Deletion of myeloid-specific Orai1 calcium channel does not affect pancreatic tissue damage in experimental acute pancreatitis.

BACKGROUND: Store-operated Ca2+ entry (SOCE) mediated by ORAI1 channel plays a crucial role in acute pancreatitis (AP). Macrophage is an important regulator in amplifying pancreatic tissue damage, but little is known about the role of ORAI1 in macrophages. In this study, we examined the effects of macrophage-specific ORAI1 on pancreatic tissue damage in AP. METHOD: Myeloid-specific Orai1 deficient mice was generated by crossing a LysM-Cre mouse line with Orai1f/f mice. Bone marrow-derived macrophages (BMDMs) were isolated, cultured, and stimulated to induce M1 or M2 macrophage polarization. Intracellular Ca2+ signals were measured by time-lapse confocal microscope imaging, with a Ca2+ indicator (Fluo 4). Experimental AP was induced by hourly intraperitoneal injections of caerulein or retrograde biliopancreatic infusion of sodium taurocholate. Pancreatic tissue damage was assessed by histopathological scoring and immunostaining. Sepsis was induced by intraperitoneal injection of lipopolysaccharide; organ damage and serum pro-inflammatory cytokines were measured. RESULT: Myeloid-specific Orai1 deletion exhibited minimal effect on SOCE in M0 macrophages and promoted M2 macrophage polarization ex vivo. Myeloid-specific Orai1 deletion did not affect pancreatic tissue damage, nor neutrophil or macrophage infiltration in two models of AP. Similarly, myeloid-specific Orai1 deletion did not influence overall survival rate in a model of sepsis, nor lung, kidney, and liver damage; while serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1ß were higher in Orai1ΔLysM mice, but were largely reduced in mice with Orai1 inhibitor. CONCLUSION: Our data suggest that ORAI1 may not be a predominant SOCE channel in macrophages and play a limited role in mediating pancreatic tissue damage in AP.

Characteristics of small pancreatic neuroendocrine tumors and risk factors for invasion and metastasis.

Background: The number of people with small pancreatic neuroendocrine tumors (pNETs) (tumors with a diameter less than or equal to 2 cm) is gradually increasing, but the selection of treatment strategy is still controversial. Our aim was to characterize small pNETs with a poor prognosis and to define the impact of aggressive small pNETs on survival and the risk factors for the development of invasive disease. Methods: Patients with pNETs diagnosed between 2004 and 2019 and a tumor diameter of 2 cm or less were selected from the SEER Registry. Kaplan-Meier survival analysis was used to identify the factors affecting patient survival, and binary logistic regression was used to identify the associated risk factors. Results: A total of 3261 patients with pNETs were enrolled in the study. Both older and younger patients benefited from surgery. Regional invasion occurred in 10% of the patients, and distant metastases occurred in 9% of the patients, but in both categories, those who underwent surgery had better survival outcomes than those who did not. There was no difference in survival between patients with a tumor diameter of 1-2 cm and those with a tumor diameter of less than 1 cm, and there was no difference in survival between patients with functional and nonfunctional small pNETs. However, the survival of patients with pNETs in the head of the pancreas was worse than that of patients with tumors in other parts of the pancreas. Survival was worse in elderly patients and in those with poorly differentiated and undifferentiated tumors. Lymphatic metastasis, regional invasion, and distant metastasis all worsened the prognosis of patients. The presence or absence of neuroendocrine function, the degree of tumor differentiation, and the location of the tumor were associated with the risk of lymphatic metastasis and regional invasion; the risk factors for distant metastasis were associated with the degree of differentiation and tumor location. Conclusion: The pNETs ≤ 2 cm in diameter could be still aggressive, and patient prognosis worsens after invasive disease develops. Attention to the characteristics of aggressive tumors can improve patient survival.

Characteristics and Incidence of Colon Complication in Necrotizing pancreatitis: A Propensity Score-Matched Study.

