Gastrointestinal symptoms of long COVID-19 related to the ectopic colonization of specific bacteria that move between the upper and lower alimentary tract and alterations in serum metabolites.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) outbreak, many COVID-19 variants have emerged, causing several waves of pandemics and many infections. Long COVID-19, or long-term sequelae after recovery from COVID-19, has aroused worldwide concern because it reduces patient quality of life after rehabilitation. We aimed to characterize the functional differential profile of the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. METHODS: We prospectively collected oral, fecal, and serum samples from 983 antibiotic-naïve patients with mild COVID-19 and performed a 3-month follow-up postdischarge. Forty-five fecal and saliva samples, and 25 paired serum samples were collected from patients with gastrointestinal symptoms of long COVID-19 at follow-up and from healthy controls, respectively. Eight fecal and saliva samples were collected without gastrointestinal symptoms of long COVID-19 at follow-up. Shotgun metagenomic sequencing of fecal samples and 2bRAD-M sequencing of saliva samples were performed on these paired samples. Two published COVID-19 gut microbiota cohorts were analyzed for comparison. Paired serum samples were analyzed using widely targeted metabolomics. RESULTS: Mild COVID-19 patients without gastrointestinal symptoms of long COVID-19 showed little difference in the gut and oral microbiota during hospitalization and at follow-up from healthy controls. The baseline and 3-month samples collected from patients with gastrointestinal symptoms associated with long COVID-19 showed significant differences, and ectopic colonization of the oral cavity by gut microbes including 27 common differentially abundant genera in the Proteobacteria phylum, was observed at the 3-month timepoint. Some of these bacteria, including Neisseria, Lautropia, and Agrobacterium, were highly related to differentially expressed serum metabolites with potential toxicity, such as 4-chlorophenylacetic acid, 5-sulfoxymethylfurfural, and estradiol valerate. CONCLUSIONS: Our study characterized the changes in and correlations between the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. Additionally, our findings reveal that ectopically colonized bacteria from the gut to the oral cavity could exist in long COVID-19 patients with gastrointestinal symptoms, with a strong correlation to some potential harmful metabolites in serum.

Silencing GS Homeobox 2 Alleviates Gemcitabine Resistance in Pancreatic Cancer Cells by Activating SHH/GLI1 Signaling Pathway.

Sonic hedgehog (SHH) signaling pathway and glioma-associated oncogene homolog 1 (GLI1) play important roles in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). GS homeobox 2 (GSX2, formerly GSH2) is a downstream target of SHH signaling, but its role in pancreatic cancer remains unclear. This study evaluates the role of GSH2 in the development and drug resistance of pancreatic cancer. Both cell culture and xenograft mouse model were used. Immunohistochemistry, Western blotting and quantitative RT-PCR were used to examine the expression of GSH2 and other related molecules. CCK8 assay was used to test the cell proliferation, and flow cytometry used to examine cell apoptosis upon gemcitabine treatment. It was found that GSH2 is overexpressed in human pancreatic cancer tissues and cells. The expression of SHH and GLI1 was reversely correlated with GSH2 in pancreatic cancer cells. SHH and GLI1 have protein-protein interactions with GSH2. GSH2 silencing in pancreatic cancer cells inhibited cell proliferation, migration and invasion, increased cell apoptosis and sensitized pancreatic cancer cells to gemcitabine treatment. Furthermore, in vivo study demonstrated that silencing GSH2 increased the efficacy of gemcitabine-based treatment. Our results indicate that GSH2 is overexpressed in pancreatic cancer. GSH2 silencing in pancreatic cancer alleviates gemcitabine resistance by activating SHH/GLI1 pathway. Thus, targeting GSH2 in PDAC could be a novel cancer therapeutic strategy.

Transgenic Expression of PRSS1R122H Sensitizes Mice to Pancreatitis.

