Still water run deep: Therapeutic TP effect of ucMSC-Ex via regulating mTOR to enhance autophagy.

Our previous study confirmed that umbilical cord mesenchymal stem cells-exosomes (ucMSC-Ex) inhibit apoptosis of pancreatic acinar cells to exert protective effects. However, the relationship between apoptosis and autophagy in traumatic pancreatitis (TP) has rarely been reported. We dissected the transcriptomics after pancreatic trauma and ucMSC-Ex therapy by high-throughput sequencing. Additionally, we used rapamycin and MHY1485 to regulate mTOR. HE, inflammatory factors and pancreatic enzymatic assays were used to comprehensively determine the local versus systemic injury level, fluorescence staining and electron microscopy were used to detect the effect of autophagy, and observe the expression levels of autophagy-related markers at the gene and protein levels. High-throughput sequencing identified that autophagy played a crucial role in the pathophysiological process of TP and ucMSC-Ex therapy. The results of electron microscopy, immunofluorescence staining, polymerase chain reaction and western blot suggested that therapeutic effect of ucMSC-Ex was mediated by activation of autophagy in pancreatic acinar cells through inhibition of mTOR. ucMSC-Ex can attenuate pancreas injury by inhibiting mTOR to regulate acinar cell autophagy after TP. Future studies will build on the comprehensive sequencing of RNA carried by ucMSC-Ex to predict and verify specific non-coding RNA.

Sildenafil increases AAV9 transduction after a systemic administration and enhances AAV9-dystrophin therapeutic effect in mdx mice.

Adeno-associated virus (AAV) vectors have been successfully used to deliver genes for treating rare diseases. However, the systemic administration of high AAV vector doses triggers several adverse effects, including immune response, the asymptomatic elevation of liver transaminase levels, and complement activation. Thus, improving AAV transduction and reducing AAV dosage for treatment is necessary. Recently, we found that a phosphodiesterase-5 inhibitor significantly promoted AAV9 transduction in vitro by regulating the caveolae and macropinocytosis pathways. When AAV9-Gaussian luciferase (AAV9-Gluc) and AAV9-green fluorescent protein (AAV9-GFP) were injected intravenously into mice pre-treated with sildenafil, the expressions of Gluc in the plasma and GFP in muscle tissues significantly increased (P < 0.05). Sildenafil also improved Evans blue permeation in tissues. Additionally, we found that sildenafil promoted Treg proliferation, inhibited B-cell activation, and decreased anti-AAV9 IgG levels (P < 0.05). Furthermore, sildenafil significantly promoted Duchenne muscular dystrophy gene therapy efficacy using AAV9 in mdx mice; it increased micro-dystrophin gene expression, forelimb grip strength, and time spent on the rotarod test, decreased serum creatine kinase levels, and ameliorated histopathology by improving muscle cell morphology and reducing fibrosis (P < 0.05). These results show that sildenafil significantly improved AAV transduction, suppressed the levels of anti-AAV9 IgG, and enhanced the efficacy of gene therapy.

The future of robotic pancreaticoduodenal surgery: a bibliometric analysis.

OBJECTIVES: Robotic pancreaticoduodenectomy (RPD) has garnered significant research attention in the last decade. However, no bibliometric studies have been conducted on this field yet. Therefore, the aim of this study is to provide an up-to-date analysis of the current state of research, as well as future trends and hotspots in RPD, through a bibliometric analysis. MATERIALS AND METHODS: We conducted a thorough search of all literature related to RPD in the Web of Science Core Collection (WoSCC). We then analyzed this literature for a variety of factors, including authorship, country of origin, institutional affiliations, and keywords. To visualize our findings, we utilized Citespace 6.1.R3, which enabled us to create network visualization maps, perform cluster analysis, and extract burst words. RESULTS: A total of 264 articles were retrieved. Zureikat is the author with the largest contribution in this field, and Surgical Endoscopy and Other International Techniques is the journal with the largest number of papers in this field. The United States is the core research country in this field. The University of Pittsburgh is the most productive institution. According to the data, outcome, pancreas fistula, definition, risk factor, stay, survival, learning curve and experience are recognized as research hotspots in this field. CONCLUSIONS: This study is the first bibliometric study in the field of RPD. Our data will help us better understand the development trend of the field, and determine research hotspots and research directions. The research results provide practical information for other scholars to understand key directions and cutting-edge information.

