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The surprising omission or reduction of vital resources (food, fluid, social partners) can induce an aversive emotion known as frustrative nonreward (FNR), which can influence subsequent behavior and physiology. FNR is an integral mediator of irritability/aggression, motivation (substance use disorders, depression), anxiety/fear/threat, learning/conditioning, and social behavior. Despite substantial progress in the study of FNR during the twentieth century, research lagged in the later part of the century and into the early twenty-first century until the National Institute of Mental Health's Research Domain Criteria initiative included FNR and loss as components of the negative valence domain. This led to a renaissance of new research and paradigms relevant to basic and clinical science alike. The COVID-19 pandemic's extensive individual and social restrictions were correlated with increased drug and alcohol use, social conflict, irritability, and suicide, all potential consequences of FNR. This article highlights animal models related to these psychiatric disorders and symptoms and presents recent advances in identifying the brain regions and neurotransmitters implicated.

Assuntos

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BACKGROUND: Whether patients with diffuse gastric cancer, which is insensitive to chemotherapy, can benefit from neoadjuvant or adjuvant chemotherapy has long been controversial. AIM: To investigate whether perioperative chemotherapy can improve survival of patients with locally advanced diffuse gastric cancer. METHODS: A total of 2684 patients with locally advanced diffuse gastric cancer from 18 population-based cancer registries in the United States were analyzed. RESULTS: Compared with surgery alone, perioperative chemotherapy improved the prognosis of patients with locally advanced gastric cancer. Before stabilized inverse probability of treatment weighting (IPTW), the median overall survival (OS) times were 40.0 months and 13.0 months (P < 0.001), respectively. After IPTW, the median OS times were 33.0 months and 17.0 months (P < 0.001), respectively. Neoadjuvant chemotherapy did not improve the prognosis of patients with locally advanced gastric cancer compared with adjuvant chemotherapy after IPTW. After IPTW, the median OS times were 38.0 months in the neoadjuvant chemotherapy group and 42.0 months in the adjuvant chemotherapy group (P = 0.472). CONCLUSION: Patients with diffuse gastric cancer can benefit from perioperative chemotherapy. There was no significant difference in survival between patients who received neoadjuvant chemotherapy and those who received adjuvant chemotherapy.

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BACKGROUND: Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world, characterized by high incidence, high malignancy, and low survival rate. Currently, 1/4 of adults in the world suffer from Non-Alcoholic Fatty Liver Disease (NAFLD), with an incidence rate of 27% in Asia. METHODS: We used TCGA and GEO public database data sets to conduct weighted gene coexpression network analysis to identify relevant gene modules, defined the intersection of tumorigenesis-related modules and NASH development-related modules as shared genes, and then used single-factor Cox, LASSO, and multivariate Cox regression analysis screened out core shared genes and verified their prognostic value. We further investigated the relationship between core shared genes and immune infiltration, tumor mutational load, and drug sensitivity. Finally, RT-qPCR was used to verify its mRNA expression in different cell lines. RESULTS: We identified Karyopherin α 2 (KPNA2) as the core shared gene between NASH and HCC. Patients were divided into low-risk groups and high-risk groups based on the expression of KPNA2. The prognosis of the low-risk group was significantly better than that of the highrisk group. Furthermore, we found significant differences in tumor immune cell infiltration, somatic mutations, microsatellite instability, and drug sensitivity between different expression groups. CONCLUSION: There are very few studies on the molecular mechanism of the relationship between NAFLD and HCC. Our study demonstrates that KPNA2 is a potential therapeutic target and immune-related biomarker for patients with NAFLD and HCC.

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The development of flexible ITO-free devices is crucial for the industrial advancement of organic photovoltaic (OPV) technology. Here, a novel ITO-free device architecture is proposed, and ITO-free OPV devices are realized on glass substrates with performance comparable to that of ITO-based devices. It is also demonstrated that the performance of ITO-free devices on polyethylene terephthalate (PET) substrates is limited due to the higher surface roughness of PET, leading to high voltage losses, low device quantum efficiency, and high device leakage current. To address the issue of high roughness on the PET surface, a polyimide (PI) modification strategy is developed and the PI-modified PET is employed as the substrate to construct flexible ITO-free OPV devices and large-area modules with an active area of up to 16.5 cm2. This approach leads to decreased trap-assisted recombination losses, enhanced exciton dissociation efficiency, and a reduced density of pinholes in flexible OPV devices, resulting in improved photovoltaic performance under both strong and weak illumination conditions. The outcomes of this work are expected to advance the industrial development of flexible organic photovoltaic technology.

