Gastrodin ameliorates neuroinflammation in Alzheimer's disease mice by inhibiting NF-κB signaling activation via PPARγ stimulation.

AIM: We investigated the effects and targets of gastrodin (GAS) for improving cognitive ability in Alzheimer's disease (AD). METHODS: The targets and mechanisms of GAS were analyzed by network pharmacology. Morris water and eight-arm radial mazes were used to detect the behaviors of 7-months-old APP/PS1 mice. The levels of IBA-1 and PPARγ were examined by histochemical staining, nerve cells were detected by Nissl staining, inflammatory cytokines were measured by ELISA, and protein expressions were monitored by Western blotting. The neurobehavioral effects of GAS on mice were detected after siRNA silencing of PPARγ. Microglia were cultured in vitro and Aß1-42 was used to simulate the pathology of AD. After treatment with GAS, the levels of inflammatory cytokines and proteins were assayed. RESULTS: Network pharmacological analysis revealed that PPARγ was the action target of GAS. By stimulating PPARγ, GAS inhibited NF-κB signaling activation and decreased neuroinflammation and microglial activation, thereby ameliorating the cognitive ability of AD mice. After silencing PPARγ, GAS could not further improve such cognitive ability. Cellular-level results demonstrated that GAS inhibited microglial injury, reduced tissue inflammation, and activated PPARγ. CONCLUSIONS: GAS can regulate microglia-mediated inflammatory response by stimulating PPARγ and inhibiting NF-κB activation, representing a mechanism whereby it improves the cognitive behavior of AD.

Simulation of the ligand-leaving process of the human heat shock protein.

The human heat shock protein plays a critical role in various diseases and is an important target for pharmacological modulation. Simulation of conformational changes and free energy profiles of the human heat shock protein derived by the ligand-leaving process is a challenging issue. In this work, steered molecular dynamics simulation was adopted to simulate the ligand-leaving process. Two composite systems of heat shock protein NHSP90 and small molecules 6FJ and 6G7 are selected as research objects. The free energy during the leaving of ligand small molecules is calculated using conventional molecular dynamics simulation, steered molecular dynamics simulation (SMD), and the umbrella sampling method. We found that the a slower pulling velocity (0.001 nm ns-1) will result in 2.19 kcal mol-1, and the umbrella sampling method gives a value of 3.26 kcal mol-1 for the free energy difference for the two systems, which reasonably agrees with experimental results. A faster-pulling velocity (0.01 nm ns-1) leads to a large overestimation of free energy. At the same time, the conformational analysis indicated that the faster pulling velocity may lead to the conformational change of NHSP90, which was proved to be false by the slower pulling velocity and the umbrella sampling method.

Cerebral glucagon-like peptide-1 receptor activation alleviates traumatic brain injury by glymphatic system regulation in mice.

AIM: We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor (GLP-1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI). METHODS: Immunofluorescence was employed to evaluate glymphatic system function. The blood-brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests. RESULTS: Cerebral GLP-1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN-020 abolished the protective effect of the GLP-1R agonist against cognitive impairment. CONCLUSION: Cerebral GLP-1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI.

Long-term outcomes of endoscopic papillary large-balloon dilation (12-15 mm) with or without limited sphincterotomy for removal of bile duct stones.