Impact of age on short-term outcomes after pancreaticoduodenectomy: A retrospective case-control study of 260 patients.

Background: Although the increase of perioperative complications in the elderly undergoing pancreaticoduodenectomy (PD) surgery has been recognized, the definition of the "old patient" of PD in the studies is different and there is no accepted cut-off value at present. Methods: 279 consecutive patients who have undergone PD in our center between January 2012 and May 2020 were analyzed. Demographic features, clinical-pathological data and short-term outcomes were collected. The patients were divided into two groups, and the cut-off value (62.5 years) is picked based on the highest Youden Index. Primary endpoints were perioperative morbidity and mortality, and complications were classified according to the Clavien-Dindo Score. Results: A total of 260 patients with PD were included in this study. Postoperative pathology confirmed pancreatic tumors in 62 patients, bile duct tumor in 105, duodenal tumor in 90, and others in 3. Age (OR = 1.09, P < 0.01), and albumin (OR = 0.34, P < 0.05) were significantly correlated with postoperative Clavien-Dindo Score ≥3b. There were 173 (66.5%) patients in the younger group (<62.5 years) and 87 (33.5%) in the elderly group (≥62.5 years). Significant difference between two groups was demonstrated for Clavien-Dindo Score ≥3b (P < 0.01), postoperative pancreatic fistula (P < 0.05), and perioperative deceases (P < 0.05). Conclusions: Age and albumin were significantly correlated with postoperative Clavien-Dindo Score ≥3b, and there was no significant difference in predicting the grade of Clavien-Dindo Score. The cut-off value of elderly patients with PD was 62.5 years old and there were useful in predicting Clavien-Dindo Score ≥3b, pancreatic fistula, and perioperative death.

The visceral pancreatic neck anterior distance may be an effective parameter to predict post-pancreaticoduodenectomy clinically relevant postoperative pancreatic fistula.

Background: The clinically relevant postoperative pancreatic fistula (CR-POPF) is significantly correlated with a high post-pancreaticoduodenectomy (PD) mortality rate. Several studies have reported an association between visceral obesity and CR-POPF. Nevertheless, there are many technical difficulties and controversies in the measurement of visceral fat. The aim of this research was to determine whether the visceral pancreatic neck anterior distance (V-PNAD) was a credible predictor for CR-POPF. Methods: We retrospectively analyzed the data of 216 patients who underwent PD in our center between January 2016 and August 2021. The correlation of patients' demographic information, imaging variables, and intraoperative data with CR-POPF was assessed. Furthermore, areas under the receiver operating characteristic curves for six distances (abdominal thickness, visceral thickness, abdominal width, visceral width, abdominal PNAD, V-PNAD) were used to identify the best imaging distance to predict POPF. Results: In the multivariate logistic analysis, V-PNAD (P < 0.01) was the most significant risk factor for CR-POPF after PD. Males with a V-PNAD >3.97 cm or females with a V-PNAD >3.66 cm were included into the high-risk group. The high-risk group had a higher prevalence of CR-POPF (6.5% vs. 45.1%, P < 0.001), intraperitoneal infection (1.9% vs. 23.9%, P < 0.001), pulmonary infection (3.7% vs. 14.1%, P = 0.012), pleural effusion (17.8% vs. 33.8%, P = 0.014), and ascites (22.4% vs. 40.8%, P = 0.009) than the low-risk group. Conclusion: Of all imaging distances, V-PNAD may be the most effective predictor of CR-POPF. Moreover, high-risk patients (males, V-PNAD >3.97 cm; females, V-PNAD >3.66 cm) have a high incidence of CR-POPF and poor short-term post-PD prognosis. Therefore, surgeons should perform PD carefully and take adequate preventive measures to reduce the incidence of pancreatic fistula when the patient has a high V-PNAD.