BACKGROUND & AIMS: Mutations in the trypsinogen gene (PRSS1) cause human hereditary pancreatitis. However, it is not clear how mutant forms of PRSS1 contribute to disease development. We studied the effects of expressing mutant forms of human PRSS1 in mice. METHODS: We expressed forms of PRSS1 with and without the mutation encoding R122H (PRSS1R122H) specifically in pancreatic acinar cells under control of a full-length pancreatic elastase gene promoter. Mice that did not express these transgenes were used as controls. Mice were given injections of caerulein to induce acute pancreatitis or injections of lipopolysaccharide to induce chronic pancreatitis. Other groups of mice were fed ethanol or placed on a high-fat diet to induce pancreatitis. Pancreata were collected and analyzed by histology, immunoblots, real-time polymerase chain reaction, and immunohistochemistry. Trypsin enzymatic activity and chymotrypsin enzymatic activity were measured in pancreatic homogenates. Blood was collected and serum amylase activity was measured. RESULTS: Pancreata from mice expressing transgenes encoding PRSS1 or PRSS1R122H had focal areas of inflammation; these lesions were more prominent in mice that express PRSS1R122H. Pancreata from mice that express PRSS1 or PRSS1R122H had increased levels of heat shock protein 70 and nuclear factor (erythroid-derived 2)-like 2, and reduced levels of chymotrypsin C compared with control mice. Increased expression of PRSS1 or PRSS1R122H increased focal damage in pancreatic tissues and increased the severity of acute pancreatitis after caerulein injection. Administration of lipopolysaccharide exacerbated inflammation in mice that express PRSS1R122H compared to mice that express PRSS1 or control mice. Mice that express PRSS1R122H developed more severe pancreatitis after ethanol feeding or a high-fat diet than mice that express PRSS1 or control mice. Pancreata from mice that express PRSS1R122H had more DNA damage, apoptosis, and collagen deposition and increased trypsin activity and infiltration by inflammatory cells than mice that express PRSS1 or control mice. CONCLUSIONS: Expression of a transgene encoding PRSS1R122H in mice promoted inflammation and increased the severity of pancreatitis compared with mice that express PRSS1 or control mice. These mice might be used as a model for human hereditary pancreatitis and can be studied to determine mechanisms of induction of pancreatitis by lipopolysaccharide, ethanol, or a high-fat diet.

Downregulation of GSTM2 enhances gemcitabine chemosensitivity of pancreatic cancer in vitro and in vivo.

Glutathione-S-transferases (GSTs) not only show cytoprotective role and their involvement in the development of anticancer drug resistance, but also transmit signals that control cell proliferation and apoptosis. However, the role of GST isoforms in chemotherapy resistance remains elusive in pancreatic cancer. Here, we demonstrated that gemcitabine treatment increased the GSTM2 expression in pancreatic cancer cell lines. Knockdown of GSTM2 by siRNA elevated apoptosis and decreased viability of pancreatic cancer cells treated with gemcitabine. Moreover, in vivo experiments further showed that shRNA induced GSTM2 downregulation enhanced drug sensitivity of gemcitabine in orthotopic pancreatic tumor mice. We also found that GSTM2 levels were lower in tumor tissues than in non-tumor tissues and higher GSTM2 expression was significantly associated with longer overall survival. In conclusion, our findings indicate that GSTM2 expression is essential for the survival of pancreatic cancer cells undergoing gemcitabine treatment and leads to chemo resistance. Downregulation of GSTM2 in pancreatic cancer may benefit gemcitabine treatment. GSTM2 expression in patients also shows significant correlation with overall survival. Thus, our study suggests that GSTM2 is a potential target for chemotherapy optimization and prognostic biomarker of pancreatic cancer.

High-Risk Characteristics Associated with Advanced Pancreatic Cystic Lesions: Results from a Retrospective Surgical Cohort.