BACKGROUND: Limited endoscopic sphincterotomy with large balloon dilation (ES-LBD) and endoscopic papillary large-balloon dilation (EPLBD) have been proven safe and effective for removal of bile duct stones. However, the long-term outcomes are not clear. The aim of this study was to assess the long-term outcomes of EPLBD (12-15 mm) with or without limited sphincterotomy for removal of common bile duct (CBD) stones. METHODS: Patients with EPLBD or ES-LBD referred for the removal of bile-duct stones between June 2008 and August 2020 were retrospectively reviewed. Complete stone clearance, endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events, and late biliary complications during long-term follow-up were analyzed. RESULTS: Basic patient characteristics were not significantly different between the groups that underwent EPLBD (n = 168) and ES-LBD (n = 57). EPLBD compared with ES-LBD resulted in similar outcomes in terms of overall successful stone removal (99.4% vs. 100%, P = 1.00) and ERCP-related adverse events (7.7% vs. 5.3%, P = 0.77). The mean duration of the follow-up were 113.6 months and 106.7 months for patients with EPLBD and ES-LBD, respectively (P = 0.13). There was no significant difference between EPLBD and ES-LBD in the incidence of stone recurrence [20 (11.9%) vs. 9 (15.8%); P = 0.49]. Multivariate analysis showed that a diameter of CBD ≥ 15 mm (OR = 3.001; 95% CI: 1.357-6.640; P = 0.007) was an independent risk factor for stone recurrence. CONCLUSIONS: The application of a large balloon (12-15 mm) via EPLBD is an effective and safe alternative to ES-LBD for extraction of large CBD stones. Endoscopic sphincterotomy prior to EPLBD may be unnecessary. A diameter of CBD ≥ 15 mm is a risk factor of stone recurrence.

The temporal dynamics of Large-Scale brain network changes in disorders of consciousness: A Microstate-Based study.

BACKGROUND AND OBJECTIVES: The resting-state brain is composed of several discrete networks, which remain stable for 10-100 ms. These functional microstates are considered the building blocks of spontaneous consciousness. Electroencephalography (EEG) microstate analysis may provide insight into the altered brain dynamics underlying consciousness recovery in patients with disorders of consciousness (DOC). We aimed to analyze microstates in the resting-state EEG source space in patients with DOC, the relationship between state-specific features and consciousness levels, and the corresponding patterns of microstates and functional networks. METHODS: We obtained resting-state EEG data from 84 patients with DOC (27 in a minimally conscious state [MCS] and 57 in a vegetative state [VS] or with unresponsive wakefulness syndrome). We conducted a microstate analysis of the resting-state (EEG) source space and developed a state-transition analysis protocol for patients with DOC. RESULTS: We identified seven microstates with distinct spatial distributions of cortical activation. Multivariate pattern analyses revealed that different functional connectivity patterns were associated with source-level microstates. There were significant differences in the microstate properties, including spatial activation patterns, temporal dynamics, state shifts, and connectivity construction, between the MCS and VS groups. DISCUSSION: Our findings suggest that consciousness depends on complex dynamics within the brain and may originate from the anterior cortex.

The accuracy of different mismatch negativity amplitude representations in predicting the levels of consciousness in patients with disorders of consciousness.

Introduction: The mismatch negativity (MMN) index has been used to evaluate consciousness levels in patients with disorders of consciousness (DoC). Indeed, MMN has been validated for the diagnosis of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS). In this study, we evaluated the accuracy of different MMN amplitude representations in predicting levels of consciousness. Methods: Task-state electroencephalography (EEG) data were obtained from 67 patients with DoC (35 VS and 32 MCS). We performed a microstate analysis of the task-state EEG and used four different representations (the peak amplitude of MMN at electrode Fz (Peak), the average amplitude within a time window -25- 25 ms entered on the latency of peak MMN component (Avg for peak ± 25 ms), the average amplitude of averaged difference wave for 100-250 ms (Avg for 100-250 ms), and the average amplitude difference between the standard stimulus ("S") and the deviant stimulus ("D") at the time corresponding to Microstate 1 (MS1) (Avg for MS1) of the MMN amplitude to predict the levels of consciousness. Results: The results showed that among the four microstates clustered, MS1 showed statistical significance in terms of time proportion during the 100-250 ms period. Our results confirmed the activation patterns of MMN through functional connectivity analysis. Among the four MMN amplitude representations, the microstate-based representation showed the highest accuracy in distinguishing different levels of consciousness in patients with DoC (AUC = 0.89). Conclusion: We discovered a prediction model based on microstate calculation of MMN amplitude can accurately distinguish between MCS and VS states. And the functional connection of the MS1 is consistent with the activation mode of MMN.

Self-assembled mononuclear complexes: open metal sites and inverse dimension-dependent catalytic activity for the Knoevenagel condensation and CO2 cycloaddition.

