Pancreatitis affects gut microbiota via metabolites and inflammatory cytokines: an exploratory two-step Mendelian randomisation study.

Previous studies have observed relationships between pancreatitis and gut microbiota; however, specific changes in gut microbiota abundance and underlying mechanisms in pancreatitis remain unknown. Metabolites are important for gut microbiota to fulfil their biological functions, and changes in the metabolic and immune environments are closely linked to changes in microbiota abundance. We aimed to clarify the mechanisms of gut-pancreas interactions and explore the possible role of metabolites and the immune system. To this end, we conducted two-sample Mendelian randomisation (MR) analysis to evaluate the casual links between four different types of pancreatitis and gut microbiota, metabolites, and inflammatory cytokines. A two-step MR analysis was conducted to further evaluate the probable mediating pathways involving metabolites and inflammatory cytokines in the causal relationship between pancreatitis and gut microbiota. In total, six potential mediators were identified in the causal relationship between pancreatitis and gut microbiota. Nineteen species of gut microbiota and seven inflammatory cytokines were genetically associated with the four types of pancreatitis. Metabolites involved in glucose and amino acid metabolisms were genetically associated with chronic pancreatitis, and those involved in lipid metabolism were genetically associated with acute pancreatitis. Our study identified alterations in the gut microbiota, metabolites, and inflammatory cytokines in pancreatitis at the genetic level and found six potential mediators of the pancreas-gut axis, which may provide insights into the precise diagnosis of pancreatitis and treatment interventions for gut microbiota to prevent the exacerbation of pancreatitis. Future studies could elucidate the mechanism underlying the association between pancreatitis and the gut microbiota.

Finite Element Analysis of Elastoplastic Elements in the Iwan Model of Bolted Joints.

The Iwan model is composed of elastoplastic elements and is widely used to represent the stiffness degradation of bolted joints under mixed-mode loading (normal and tangential loading). The latest static methods of parameter identification established the relationship between the elastoplastic elements and the contact pressure under normal loading. Under mixed-mode loading, the parameters of the Iwan model are dynamic for the evolution of contact conditions. Therefore, static parameter identification methods are not suitable for the dynamic Iwan model. A new technique was proposed to identify the parameters of the elastoplastic elements in this paper. Firstly, several different finite element models were established. The influence of the contact method and the thread structure were analyzed, and a reliable and efficient bolted-joint modeling method was proposed. Secondly, the evolution of contact conditions was studied. The dynamic elliptical contact model and the ellipticity discrete method were proposed. Finally, the residual stiffness of the Iwan model was analyzed to establish the mapping between the residual stiffness and the bending of the screw. The results can provide a technique for identifying the parameters of the dynamic Iwan model.

[Sexual Violence Against Women and Their Help-Seeking in Taiwan].

BACKGROUND: Sexual violence is a global health and human rights issue that impacts the physical and mental health of victims and increases healthcare costs. PURPOSE: This research was developed to investigate the prevalence of sexual violence against women in Taiwan and the help-seeking behavior of these women. Based on the findings, suggestions are provided for both government policymakers and frontline medical staffs. METHODS: Data for this study were collected using a face-to-face interview survey conducted with women aged 18 to 74 years nationwide. RESULTS: Of the 1,504 women surveyed, 87 (5.76%) reported having suffered from sexual violence. The one-year prevalence was 1.41%, while the lifetime prevalence was 5.76%. Although sexual violence is known to impact physical and mental health, most victims are reluctant to seek help from formal support systems. CONCLUSIONS: Victims of sexual violence often delay seeking help from medical settings. Although the victims identified in this study endured chronic symptoms and psychological trauma, few had made formal disclosures of intimate partner sexual violence (IPSV) incidents. Frontline medical staffs have the opportunity to play an important role in sexual-violence response if they are made aware of incidents of IPSV / non-IPSV. Thus, to facilitate disclosure, screening for IPSV and non-IPSV should be made standard practice in high-risk medical settings.