BACKGROUND AND AIM: The management of pancreatic cystic lesions (PCLs) remains controversial. We performed a retrospective study to determine characteristics associated with advanced PCLs (A-PCLs) and whether these characteristics vary in different pathological types of PCLs. The additional diagnostic value of endoscopic ultrasound (EUS) was also evaluated. METHODS: Patients who underwent surgical resection for an identified PCLs by imaging modalities were included. A logistic regression model was developed to identify significant characteristics for A-PCLs. EUS data was assessed separately. RESULTS: Three hundred and fifty-three patients were included, and 125 patients (35.4%) were A-PCLs. The presence of main pancreatic duct (MPD) diameter ≥ 10 mm (odds ratio [OR], 11.7; 95% confidence interval [CI], 1.53-89.2; P = 0.018), mural nodules ≥ 5 mm (OR, 11.67; 95% CI, 2.3-59.05; P = 0.003), solid components within cysts (OR, 30.87; 95% CI, 7.23-131.7; P < 0.0001) and high serum CA19-9 levels (OR, 1.006; 95% CI, 1.001-1.011; P = 0.02) were independently associated with the presence of A-PCLs. The presence of septa was independently associated with the presence of non-A-PCLs (OR, 0.147; 95% CI, 0.04-0.6; P = 0.008). Males who had a history of tobacco abuse (P < 0.0001) and had a greatly dilated MPD (P < 0.0001) were more common in advanced intraductal papillary mucinous neoplasms (IPMC) patients. Solid pseudopapillary neoplasm (SPT) often occurred in young women (P < 0.0001), mostly asymptomatically (P < 0.0001) and with lower serum CA19-9 levels (P < 0.0001). In the 124 patients who underwent EUS-guided fine-needle aspiration (EUS-FNA), five additional characteristics (4 mural nodules and 1 MPD involvement) were identified by EUS imaging and 17 patients were identified with abnormal cytological results (13 atypical cells and 4 suspicious for malignancy cells) by EUS-FNA. CONCLUSION: On the basis of a retrospective study with large sample size, the presence of MPD ≥ 10 mm, mural nodules, solid components, and high serum CA19-9 levels were independently associated with the presence of A-PCLs. The high-risk characteristics may vary across different types of A-PCLs. EUS and EUS-FNA could provide additional diagnostic information for PCLs.

Validation of European evidence-based guidelines and American College of Gastroenterology guidelines as predictors of advanced neoplasia in patients with suspected mucinous pancreatic cystic neoplasms.

BACKGROUND AND AIM: The European evidence-based guidelines (EEG) and American College of Gastroenterology Guidelines (ACGG) have been published to guide the management of pancreatic cystic lesions. We aim to evaluate the value of both guidelines in predicting advanced pancreatic cystic lesions (A-PCLs) with preoperatively imaging-suspected cystic mucinous pancreatic neoplasms (cMNs). METHODS: One hundred ninety-eight patients who underwent resections from 2013 to 2019 for suspected cMNs were retrospectively reviewed. Receiver operating characteristic curves were calculated and compared with measure diagnostic value. RESULTS: Sixty-two patients were diagnosed with A-PCLs pathologically. Cross-imaging modalities had comparable diagnostic accuracy to endoscopic ultrasound in type classification and A-PCLs prediction. Receiver operating characteristic curve comparison analyses showed that EEG absolute + MCN (EEGAM ) and EEG relative + MCN (EEGRM ) having at least one indications criteria were comparable to the ACGG (P = 0.21 and P = 0.45). For the criteria having at least two indications, ACGG was superior to EEGAM (P = 0.001) but comparable to EEGRM (P = 0.12). EEGAM ≥ 1 indication criteria was superior to ≥ 2 indications criteria (P = 0.02). EEGRM ≥ 1 indication criteria had comparable diagnostic performance with ≥ 2 indications criteria (P = 0.86). ACGG ≥ 2 indications criteria was superior to ≥ 1 indication criteria (P = 0.02). CONCLUSION: On the basis of cross-imaging evaluations, both sets of guidelines were found to be helpful in identifying A-PCLs in suspected cMNs with comparable performance. EEGAM  ≥ 1 indication criteria was superior to ≥ 2 indications criteria. ACGG ≥ 2 indications criteria was superior to ≥ 1 indication criteria.