To lessen the greenhouse effect, measures such as improving the recovery of crude oil and converting carbon dioxide (CO2) into valuable chemicals are necessary to create a sustainable low-carbon future. To this end, the development of efficient new oil-displacing agents and CO2 conversion has aroused great interest in both academia and industry. The Knoevenagel condensation and CO2 cycloaddition are the key reactions to solve the above problems. Four Cu- or Zn-based molecular complexes built from different ligands possessing hydrophilic-hydrophobic layers and different dimensionalities were chosen as solid catalysts for this study. Structural analysis revealed the presence of hydrophilic-hydrophobic layers and open metal sites in the low-dimensional complexes. To obtain deep insight into the reaction mechanism, first-principles density functional theory (DFT) calculations were carried out. These calculations confirmed that in the Knoevenagel condensation reaction, the final formation of benzylidenemalononitrile is the rate-determining step (an energy barrier (ΔE) value of 73.2 kJ mol-1). The zero-dimensional (0D) Cu molecular complex with unsaturated metal centers, hydrophilic and hydrophobic layers, exhibited higher catalytic activity (yield: 100%, temperature: room temperature, and time: 2 h) compared with one- and two-dimensional Cu complexes. In the presence of a 0D Zn complex co-catalyzed with Br- in the CO2 cycloaddition reaction, the ΔE value reduces to 35.5 kJ mol-1 for the ring opening of styrene oxide (SO), which is significantly lower than Br- catalyzed (80.9 kJ mol-1) reactions. The roles of unsaturated metal centers, hydrophilic-hydrophobic layers and dimensionality in the Knoevenagel condensation and CO2 cycloaddition were explained in the results of structure-activity relationships.

Brain re-expansion predict the recurrence of unilateral CSDH: A clinical grading system.

Objective: Assessing the risk of postoperative recurrence of chronic subdural hematoma (CSDH) is a clinical focus. To screen the main factors associated with the perioperative hematoma recurrence. The brain re-expansion is the core factor of recurrence. A clinical prognostic scoring system was also proposed. Methods: We included 295 patients with unilateral CSDH as the training group for modeling. Factors predicting postoperative recurrence requiring reoperation (RrR) were determined using univariate and multivariate regression analyses, and bivariate Pearson correlation coefficient analysis was used to exclude related factors. Receiver operating characteristic curve analysis evaluates the ability of main factors to predict RrR and determines the cut-off value of brain re-expansion rate. We developed a prognostic scoring system and conducted preliminary verification. A verification group including 119 patients with unilateral CSDH was used to verify the grading systems. Results: The key factors for predicting unilateral CSDH recurrence were cerebral re-expansion rate (≤ 40%) at postoperative days 7-9 (OR 25.91, p < 0.001) and the preoperative CT density classification (isodense or hyperdense, or separated or laminar types) (OR 8.19, p = 0.007). Cerebral atrophy played a key role in brain re-expansion (OR 2.36, p = 0.002). The CSDH prognostic grading system ranged from 0 to 3. An increased score was associated with a more accurate progressive increase in the RrR rate (AUC = 0.856). Conclusions: Our prognostic grading system could screen clinically high-risk RrR patients with unilateral CSDH. However, increased attention should be paid to brain re-expansion rate after surgery in patients with CSDH.

Multidimensional Assessment of Electroencephalography in the Neuromodulation of Disorders of Consciousness.