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Anode cell reversal typically leads to severe carbon corrosion and catalyst layer collapse, which significantly compromises the durability of proton exchange membrane fuel cells. Herein, three types of commercial carbon supports with various structures are facilely coated by polyaniline (PANI) and subsequently fabricated into reversal-tolerant anodes (RTAs). Consequently, the optimized PANI-coated catalyst RTAs demonstrate enhanced polarization performance and improved reversal tolerance compared to their uncoated counterparts, thus confirming the universality of this coating strategy. Essentially, the surface engineering introduced by PANI coating incorporates abundant N-groups and enhances coulombic interactions with ionomer side chains, which in turn reduces lower carbon exposure, promotes more uniform Pt deposition, and ensures better ionomer distribution. Accordingly, the membrane-electrode-assembly containing the Pt/PANI/XC-72R-1+IrO2 RTA presents a 100 mV (at 2500 mA cm-2) polarization performance improvement and 26-fold reduction in the degradation rate compared to the uncoated counterpart. This work provides a universal strategy for developing durable anodes and lays the groundwork for the practical fabrication of high-performance, low-degradation RTA.

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The rapid and accurate detection of programmed death-ligand 1 (PD-L1) expression is of great value in the diagnosis and treatment of tumors. ELISA-based traditional method is the gold standard for protein detection, but there are still some shortcomings, especially the antigen-antibody dependence, greatly increased the detection time and cost. This work constructed a label-free fluorescent probe for rapid and sensitive detection of PD-L1 using a truncated aptamer as recognition molecules and double-stranded DNA specific dyes (SYBR Green I) as signal units. After a series of optimization conditions, this probe has good detection capability for PD-L1 in buffer solution with the detection limit as low as 0.68 ng/mL. Due to the specific recognition ability of aptamer and target, this method also has good selectivity for PD-L1 detection. The recovery of PD-L1 in human serum samples ranges from 86.20 to 96.36%. Compared with other methods, this strategy does not need to be marked, and does not need other complex design and purification process, but simple operation process and strong anti-interference ability. The whole detection process can be completed within 20 min and has good application prospect. This work will provide reference for drug dosage and prognosis evaluation of specific tumor therapy.

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Sepsis represents a primary cause of acute kidney injury (AKI), yet the underlying mechanisms of septic AKI remain poorly understood. Thus, there exists an urgent need for a deeper understanding of its underlying mechanisms and the development of effective therapeutic strategies. Our study reveals a notable induction in microRNA-202-5p (miR-202-5p) levels within renal tubular cells in septic AKI both in vivo and in vitro models. Treatment of renal tubular cells with LPS induced NF-κB activation, which was linked to the induction of miR-202-5p. ChIP assays confirmed NF-κB binding to the miR-202-5p gene promoter upon LPS stimulation. Functionally, miR-202-5p mimics attenuated tubular cell death, kidney injury, and intra-renal inflammatory cytokine production, whereas inhibition of miR-202-5p conferred injurious effects in septic AKI. Notably, miR-202-5p suppressed the expression of High Mobility Group Box 2 (HMGB2) in both in vitro and in vivo septic AKI models. Luciferase microRNA target assays further validated HMGB2 as a direct target of miR-202-5p. Knockdown of HMGB2 inhibits LPS-induced NF-κB activation in septic AKI, as evidenced by HMGB2 siRNA transfection significantly inhibited the nuclear translocation of NF-κB. Together, these findings elucidate the NF-κB/miR-202-5p/HMGB2 negative feedback loop which can attenuate kidney injury by inhibiting renal inflammation in septic AKI. Our findings open new avenues for developing targeted therapies to manage septic AKI effectively.