Objective: To clarify the incidence of colonic complications in patients with NP and their impact on prognosis. Methods: The clinical data of NP patients admitted to the Department of General Surgery of Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of colonic complications, and the clinical prognosis of the two groups was analyzed after matching using a 1:1 propensity score, The primary study endpoint was patient mortality during hospitalization. Data are reported as median (range) or percentage of patients (%). Results: A total of 306 patients with NP were included in this study, and the incidence of colonic complications was 12.4%, including 15 cases of colonic obstruction, 17 cases of colonic fistula, and 9 cases of colonic hemorrhage. Before matching, patients in the colonic group had severe admissions and poor clinical outcomes (P<0.05). After matching, the baseline data and clinical characteristics at admission were comparable between the two groups of patients. In terms of clinical outcomes, although the mortality was similar in the two groups (P>0.05), but patients in the colonic group were more likely to have multiorgan failure, length of nutrition support, number of minimally invasive interventions, number of extra-pancreatic infections, length of ICU stay and total length of stay were significantly higher than those of patients in the group without colonic complications (P<0.05). During long-term follow-up, patients in the colonic group were more likely to develop recurrent pancreatitis. Conclusion: About 12.4% of NP patients developed colonic complications, and after PSM it was found that colonic complications only led to a longer hospital stay and an increased number of clinical interventions in NP patients and did not increase the mortality.

Identification of key microRNAs in exosomes derived from patients with the severe acute pancreatitis.

OBJECTIVE: Exosomes have been identified as important carriers of various genetic materials, including microRNAs (miRNAs). Increasing evidence indicates that the course of severe acute pancreatitis (SAP) is associated with miRNAs transported by exosomes. We aimed to identify the signature miRNAs as biomarkers of SAP. METHODS: We obtained exosomes from the SAP patients' blood. After separation, purification, and identification, we performed high-throughput sequencing and screened the differentially expressed(DE) miRNAs in the exosomes. Bioinformatics analysis was performed to identified the target genes of the miRNAs and the pathways enriched based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and selected the key miRNAs related to SAP. Total RNA was extracted from patient serum exosomes to detect the expression levels of the selected miRNAs in exosomes of three experimental groups (mild -, moderately severe -, and severe AP) and a control group, using Real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: 272 DE miRNAs were identified between SAP and control group. Using bioinformatics analysis, we determined that the functions of the target genes were enriched in six signaling pathways including focal adhesion. Based on this, seven candidate signature miRNAs were selected: miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, and miR-583. The RT-qPCR results of the seven miRNAs in the SAP group were consistent with the sequencing results. CONCLUSION: Exosome-derived miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, miR-583 are positively correlated with SAP, which might provide new insights into the pathogenesis of SAP and serve as the biomarkers of SAP.

Risk Factors and Outcomes of Multidrug-Resistant Bacteria Infection in Infected Pancreatic Necrosis Patients.

Objective: The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40-70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients. Methods: Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed. Results: IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381-12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502-4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109-6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients. Conclusion: We identified common infectious strains and risk factors for MDRB infection in IPN patients.

Prognostic biomarkers of pancreatic cancer identified based on a competing endogenous RNA regulatory network.

Background: Pancreatic cancer is an insidious and heterogeneous malignancy with poor prognosis that is often locally unresectable. Therefore, determining the underlying mechanisms and effective prognostic indicators of pancreatic cancer may help optimize clinical management. This study was conducted to develop a prognostic model for pancreatic cancer based on a competing endogenous RNA (ceRNA) network. Methods: We obtained transcriptomic data and corresponding clinicopathological information of pancreatic cancer samples from The Cancer Genome Atlas (TCGA) database (training set). Based on the ceRNA interaction network, we screened candidate genes to build prediction models. Univariate Cox regression analysis was performed to screen for genes associated with prognosis, and least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to construct a predictive model. A receiver operating characteristic (ROC) curve was drawn, and the C-index was calculated to evaluate the accuracy of the prediction model. Furthermore, we downloaded transcriptomic data and related clinical information of pancreatic cancer samples from the Gene Expression Omnibus database (validation set) to evaluate the robustness of our prediction model. Results: Eight genes (ANLN, FHDC1, LY6D, SMAD6, ACKR4, RAB27B, AUNIP, and GPRIN3) were used to construct the prediction model, which was confirmed as an independent predictor for evaluating the prognosis of patients with pancreatic cancer through univariate and multivariate Cox regression analysis. By plotting the decision curve, we found that the risk score model is an independent predictor has the greatest impact on survival compared to pathological stage and targeted molecular therapy. Conclusions: An eight-gene prediction model was constructed for effectively and independently predicting the prognosis of patients with pancreatic cancer. These eight genes identified show potential as diagnostic and therapeutic targets.

Role of m6A writers, erasers and readers in cancer.

The N(6)-methyladenosine (m6A) modification is the most pervasive modification of human RNAs. In recent years, an increasing number of studies have suggested that m6A likely plays important roles in cancers. Many studies have demonstrated that m6A is involved in the biological functions of cancer cells, such as proliferation, invasion, metastasis, and drug resistance. In addition, m6A is closely related to the prognosis of cancer patients. In this review, we highlight recent advances in understanding the function of m6A in various cancers. We emphasize the importance of m6A to cancer progression and look forward to describe future research directions.