The pathological features and prognoses of intraductal papillary mucinous neoplasm and mucinous cystic neoplasm after surgical resection: a single institution series.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) represent the tumors with malignant transformation potential. The objective of the study was to verify their pathological characteristics, prognoses, and recurrence factors. METHODS: Two hundred eighteen IPMNs and 27 MCNs resected at a single institution were included. The demographic, preoperative, histopathological, and follow-up data of the patients were recorded and analyzed. Overall survival (OS) and disease-free survival (DFS) were defined as the interval from the date of initial surgery to death or the last follow-up (OS) and to diagnosis of recurrence or death at follow-up (DFS). RESULTS: Of the 218 IPMN and 27 MCN patients, 93 (42.7%) and 8 (29.6%) cases were malignant, respectively. IPMNs occurred in older patients compared with MCN patients (median 63 years vs 54 years, P < 0.0001), and MCNs occurred exclusively in females (100%). Of the overall study cohort, the pathological specimens presented peripheral invasion in 37 (15.1%) patients and incisal margin invasion was observed in 46 (18.8%) patients. After a median follow-up of 34 months, 37 (14.9%) patients relapsed. The 5-year OS and DFS rates of IPMNs were 97.5% and 80.6%; and the OS and DFS rates of MCNs were 95.7% and 87.0%, respectively. There were four independent risk factors associated with recurrence: pathological diagnoses with malignancy (odds ratio, OR = 3.65), presence of oncocytic type for IPMN (OR = 1.69), peripheral invasion (OR = 12.87), and incisal margin invasion (OR = 1.99). CONCLUSIONS: IPMNs and MCNs are indolent tumors with favorable prognoses after surgical resection in terms of their relatively high OS and DFS rate. Patients with malignant pathological-related diagnoses should accept strict tumor surveillance in view of their higher risk of recurrence.

Transgenic expression of cyclooxygenase-2 in pancreatic acinar cells induces chronic pancreatitis.

Replacement of the exocrine parenchyma by fibrous tissue is a main characteristic of chronic pancreatitis. Understanding the mechanisms of pancreatic fibrogenesis is critical for the development of preventive and therapeutic interventions. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin synthesis, is expressed in patients with chronic pancreatitis. However, it is unknown whether COX-2 can cause chronic pancreatitis. To investigate the roles of pancreatic acinar COX-2 in fibrogenesis and the development of chronic pancreatitis, COX-2 was ectopically expressed specifically in pancreatic acinar cells in transgenic mice. Histopathological changes and expression levels of several profibrogenic factors related to chronic pancreatitis were evaluated. COX-2 was expressed in the pancreas of the transgenic mice, as detected by Western blot analysis. Immunohistochemical staining showed COX-2 was specifically expressed in pancreatic acinar cells. COX-2 expression led to progressive changes in the pancreas, including pancreas megaly, persistent inflammation, collagen deposition, and acinar-to-ductal metaplasia. Quantitative RT-PCR and immunostaining showed that profibrogenic factors were upregulated and pancreatic stellate cells were activated in the COX-2 transgenic mice. Expression of COX-2 in pancreatic acinar cells is sufficient to induce chronic pancreatitis. Targeting this pathway may be valuable in the prevention of chronic pancreatitis. NEW & NOTEWORTHY COX-2 expression is observed in pancreatic tissues of human chronic pancreatitis. In this study, we showed that COX-2 expression caused the development of chronic pancreatitis in transgenic mice, supporting the idea that COX-2 inhibition may be an effective preventive and therapeutic strategy.

Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates.