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Dwarf or semi-dwarf plant structures are well-suited for intensive farming, maximizing yield, and minimizing labor costs. Watermelon (Citrullus lanatus) is classified as an annual vine plant with elongated internodes, yet the mechanism governing watermelon dwarfing remains unclear. In this study, a compact watermelon mutant dwarf, induced by the insertion of T-DNA, was discovered. Through re-sequencing, a gene named domain of unknown function 21 (ClDUF21), located downstream of the T-DNA insertion site, was identified as the candidate gene for the dwarf mutant, and its functionality was subsequently confirmed. Watermelon mutants generated through CRISPR/Cas9-mediated knockout of ClDUF21 revealed that homozygous mutants displayed a pronounced dwarfing phenotype, and protein-protein interaction analysis confirmed the direct interaction between ClDUF21 and ClDWF1. Subsequently, we employed CRISPR/Cas9 technology to precisely modify the homologous gene CsDUF21 in cucumber (Cucumis sativus) and performed protein interaction validation between CsDUF21 and CsDWF1, thereby demonstrating that the CsDUF21 gene also exhibits analogous functionality in plant dwarfing. These findings demonstrate that ClDUF21 governs plant dwarfism by modulating the brassinosteroid synthesis pathway via ClDWF1.

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ABSTRACT: Back pain is a significant public health problem that accounts for a high percentage of morbidity and disability worldwide. Low back pain is a frequent cause of missed workdays and job-specific disability and is associated with poor outcomes for employees and employers. An online learning module that focused on normal anatomy of the spine, common pathophysiologic diagnosis or findings that may contribute to back pain, and techniques for back pain reduction was created for employees at risk due to the nature of their labor-intensive jobs. This module also contained case studies and graphics that demonstrated ways to reduce risks or hazards by incorporating job-specific changes in the work environment. A mixed method statistical analysis of knowledge change was completed after participation in the online module. This demonstrated that participants had a marked increase in knowledge in all areas examined. In addition, participants perceived the module as beneficial for grasping anatomical concepts, understanding injury prevention and management strategies, valuing the shared information, leveraging visual aids, and applying practical examples per qualitative questions answered. Participants gained knowledge that can be used on the job to decrease risk of sustaining back pain or injury. The intervention approach enhances the understanding of back pain among industrial workers and holds profound implications for public health on a broader scale. Monitoring population health and preventing back pain and injury while at work is essential for safety and is also a core competency in public health.

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The blood-brain barrier is known to consist of a variety of cells and complex inter-cellular junctions that protect the vulnerable brain from neurotoxic compounds; however, it also complicates the pharmacological treatment of central nervous system disorders as most drugs are unable to penetrate the blood-brain barrier on the basis of their own structural properties. This dramatically diminished the therapeutic effect of the drug and compromised its biosafety. In response, a number of drugs are often delivered to brain lesions in invasive ways that bypass the obstruction of the blood-brain barrier, such as subdural administration, intrathecal administration, and convection-enhanced delivery. Nevertheless, these intrusive strategies introduce the risk of brain injury, limiting their clinical application. In recent years, the intensive development of nanomaterials science and the interdisciplinary convergence of medical engineering have brought light to the penetration of the blood-brain barrier for brain-targeted drugs. In this paper, we extensively discuss the limitations of the blood-brain barrier on drug delivery and non-invasive brain-targeted strategies such as nanomedicine and blood-brain barrier disruption. In the meantime, we analyze their strengths and limitations and provide outlooks on the further development of brain-targeted drug delivery systems.