How to Identify the Indications for Early Intervention in Acute Necrotizing Pancreatitis Patients: A Long-Term Follow-Up Study.

Aim: To explore the indications for early intervention in patients with acute necrotizing pancreatitis (ANP) and evaluate the effect of early intervention on the prognosis of ANP patients. Methods: The clinical data of patients with ANP who underwent general surgery at Xuanwu Hospital of Capital Medical University from January 1, 2014, to December 31, 2020, were collected retrospectively. The patients were followed-up every 6 months after discharge, and the last follow-up date was June 30, 2021. Results: A total of 98 patients with ANP were included in the study. They were divided into an early group (n= 43) and a delayed group (n = 55) according to the first percutaneous drainage (PCD) intervention time (≤ 4 weeks or > 4 weeks). Body temperature, inflammatory factor levels, and the number of patients with persistent organ failure (POF) were higher in the early group than in the delayed group. After the minimally invasive intervention, the body temperature and inflammatory factors of the two groups decreased significantly, most patients with POF improved, and the number of patients with reversal of POF in the early group was higher than that in the delayed group. Although the patients in the early group required more surgical intervention than those in the delayed group, there was no significant difference in mortality, incidence of postoperative complications, total length of hospital stay, or operation cost between the two groups. During long-term follow-up, there was no significant difference in the incidence of short-term and long-term complications and overall survival between the two groups. Conclusions: Compared to patients in the delayed group, early intervention did not affect the prognosis of patients with ANP. It may be more suitable for patients with ANP with deterioration [such as POF or infected pancreatic necrosis (IPN)].

"One-step" approach versus "Step-up" approach minimally invasive treatment for infected pancreatic necrosis: a study protocol for a single-center, prospective, randomized controlled trial.

BACKGROUND: Currently, the minimally invasive "Step-up" surgical strategy is still the main treatment for infected pancreatic necrosis (IPN). However, indiscriminate implementation of the "Step-up" strategy can lead to increased numbers of operations and prolonged hospital stay. The "Step-up" approach is not appropriate for some patients due to unavailabilty of a safe puncture path. Therefore, we developed the "One-step" surgical approach to treat IPN, which is safety. However, there is still a lack of comparison of the short and long-term efficacy between the "One-step" and "Step-up" approach. Consequently, we are conducting this clinical trial to provide a reference for IPN treatment. METHODS: This is an ongoing, single-center, randomized controlled trial of patients with IPN. The total sample size required for the trial (May 2021-December 2023) is approximately 128 patients. Patients will be randomly assigned to either an experimental group (One-step) or a control group (Step-up) at a ratio of 1:1 using the block randomization method. We used the case report forms and electronic data capture systems to obtain demographic information, preoperative laboratory examination, auxiliary examination results, surgery data, postoperative recovery outcomes, and follow-up outcomes. The patients will be followed up for 2 years after surgery. The primary endpoint is a composite endpoint, consisting of mortality and severe complications. The secondary endpoints include the incidence of organ dysfunction, the number of surgical procedures, mortality (the incidence of death in hospital and deaths within 30 days of discharge), hospital stay, intensive care unit stay, hospitalization costs, perioperative inflammatory marker changes, and short-and long-term complications. DISCUSSION: Compared with the "Step-up," the "One-step" minimally invasive surgery can significantly reduce the number of operations, reduce the length of hospital stay and hospitalization costs without increasing the incidence of composite endpoint events, and has better short- and long-term efficacy and safety. Additionally, there was no statistically significant difference in perioperative complications and mortality between "Step-up" and "One-step". This study will assist with the formulation of an effective and scientific "One-step" minimally invasive treatment strategy for IPN, and an understanding of this technique will facilitate clinical decision-making for IPN. Trial Registration ChiCTR2100044348. Trial status: Ongoing.

Comparison of safety, efficacy, and long-term follow-up between "one-step" and "step-up" approaches for infected pancreatic necrosis.

