Integrative metagenomic and metabolomic analyses reveal the potential of gut microbiota to exacerbate acute pancreatitis.

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.

High-Resolution Quantum Dot Light-Emitting Diodes by Electrohydrodynamic Printing.

Quantum dot light-emitting diodes (QLEDs) have attracted increasing attention due to their excellent electroluminescent properties and compatibility with inkjet printing processes, which show great potential in applications of pixelated displays. However, the relatively low resolution of the inkjet printing technology limits its further development. In this paper, high-resolution QLEDs were successfully fabricated by electrohydrodynamic (EHD) printing. A pixelated quantum dot (QD) emission layer was formed by printing an insulating Teflon mesh on a spin-coated QD layer. The patterned QLEDs show a high resolution of 2540 pixels per inch (PPI), with a maximum external quantum efficiency (EQE) of 20.29% and brightness of 35816 cd/m2. To further demonstrate its potential in full-color display, the fabrication process for the QD layer was changed from spin-coating to EHD printing. The as-printed Teflon effectively blocked direct contact between the hole transport layer and the electron transport layer, thus preventing leakage currents. As a result, the device showed a resolution of 1692 PPI with a maximum EQE of 15.40%. To the best of our knowledge, these results represent the highest resolution and efficiency of pixelated QLEDs using inkjet printing or EHD printing, which demonstrates its huge potential in the application of high-resolution full-color displays.

Interface-Induced Crystallinity Enhancement of Perovskite Quantum Dots for Highly Efficient Light-Emitting Diodes.

Perovskite quantum dot light-emitting diodes (QLEDs) with high color purity and wide color gamut have good application prospects in the next generation of display technology. However, colloidal perovskite quantum dots (PQDs) may introduce a large number of defects during the film-forming process, which is not conducive to the luminous efficiency of the device. Meanwhile, the disordered film formation of PQDs will form interfacial defects and reduce the device performance. Here, we report an interface-induced crystallinity enhancement (IICE) strategy to increase the crystallinity of PQDs at the hole transport layer (HTL)/PQD interface. As a result, both the Br- vacancies in the PQD film and the interfacial defects were well passivated and the leakage current was also suppressed. We achieved QLEDs with a maximum external quantum efficiency (EQE) of 16.45% and current efficiency (CE) of 61.77 cd/A, showing improved performance to more than twice that of the control devices. The IICE strategy paves a new way to enhance the crystallinity of PQD films, so as to improve the performance of QLEDs for application in the future display field.

Diagnostic accuracy of updated risk assessment criteria and development of novel computational prediction models for patients with suspected choledocholithiasis.

BACKGROUND: There are risks of choledocholithiasis in symptomatic gallstones, and some surgeons have proposed the identification of choledocholithiasis before cholecystectomy. Our goal was to evaluate the diagnostic accuracy of the latest guidelines and create computational prediction models for the accurate prediction of choledocholithiasis. METHODS: We retrospectively reviewed symptomatic gallstone patients hospitalized with suspected choledocholithiasis. The diagnostic performance of 2019 and 2010 guidelines of the American Society for Gastrointestinal Endoscopy (ASGE) and 2019 guideline of the European Society of Gastrointestinal Endoscopy (ESGE) in different risks. Lastly, we developed novel prediction models based on the preoperative predictors. RESULTS: A total of 1199 patients were identified and 681 (56.8%) had concurrent choledocholithiasis and were included in the analysis. The specificity of the 2019 ASGE, 2010 ASGE, and 2019 ESGE high-risk criteria was 85.91%, 72.2%, and 88.42%, respectively, and their positive predictive values were 85.5%, 77.4%, and 87.3%, respectively. For Mid-risk patients who followed 2019 ASGE about 61.8% of them did not have CBD stones in our study. On the choice of surgical procedure, laparoscopic cholecystectomy + laparoscopic transcystic common bile duct exploration can be considered the optimal treatment choice for cholecysto-choledocholithiasis instead of Endoscopic Retrograde Cholangio-Pancreatography (ERCP). We build seven machine learning models and an AI diagnosis prediction model (ModelArts). The area under the receiver operating curve of the machine learning models was from 0.77 to 0.81. ModelArts AI model showed predictive accuracy of 0.97, recall of 0.97, precision of 0.971, and F1 score of 0.97, surpassing any other available methods. CONCLUSION: The 2019 ASGE guideline and 2019 ESGE guideline have demonstrated higher specificity and positive predictive value for high-risk criteria compared to the 2010 ASGE guideline. The excellent diagnostic performance of the new artificial intelligence prediction model may make it a better choice than traditional guidelines for managing patients with suspected choledocholithiasis in future.