Multi-level integrative analysis of the roles of lncRNAs and differential mRNAs in the progression of chronic pancreatitis to pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and approximately 5% of patients with chronic pancreatitis (CP) inevitably develop PDAC. This study aims explore the key gene regulation involved in the progression of CP to PDAC, with a particular emphasis on the function of lncRNAs. RESULTS: A total of 103 pancreatic tissue samples collected from 11 to 92 patients with CP and PDAC, respectively, were included in this study. After normalizing and logarithmically converting the original data, differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEGs) in each dataset were selected. To determine the main functional pathways of differential mRNAs, we further annotated DEGs using gene ontology (GO) and analyzed the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. In addition, the interaction between lncRNA-miRNA-mRNA was clarified and the protein-protein interaction (PPI) network was constructed to screen for key modules and determine hub genes. Finally, quantitative real-time polymerase chain reaction (qPCR) was used to detect the changes in non-coding RNAs and key mRNAs in the pancreatic tissues of patients with CP and PDAC. In this study, 230 lncRNAs and 17,668 mRNAs were included. There were nine upregulated lncRNAs and 188 downregulated lncRNAs. Furthermore, 2334 upregulated differential mRNAs and 10,341 downregulated differential mRNAs were included in the enrichment analysis. From the KEGG enrichment analysis, cytokine-cytokine receptor interaction, calcium signaling pathway, cAMP signaling pathway, and nicotine addiction exhibited significant differences. Additionally, a total of 52 lncRNAs, 104 miRNAs, and 312 mRNAs were included in the construction of a potential lncRNA-miRNA-mRNA regulatory network. PPI network was established and two of the five central DEGs were created in this module, suggesting that lysophosphatidic acid receptor 1 (LPAR1) and regulator of calcineurin 2 (RCAN2) may play significant roles in the progression from CP to PDAC. Finally, the PCR results suggested that LINC01547/hsa-miR-4694-3p/LPAR1 and LINC00482/hsa-miR-6756-3p/RCAN2 play important roles in the carcinogenesis process of CP. CONCLUSION: Two signaling axes critical in the progression of CP to PDAC were screened out. Our findings will be useful for novel insights into the molecular mechanism and potential diagnostic or therapeutic biomarkers for CP and PDAC.

Human umbilical cord mesenchymal stem cells-derived exosomes for treating traumatic pancreatitis in rats.

BACKGROUND: The therapeutic and protective effects of human umbilical cord mesenchymal stem cells-exosomes (hucMSC-Exs) on traumatic pancreatitis (TP) remain unknown. Here, we established a rat model of TP and evaluated and compared the therapeutic effects of hUC-MSCs and hucMSC-Exs. METHODS: HucMSC-Exs were obtained by ultracentrifugation and identified using transmission electron microscopy and western blot analysis. TP rats were treated by tail vein injection of hUC-MSCs and hucMSC-Exs. Their homing in rats was observed by performing fluorescence microscopy. The degree of pancreatic tissue damage was assessed by HE staining, the expression levels of amylase, lipase, and inflammatory cytokines were detected by ELISA, apoptosis was detected by TUNEL assay, and the expression levels of various apoptosis-related proteins were detected by western-blot. The expression levels of apoptosis-related molecular markers were detected by RT-qPCR. RESULTS: The colonization of exosomes was observed in pancreatic tissue. Compared to TP group, the histopathological score of pancreas was significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05). Compared to TP group, the activity of serum amylase and lipase was significantly decreased (P < 0.05). The expression levels of IL-6 and TNF-α were significantly decreased, while those of IL-10 and TGF-ß were significantly increased (P < 0.05). The apoptosis index of the TP group was significantly increased (P < 0.05), whereas that of the TP + hUC-MSCs and TP + hucMSC-Exs groups was significantly decreased (P < 0.05). Compared to TP group, the expression levels of Bax, Bcl-2, and Caspase-3 were significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05). CONCLUSION: HucMSC-Exs can colonize injured pancreatic tissue, inhibit the apoptosis of acinar cells, and control the systemic inflammatory response to facilitate the repair of pancreatic tissue.