BACKGROUND: Although the "Step-up" strategy is the primary surgical treatment for infected pancreatic necrosis, it is not suitable for all such patients. The "One-step" strategy represents a novel treatment, but the safety, efficacy, and long-term follow-up have not yet been compared between these two approaches. AIM: To compare the safety, efficacy, and long-term follow-up of two surgical approaches to provide a reference for infected pancreatic necrosis treatment. METHODS: This was a retrospective analysis of infectious pancreatic necrosis patients who underwent "One-step" or "Step-up" necrosectomy at Xuan Wu Hospital, Capital Medical University, from May 2014 to December 2020. The primary outcome was the composite endpoint of severe complications or death. Patients were followed up every 6 mo after discharge until death or June 30, 2021. Statistical analysis was performed using SPSS 21.0 and GraphPad Prism 8.0, and statistical significance was set at P < 0.05. RESULTS: One-hundred-and-fifty-eight patients were enrolled, of whom 61 patients underwent "One-step" necrosectomy and 97 patients underwent "Step-up" necrosectomy. During the long-term follow-up period, 40 patients in the "One-step" group and 63 patients in the "Step-up" group survived. The time from disease onset to hospital admission (53.69 ± 38.14 vs 32.20 ± 20.75, P < 0.001) and to initial surgical treatment was longer in the "Step-up" than in the "One-step" group (54.38 ± 10.46 vs 76.58 ± 17.03, P < 0.001). Patients who underwent "Step-up" necrosectomy had a longer hospitalization duration (65.41 ± 28.14 vs 52.76 ± 24.71, P = 0.02), and more interventions (4.26 ± 1.71 vs 3.18 ± 1.39, P < 0.001). Postoperative inflammatory indicator levels were significantly lower than preoperative levels in each group. Although the incisional hernia incidence was higher in the "One-step" group, no significant difference was found in the composite outcomes of severe complications or death, new-onset organ failure, postoperative complications, inflammatory indicators, long-term complications, quality of life, and medical costs between the groups (P > 0.05). CONCLUSION: Compared with the "Step-up" approach, the "One-step" approach is a safe and effective treatment method with better long-term quality of life and prognosis. It also provides an alternative surgical treatment strategy for patients with infected pancreatic necrosis.

Anterior abdominal abscess - a rare manifestation of severe acute pancreatitis: A case report.

BACKGROUND: Severe acute pancreatitis (SAP) is a common critical disease of the digestive system. In addition to the clinical manifestations and biochemical changes of acute pancreatitis, SAP is also accompanied by organ failure lasting more than 48 h. SAP is characterized by focal or extensive pancreatic necrosis, hemorrhage and obvious inflammation around the pancreas. The peripancreatic fat space, fascia, mesentery and adjacent organs are often involved. The common local complications include acute peripancreatic fluid collection, acute necrotic collection, pancreatic pseudocyst, walled off necrosis and infected pancreatic necrosis. After reviewing the literature, we found that in very few cases, SAP patients have complications with anterior abdominal wall abscesses. CASE SUMMARY: We report a 66-year-old Asian male with severe acute pancreatitis who presented with intermittent abdominal pain and an increasing abdominal mass. The abscess spread from the retroperitoneum to the anterior abdominal wall and the right groin. In the described case, drainage tubes were placed in the retroperitoneal and anterior abdominal wall by percutaneous puncture. After a series of symptomatic supportive therapies, the patient was discharged from the hospital with a retroperitoneal drainage tube after the toleration of oral feeding and the improvement of nutritional status. CONCLUSION: We believe that patients with SAP complicated with anterior abdominal abscess can be treated conservatively to avoid unnecessary exploration or operation.

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miR-100-5p.

