Fentanyl and its derivatives: Pain-killers or man-killers?

Fentanyl is a synthetic µ-opioid receptor agonist approved to treat severe to moderate pain with faster onset of action and about 100 times more potent than morphine. Over last two decades, abuse of fentanyl and its derivatives has an increased trend, globally. Currently, the United States (US) faces the most serious situation related to fentanyl overdose, commonly referred to as the opioid epidemic. Nowadays, fentanyl is considered as the number one cause of death for adults aged 18-45 in the US. Synthesis and derivatization of fentanyl is inexpensive to manufacture and easily achievable. Indeed, more than 1400 fentanyl derivatives have been described in the scientific literature and patents. In addition, accessibility and efficacy of fentanyl and its derivatives can play a potential role in misuse of these compounds as a chemical weapon. In this review, the properties, general pharmacology, and overdose death cases associated with fentanyl and selected derivatives are presented. Moreover, current opioid epidemic in the US, Moscow theatre hostage crisis, and potential misuse of fentanyl and its derivatives as a chemical weapon are disclosed.

New insight into mycotoxins and bacterial toxins: Toxicity assessment, molecular mechanism and food safety (preface to the special issue of food and chemical toxicology on the outcomes of Myco & bacterial toxin).

The special issue "New Insight into Mycotoxins and Bacterial Toxins: Toxicity Assessment, Molecular Mechanism and Food Safety" in Food and Chemical Toxicology contains 19 articles on current hot topics in mycotoxins and bacterial toxins. Dietary exposure to mycotoxins and risk assessments are reported in this issue. Molecular mechanisms of multiple mycotoxins and emerging mechanisms of toxicity are especially concerned by researchers. Moreover, mycotoxin-detoxifying substances and antimicrobial agents are also fully investigated in the context. This special issue will help to further understand the mycotoxins and bacterial toxins, casting new light for the control of food safety.

Protective Effects of Astaxanthin on Ochratoxin A-Induced Liver Injury: Effects of Endoplasmic Reticulum Stress and Mitochondrial Fission-Fusion Balance.

Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect against OTA-induced hepatotoxicity; however, its mechanism of action remains unclear. In the present study, we elucidate the protective effects of ASTA on the OTA-induced damage of the endoplasmic reticulum and mitochondria in broiler liver samples by serum biochemical analysis, antioxidant analysis, qRT-PCR, and Western blot analysis. ASTA inhibited the expressions of ahr, pxr, car, cyp1a1, cyp1a5, cyp2c18, cyp2d6, and cyp3a9 genes, and significantly alleviated OTA-induced liver oxidative damage (SOD, GSH-Px, GSH, MDA). Furthermore, it inhibited OTA-activated endoplasmic reticulum stress genes and proteins (grp94, GRP78, atf4, ATF6, perk, eif2α, ire1, CHOP). ASTA alleviated OTA-induced mitochondrial dynamic imbalance, inhibited mitochondrial division (DRP1, mff), and promoted mitochondrial fusion (OPA1, MFN1, MFN2). In conclusion, ASTA can decrease OTA-induced oxidative damage, thereby alleviating endoplasmic reticulum stress and mitochondrial dynamic imbalance.

Bacillus velezensis A2 Can Protect against Damage to IPEC-J2 Cells Induced by Zearalenone via the Wnt/FRZB/ß-Catenin Signaling Pathway.