Ubiquitous pollution due to microplastics through the food chain is a major cause of various deleterious effects on the human health. The aim of this study was to determine the existence of microplastics and the internal mechanism of microplastics as accelerators of cholelithiasis. Gallstones were collected from 16 patients after cholecystectomy, and microplastics in the gallstones were detected through laser direct infrared and pyrolysis gas chromatographymass spectrometry examinations. Mice model of gallstone were constructed with or without different diameters of microplastic (0.5, 5 and 50 µm). The affinity between microplastic and cholesterol or bilirubin was tested by co-culturing and qualified using molecular dynamics simulations. Finally, altered gut microbiota among the groups were identified using 16 s rRNA sequencing. The presence of microplastics in the gallstones of all the patients were confirmed. Microplastic content was significantly higher in younger chololithiasis patients (age<50 years). Mice fed a high-cholesterol diet with microplastic drinks showed more severe chololithiasis. In terms of the mechanism, microplastics showed a higher affinity for cholesterol than for bilirubin. Significant alterations in the gut microbiota have also been identified after microplastic intake in mice. Our study revealed the presence of microplastics in human gallstones, showcasing their potential to aggravate chololithiasis by forming large cholesterol-microplastic heteroaggregates and altering the gut microbiota.

Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated. METHODS: We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (three each from CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. RESULTS: Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. CONCLUSIONS: Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Factors and techniques associated with endoscopic retrograde cholangiopancreatography outcomes in patients with periampullary diverticulum: Results from a large tertiary center.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) for patients with periampullary diverticulum (PAD) remains a challenge. This study aims to investigate the factors and techniques related to successful and safe ERCP in patients with PAD. Methods: We enrolled patients who underwent ERCP in a large tertiary center. The difficult cannulation rate, technical success rate, clinical success rate, and adverse events (AEs) rate were compared between patients with or without PAD. Three independent logistic regression models were established to identify factors and techniques associated with difficult cannulation, clinical success, and AEs. Results: Five thousand five hundred and ninety patients were included, of which 705 (12.6%) were diagnosed with PAD. Patients with PAD had a significantly higher difficult cannulation rate compared with patients without PAD (10.6% vs 8.0%, P < 0.0001), but the rates of technical success (clinical success (95.2% vs 95.2%, P = 0.951), and AEs (16.5% vs 14.4%, P = 0.156) were similar. Type I PAD (odds ratio [OR] = 2.114, 95% confidence interval [CI]:1.05-5.25) and ERCP indication for pancreatic diseases (OR = 1.196, 95%CI: 1.053-1.261) were independently associated with difficult cannulation. Small endoscopic sphincterotomy (EST) with balloon dilatation (OR = 1.581, 95%CI: 1.044-2.393) was independently associated with clinical success. Somatostatin injection showed no preventive effect on post-ERCP pancreatitis (OR = 1.144, 95%CI: 1.044-1.254). Moreover, the auxiliary cannulation techniques were safe for PAD patients. Conclusions: PAD did not affect ERCP outcomes. However, the choice of techniques and AE prophylactic measures should be more specific, especially for patients with type I PAD.

Molecular mechanisms of pruritus in prurigo nodularis.

Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients' quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained "itch-scratch" vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune network; however, the underlying mechanism remains undetermined. Itch mediators play a key role in pruritus amplification in PN and understanding their action mechanism will undoubtedly lead to the development of novel targeted antipruritic agents. In this review, we describe a series of pruritogens and receptors involved in mediating itching in PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, and intracellular signaling pathways. Moreover, we provide a prospective outlook on potential therapies based on existing findings.

The value of artificial intelligence techniques in predicting pancreatic ductal adenocarcinoma with EUS images: A meta-analysis and systematic review.