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BACKGROUND: Breast cancer poses a significant health risk to women worldwide, with approximately 30% being diagnosed annually in the United States. The identification of cancerous mammary tissues from non-cancerous ones during surgery is crucial for the complete removal of tumors. RESULTS: Our study innovatively utilized machine learning techniques (Random Forest (RF), Support Vector Machine (SVM), and Convolutional Neural Network (CNN)) alongside Raman spectroscopy to streamline and hasten the differentiation of normal and late-stage cancerous mammary tissues in mice. The classification accuracy rates achieved by these models were 94.47% for RF, 96.76% for SVM, and 97.58% for CNN, respectively. To our best knowledge, this study was the first effort in comparing the effectiveness of these three machine-learning techniques in classifying breast cancer tissues based on their Raman spectra. Moreover, we innovatively identified specific spectral peaks that contribute to the molecular characteristics of the murine cancerous and non-cancerous tissues. CONCLUSIONS: Consequently, our integrated approach of machine learning and Raman spectroscopy presents a non-invasive, swift diagnostic tool for breast cancer, offering promising applications in intraoperative settings.

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We present a method for detecting evidence of natural selection in ancient DNA time-series data that leverages an opportunity not utilized in previous scans: testing for a consistent trend in allele frequency change over time. By applying this to 8433 West Eurasians who lived over the past 14000 years and 6510 contemporary people, we find an order of magnitude more genome-wide significant signals than previous studies: 347 independent loci with >99% probability of selection. Previous work showed that classic hard sweeps driving advantageous mutations to fixation have been rare over the broad span of human evolution, but in the last ten millennia, many hundreds of alleles have been affected by strong directional selection. Discoveries include an increase from ∼0% to ∼20% in 4000 years for the major risk factor for celiac disease at HLA-DQB1 ; a rise from ∼0% to ∼8% in 6000 years of blood type B; and fluctuating selection at the TYK2 tuberculosis risk allele rising from ∼2% to ∼9% from ∼5500 to ∼3000 years ago before dropping to ∼3%. We identify instances of coordinated selection on alleles affecting the same trait, with the polygenic score today predictive of body fat percentage decreasing by around a standard deviation over ten millennia, consistent with the "Thrifty Gene" hypothesis that a genetic predisposition to store energy during food scarcity became disadvantageous after farming. We also identify selection for combinations of alleles that are today associated with lighter skin color, lower risk for schizophrenia and bipolar disease, slower health decline, and increased measures related to cognitive performance (scores on intelligence tests, household income, and years of schooling). These traits are measured in modern industrialized societies, so what phenotypes were adaptive in the past is unclear. We estimate selection coefficients at 9.9 million variants, enabling study of how Darwinian forces couple to allelic effects and shape the genetic architecture of complex traits.

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BACKGROUND: The robotic hair transplant technology, ARTAS, has a series of fine mechanical structure and an intelligent recognition system that allows it to independently select hair follicular units (FUs) and effectively harvest hair. After entering China in 2016, ARTAS has attracted the attention of hair transplant surgeons and hair loss patients given its advantages in a short learning curve and simple operation. OBJECTIVE: To compare the efficacy and safety between the ARTAS system and follicular unit excision (FUE) in the treatment of male androgenetic alopecia (AGA) and to further promote the improvement and upgrading of ARTAS technology concerning hair transplantation. METHODS: Thirteen Chinese male patients with Norwood-Hamilton II-IV AGA aged 25-35 years were enrolled in this study. The donor site of each patient was randomly divided into left and right regions, receiving ARTAS on one side and FUE on the other. Yield, transection, and discard rates of hair FUs from both sides were compared. Safety of the procedures in whole, as well as follow-up results were investigated and evaluated. RESULTS: The total yield rate on the ARTAS side was lower than on the FUE side (82.05% vs. 90.03%, p > 0.05); the total discard rate on the ARTAS side was higher than on the FUE side (10.71% vs. 5.46%, p < 0.05); the total transection rate on the ARTAS side was lower than on the FUE side (13.17% vs. 13.96%, p > 0.05). No significant difference was found in patient satisfaction (efficacy), and no side effects or complications were detected during or after all surgeries. CONCLUSION: The current iteration of Robotic hair transplant technology is effective and safe, and can be recommended for AGA hair transplantation surgery.