Zearalenone (ZEA) has adverse effects on human and animal health, and finding effective strategies to combat its toxicity is essential. The probiotic Bacillus velezensis A2 shows various beneficial physiological functions, including the potential to combat fungal toxins. However, the detailed mechanism by which the Bacillus velezensis A2 strain achieves this protective effect is not yet fully revealed. This experiment was based on transcriptome data to study the protective mechanism of Bacillus velezensis A2 against ZEA-induced damage to IPEC-J2 cells. The experiment was divided into CON, A2, ZEA, and A2+ZEA groups. This research used an oxidation kit to measure oxidative damage indicators, the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method to detect cell apoptosis, flow cytometry to determine the cell cycle, and transcriptome sequencing to screen and identify differentially expressed genes. In addition, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were adopted to screen out relevant signaling pathways. Finally, to determine whether A2 can alleviate the damage caused by ZEA to cells, the genes and proteins involved in inflammation, cell apoptosis, cell cycles, and related pathways were validated using a quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot methods. Compared with the CON group, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the ZEA group increased significantly (p < 0.01), while the levels of antioxidant enzyme activity, total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX), total antioxidant capacity (T-AOC), and catalase (CAT) decreased significantly (p < 0.01). Compared with the ZEA group, the A2+ZEA group showed a significant decrease in ROS and MDA levels (p < 0.01), while the levels of T-SOD, GSH-PX, T-AOC, and CAT increased significantly (p < 0.01). TUNEL and cell cycle results indicated that compared with the ZEA group, the A2+ZEA group demonstrated a significant decrease in the cell apoptosis rate (p < 0.01), and the cell cycle was restored. Combining transcriptome data, qRT-PCR, and Western blot, the results showed that compared with the CON group, the mRNA and protein expression levels of Wnt10 and ß-catenin increased significantly (p < 0.01), while the expression level of FRZB decreased significantly (p < 0.01); compared with the ZEA group, the expression levels of these mRNA and proteins were reversed. Bacillus velezensis A2 can increase the antioxidant level, reduce inflammatory damage, decrease cell apoptosis, and correct the cell cycle when that damage is being caused by ZEA. The protective mechanism may be related to the regulation of the Wnt/FRZB cell/ß-catenin signaling pathway.

Codonopsis lanceolata polysaccharide ameliorates high-fat diet induced-postpartum hypogalactia via stimulating prolactin receptor-mediated Jak2/Stat5 signaling.

This study aims to investigate the ameliorative effect of Codonopsis lanceolata polysaccharide (PCL) on mice with hypogalatia induced by a high-fat diet (HFD) and the potential underlying mechanism. We found that oral administration of PCL demonstrated significant benefits in countering the negative effects of HFD, including weight gain, hepatic steatosis, mesenteric adipocyte hypertrophy, and abnormal glucose/lipid metabolism. In addition, PCL improved mammary gland development and enhanced lactogenesis performance. Histologically, PCL ameliorated the retardation of ductal growth, reduced mammary fat pad thickness, improved the incomplete linear encapsulation of luminal epithelium and myoepithelium, and increased the proliferation of mammary epithelial cells. Flow cytometry analysis showed that PCL mitigated the detrimental effects of HFD on mammary gland development by promoting the proliferation and differentiation of mammary epithelial cells. Mechanistic studies revealed that PCL upregulated the levels of prolactin (PRL) and its receptor (PRLR) in the mammary gland, activated JAK2/STAT5 signaling pathway, and increased the expression of p63, ERBB4, and NRG1. Overall, PCL can ameliorate HFD-induced hypogalactia by activating PRLR-mediated JAK2/STAT5 signaling. Our findings offer a methodological and theoretical foundation for investigating the functional constituents of traditional Chinese medicine in the treatment of hypogalactia.

Mechanisms by which microbial enzymes degrade four mycotoxins and application in animal production: A review.

Mycotoxins are toxic compounds that pose a serious threat to animal health and food safety. Therefore, there is an urgent need for safe and efficient methods of detoxifying mycotoxins. As biotechnology has continued to develop, methods involving biological enzymes have shown great promise. Biological enzymatic methods, which can fundamentally destroy the structures of mycotoxins and produce degradation products whose toxicity is greatly reduced, are generally more specific, efficient, and environmentally friendly. Mycotoxin-degrading enzymes can thus facilitate the safe and effective detoxification of mycotoxins which gives them a huge advantage over other methods. This article summarizes the newly discovered degrading enzymes that can degrade four common mycotoxins (aflatoxins, zearalenone, deoxynivalenol, and ochratoxin A) in the past five years, and reveals the degradation mechanism of degrading enzymes on four mycotoxins, as well as their positive effects on animal production. This review will provide a theoretical basis for the safe treatment of mycotoxins by using biological enzyme technology.