In the present study, we aimed to elucidate changes in electroencephalography (EEG) metrics during recovery of consciousness and to identify possible clinical markers thereof. More specifically, in order to assess changes in multidimensional EEG metrics during neuromodulation, we performed repeated stimulation using a high-density transcranial direct current stimulation (HD-tDCS) protocol in 42 patients with disorders of consciousness (DOC). Coma Recovery Scale-Revised (CRS-R) scores and EEG metrics [brain network indicators, spectral energy, and normalized spatial complexity (NSC)] were obtained before as well as fourteen days after undergoing HD-tDCS stimulation. CRS-R scores increased in the responders (R +) group after HD-tDCS stimulation. The R + group also showed increased spectral energy in the alpha2 and beta1 bands, mainly at the frontal and parietal electrodes. Increased graphical metrics in the alpha1, alpha2, and beta1 bands combined with increased NSC in the beta2 band in the R + group suggested that improved consciousness was associated with a tendency toward stronger integration in the alpha1 band and greater isolation in the beta2 band. Following this, using NSC as a feature to predict responsiveness through machine learning, which yielded a prediction accuracy of 0.929, demonstrated that the NSC of the alpha and gamma bands at baseline successfully predicted improvement in consciousness. According to our findings reported herein, we conclude that neuromodulation of the posterior lobe can lead to an EEG response related to consciousness in DOC, and that the posterior cortex may be one of the key brain areas involved in the formation or maintenance of consciousness.

Single-ion chelation strategy for synthesis of monodisperse Pd nanoparticles anchored in MOF-808 for highly efficient hydrogenation and cascade reactions.

Ultrafine Pd nanoparticles are prepared using a single-ion precursor on a MOF-808 carrier. The ligand 2,3-pyrazinedicarboxylic acid (Pza) is dispersed in porous MOF-808 via grafting on formic acid sites, and thus Pd2+ ions are chelated by Pza to form a new single-ion precursor Pd@MOF-808-Pza. Then a Pd-nano@MOF-808-Pza catalyst is prepared by direct reduction of this precursor using NaBH4. Material characterization reveals the homogeneous dispersion of 3-6 nm Pd nanoparticles within the MOF-808 matrix. Pd-nano@MOF-808-Pza exhibits excellent catalytic activity in the hydrogenation of unsaturated nitrogen-containing compounds, and other typical reactions, such as the Knoevenagel condensation, Suzuki/Heck cross-coupling, and hydrogen tandem reactions. In addition, density functional theory (DFT) calculations are carried out to elucidate the chelation of Pd2+ ions by Pza on MOF-808 and propose mechanisms of hydrogenation reactions. This work provides an effective reduction catalyst, and more importantly, a single-ion chelation strategy for design and synthesis of metal supported catalysts.

Factors correlated with the postoperative recurrence of chronic subdural hematoma: An umbrella study of systematic reviews and meta-analyses.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurological disease, and the surgical evacuation of subdural collection remains the primary treatment approach for symptomatic patients. Postoperative recurrence is a serious complication, and several factors are correlated with postoperative recurrence. METHODS: We searched Embase, Web of Science, PubMed, and Cochrane Library from their establishment to September 2020. Reports on randomized, prospective, retrospective, and overall observational studies on the management of surgical patients with CSDH were searched, and an independent reviewer performed research quality assessment. Factors that affect the postoperative recurrence of CSDH were extracted: social demographics, drugs (as the main or auxiliary treatment), surgical management, imaging, and other risk factors. We evaluated the recurrence rate of each risk factor. A random effect model was used to perform a meta-analysis, and each risk factor affecting the postoperative recurrence of CSDH was then evaluated and graded. FINDINGS: In total, 402 studies were included in this analysis and 32 potential risk factors were evaluated. Among these, 21 were significantly associated with the postoperative recurrence of CSDH. Three risk factors (male, bilateral hematoma, and no drainage) had convincing evidence. The classification of evidence can help clinicians identify significant risk factors for the postoperative recurrence of CSDH. INTERPRETATION: Only few associations were supported by high-quality evidence. Factors with high-quality evidence may be important for treating and preventing CSDH recurrence. Our results can be used as a basis for improving clinical treatment strategies and designing preventive methods. FUNDING: No funding was received.

Evaluation of the prognosis of acute subdural hematoma according to the density differences between gray and white matter.