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BACKGROUND: For premalignant main duct intraductal papillary mucinous neoplasms (MD-IPMN), laparoscopic duodenum and spleen-preserving subtotal or total pancreatectomy (LDSP-STP/TP) seems to be a viable option for parenchyma-sparing pancreatectomy. PATIENTS AND METHODS: On the basis of the imaging features, family history, genomic alterations, intraoperative ultrasound examination, and frozen section evaluation, we have proposed patient selection strategies for the LDSP-STP/TP technique for the first time. Additionally, a comprehensive step-by-step overview of this technique has been provided. To date, we have performed five LDSP-STP procedures and one LDSP-TP procedure. RESULTS: We successfully performed selective resection of the affected pancreatic parenchyma while preserving the duodenum, common bile duct (CBD), spleen, and splenic artery and vein. The operation time ranged from 295 to 495 min, with blood loss ranging from 100 to 300 mL. Postoperative pathological results revealed low-grade dysplasia in the resected pancreatic samples and margins. The patients resumed eating within 3-5 days after surgery, and all postoperative complications were classified as grade I according to the Clavien-Dindo classification. At the 3-month follow-up, there were no cases of CBD ischemic stenosis, splenic ischemia, or pseudocyst formation observed. For patients who received LDSP-STP, the longitudinal diameter of the remaining pancreatic tail ranged from 2.2 to 4.6 cm, and they demonstrated satisfactory long-term blood glycemic control. CONCLUSIONS: LDSP-STP/TP demonstrates technical feasibility and safety. It allows for the selective resection of the affected pancreatic parenchyma, thereby minimizing the impact of pancreatic functional impairment. However, it is crucial to validate this technique through long-term prospective observations.

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Rebuilding a clear-water state dominated by submerged macrophytes is essential for addressing eutrophication, yet the impact of benthic fish on water quality is complex. We conducted two experiments to explore the interaction of submerged plants and benthic fish on the water quality. Experiment I investigated the water clearing effects of submerged macrophytes with varying coverage (from 0% to 40%) before and after the removal of benthic fish. Experiment II explored the impacts of benthic fish at different densities on aquatic ecosystems with and without submerged macrophytes. The results showed that an increase in submerged macrophytes coverage significantly enhanced the reduction of some major water quality parameters. We assert that the coverage of submerged macrophytes should not be lower than 40% to establish and sustain a clear-water state in shallow lakes. However, benthic fish significantly weaken the ability of submerged macrophytes to improve water quality. Surprisingly, the presence or absence of macrophytes may reverse the role of benthic fish in freshwater ecosystems. When macrophytes are present, benthic fish can cause water quality to deteriorate. Conversely, when macrophytes are absent, benthic fish with a density of ≤ 10 g/m3 can restrict the growth of phytoplankton by directly consuming algae or by disturbing sediments to increase turbidity, thereby potentially improving water quality. But the detrimental effects of benthic fish with higher densities may gradually outweigh their benefits to water clarity. Therefore, the percentage of submerged macrophyte cover in combination with the density of benthic fish play crucial roles in shaping the ecological effects of benthic fish and overall ecosystem dynamics. These findings underscore the importance of understanding ecosystem interactions and have practical implications for the management of shallow lakes.

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This study aimed to investigate the dynamic changes in the physicochemical properties of polysaccharides from nine common Polygonatum spp. during in vitro simulated saliva-gastrointestinal digestion, in vitro fermentation, and their subsequent effects on human gut microbiota. Results revealed that the total sugar contents of Polygonatum spp. polysaccharides almost had little changes during the vitro digestion, and the molecular weight presented a downward trend. The in vitro digestion process produced almost no free monosaccharide, with small variations on FT-IR spectroscopy analysis. However, during the in vitro fermentation process, the polysaccharides generated remarkable changes, the total sugar showed a downward trend, and the molecular weight was degraded. There were significant changes in the monosaccharide composition, and possibly the sugar occurred isomerism. Regarding the concentrations of short-chain fatty acids, both acetic acid and propionic acid were found to be significantly elevated in the treatment group compared to the control group, and the pH value dramatically decreased. Simultaneously, Polygonatum spp. polysaccharides could remarkably modulate the richness of microbial communities and improved their diversity, especially Narrowly Defined Clostridium, and Bacteroidetes. In general, this study can be helpful to better understand the potential digestion and fermentation mechanism of the genus Polygonatum polysaccharides.