Role of epigenetics in mycotoxin toxicity: A review.

Mycotoxins can induce cell cycle disorders, cell proliferation, oxidative stress, and apoptosis through pathways such as those associated with MAPK, JAK2/STAT3, and Bcl-w/caspase-3, and cause reproductive toxicity, immunotoxicity, and genotoxicity. Previous studies have explored the toxicity mechanism of mycotoxins from the levels of DNA, RNA, and proteins, and proved that mycotoxins have epigenetic toxicity. To explore the toxic effects and mechanisms of these changes in mycotoxins, this paper summarizes the changes in DNA methylation, non-coding RNA, RNA and histone modification induced by several common mycotoxins (zearalenone, aflatoxin B1, ochratoxin A, deoxynivalenol, T-2 toxin, etc.) based on epigenetic studies. In addition, the roles of mycotoxin-induced epigenetic toxicity in germ cell maturation, embryonic development, and carcinogenesis are highlighted. In summary, this review provides theoretical support for a better understanding of the regulatory mechanism of mycotoxin epigenotoxicity and the diagnosis and treatment of diseases.

The Gene Ontology knowledgebase in 2023.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.

Lactobacillus salivarius WZ1 Inhibits the Inflammatory Injury of Mouse Jejunum Caused by Enterotoxigenic Escherichia coli K88 by Regulating the TLR4/NF-κB/MyD88 Inflammatory Pathway and Gut Microbiota.

Replacing antibiotics with probiotics has become an important way to safely and effectively prevent and treat some gastrointestinal diseases. This study was conducted to investigate whether Lactobacillus salivarius WZ1 (L.S) could reduce the inflammatory injury to the mouse jejunum induced by Escherichia coli (ETEC) K88. Forty Kunming mice were randomly divided into four groups with 10 mice in each group. From day 1 to day 14, the control group and the E. coli group were administered with normal saline each day, while the L.S group and the L.S + E. coli group were gavaged with Lactobacillus salivarius WZ1 1 × 108 CFU/mL each day. On the 15th day, the E. coli group and the L.S + E. coli group were intragastrically administered ETEC K88 1 × 109 CFU/mL and sacrificed 24 h later. Our results show that pretreatment with Lactobacillus salivarius WZ1 can dramatically protect the jejunum morphological structure from the changes caused by ETEC K88 and relieve the morphological lesions of the jejunum, inhibiting changes in the mRNA expressions of TNF-α, IL-1ß and IL-6 and the protein expressions of TLR4, NF-κB and MyD88 in the intestinal tissue of mice caused by ETEC K88. Moreover, pretreatment with Lactobacillus salivarius WZ1 also increased the relative abundance of beneficial genera such as Lactobacillus and Bifidobacterium and decreased the abundance of harmful genera such as Ralstonia and Helicobacter in the gut. These results demonstrate that Lactobacillus salivarius WZ1 can inhibit the inflammatory damage caused by ETEC K88 in mouse jejunum by regulating the TLR4/NF-κB/MyD88 inflammatory pathway and gut microbiota.

Immunotoxicity of Three Environmental Mycotoxins and Their Risks of Increasing Pathogen Infections.