Application of exosomes in the diagnosis and treatment of pancreatic diseases.

Pancreatic diseases, a serious threat to human health, have garnered considerable research interest, as they are associated with a high mortality rate. However, owing to the uncertain etiology and complex pathophysiology, the treatment of pancreatic diseases is a challenge for clinicians and researchers. Exosomes, carriers of intercellular communication signals, play an important role in the diagnosis and treatment of pancreatic diseases. Exosomes are involved in multiple stages of pancreatic disease development, including apoptosis, immune regulation, angiogenesis, cell migration, and cell proliferation. Thus, extensive alterations in the quantity and variety of exosomes may be indicative of abnormal biological behaviors of pancreatic cells. This phenomenon could be exploited for the development of exosomes as a new biomarker or target of new treatment strategies. Several studies have demonstrated the diagnostic and therapeutic effects of exosomes in cancer and inflammatory pancreatic diseases. Herein, we introduce the roles of exosomes in the diagnosis and treatment of pancreatic diseases and discuss directions for future research and perspectives of their applications.

Co-circulation of multiple reassortant H6 subtype avian influenza viruses in wild birds in eastern China, 2016-2017.

BACKGROUND: H6 subtype influenza viruses were prevalent in domestic poultry and wild birds, which also could pose potential threat to humans. However, little is known about the prevalence of H6 subtype viruses in wild birds in eastern China, a crucial stopover or wintering site for migratory wild birds along the East Asian-Australasian Flyway. METHODS: During the routine surveillance in 2016-2017, H6 subtype AIVs positive samples were identified, and the representative strains were selected for further sequence and phylogenetic analysis and the pathogenicity in mice were evaluated. RESULTS: Among the 30 H6 positive samples, there were at least four subtypes H6N1, H6N2, H6N5 and H6N8 co-circulated in Shanghai, China. Genetic analysis showed the 8 representative isolates shared homology with different AIV sub-lineages isolated from domestic ducks or wild birds in different countries along the East Asian-Australasian flyways, and were classified into 7 new genotypes. The pathogenicity to mice showed that these H6 viruses could replicate efficiently in the lungs without prior adaptation, but could not cause mice death. CONCLUSIONS: Eight novel strains belonged to H6N1, H6N2, H6N5 and H6N8 subtypes were isolated. Phylogenetic analyses revealed multiple origins of internal genes indicative of robust reassortment events and frequent wild birds-poultry interaction encouraging the evolution and emergence of new genotypes. The pathogenicity to mammals should be closely monitored to prevent the emergence of novel pandemic viruses.

Two novel reassortant H11N8 avian influenza viruses occur in wild birds found in East Dongting Lake, China.

During the surveillance of avian influenza viruses in East Dongting Lake, China (2014-2015), two H11N8 avian influenza viruses were detected in the bean goose (Anser fabalis) and the falcated teal (Anas falcata). Phylogenetic analysis showed that these two novel reassortant H11N8 avian influenza viruses contain genes from poultry and wild birds. This is the first report detecting the H11N8 subtype influenza virus from wild birds in Asia. These findings indicate a dissemination of avian influenza virus along the East Asian-Australian flyway. In addition, the interaction between poultry and wild birds was addressed suggesting the need for intensive surveillance of wild bird populations.

Identification of two novel avian influenza a (H5N6) viruses in wild birds, Shanghai, in 2016.

The H5N6 avian influenza virus (AIV) has been continuously reported in wild birds, which may contribute to further geographical spread during their long-distance migrations. Active AIV surveillance in wild birds was conducted during October and November 2016 in Shanghai, China. Two novel influenza A (H5N6) viruses were detected in samples from migratory waterfowl that are genetically similar to recent South Korea and Japan H5N6 viruses collected in 2016 and 2017, highlighting the role of migratory waterfowl in the dissemination of H5N6 viruses along migratory flyways.