Conventional EUS plays an important role in identifying pancreatic cancer. However, the accuracy of EUS is strongly influenced by the operator's experience in performing EUS. Artificial intelligence (AI) is increasingly being used in various clinical diagnoses, especially in terms of image classification. This study aimed to evaluate the diagnostic test accuracy of AI for the prediction of pancreatic cancer using EUS images. We searched the Embase, PubMed, and Cochrane Library databases to identify studies that used endoscopic ultrasound images of pancreatic cancer and AI to predict the diagnostic accuracy of pancreatic cancer. Two reviewers extracted the data independently. The risk of bias of eligible studies was assessed using a Deek funnel plot. The quality of the included studies was measured by the QUDAS-2 tool. Seven studies involving 1110 participants were included: 634 participants with pancreatic cancer and 476 participants with nonpancreatic cancer. The accuracy of the AI for the prediction of pancreatic cancer (area under the curve) was 0.95 (95% confidence interval [CI], 0.93-0.97), with a corresponding pooled sensitivity of 93% (95% CI, 0.90-0.95), specificity of 90% (95% CI, 0.8-0.95), positive likelihood ratio 9.1 (95% CI 4.4-18.6), negative likelihood ratio 0.08 (95% CI 0.06-0.11), and diagnostic odds ratio 114 (95% CI 56-236). The methodological quality in each study was found to be the source of heterogeneity in the meta-regression combined model, which was statistically significant (P = 0.01). There was no evidence of publication bias. The accuracy of AI in diagnosing pancreatic cancer appears to be reliable. Further research and investment in AI could lead to substantial improvements in screening and early diagnosis.

A new method for treating chronic pancreatitis and preventing fibrosis using bioactive calcium silicate ion solution.

Chronic pancreatitis (CP) is a multifactorial fibroinflammatory syndrome. At present, there is no effective way to treat it clinically. In this study, we proposed a new approach by application of a highly active calcium silicate ion solution derived from calcium silicate (CS) bioceramics, which effectively inhibited the development of CP. This bioceramic derived bioactive ionic solution mainly regulated pancreatic acinar cells (PACs), macrophages and pancreatic stellate cells (PSCs) by SiO32- ions to inhibit inflammation and fibrosis and promote acinar regeneration. The possible mechanism of the therapeutic effect of CS ion solution mainly includes the inhibition of PAC apoptosis by down-regulating the c-caspase3 signal pathway and promotion of the regeneration of PACs by up-regulating the WNT/ß-catenin signaling pathway. In addition, the CS ion solution also effectively down-regulated the NF-κB signaling pathway to reduce macrophage infiltration and PAC inflammatory factor secretion, thereby reducing PSC mediated pancreatic fibrosis. This bioceramics-based ion solution provides a new idea for disease treatment using biomaterials, which may have the potential for the development of new therapy for CP.

Trends of calcium silicate biomaterials in medical research and applications: A bibliometric analysis from 1990 to 2020.

Background: Calcium silicate biomaterials (CSB) have witnessed rapid development in the past 30 years. This study aimed to accomplish a comprehensive bibliometric analysis of the published research literature on CSB for biomedical applications and explore the research hotspot and current status. Methods: Articles related to CSB published in the last three decades (1990-2020) were retrieved from Web of Science Core Collection. The R bibliometrix package and VOSviewer were used to construct publication outputs and collaborative networking among authors, their institutes, countries, journals' matrices and keywords plus. Results: A total of 872 publications fulfilling the search criteria were included. CSB is mainly reported for bone tissues and dental applications. Among researchers, Chang J from Chinese Academy of Sciences and Gandolfi MG from the University of Bologna are the most productive author in these two fields, respectively. China was the leading contributor to the research on CSB in the medical field. A total of 130 keywords appeared more ten or more times were identified. The term "mineral trioxide aggregate" ranked first with 268 occurrences. The co-occurrence analysis identified three major clusters: CSB in dentistry, bone tissue and vitro bioactivity. Conclusion: Calcium silicate biomaterials have a promising scope for various biomedical applications ranging from regeneration of hard tissues (bone and teeth) to skin, tumor, cardiac muscle and other soft tissues. This study may help researchers further understand the frontiers of the field.