PURPOSE: Although human umbilical cord mesenchymal stem cells (hucMSCs) can contribute to the growth of tumors, including pancreatic ductal adenocarcinoma (PDAC), however, little is known about the exact mechanisms by which the exosomes secreted from hucMSCs (hucMSCs-exo) have an oncogenic effect on the physiopathology of PDAC. The effects of hucMSCs on tumor development are attributed to hucMSCs-exo, which deliver unique proteins and miRNAs to cancer cells. METHODS: HucMSCs and exosomes were isolated and confirmed via transmission electron microscopy, nanoparticle tracking analysis and western blot. The nude mice were inoculated subcutaneously on both flanks with human pancreatic cancer Panc-1 cells (1 × 106), and hucMSCs-exo were directly administered via intratumoral injection once a day for three days each week. Cell proliferation assays were performed using a Cell Counting Kit-8 assay and the cell invasion assay was performed using Transwell assay. The miRNA data were predicted and analyzed by miRanda software. The analysis of the target genes of the miRNAs was proformed with the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. RESULTS: Firstly, we observed that hucMSCs-exo promoted Panc-1 and BxPC3 cell growth by increasing proliferation and migration in vitro. Secondly, in a xenograft tumor model, hucMSCs-exo increased the growth of Panc-1 cells. Thirdly, high-throughput sequencing of hucMSCs-exo showed that hsa-miR-148a-3p, hsa-miR-100-5p, hsa-miR-143-3p, hsa-miR-21-5p and hsa-miR-92a-3p were highly expressed. For the five identified miRNAs, 1308 target genes were predicted by miRanda software. From the GO and KEGG analyses of the target genes of the identified miRNAs, it was found that the main GO function was the regulation of cellular glucuronidation, and the main KEGG metabolic pathway involved the metabolism of ascorbic acid and aldehyde acid. These processes are related to the occurrence and development of pancreatic cancer. Finally, we observed that miR-100-5p promoted Panc-1 and BxPC3 cell growth in vitro and in vivo. CONCLUSION: Here, by utilizing exosomes secreted from hucMSCs, we systematically investigated the effects of hucMSCs-exo on PDAC growth in vitro and in vivo for the first time. Building on these results, we provided new insights into the role of hucMSCs-exo in the PDAC growth and revealed the attractive communication between hucMSCs and PDAC cells that occurs through MSCs-exosomes-miRNAs.

Extracellular vesicles and pancreatitis: mechanisms, status and perspectives.

Comprehensive reviews and large population-based cohort studies have played an important role in the diagnosis and treatment of pancreatitis and its sequelae. The incidence and mortality of pancreatitis have been reduced significantly due to substantial advancements in the pathophysiological mechanisms and clinically effective treatments. The study of extracellular vesicles (EVs) has the potential to identify cell-to-cell communication in diseases such as pancreatitis. Exosomes are a subset of EVs with an average diameter of 50~150 nm. Their diverse and unique constituents include nucleic acids, proteins, and lipids, which can be transferred to trigger phenotypic changes of recipient cells. In recent years, many reports have indicated the role of EVs in pancreatitis, including acute pancreatitis, chronic pancreatitis and autoimmune pancreatitis, suggesting their potential influence on the development and progression of pancreatitis. Plasma exosomes of acute pancreatitis can effectively reach the alveolar cavity and activate alveolar macrophages to cause acute lung injury. Furthermore, upregulated exosomal miRNAs can be used as biomarkers for acute pancreatitis. Here, we summarized the current understanding of EVs in pancreatitis with an emphasis on their biological roles and their potential use as diagnostic biomarkers and therapeutic agents for this disease.

Head and body/tail pancreatic neuroendocrine tumors have different biological characteristics and clinical outcomes.

PURPOSE: The incidence of pancreatic neuroendocrine tumors (pNETs) has continued to increase, but for pNETs, there is still no distinction between treatments based on anatomical location. We aim to determine whether NETs located at the head and body/tail of the pancreas are different. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we focused on pNETs patients with comprehensive information. The patients were divided into two groups based on tumors' location. We compared the characteristics of the two groups and assessed the risk factors for lymphatic metastasis. Survival analysis was performed based on the biological characteristics of the tumor. RESULTS: In all 3011 patients, pNETs were more common in the body/tail (62.94%) than in the head (37.06%) of the pancreas. The risk factors for lymph node metastasis in the two groups were different. Nonmetastatic, low-grade pancreatic body/tail NETs had the best prognosis (p < 0.001). For low-grade tumors (G1-G2), lymphatic metastasis did not significantly affect the prognosis of patients with pancreatic head NETs (p = 0.098) but affected the overall survival of patients with pancreatic body/tail NETs (p < 0.001). The tumors at the pancreatic head were larger (p = 0.001), more likely to have positive lymph nodes (p < 0.001) and more prone to locally advanced and distant invasion (p < 0.001). The prognosis of pancreatic head NETs 21-40 mm was worse than that of body/tail pNETs (p < 0.001). For non-functional NETs, the overall survival of pancreatic body/tail tumors was better (p < 0.001). CONCLUSION: The pancreatic head and pancreatic body/tail NETs have different biological characteristics and clinical outcomes and they should be treated differently.

Two cases of agenesis of the dorsal pancreas and a review of the literature.