Gut Microbiota-Derived Diaminopimelic Acid Promotes the NOD1/RIP2 Signaling Pathway and Plays a Key Role in the Progression of Severe Acute Pancreatitis.

Impaired intestinal barrier function and gut microbiota dysbiosis are believed to be related to exacerbation of acute pancreatitis (AP). As a bacterial cell wall peptidoglycan component, diaminopimelic acid (DAP) is a specific ligand of NOD1 that regulates the NOD1/RIP2/NF-kB signaling pathway. Here, we investigated the role of DAP in the crosstalk between the gut microbiota and pancreas during the occurrence of AP. Upregulation of NOD1/RIP2/NF-kB and elevated serum DAP levels were found in severe AP (SAP) model rats. The accumulation of DAP in SAP patients corroborated its ability to serve as an indicator of disease severity. Subsequently, SAP rats were treated with oral administration of the traditional Chinese medicine Qingyi Keli (QYKL) as well as neomycin, which can widely eliminate DAP-containing bacteria. Both QYKL and neomycin intervention ameliorated intestinal and pancreatic damage and systemic inflammation in SAP rats. Through 16S rDNA sequencing, we found that QYKL could rehabilitate the gut microbiota structure and selectively inhibit the overgrowth of enteric bacteria, such as Helicobacter and Lactobacillus, in SAP rats without affecting some protective strains, including Romboutsia and Allobaculum. Interestingly, we demonstrated that the decrease in serum DAP was accompanied by suppression of the NOD1/RIP2/NF-kB signaling pathway in both the intestine and pancreas of the two intervention groups. Taken together, these results suggested that the gut microbiota-DAP-NOD1/RIP2 signaling pathway might play a critical role in the progression of AP and that SAP could be alleviated via intervention in the signaling pathway. Our work provides new potential early warning indicators of SAP and targets for intervention.

Challenges in treatment of a patient suffering from neuroendocrine tumor G1 of the hilar bile duct: a case report.

BACKGROUND: Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are extremely rare in the biliary tract. Currently, there are no guidelines for the diagnosis and treatment of biliary NETs. We presented a case with NETs G1 of the hilar bile duct and the challenges for her treatment. CASE PRESENTATION: A 24-year-old woman was presented to our department with painless jaundice and pruritus, and the preoperative diagnosis was Bismuth type II hilar cholangiocarcinoma. She underwent Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy. Unexpectedly, postoperative pathological and immunohistochemical examination indicated a perihilar bile duct NETs G1 with the microscopic invasion of the resected right hepatic duct. Then the patient received 3 cycles of adjuvant chemotherapy (Gemcitabine and tegafur-gimeracil-oteracil potassium capsule). At present, this patient has been following up for 24 months without recurrence or disease progression. CONCLUSION: We know little of biliary NETs because of its rarity. There are currently no guidelines for the diagnosis and treatment of biliary NETs. We reported a case of perihilar bile duct NETs G1 with R1 resection, as far as we know this is the first report. More information about biliary NETs should be registered.

Bright Triplet Self-Trapped Excitons to Dopant Energy Transfer in Halide Double-Perovskite Nanocrystals.

For inorganic semiconductor nanostructure, excitons in the triplet states are known as the "dark exciton" with poor emitting properties, because of the spin-forbidden transition. Herein, we report a design principle to boost triplet excitons photoluminescence (PL) in all-inorganic lead-free double-perovskite nanocrystals (NCs). Our experimental data reveal that singlet self-trapped excitons (STEs) experience fast intersystem crossing (80 ps) to triplet states. These triplet STEs give bright green color emission with unity PL quantum yield (PLQY). Furthermore, efficient energy transfer from triplet STEs to dopants (Mn2+) can be achieved, which leads to white-light emitting with 87% PLQY in both colloidal and solid thin film NCs. These findings illustrate a fundamental principle to design efficient white-light emitting inorganic phosphors, propelling the development of illumination-related applications.

Emodin attenuates adenosine triphosphate­induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway.

Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality rates. Pancreatic ductal cells are the most susceptible of all cell types that are exposed to the noxious stimuli of pancreatitis. Our previous studies demonstrated that emodin, a natural product extracted from Rheum palmatum L., protected pancreatic acinar cells from injutyh due to its anti­inflammatory activity. In the present study, in order to investigate the protective effects and molecular mechanisms of action of emodin on injured pancreatic ductal cells, an adenosine triphosphate (ATP)­induced model of cell injury was established using the human pancreatic ductal epithelial cell line, HPDE6­C7. The results revealed that emodin attenuated ATP­induced HPDE6­C7 cell injury by decreasing the levels of inflammatory factors, including interleukin (IL)­1ß and IL­18. Furthermore, emodin significantly downregulated the protein levels of purinergic receptor P2X, ligand­gated ion channel, 7 (P2X7), NOD­like receptor protein 3 (NLRP3), apoptosis­associated speck­like protein containing a CARD (ASC) and caspase­1 in the injured HPDE6­C7 cells. The results also indicated that emodin attenuated HPDE6­C7 cell injury at least partially through the inhibition of the P2X7/NLRP3 signaling pathway. The protective effects of emodin were abrogated upon pre­treatment with P2X7 overexpression plasmid, which further confirmed that the P2X7 signaling pathway is the drug target of the effects of emodin against ATP­induced pancreatic ductal cell injury. Collectively, the findings of this study demonstrate that emodin attenuates ATP­induced pancreatic ductal cell injury in AP mainly through the inhibition of the P2X7/NLRP3 signaling pathway. This study suggests that emodin may be further developed for its application in future medical therapy.

Emerging Role of Chinese Herbal Medicines in the Treatment of Pancreatic Fibrosis.

Pancreatic fibrosis is the main pathologic characteristic in chronic pancreatitis (CP), a common disease that arises from surgery. Pancreatitis is caused by various etiologies, but the mechanism of fibrosis is not completely understood. Existing clinical approaches mainly focus on mitigating the symptoms and therefore do not cure the phenomena. In recent years, there has been a heightened interest in the use of Chinese herbal medicine (CHMs) in the prevention and cure of CP as expressed by increasing numbers of clinical and experimental research. Despite early cell culture and animal models, CHMs are able to interact with plenty of molecular targets involved in the pathogenesis of pancreatic fibrosis mostly via the TGF- ß /Smads pathway; however, integrated and up-to-date communication in this domain is unavailable. This review focuses on the research progress of CHMs against pancreatic fibrosis due to CP in vitro and in vivo and summarizes the potential mechanisms. We also outlined the toxicology of some CHMs for fibrosis treatment in order to provide a fuller understanding of drug safety. This review may provide reference for further innovative drug research and the future development of treatments for CP with pancreatic fibrosis.

Therapeutic effect of a temporary transpyloric stent in refractory post-surgical gastroparesis: a case report.

BACKGROUND: Gastroparesis is a syndrome characterized by delayed gastric emptying with associated symptoms. It was reported that the symptoms of diabetic gastroparesis had been greatly improved by transpyloric stent placement. However, the use of stents in benign conditions is considered to be contraindicated because of the increasing risk of complications, such as stent migration, reflux, perforation, bleeding, and, most importantly, new strictures caused by stent-induced tissue hyperplasia. While temporary placement of a self-expanding metallic stent (SEMC) can drastically reduce the risk of complications, few reports are available on the treatment of refractory PSG by temporary transpyloric stent. Does it have a long-term clinical effect after the stent being retrieved? CASE PRESENTATION: After accepting partial resection of the lesser curvature in another hospital, a patient developed refractory gastroparesis. The symptoms hadn't been improved after long-term drug therapy and balloon dilation therapy. Four months after surgery, a fully covered SEMC was placed by endoscopy in our hospital. Gastroparesis had been greatly improved. Two weeks later, the transpyloric stent was retrieved and the patient didn't show recurrent symptoms. Follow-ups were arranged at 3 months, 6 months and 1 year respectively, and there was no evidence of recurrence was found. CONCLUSIONS: This case indicates that temporary transpyloric SEMC is a safe, effective and less invasive alternative for post-surgical gastroparesis patients.

Emodin attenuated severe acute pancreatitis via the P2X ligand­gated ion channel 7/NOD­like receptor protein 3 signaling pathway.