Objective: Acute subdural hematoma (ASDH) is a common neurological emergency, and its appearance on head-computed tomographic (CT) imaging helps guide clinical treatment. To provide a basis for clinical decision-making, we analyzed that the density difference between the gray and white matter of the CT image is associated with the prognosis of patients with ASDH. Methods: We analyzed the data of 194 patients who had ASDH as a result of closed traumatic brain injury (TBI) between 2018 and 2021. The patients were subdivided into surgical and non-surgical groups, and the non-surgical group was further subdivided into "diffused [hematoma]" and "non-diffused" groups. The control group's CT scans were normal. The 3D Slicer software was used to quantitatively analyze the density of gray and white matter depicted in the CT images. Results: Imaging evaluation showed that the median difference in density between the gray and white matter on the injured side was 4.12 HU (IQR, 3.91-4.22 HU; p < 0.001) and on the non-injured side was 4.07 HU (IQR, 3.90-4.19 HU; p < 0.001), and the hematoma needs to be surgically removed. The median density difference value of the gray and white matter on the injured side was 3.74 HU (IQR, 3.53-4.01 HU; p < 0.001) and on the non-injured side was 3.71 HU (IQR, 3.69-3.73 HU; p < 0.001), and the hematoma could diffuse in a short time. Conclusion: Quantitative analysis of the density differences in the gray and white matter of the CT images can be used to evaluate the clinical prognosis of patients with ASDH.

Molecular mechanism of methyl-dependent and spatial-specific DNA recognition of c-Jun homodimer.

DNA methylation is important in regulation of gene expression and normal development because it alters the interplay between protein and DNA. Experiments have shown that a single 5-methylcytosine at different CpG sites (mCpG) might have different effects on specific recognition, but the atomistic origin and dynamic details are largely unclear. In this work, we investigated the mechanism of monomethylation at different CpG sites in the cognate motif and the cooperativity of full methylation. By constructing four models of c-Jun/Jun protein binding to the 5[Formula: see text]-XGAGTCA-3[Formula: see text] (X represents C or methylated C) motif, we characterized the dynamics of the contact interface using the all-atom molecular dynamics method. Free energy analysis of MM/GBSA suggests that regardless of whether the C12pG13 site of the bottom strand is methylated, the effects from mC25 of the top strand are dominant and can moderately enhance the binding by [Formula: see text] 31 kcal/mol, whereas mC12 showed a relatively small contribution, in agreement with the experimental data. Remarkably, we found that this spatial-specific influence was induced by different regulatory rules. The influence of the mC25 site is mainly mediated by steric hindrance. The additional methyl group leads to the conformational changes in nearby residues and triggers an obvious structural bending in the protein, which results in the formation of a new T-Asn-C triad that enhances the specific recognition of TCA half-sites. The substitution of the methyl group at the mC12 site of the bottom strand breaks the original H-bonds directly. Such changes in electrostatic interactions also lead to the remote allosteric effects of protein by multifaceted interactions but have negligible contributions to binding. Although these two influence modes are different, they can both fine-tune the local environment, which might produce remote allosteric effects through protein-protein interactions. Further analysis reveals that the discrepancies in these two modes are primarily due to their location. Moreover, when both sites are methylated, the major determinant of binding specificity depends on the context and the location of the methylation site, which is the result of crosstalk and cooperativity.

Toward the Prediction of Multi-Spin State Charges of a Heme Model by Random Forest Regression.

The random forest regression (RFR) model was introduced to predict the multiple spin state charges of a heme model, which is important for the molecular dynamic simulation of the spin crossover phenomenon. In this work, a multiple spin state structure data set with 39,368 structures of the simplified heme-oxygen binding model was built from the non-adiabatic dynamic simulation trajectories. The ESP charges of each atom were calculated and used as the real-valued response. The conformational adapted charge model (CAC) of three spin states was constructed by an RFR model using symmetry functions. The results show that our RFR model can effectively predict the on the fly atomic charges with the varying conformations as well as the atomic charge of different spin states in the same conformation, thus achieving the balance of accuracy and efficiency. The average mean absolute error of the predicted charges of each spin state is <0.02 e. The comparison studies on descriptors showed a maximum 0.06 e improvement in prediction of the charge of Fe 2+ by using 11 manually selected structural parameters. We hope that this model can not only provide variable parameters for developing the force field of the multi-spin state but also facilitate automation, thus enabling large-scale simulations of atomistic systems.

