bile duct, and periampullary cancers. In recent years, with the continuous development of laparoscopic technology and equipment, laparoscopic pancreaticoduodenectomy (LPD) has been performed gradually in many high-volume surgical centers. However, it is still challenging even for experienced pancreatic surgeons to perform LPD, at the same time, with the accumulation of surgical experience, different surgical approaches are also constantly discussed. Methods: We retrospectively analyzed the clinical data of 323 patients who received LPD at a single institution. Among them, 200 patients received operations with retrocolic approach, 123 patients were treated with traditional approach. In this study, we analyzed perioperative data and compared survival time for patients with pancreatic cancers in two groups. Result: Compared with traditional approach, retrocolic approach with uncinate process priority has a shorter operative time (94.25 ± 6.46 minutes versus 116.43 ± .4.78 minutes, P = .009) and less intraoperative blood loss (80 mL versus 150 mL, P = .562). However, there is no statistical significance in the incidence of postoperative complications (≥ Clavien-Dindo [CD] III) (65 [32.5%] versus 45 [36.58%], P = .871), R0 resection rates (41 versus 38, P = .826), and the number of lymph nodes harvested (16.64 ± 5.93 versus 15.37 ± 4.65, P = .785) between two groups. Meanwhile, the median survival time of patients with pancreatic cancers in posterior approach group was longer than those in traditional approach group (30.34 months versus 28.54 months, P > .05); however, there was no statistical significance between them. Conclusion: Retrocolic approach with uncinate process priority is a feasible method for pancreatic cancer, which could reduce operating time and intraoperative bleeding, meanwhile, not increase the incidence of postoperative complications. Retrocolic approach with uncinate process priority can be generalized to larger group sizes.

Prognostic Significance of PNI in Patients With Pancreatic Head Cancer Undergoing Laparoscopic Pancreaticoduodenectomy.

Background: Recently, several prognosis indicators based on inflammatory and nutritional factors, such as the neutrophil-to-lymphocyte ratio (NLR), plated-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR) and prognosis nutritional index (PNI), have been proposed as prognosis factors for several cancers. However, few studies have looked into PNI. The goal of this research was to see if preoperative PNI had any predictive value in patients with pancreatic head cancer who were having a laparoscopic pancreaticoduodenectomy. Methods: From February 11, 2018 to May 31, 2019, two hundred and fifty-one pancreatic head carcinoma patients were retrospectively enrolled. The receiver operator characteristic (ROC) curve was used to determine the cut-off value. Patients were divided into two groups: PNI > 45.1 (high PNI group) and PNI < 45.1 (low PNI group), and clinic-pathological data was compared between the two groups. The link between PNI and NLR, PLR, and LMR, and their effect on overall survival. In addition, the factors of postoperative survival were analyzed univariate and multivariate. Results: PNI, NLR, PLR and LMR cut-off values were 45.1, 3.7,287.2 and 3.6, respectively. Between the two groups of patients, the low PNI group exhibited considerably higher PLR and lower LMR. PNI had a negative correlation with PLR and NLR (r = -0.329, p < 0.001 and r = 0.170, p = 0.014), but a positive correlation with LMR (r = 0.476, p < 0.001). The high PNI group had a considerably greater survival rate than the low PNI group (median survival days, 217 vs. 468, log-rank = 45.92, p < 0.001). PNI < 45.1(HR: 0.357, 95 percent CI, 0.263-0.485, p < 0.001) and LMR <3.6(HR: 0.705, 95 percent CI, 0.528-0.942, p < 0.018) were revealed to be possible predictive variable in univariate analysis. Only PNI <45.1 was found to be an independent predictive factor in multivariate analysis (HR: 0.359, 95%CI,: 0.256-0.502, p < 0.001). Conclusions: Our findings shoe that PNI is linked to a variety of systemic inflammatory response and can be used to predict survival in individuals with pancreatic head cancer.

Periostin renders cardiomyocytes vulnerable to acute myocardial infarction via pro-apoptosis.

AIMS: As a severe cardiovascular disease, acute myocardial infarction (AMI) could trigger congestive heart failure. Periostin (Postn) has been elucidated to be dramatically up-regulated in myocardial infarction. Abundant expression of Postn was also observed in the infarct border of human and mouse hearts with AMI. This work is dedicated to explore the mechanism through which Postn exerts its functions on AMI. METHODS AND RESULTS: The expression of Postn in AMI mice and hypoxia-treated neonatal mouse cardiomyocytes (NMCMs) was quantified by qRT-PCR. The biological functions of Postn in AMI were explored by trypan blue, TUNEL, flow cytometry analysis, and JC-1 assays. Luciferase activity or MS2-RIP or RNA pull-down assay was performed to study the interaction between genes. Postn exhibited up-regulated expression in AMI mice and hypoxia-treated NMCMs. Functional assays indicated that cell apoptosis in NMCMs was promoted via the treatment of hypoxia. And Postn shortage could alleviate cell apoptosis in hypoxia-induced NMCMs. Postn was verified to bind to mmu-miR-203-3p and be down-regulated by miR-203-3p overexpression. Postn and miR-203-3p were spotted to coexist with small nucleolar RNA host gene 8 (Snhg8) in RNA-induced silencing complex. The affinity between Snhg8 and miR-203-3p was confirmed. Afterwards, Snhg8 was validated to promote cell apoptosis in hypoxia-induced NMCMs partially dependent on Postn. Furthermore, vascular endothelial growth factor A (Vegfa) was revealed to bind to miR-203-3p and be implicated in the Snhg8-mediated AML cell apoptosis and angiogenesis. CONCLUSIONS: miR-203-3p availability is antagonized by Snhg8 for Postn and Vegfa-induced AMI progression.