BACKGROUND: Agenesis of the dorsal pancreas (ADP) is a very rare disease with no specific symptoms, and the pathogenesis is not clear. Some patients will be accompanied by other diseases, such as pancreatic tumor or pancreatitis. But most cases are very atypical and difficult to distinguish. Some syndromes of pancreatic exocrine insufficiency are common in patients with ADP. Here, we report two cases of ADP and summarize the clinical features, diagnosis, and treatment of ADP. CASE PRESENTATION: Case A is a 65-year-old Chinese woman who presented with abdominal pain accompanied by nausea, bloating and acid reflux. The enhanced abdominal CT scan found nothing meaningful except the absence of the body and tail of the pancreas. The diagnosis was considered as gastrointestinal dysfunction cause by exocrine pancreatic insufficiency and recovered after symptomatic treatment. Case B is a 61-year-old Chinese woman who presented with abdominal pain accompanied by fever, vomiting and bloating. The abdominal CT showed multiple stones in the gallbladder, and the body and tail of the patient's pancreas were absent. She was diagnosed with cholelithiasis and recovered after laparoscopic cholecystectomy. CONCLUSION: Agenesis of the dorsal pancreas (ADP) is a rare congenital disease with an unclear pathogenesis that presents multiple symptoms. It should be considered when the patients have non-specific, persistent and unexplained symptoms such as bloating or uncontrolled blood sugar. Imaging examination is helpful for diagnosis. And it does not require surgical intervention unless it accompanies other diseases, EPI need to be considered when the non-specific gastrointestinal symptoms appear.

Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression.

The roles of miRNAs in the development of cancer have made them promising tools for novel therapeutic approaches. However, the successful delivery of miRNAs to cancer cells has been hampered by difficulties in developing an effective and sustainable delivery mechanism. Exosomes are small endogenous membrane vesicles that mediate communication between cells by delivering genetic materials. Thus, given their intrinsic properties, exosomes have been a focus for use as biological delivery vehicles for miRNAs transfer. Whether exosomes can effectively deliver exogenous miRNAs to pancreatic ductal adenocarcinoma (PDAC) cells has not been thoroughly investigated. Here, we used exosomes from human umbilical cord mesenchymal stromal cells (hucMSCs) to deliver exogenous miR-145-5p, which inhibited PDAC cell proliferation and invasion and increased apoptosis and cell cycle arrest, concomitant with decreased Smad3 expression in vitro. Using a mouse model, we also demonstrated that overexpressing miR-145-5p significantly reduced the growth of xenograft tumors in vivo. Our findings provide novel insights that exosomes might be an attractive therapeutic vehicle for the clinical administration of miRNAs in patients with PDAC.

Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of ß-catenin.

The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis (RA), particularly bone loss, have not been clearly explored. The imbalance between osteoblasts and osteoclasts is a major reason for bone loss. The dysfunction of osteoblasts, which are derived from mesenchymal stem cells (MSCs), induced bone erosion occurs earlier and is characterized as more insidious. Here, we showed that the nuclear expression and translocation of Ahr were both significantly increased in MSCs from collagen-induced arthritis (CIA) mice. The enhanced Ahr suppressed the mRNA levels of osteoblastic markers including Alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2) in the differentiation of MSCs to osteoblasts in CIA. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated activation of Ahr dose-dependently suppressed the expression of osteoblastic markers. In addition, the expression of ß-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited ß-catenin expression. The Wnt3a-induced the activation of Wnt/ß-catenin pathway partly rescued the osteogenesis decline induced by TCDD. Taken together, these results indicate that activated Ahr plays a negative role in CIA MSCs osteogenesis, possibly by suppressing the expression of ß-catenin.

A Truncated IL-17RC Peptide Ameliorates Synovitis and Bone Destruction of Arthritic Mice.

Peptide-based therapy, such as modified peptides, has attracted increased attention. IL-17 is a promising therapeutic target for autoimmune diseases, and levels of circulating bioactive IL-17 are associated with rheumatoid arthritis severity. In this study, a modified truncated IL-17RC is generated to ameliorate inflammation and bone destruction in arthritis. The truncated IL-17RC binds to both IL-17A and IL-17F with higher binding capacity compared to nonmodified IL-17RC. In addition, the truncated IL-17RC reduces the secretion of inflammatory and osteoclastogenic factors induced by IL-17A/F in vitro. Moreover, the administration of truncated IL-17RC dramatically improves symptoms of inflammation and inhibited bone destruction in collagen-induced arthritis mice. Collectively, these data demonstrate that modified truncated IL-17RC peptide may be a more effective treatment strategy in the simultaneous inhibition of both IL-17A and IL-17F signaling, whereas the existing agents neutralize IL-17A or IL-17F alone. These suggest that the truncated IL-17RC may be a potential candidate in the treatment of inflammatory associated bone diseases.