Development and validation of a flexible DNA extraction (PAN) method for liquid biopsy of multiple sample types.

BACKGROUND: Liquid biopsy is gaining increasing popularity in cancer screening and diagnosis. However, there is no relatively mature DNA isolation method or commercial kit available that is compatible with different LB sample types. This study developed a PAN-sample DNA isolation method (PAN method) for liquid biopsy samples. METHODS: The PAN method has two key steps, including biosample-specific pretreatments for various LB sample types and high concentration guanidine thiocyanate buffer for lysis and denaturation procedure. Subsequently, the performance of PAN method was validated by a series of molecular analyses. RESULTS: The PAN method was used to isolate DNA from multiple sample types related to LB, including plasma, serum, saliva, nasopharyngeal swab, and stool. All purified DNA products showed good quality and high quantity. Comparison of KRAS mutation analysis using DNA purified using PAN method versus QIAamp methods showed similar efficiency. Epstein-Barr virus DNA was detected via Q-PCR using DNA purified from serum, plasma, nasopharyngeal swab, and saliva samples collected from nasopharyngeal carcinoma patients. Similarly, methylation sequencing of swab and saliva samples revealed good coverage of target region and high methylation of HLA-DPB1 gene. Finally, 16S rDNA gene sequencing of saliva, swab, and stool samples successfully defines the relative abundance of microbial communities. CONCLUSIONS: This study developed and validated a PAN-sample DNA isolation method that can be used for different LB samples, which can be applied to molecular epidemiological research and other areas.

Prognostic and Predictive Value of BGN in Colon Cancer Outcomes and Response to Immunotherapy.

BACKGROUND: Colon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation. METHODS: The differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms. RESULTS: BGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients. CONCLUSION: BGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.

[Pharmacological activities of myricetin and its glycosides].

Myricetin and its glycosides are important flavonols commonly found in plants, and they are natural organic compounds with diverse pharmacological activities. Numerous studies have demonstrated that myricetin and its glycosides are strong antioxidants that have great potential in preventing, alleviating and assisting the treatment of chronic non-infectious diseases such as cancer, diabetes, and cardiovascular diseases. In addition, myricetin and its glycosides also have antiviral, antibacterial, anti-inflammatory, analgesic, liver protection and other pharmacological activities. Myricetin contains more hydroxyl groups in the parent ring structure than other flavonoids, so myricetin and its glycosides have stronger pharmacological activities than other flavonols or flavonoids such as quercetin and kaempferol. Therefore, myricetin and its glycosides have great development and application prospects. In this paper, the classification and distribution of myricetin and its glycosides, their pharmacological activity and mechanism, as well as comparison with other flavonoids were reviewed. In addition, limitations of the current research and application of myricetin and its glycosides were analyzed, and the further studies on pharmacological activities as well as their dose-activity relationship, structure-activity relationship, chemical modification, biosynthesis and application prospects of myricetin and its glycosides were discussed and proposed.

CD11b deficiency suppresses intestinal tumor growth by reducing myeloid cell recruitment.

Mac-1 (CD11b) is expressed on bone marrow-derived immune cells. CD11b binds to ligands to regulate leukocyte adhesion and migration across the endothelium or epithelium. Here, we employed CD11b knockout mice and an Apc(Min/+) spontaneous intestinal adenoma mouse model to clarify the function of CD11b in intestinal tumorigenesis. We showed that CD11b deficiency may contribute to the inhibition of myeloid cell trafficking to the tumor microenvironment and inactivated Wnt/ß-catenin pathway to suppress tumor growth. This effect was partly mediated by inhibiting the myeloid cell-mediated decrease in TNF-α secretion, which inhibits the recruitment of myeloid-derived suppressor cells to the tumor microenvironment and subsequently induces IFN-γ and CXCL9 production. This work provides evidence for the mechanism by which CD11b may function as an important oncogene and highlights the potential of CD11b as a therapeutic target in CRC.