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The field of 3D medical image segmentation is witnessing a growing trend in the utilization of combined networks that integrate convolutional neural networks and transformers. Nevertheless, prevailing hybrid networks are confronted with limitations in their straightforward serial or parallel combination methods and lack an effective mechanism to fuse channel and spatial feature attention. To address these limitations, we present a robust multi-scale 3D medical image segmentation network, the Transformer-Driven Pyramid Attention Fusion Network, which is denoted as TPAFNet, leveraging a hybrid structure of CNN and transformer. Within this framework, we exploit the characteristics of atrous convolution to extract multi-scale information effectively, thereby enhancing the encoding results of the transformer. Furthermore, we introduce the TPAF block in the encoder to seamlessly fuse channel and spatial feature attention from multi-scale feature inputs. In contrast to conventional skip connections that simply concatenate or add features, our decoder is enriched with a TPAF connection, elevating the integration of feature attention between low-level and high-level features. Additionally, we propose a low-level encoding shortcut from the original input to the decoder output, preserving more original image features and contributing to enhanced results. Finally, the deep supervision is implemented using a novel CNN-based voxel-wise classifier to facilitate better network convergence. Experimental results demonstrate that TPAFNet significantly outperforms other state-of-the-art networks on two public datasets, indicating that our research can effectively improve the accuracy of medical image segmentation, thereby assisting doctors in making more precise diagnoses.

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Although the xylose mutarotation and transformation have been investigated largely separately, their relationship has been rarely systematically elaborated. The effect of several factors such as xylose concentration, temperature, and salt concentration, affecting the mutarotation of xylose are discussed. Nine alkali halides (LiCl, NaCl, KCl, LiBr, NaBr, KBr, LiI, NaI, and KI) are used to test salt effects. The relationship between xylose rotation rate constant (kM), specific optical rotation at equilibrium ([α]eqm), α/ß ratio, H chemical shift difference (ΔΔδ), Gibbs free energy difference (ΔG), hydrogen ion or hydroxide ion concentration ([H+] or [OH-]), and xylose conversion is discussed. Different salts dissolved in water result in different pH of the solutions, which affect the mutarotation of xylose, with the nature of both cation and anion. Shortly, the smaller the cation radius is and the larger the anion radius is, the greater the mutarotation rate is. In the dehydration of xylose to furfural in salty solutions, xylose conversion is positively correlated to mutarotation rate, H+ or OH- concentration, and the energy difference between α-xylopyranose and ß-xylopyranose. Although the [α]eqm of xylose is positively correlated with α/ß configuration ratio, there is no obvious correlation with xylose dehydration. The conversion to furfural in chlorides is superior to that in bromines and iodides, which is due to the fact that the pH of chloride salts is smaller than that of the corresponding bromide and iodized salts. Higher H+ concentration prefers to accelerate the formation of furfural. In basic salt solutions, the xylulose selectivity is higher than that of furfural at the initial stage of reaction. The furfural selectivity and carbon balance are better in acidic condition rather than in basic condition. In H2O-MTHF (2-Methyltetrahydrofuran) biphasic system, the optimal furfural selectivity of 81.0 % is achieved at 190 °C in 1 h with the assistance of LiI and a little HCl (0.2 mmol, 8 mmol/L in aqueous phase). A high mutarotation rate represents rapid xylose conversion, but a high furfural selectivity prefers in acidic solutions, which would be perfect if organic solvents were available to form biphasic systems.

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Biliary obstruction is a common gastrointestinal disorder with many etiological factors, such as benign and malignant diseases of the biliary tract, pancreas, and liver. Endoscopic ultrasound guided biliary drainage provides a new method for the treatment of biliary obstruction when ERCP cannula fails.

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Postoperative anastomotic stenosis is a common complication after biliary, pancreatic and gastrointestinal surgery, which may be caused by multiple factors such as tissue proliferation and cancer recurrence. Endoscopic therapy is often hampered when the lens is difficult to pass through. A patient with intestinal stricture complicated by bilioenterostomy stenosis was treated by superselection of guide wire and stent.