Acute pancreatitis (AP) is an aseptic inflammation characterized with an annual incidence rate, and ~20% patients progressing to severe AP (SAP) with a high mortality rate. Although Qingyi decoction has been frequently used for SAP treatment over the past 3 decades in clinic, the actual mechanism of its protective effects remains unknown. As the major active ingredient of Qingyi decoction, emodin was selected in the present study to investigate the effect of emodin against severe acute pancreatitis (SAP) in rats through NOD­like receptor protein 3 (NLRP3) inflammasomes. The rats were randomly divided into a sham operation group, an SAP model group induced by a standard retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct, and low­dose (30 mg/kg) and high­dose (60 mg/kg) emodin­treated groups. At 12 h after the event, the plasma amylase, lipase, interleukin (IL)­1ß, IL­18 and myeloperoxidase (MPO) activities were examined. Furthermore, the pathological scores of pancreases were evaluated by hematoxylin and eosin staining. The expression levels of P2X ligand­gated ion channel 7 (P2X7), NLRP3, apoptosis­associated speck­like protein containing a C­terminal caspase recruitment domain and caspase­1 were also analyzed by western blot analysis. The data demonstrated that, compared with the SAP group, emodin could significantly relieve the pancreatic histopathology and acinar cellular structure injury, and notably downregulate the plasma amylase and lipase levels, as well as the MPO activities in pancreatic tissues, in a dose­dependent manner. Furthermore, emodin inhibited the P2X7/NLRP3 signaling pathway followed by the decrease of pro­inflammatory factors, and the latter is beneficial for the recovery of SAP. Collectively, the data indicated that emodin may be an efficient candidate natural product for SAP treatment.

Corrigendum: Yin-Chen-Hao Tang Attenuates Severe Acute Pancreatitis in Rat: An Experimental Verification of In silico Network Target Prediction.

[This corrects the article DOI: 10.3389/fphar.2016.00378.].

Novel High-Energy-Density Rechargeable Hybrid Sodium-Air Cell with Acidic Electrolyte.

Low-cost, high-energy-density, and highly efficient devices for energy storage have long been desired in our society. Herein, a novel high-energy-density hybrid sodium-air cell was fabricated successfully on the basis of acidic catholytes. Such a hybrid sodium-air cell possess a high theoretical voltage of 3.94 V, capacity of 1121 mAh g-1, and energy density of 4418 Wh kg-1. First, the buffering effect of an acidic solution was demonstrated, which provides relatively long and stable cell discharge behaviors. Second, the catholytes of hybrid sodium-air cells were optimized systematically from the solutions of 0.1 M H3PO4 + 0.1 M Na2SO4 to 0.1 M HAc + 0.1 M NaAc and it was found that the cells with 0.1 M H3PO4 + 0.1 M Na2SO4 displayed a maximum power density of 34.9 mW cm-2. The cell with 0.1 M H3PO4 + 0.1 M Na2SO4 displayed higher discharge capacity of 896 mAh g-1. Moreover, the fabricated acidic hybrid sodium-air cells exhibited stable cycling performance in ambient air and they delivered a low voltage gap around 0.3 V when the current density is 0.13 mA cm-2, leading to a high energy efficiency up to 90%. Therefore, the present study provides new opportunities to develop highly cost-effective energy storage technologies.

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms.

Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP.

One Distinctive Presentation in Radiology of Pancreatic Cancer: A Rare Case Report.

Background: Pancreatic cancer is an aggressive and malignant disease that usually presents as an isodense or hypodense lesion with no significant enhancement in contrast CT. CT scan plays an important role in the diagnosis of pancreatic diseases, especially in pancreatic cancer and pancreatic neuroendocrine tumors. Presentation: This report includes a case of a 53-year-old female patient presenting a high-density mass in the pancreas on contrast CT. The mass was surgically removed, and the pathology confirmed the diagnosis of pancreatic adenocarcinoma. Conclusion: Sometimes the contrast CT of pancreatic cancer can be expressed as high density, which is similar to pancreatic neuroendocrine tumors. It is necessary for us to identify carefully.

Yin-Chen-Hao Tang Attenuates Severe Acute Pancreatitis in Rat: An Experimental Verification of In silico Network Target Prediction.