Aflatoxin B1 (AFB1), ochratoxin A (OTA), and deoxynivalenol (DON) are the three mycotoxins that have received the most scholarly attention and have been tested most routinely in clinics. These mycotoxins not only suppress immune responses but also induce inflammation and even increase susceptibility to pathogens. Here, we comprehensively reviewed the determining factors for the bidirectional immunotoxicity of the three mycotoxins, their effects on pathogens, and their action mechanisms. The determining factors include mycotoxin exposure doses and times, as well as species, sex, and some immunologic stimulants. Moreover, mycotoxin exposure can affect the infection severity of some pathogens, including bacteria, viruses, and parasites. Their specific action mechanisms include three aspects: (1) mycotoxin exposure directly promotes the proliferation of pathogenic microorganisms; (2) mycotoxins produce toxicity, destroy the integrity of the mucosal barrier, and promote inflammatory response, thereby improving the susceptibility of the host; (3) mycotoxins reduce the activity of some specific immune cells and induce immune suppression, resulting in reduced host resistance. The present review will provide a scientific basis for the control of these three mycotoxins and also provide a reference for research on the causes of increased subclinical infections.

Mycotoxins: Emerging toxic mechanisms, and unanswered research questions.

Recently, a series of toxic mechanisms have been explored in mycotoxins. Emerging evidence show that mycotoxins may induce human neurodegenerative diseases (ND); however, this idea is still unproven. Besides to identify this hypothesis, some questions, for example, how the mycotoxins induce this disease and what the molecular mechanism is, as well as whether the brain-gut axis is involved in this context, should be answered. Very recent studies further reported an "immune evasion" mechanism in trichothecenes; moreover, hypoxia seems to play important function in this process; nevertheless, whether this "immune evasion" process is present in other mycotoxins, especially in aflatoxins, should be tested. In this work, we mainly discussed some key scientific questions that need to be answered in the toxic mechanisms of mycotoxins. We especially focused on the research questions in the key signaling pathways, balance mechanism of immunostimulatory and immunosuppressive effects, and the relationship between autophagy and apoptosis. Interesting topics such as mycotoxins and aging, cytoskeleton and immunotoxicity are also discussed. More importantly, we compile a special issue: "New insight into mycotoxins and bacterial toxins: toxicity assessment, molecular mechanism and food safety" for Food and Chemical Toxicology. Researchers are encouraged to submit their newest work to this special issue.

Detoxification of Selenium Yeast on Mycotoxins and Heavy Metals: a Review.

Mycotoxins are secondary metabolites produced by specific fungi. More than 400 different mycotoxins are known in the world, and the concentration of these toxins in food and feed often exceeds the acceptable limit, thus causing serious harm to animals and human body. At the same time, modern industrial agriculture will also bring a lot of environmental pollution in the development process, including the increase of heavy metal content, and often the clinical symptoms of low/medium level chronic heavy metal poisoning are not obvious, thus delaying the best treatment opportunity. However, the traditional ways of detoxification cannot completely eliminate the adverse effects of these toxins on the body, and sometimes bring some side effects, so it is essential to find a new type of safe antidote. Trace element selenium is among the essential mineral nutrient elements of human and animal bodies, which can effectively remove excessive free radicals and reactive oxygen species in the body, and has the effects of antioxidant, resisting stress, and improving body immunity. Selenium is common in nature in inorganic selenium and organic selenium. In previous studies, it was found that the use of inorganic selenium (sodium selenite) can play a certain protective role against mycotoxins and heavy metal poisoning. However, while it plays the role of antioxidant, it will also have adverse effects on the body. Therefore, it was found in the latest study that selenium yeast could not only replace the protective effect of sodium selenite on mycotoxins and heavy metal poisoning, but also improve the immunity of the body. Selenium yeast is an organic selenium source with high activity and low toxicity, which is produced by selenium relying on the cell protein structure of growing yeast. It not only has high absorption rate, but also can be stored in the body after meeting the physiological needs of the body for selenium, so as to avoid selenium deficiency again in the short term. However, few of these studies can clearly reveal the protective mechanism of yeast selenium. In this paper, the detoxification mechanism of selenium yeast on mycotoxins and heavy metal poisoning was reviewed, which provided some theoretical support for further understanding of the biological function of selenium yeast and its replacement for inorganic selenium. The conclusions suggest that selenium yeast can effectively alleviate the oxidative damage by regulating different signaling pathways, improving the activity of antioxidant enzymes, reversing the content of inflammatory factors, regulating the protein expression of apoptosis-related genes, and reducing the accumulation of mycotoxins and heavy metals in the body.