A novel highly pathogenic H5N8 avian influenza virus isolated from a wild duck in China.

Migrating wild birds are considered natural reservoirs of influenza viruses and serve as a potential source of novel influenza strains in humans and livestock. During routine avian influenza surveillance conducted in eastern China, a novel H5N8 (SH-9) reassortant influenza virus was isolated from a mallard duck in China. blast analysis revealed that the HA, NA, PB1, PA, NP, and M segments of SH-9 were most closely related to the corresponding segments of A/duck/Jiangsu/k1203/2010 (H5N8). The SH-9 virus preferentially recognized avian-like influenza virus receptors and was highly pathogenic in mice. Our results suggest that wild birds could acquire the H5N8 virus from breeding ducks and spread the virus via migratory bird flyways.

Characterization of the antiviral activity for influenza viruses M1 zinc finger peptides.

We sought to investigate the cellular uptake and antiviral activity for the M1 zinc finger peptides derived from influenza A and influenza B viruses in vitro. No cellular uptake was detected by fluorescent microscopy for the synthetic zinc finger peptides. When flanked to a cell permeable peptide Tp10, the zinc finger recombinant proteins were efficiently internalized by MDCK cells. However, no antiviral activity was detected against homologous or heterologous virus infections for the synthetic peptides or the Tp10-flanked recombinant proteins, regardless treated with or without Zn(2+). Nevertheless, MDCK cell constitutively expressing the M1 zinc finger peptides in cell nuclei potently inhibited replication of homologous, but not heterologous influenza viruses. Adenoviral vector delivered M1 zinc finger peptides also exhibited potent antiviral activity against homologous viruses challenge. Transduction at 100 PFU dose of recombinant adenovirus efficiently protected 99% of the cells from 100 TCID(50) of different virus infections for both peptides. These results brought new insight to the antiviral researches against influenza virus infections.

[Microclimate and comfortable degree of Shanghai urban open spaces in summer].

Based on the observation data of air temperature, relative humidity, wind speed, and solar radiation from May to August 2006, the regulation effects of five types of open spaces (square, fountain, grassplot, corridor, and woodland) in Shanghai urban districts on the microclimate were analyzed, and discomfort index (DI) was introduced to evaluate the effects of these five types of open spaces on human body' s comfortable degree. The results showed that there existed definite differences in the air temperature and relative humidity among the open spaces, with the mean temperature decreased in the order of square > grassplot > fountain > corridor > woodland, and the mean relative humidity decreased in the order of woodland > corridor > fountain > grassplot > square. The area of the square, the wind speed and direction near the fountain, the grass species on the grass-plot, the width and tree coverage of the corridor, and the tree coverage and canopy height of the woodland had significant correlations with the microclimate parameters of corresponding open spaces. Comparing with other three types of open spaces, woodland and corridor had better regulation effects on the microclimate via shading, decreasing air temperature, and increasing relative humidity.

[Seasonal fluctuation of macrobenthos community in Jiuduansha intertidal wetland of Yangtze River Estuary].

From November 2004 to October 2005, an investigation was made on the seasonal fluctuation of macrobenthos community in the Jiuduansha intertidal wetland of Yangtze River Estuary, with the correlations between this fluctuation and sediment factors studied. 864 samples were collected seasonally from 216 sites in 7 sampling transects. A total of 30 species were identified, mainly belonging to Mollusca, Annelida, Crustacea and insect. The dominant species were Stenothyra glabra, Assiminea violacea, Potamocorbula ustulata, Glaucomya chinensis, and Ilyrplax deschampsi. In spring, macrobenthos had the highest density and biomass and the richest diversity, but in summer, the density and biomass were the lowest, the diversity was on a lower level, and the distribution was uneven. There were no significant differences in the species number and biomass between autumn and winter, but the density was higher in winter than in autumn. In spring, summer and autumn, the species number, density, and biomass of macrobenthos had no significant correlations with sediment factors, but in winter, macrobenthos density had significant correlations with the humidity and organic matter content of sediment.