Yin-Chen-Hao Tang (YCHT) is a classical Chinese medicine compound that has a long history of clinical use in China for the treatment of inflammatory diseases. However, the efficacy and mechanisms of YCHT for the treatment of severe acute pancreatitis (SAP) are not known. The current study investigated the pharmacological properties of YCHT against SAP and its underlying mechanisms. A computational prediction of potential targets of YCHT was initially established based on a network pharmacology simulation. The model suggested that YCHT attenuated SAP progress by apoptosis inducement, anti-inflammation, anti-oxidation and blood lipid regulation. These effects were validated in SAP rats. YCHT administration produced the following results: (1) significantly inhibited the secretion of pancreatic enzymes and protected pancreatic tissue; (2) obviously increased the number of in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and induced apoptosis; (3) markedly inhibited neutrophil infiltration to the impaired pancreas and reduced the inflammatory reaction; (4) notably enhanced the activities of antioxidant enzymes and decreased the nitric oxide synthase levels; (5) significantly reduced the levels of triglycerides, total cholesterol and low-density lipoprotein and increased high-density lipoprotein; and (6) significantly up-regulated peroxisome proliferator-activated receptor-γ (PPARγ) and down-regulated nuclear factor-kappa B (NF-κB). In summary, these results demonstrated that YCHT attenuated SAP progress by inducing apoptosis, repressing inflammation, alleviating oxidative stress and regulating lipid metabolism partially via regulation of the NF-κB/PPARγ signal pathway.

[1:2 matched case-control study on the risk factors related to congenital heart disease during the peri-conceptional period].

OBJECTIVE: To explore the possible risk factors during the periconceptional period relevant on the occurrence of congenital heart diseases (CHD) in the offspring. METHODS: A 1:2 matched case-control study was designed. From January 2012 to January 2014 in a district from Wuhan city, HuBei province, children were proved by MCH institutions through the "free screening for congenital heart disease" program. Cases with CHD were screened out by conventional auscultation, echocardiography figure and confirmed by physicians from the high-level hospitals. According to age, gender, community paired healthy children were chosen as controls. EpiData 3.1 software was used to input data, using SPSS 11.5 software to analyze the possible risk factors under simple and multiple factors logistic regression. RESULTS: Information from parents of 138 cases and 276 controls was collected. 27 major factors from the conditional logistic regression analysis showed that factors as:mental stress during early pregnancy, calcium supplement in the early stage of pregnancy, pregnancy malnutrition, having histories of abnormal childbearing, women with multiparous experiences and residence nearby sources of pollution (enterprises) etc. were associated with the incidence of congenital heart disease in the offspring. Data from the multivariate logistic regression analysis showed that factors as:mental stress during early pregnancy (HR = 3.35, 95%CI: 1.28-8.79), pregnancy malnutrition during pregnancy (HR = 1.50, 95% CI:1.10-2.03) and with abnormal childbearing history (HR = 1.62, 95% CI:1.03-2.57) were risk factors. However, calcium supplement during early pregnancy (HR = 0.40, 95% CI:0.25-0.65) could reduce the risk of CHD. CONCLUSION: The occurrence of CHD might be related to factors as:mental stress during early pregnancy, calcium supplement during early pregnancy, pregnancy malnutrition and having histories of abnormal childbearing. Peri-conceptional care should be strengthened to reduce the incidence of congenital heart disease.

Resolution of intussusception after spontaneous expulsion of an ileal lipoma per rectum: a case report and literature review.

We herein report a case of spontaneous rectal expulsion of an ileal lipoma in a 65-year-old female patient who presented with recurrent attacks of subacute intestinal obstruction. During each episode, the patient developed severe abdominal pain and expelled a fleshy mass from her rectum. The fleshy mass was histopathologically diagnosed as a lipoma comprising fat cells, fibers, and blood vessels. Upon expulsion, the pain disappeared and the intussusception was immediately resolved. Colonoscopic examination revealed a 2.5-cm diameter ulcerated lesion near the ileocecal valve, which was confirmed to be inflammation by pathological examination. A subsequent barium series revealed a normal colonic tract, and the patient remained completely symptom-free for 4 months after the incident. According to the relevant literature and our clinical experience, the treatment method for a lipoma depends on the patient's clinical manifestations and the size of the tumor. However, the various diagnostic and therapeutic modalities currently available continue to be debated; whether an asymptomatic lipoma requires treatment is controversial. When histopathological examination results allow for the exclusion of malignant lesions such as sarcoma, a lipoma can be resected surgically.