The Impact of Aberrant Hepatic Artery on Resection Margin and Outcomes of Laparoscopic Pancreatoduodenectomy: A Single-Center Report.

BACKGROUND: Variations in the anatomy of the hepatic artery are common. This study was aimed at sharing our experience with identifying and protecting the aberrant hepatic artery (AHA) and discussing its impact on the resection margin and outcomes of laparoscopic pancreatoduodenectomy (LPD). METHODS: A total of 576 patients who underwent LPD between 2015 and 2020 were retrospectively selected and divided into AHA and no AHA groups for this study. The demographics of the patients, pathological features, surgical data, and postoperative complications were further compared and analyzed between the two groups. RESULTS: The AHA group included 127 patients (22.05%). No statistically significant differences were found between the AHA and no AHA groups in the intraoperative data, postoperative complications, and long-term survival with malignant tumor. There was also no significant difference in the R1 rate for pancreatic adenocarcinoma. CONCLUSIONS: AHA appears frequently; however, it does not change the incidence of perioperative adverse events following LPD or the long-term prognosis of malignant tumor. The preservation of AHA during surgery can be achieved with a well-planned approach and careful dissection.

Nitazoxanide impairs mitophagy flux through ROS-mediated mitophagy initiation and lysosomal dysfunction in bladder cancer.

Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Herein, we find that NTZ induces mitochondrial damage and mitophagy initiation through PINK1-generated phospho-ubiquitin(pS65-Ub) and autophagy receptor-mediated pathway even in the absence of Atg5/Beclin1. Meanwhile, NTZ inhibits lysosomal degradation activity, leading to mitophagy flux impairment at late stage. Mitochondrial reactive oxygen species (ROS) production is critical in this process, as eliminating ROS with N-acetylcysteine (NAC) efficiently inhibits PINK1 signaling-mediated mitophagy initiation and alleviates lysosomal dysfunction. Co-treatment with NTZ and autophagy inhibitor Chloroquine (CQ) to aggravate mitophagy flux impairment promotes NTZ-induced apoptosis, while alleviation of mitophagy flux impairment with ROS scavenger reduces cell death. Moreover, we also discover a similar signaling response in the 3D bladder tumor spheroid after NTZ exposure. In vivo study reveals a significant inhibition of orthotopic bladder tumors with no obvious systemic toxicity. Together, our results uncover the anti-tumor activities of NTZ with the involvement of ROS-mediated mitophagy modulation at different stages and demonstrate it as a potential drug candidate for fighting against bladder tumors.

Transmucosal Delivery of Self-Assembling Photosensitizer-Nitazoxanide Nanocomplexes with Fluorinated Chitosan for Instillation-Based Photodynamic Therapy of Orthotopic Bladder Tumors.

Theoretically, on account of improved local bioavailability of photosensitizers and attenuated systemic phototoxicity, intravesical instillation-based photodynamic therapy (PDT) for bladder cancer (BCa) would demonstrate significant advantages in comparison with the intravenous route. Actually, the low transmucosal efficiency, hypoxia regulation deficiency, as well as the biosafety risks of intravesical drug agents all have greatly limited the clinical development of instillation-based PDT for BCa. Herein, based on our recent findings on bladder intravesical vectors and photodynamic treatment, we explore and find that the conventional antiparasitic agent nitazoxanide (NTZ) by mixing with chlorine e6 (Ce6) conjugated human serum albumin (HSA), HSA-Ce6, is capable of forming self-assembled HSA-Ce6/NTZ nanoparticles (NPs). Then, the HSA-Ce6/NTZ complexes further fabricate with fluorinated chitosan (FCS), the synthesized transmucosal carrier, to form a biocompatible nanoscale system HSA-Ce6/NTZ/FCS NPs, which exhibit remarkably improved transmucosal delivery and uptake capacities compared with HSA-Ce6/NTZ alone or non-fluorinated HSA-Ce6/NTZ/CS NPs. Meanwhile, due to the metabolic regulation of tumor cells by NTZ, the tumor hypoxia could be efficaciously ameliorated to further favor PDT. This work represents a new photosensitizer nanomedicine formulation for the perfection of PDT performance through the modulation of tumor hypoxia by clinically approved agents. Thus, intravesical instillation of HSA-Ce6/NTZ/FCS NPs with favorable biocompatibility, followed by cystoscope-mediated PDT, could achieve a dramatically improved therapeutic effect to ablate orthotopic bladder tumors.

Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy.

Bladder cancer is a significant public health concern and social burden due to its high recurrence risk. Intravesical drug instillation is the primary therapy for bladder cancer to prevent recurrence. However, the intravesical drug therapeutic effect is limited by bladder penetrating barriers. The inadequate intravesical treatment might cause the low drug concentration in lesions, resulting in a high recurrence/progression rate of bladder cancer. Many strategies to get drugs across bladder penetrating barriers have been developed to improve intravesical treatment, including physical and chemical methods. This review summarizes the classical and updated literature and presents insights into great therapeutic potential strategies to overcome bladder penetrating barriers for improving the intravesical treatment of bladder cancer.

The operation training for magnetically controlled capsule endoscopy.

BACKGROUND AND AIM: Magnetically controlled capsule endoscopy (MCE) is a safe, noninvasive examination and has a diagnostic accuracy similar to that of standard gastroscopy. Now, MCE is widely used in the clinical practice. However, there is no studies about MCE training. This study aims to report the operation training course of MCE. METHODS: The MCE training data of trainees without gastroscopy experience was reviewed. The characteristics of trainees, training course, training time and training results were recorded. RESULTS: The MCE training data of five technical people were included in the present study. All participants were females with mean age of 32-years-old (range 30-34 years). All the participants finished the training course in 4 days. We reviewed the data of the first 10 MCE examination performed by the participant. Three participants could finish the whole stomach observation in all 10 patients (10/10). Two participants could finish the whole stomach observation in nine patients (9/10). CONCLUSION: After the systematic training course, technical staff can be trained for MCE operation. Further studies should be conducted to observe the learning curve of MCE operation.

Effect of rs4719839 polymorphism on risk of ventilator-associated pneumonia, expression of microRNA-148 and autophagy-related 16-like 1 (ATG16L1).

MiR-148 is a negative regulator of autophagy 16-like 1 (ATG16L1), a gene implicated in the pathogenesis of ventilator-associated pneumonia (VAP). Therefore, the role of miR-148 polymorphism in the pathogenesis of VAP was studied here. The expression of miR-148, ATG16L1, Beclin-I, LC3-II, TNF-α and IL-6 in serum and peripheral blood mononuclear cells (PBMCs) of VAP patients was detected to study their relationship in the pathogenesis of VAP. Chronic obstructive pulmonary disease patients carrying the AA/AG genotypes of miR-148 rs4719839 single nucleotide polymorphism (SNP) were more prone to VAP due to the higher expression of miR-148, TNF-α and IL-6 along with suppressed expression of ATG16L1, Beclin-I and LC3-II in their serum and PBMCs. Transfection of miR-148 mimics to primary PBMCs genotyped as GG and AA decreased the expression of ATG16L1, Beclin-I and LC3-II. Finally, cells carrying the AA genotype of rs4719839 SNP were more sensitive to the role of LPS stimulation in suppressing ATG16L1, Beclin-I and LC3-II expression while activating TNF-α and IL-6 expression. Our work presented detailed evidence, suggesting that the rs4719839 polymorphism can affect the risk of VAP.

IL-17A-producing T cells exacerbate fine particulate matter-induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR-mediated autophagy.

Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL-17A in lung injury, while its contribution to PM2.5-induced lung injury remains largely unknown. Here, we probed into the possible role of IL-17A in mouse models of PM2.5-induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate γδT and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway-, autophagy- and PI3K/Akt/mTOR signalling pathway-related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL-17A by γδT/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up-regulating IL-17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL-17A impaired the energy metabolism of airway epithelial cells in the PM2.5-induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL-17A in γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.

Neuroendocrine tumors of the gallbladder.

A gallbladder neuroendocrine neoplasm (GB-NEN) is a unique heterogeneous neoplasm, originating from neuroendocrine cells and able to secrete peptides as its neurotransmitter. Among all the neuroendocrine tumors (NETs), the GB-NEN prevalence is 0.5%, which accounts for ~2.1% of all gallbladder tumors. The current study aimed to present an up-to-date review of the clinical features, diagnosis and treatment of NETs of the gallbladder. A systematic literature search was performed in order to identify all relevant studies published. Thus far, the etiology and pathogenesis of GB-NEN remains unclear. Moreover, an ambiguous clinical manifestation exists as observed during laboratory examinations. As GB-NEN is a rare gallbladder lesion and is seldom seen in clinical practice, there is a limited availability of review reports, and it is therefore often considered only as a case study. It is difficult to distinguish GB-NEN from other gallbladder diseases using imaging diagnostic techniques. Although chemotherapy treatment provides prolonged progression-free survival, surgery is considered the best option. Thus, to overcome the inherent risks or shortfalls of traditional surgery; early detection, diagnosis and treatment of GB-NEN are required to improve patient longevity.