Cancer incidence and mortality of children in urban districts of Guangzhou between 2000 and 2004.

BACKGROUND AND OBJECTIVE: Cancer is one of the most primary causes of death for children. The study was to analyze the cancer incidence and mortality of children in urban districts of Guangzhou between 2000 and 2004, to explore the incidence regularity of pediatric cancers and to provide a reference for prevention and treatment of pediatric cancers. METHODS: The data of cancer incidence and mortality of children during 2000-2004 were collected from Guangzhou Population-based Cancer Registry, and were calculated and analyzed. RESULTS: The cancer incidence of children between 2000 and 2004 in Guangzhou was 17.91 per 100,000 (18.92 per 100,000 in males, 16.70 per 100,000 in females); the cancer mortality was 4.73 per 100,000 (4.65 per 100,000 in males, 4.83 per 100,000 in females). The incidence of lymphoid leukemia ranked first followed by cancer of central nervous system and non-Hodgkin's lymphoma. Cancer incidence was 77.52 per 100 000 in children of less than one year old, 21.49 per 100,000 in 1-4 years, 9.66 per 100,000 in 5-9 years and 17.11 per 100 000 in 10-14 years, with significant difference among the four groups (Chi(2) = 307.602, P < 0.001). CONCLUSION: Lymphoid leukemia, cancer of central nervous system and non-Hodgkin's lymphoma are the most common cancers in children. The children of 0-4 years old are the population with high cancer incidence.

[Incidence of colorectal cancer in Guangzhou City from 2000 to 2002].

BACKGROUND AND OBJECTIVE: The incidence of colorectal cancer is increasing with the change of the diet habit. This study was to analyze the incidence of colorectal cancer in Guangzhou City, thus to provide references and information for the prevention and treatment of this disease. METHODS: Data of colorectal cancer patients during 2000-2002 were collected from Guangzhou population-based cancer registry. Incidence and mortality of colorectal cancer were calculated and analyzed. RESULTS: The crude incidence and mortality of colon cancer in Guangzhou from 2000 to 2002 were 13.4 per 100000 (13.5 per 100000 in males, 13.3 per 100000 in females) and 7.1 per 100000 (7.3 per 100000 in males, 6.9 per 100000 in females), respectively. The crude incidence and mortality of rectal cancer in Guangzhou from 2000 to 2002 were 9.6 per 100000 (10.8 per 100000 in males, 8.2 per 100000 in females) and 5.0 per 100000 (5.5 per 100000 in males, 4.5 per 100000 in females), respectively. The incidence of colon cancer and rectal cancer ranked the fifth and seventh respectively among all cancers. The incidence of colorectal cancer was increased with age. CONCLUSIONS: The incidence rate of colorectal cancer is high in Guangzhou. Studies on prevention and treatment of colorectal cancer should be enhanced.

[Cancer incidence and mortality in Guangzhou City from 2000 to 2002].

BACKGROUND & OBJECTIVE: Population-based cancer registration has never been carried out before in Guangzhou. This study was to analyze the cancer incidence and mortality in Guangzhou and to provide references for prevention and treatment of cancer. METHODS: Data of cancer incidence and mortality during 2000--2002 were collected from Guangzhou Population-based Cancer Registry. Cancer incidence and mortality were calculated and analyzed. RESULTS: The crude cancer incidence during 2000--2002 in Guangzhou was 227.7 per 100,000 (257.0 per 100,000 in males and 196.5 per 100,000 in females)û the crude cancer mortality was 147.9 per 100,000 (183.6 per 100,000 in males and 109.7 per 100,000 in females). The incidence of lung cancer ranked first followed by those of liver cancer, nasopharyngeal cancer, gastric cancer and colon cancer in males. Breast cancer was the leading cancer in females followed by those of lung cancer, liver cancer, colon cancer and nasopharyngeal cancer. The cancer incidence and mortality increased with age. CONCLUSION: Cancer incidence is high in Guangzhou, and the research for prevention and treatment of cancer should be enhanced.