Bibliometric Analysis of Cathepsin B Research From 2011 to 2021.

Cathepsin B (CTSB) is a lysosomal protease implicated in the progression of various diseases. A large number of CTSB-related studies have been conducted to date. However, there is no comprehensive bibliometric analysis on this subject. In our study, we performed quantitative analysis of CTSB-related publications retrieved from the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (reference period: 2011-2021). A total of 3,062 original articles and reviews were retrieved. The largest number of publications were from USA (n = 847, 27.66%). The research output of each country showed positive correlation with gross domestic product (GDP) (r = 0.9745, P < 0.0001). Active collaborations between countries/regions were also observed. Reinheckel T and Sloane BF were perhaps the most impactful researchers in the research landscape of CTSB. Plos ONE was the most prevalent (119/3,062, 3.89%) and cited journal (3,021 citations). Comprehensive analysis of the top citations, co-citations, and keywords was performed to acquire the theoretical basis and hotspots of CTSB-related research. The main topics included CTSB-related cancers and inflammatory diseases, CTSB-associated cell death pattern, and the applications of CTSB. These results provide comprehensive insights into the current status of global CTSB-related research especially in pancreas, which is worthy of continued follow-up by practitioners and clinicians in this field.

The Global Status and Trends of Enteropeptidase: A Bibliometric Study.

BACKGROUND: Enteropeptidase (EP) is a type II transmembrane serine protease and a physiological activator of trypsinogen. Extensive studies related to EP have been conducted to date. However, no bibliometric analysis has systematically investigated this theme. Our study aimed to visualize the current landscape and frontier trends of scientific achievements on EP, provide an overview of the past 120 years and insights for researchers and clinicians to facilitate future collaborative research and clinical intervention. METHODS: Quantitative analysis of publications relating to EP from 1900 to 2020 was interpreted and graphed through the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE). Microsoft office 2019, GraphPad Prism 8, VOSviewer, and R-bibliometrix were used to conduct the bibliometric analysis. RESULTS: From 1900 to 2020, a total of 1,034 publications were retrieved. The USA had the largest number of publications, making the greatest contribution to the topic (n = 260, 25.15%). Active collaborations between countries/regions were also enrolled. Grant and Hermontaylor were perhaps the most impactful researchers in the landscape of EP. Protein Expression and Purification and the Journal of Biological Chemistry were the most prevalent (79/1,034, 7.64%) and cited journals (n = 2,626), respectively. Using the top 15 citations and co-citations achievements clarified the theoretical basis of the EP research field. Important topics mainly include the structure of EP, the affective factors for activating substrates by EP, EP-related disorders, and inhibitors of EP. CONCLUSION: Based on the bibliometric analysis, we have gained a comprehensive analysis of the global status and research frontiers of studies investigating EP, which provides some guidance and reference for researchers and clinicians engaged in EP research.

Novel insight on marker genes and pathogenic peripheral neutrophil subtypes in acute pancreatitis.

Acute pancreatitis is a common critical and acute gastrointestinal disease worldwide, with an increasing percentage of morbidity. However, the gene expression pattern in peripheral blood has not been fully analyzed. In addition, the mechanism of coronavirus disease 2019 (COVID-19)-induced acute pancreatitis has not been investigated. Here, after bioinformatic analysis with machine-learning methods of the expression data of peripheral blood cells and validation in local patients, two functional gene modules in peripheral blood cells of acute pancreatitis were identified, and S100A6, S100A9, and S100A12 were validated as predictors of severe pancreatitis. Additionally, through a combination analysis of bulk sequencing and single-cell sequencing data of COVID-19 patients, a pivotal subtype of neutrophils with strong activation of the interferon-related pathway was identified as a pivotal peripheral blood cell subtype for COVID-19-induced acute pancreatitis. These results could facilitate the prognostic prediction of acute pancreatitis and research on COVID-19-induced acute pancreatitis.