Parthenolide inhibits the proliferation and induces the apoptosis of human uveal melanoma cells.

AIM: To explore the effect of parthenolide (PTL) on human uveal melanoma (UM) cells (C918 and SP6.5 cells) and its molecular mechanism. METHODS: Carboxyfluorescein succinimidyl amino ester (CFSE) assays and cell counting kit-8 (CCK-8) were performed to detect the cell viability. Flow cytometry was used to analyze cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were performed to measure proliferation-related and apoptosis-related factors. RESULTS: Firstly, PTL decreased the viability of C918 and SP6.5 cells in a dose-dependent manner, and the effect of PTL on C918 cells was stronger than on SP6.5; however, it did not affect normal cells. Secondly, PTL increased the proportion of cell number at cell cycle G1 phase in C918 cells, and decreased the proportion of cell number at S phase, but the proportion did not change at G2 phase. In addition, PTL induced the apoptosis of C918 cells, and decreased the expressions of Cyclin D1, B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-XL). Also, PTL increased Cyclin inhibition protein 1 (P21), Bcl-2-associated X protein (Bax), Cysteinyl aspartate specific proteinas-3 (Caspase-3) and Caspase-9 expression. However, the expression of Caspase-8 was not changed. CONCLUSION: PTL inhibites proliferation and induces apoptosis in UM cells by arresting G1 phase and regulating mitochondrial pathway, however, it does not affect normal cells.

Long-term outcomes of therapeutic ERCP in pediatric patients with pancreas divisum presenting with acute recurrent or chronic pancreatitis.

OBJECTIVES: The aim of this study was to evaluate the long-term outcomes of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for pediatric patients with pancreas divisum (PD) presenting with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). METHODS: Between May 2008 and August 2017, pediatric patients with PD who received endotherapy at Ruijin Hospital were identified and grouped according to clinical presentation, namely ARP and CP. Primary success was defined as patients' improvement in symptoms after index ERCPs, without further intervention or any analgesic. RESULTS: A total of 74 ERCPs were performed in 38 pediatric patients. The frequency of at least 1 genetic mutation identified in patients with ARP and CP was 44.4% and 68.4%, respectively. Patients with CP required more ERCPs than those with ARP (2.4 ±â€¯1.7 vs. 1.1 ±â€¯0.4, P = 0.005). The incidence of post-ERCP complications was 14.9%, including pancreatitis of 13.5% and hemorrhage of 1.4%. During a median follow-up duration of 41 months (range, 12-123 months), the frequency of pancreatitis episodes decreased significantly from 2.31 to 0.45 (P < 0.0001). The 25% recurrence and reintervention rates were estimated at 25 and 48 months, respectively, without significant difference between patients with ARP or CP. There was a nonsignificant trend towards a higher rate of primary success in patients with ARP than those with CP (92.9% vs. 69.6%, P = 0.123). After further endotherapy, 91.3% patients with CP improved clinically. CONCLUSIONS: Therapeutic ERCP is an effective and safe intervention for pediatric patients with symptomatic PD. Patients presenting with CP seem to achieve improvement after additional ERCPs.

Neural activities are unfavorable for the prognosis of ovarian cancer through mRNA expression analysis.

Aim: Ovarian cancer (OC) is the leading lethal gynecological cancer in women worldwide. Understanding the molecular mechanism of OC is very important for the identification of highly sensitive biomarkers for its prognosis. Methodology: We detected prognostic-related mRNA of OC in OncoLnc database. The main features between the unfavorable and favorable prognostic OC mRNAs were analyzed and Kyoto Encyclopedia of Genes and Genomes pathway enrichment as well as correlation analysis was conducted in our study. Conclusion: Our findings suggest that neural activities can promote OC progression, indicating poor prognosis, among which axon guidance functions most significantly govern the main neural activities, followed by neurogenesis and angiogenesis. Four neural genes (NTN1, UNC5B, EFNB2 and EFNA5) could serve as promising biomarkers and therapeutic targets for precision medicine to treat OC patients.

Correction to: Minichromosome Maintenance (MCM) family as potential diagnostic and prognostic tumor markers for human gliomas.

Following publication of the original article [1], the author noticed that there are some errors with Table 1 and Table 2. Please see the correct tables below. The authors apologize for any inconvenience caused.

Comparison of efficacy and safety of transpancreatic septotomy, needle-knife fistulotomy or both based on biliary cannulation unintentional pancreatic access and papillary morphology.

BACKGROUND: Precut sphincterotomy has been widely performed to facilitate selective biliary access when standard cannulation attempts failed during endoscopic retrograde cholangiopancreatography (ERCP). However, scarce data are available on different precut techniques for difficult biliary cannulation. This study aimed to evaluate the efficacy and safety of transpancreatic septotomy (TPS), needle-knife fistulotomy (NKF) or both based on the presence of unintentional pancreatic access and papillary morphology. METHODS: Between March 2008 and December 2016, 157 consecutive patients undergoing precutting for an inaccessible bile duct during ERCP were identified. Precut techniques were chosen depending on repetitive inadvertent pancreatic cannulation and the papillary morphology. We retrospectively assessed the rates of cannulation success and procedure-related complications among three groups, namely TPS, NKF, and TPS followed by NKF. RESULTS: The baseline characteristics of the three groups were comparable. The overall success rate of biliary cannulation reached 98.1%, including 111 of 113 (98.2%) with TPS, 35 of 36 (97.2%) with NKF and 8 of 8 (100%) with NKF following TPS, without significant difference among groups. The incidences of total complications and post-ERCP pancreatitis were 9.6% and 7.6%, respectively. There was a trend towards less frequent post-ERCP pancreatitis after NKF (0%) compared with 11 cases (9.7%) after TPS and one case (12.5%) after NKF following TPS, but not significantly different (P = 0.07). No severe adverse event occurred during this study period. CONCLUSIONS: The choice of precut techniques by the presence of unintended pancreatic access and the papillary morphology brought about a high success rate without increasing risk in difficult biliary cannulation.

Long-term outcomes of endoscopic papillary balloon dilation for removal of bile duct stones in Billroth II gastrectomy patients.

BACKGROUND: Endoscopic papillary balloon dilation (EPBD) for common bile duct (CBD) stones removal in Billroth II gastrectomy patients is feasible. However, the long-term outcomes of this technique are not clear. The aim of this study was to evaluate the procedural and long-term outcomes of EPBD for removal of CBD stones in Billroth II gastrectomy patients. METHODS: The records of patients with previous Billroth II gastrectomy referred for CBD stones removal with endoscopic retrograde cholangiopancreatography (ERCP) between July 1, 2008 and September 1, 2016 were retrospectively reviewed. The main outcomes of stone clearance, ERCP-related adverse events, and stone recurrence were analyzed. RESULTS: A total of 83 patients with previous Billroth II gastrectomy underwent ERCP in our center were reviewed. Forty-nine consecutive patients with previous Billroth II gastrectomy referred to EPBD for removal of CBD stones underwent 59 ERCP procedures were enrolled in the end. The overall successful CBD stones clearance was achieved in 42 patients (85.7%). ERCP-related adverse events was in 3 ERCP procedures (5.1%). Severe complications, including perforation and bleeding, were not observed. Six of 49 patients (12.2%) had stone recurrence after a median period of 22.5 months (range 6-71 months) from the end of stone removal treatment. Female [odds ratio (OR) = 11.352; 95% confidence interval (95% CI): 1.040-123.912; P = 0.046] and previous mechanical lithotripsy (OR = 13.423; 95% CI: 1.070-168.434; P = 0.044) were significantly associated with stone recurrence. CONCLUSIONS: At long-term follow-up, EPBD for removal of CBD stones appeared to be safe and effective in Billroth II gastrectomy patients. Female and previous mechanical lithotripsy may be risk factors for stone recurrence.