Alveolar Macrophages Participate in the Promotion of Influenza Virus Infection by Aflatoxin B1 at an Early Stage.

Aflatoxin B1 (AFB1), one of the most common environmental mycotoxin contaminations in food and feed, poses significant threats to human and animal health. Our previous study indicated that even non-toxic AFB1 concentrations could promote influenza virus replication and induce influenza virus-infected alveolar macrophages polarizing from M1 (immunostimulatory phenotype) to M2 (immunosuppressive phenotype) over time. However, whether AFB1 promotes influenza replication via modulating the polarization of alveolar macrophages is unknown. Here, we specifically depleted alveolar macrophages using clodronate-containing liposomes in swine influenza virus (SIV)-infected mice to explore the mechanism the promotion of SIV replication by AFB1. The results show that the depletion of alveolar macrophages significantly alleviated the AFB1-induced weight loss, inflammatory responses, and lung and immune organ damage of the SIV-infected mice after 14 days and greatly diminished the AFB1-promoted SIV replication. In contrast, the depletion of alveolar macrophages did not alleviate the AFB1-induced weight loss, and lung and immune organ damage of the SIV-infected mice after 28 days and slightly diminished the AFB1-promoted SIV replication. Collectively, the data indicate that alveolar macrophages play a crucial role the promotion of SIV infection by AFB1 in the early rather than late stage, and AFB1 can promote SIV replication by inducing alveolar macrophages to polarize towards M1 macrophages. This research provides novel targets for reducing the risk of AFB1-promoted influenza virus infection.

Inhibitory Effects of Bacillus Coagulans TL3 on the Ileal Oxidative Stress and Inflammation Induced by Lipopolysaccharide in Rats.

This study aimed to explore the effect and mechanism of Bacillus coagulans TL3 (B. coagulans TL3) on ileal inflammatory injury induced by lipopolysaccharide (LPS). Animal models were established wherein male Wistar rats were randomly divided into four groups: a control group, an LPS group, a high-concentration B. coagulans (HBC) group, and a low-concentration B. coagulans (LBC) group. The results showed that the biochemical indices changed, significant pathological changes were found, the number of apoptotic cells increased in the ileal tissue of the LPS group rats; the protein expressions of NFκB, MYD88, TLR4, TNF-α, Il-6, IL-1ß, Claudin-1, Occludin, and ZO-1 in the LPS group were significantly decreased. The biochemical indices, pathological changes, and protein expressions in rats subjected to intragastric administration with high or low concentrations of B. coagulans TL3, were significantly reversed compared with the LPS group. These results indicated that TL3 strain could protect rats against ileal oxidative stress and inflammation induced by LPS and the protective mechanism was related to inhibition of the toll-like receptor 4 (TLR4) / myeloid differentiation factor-88 (MyD88) signaling pathway.

Bacillus amyloliquefaciens B10 Alleviates the Immunosuppressive Effects of Deoxynivalenol and Porcine Circovirus Type 2 Infection.

As one of the most common mycotoxins, deoxynivalenol (DON) can contaminate a wide range of crops and foods. Porcine circovirus 2 (PCV2) is a kind of immunosuppressive virus, which can cause porcine circovirus associated disease (PCVD) in pig farms infected with PCV2. Pigs are extremely sensitive to DON, and PCV2-infected pig farms are often contaminated with DON. Our previous studies indicated that Bacillus amyloliquefaciens B10 (B10) has the potential to alleviate the toxicity of mycotoxins. The research was aimed at investigating the effects of Bacillus amyloliquefaciens B10 on the immunosuppressive effects caused by both DON and PCV2 infection. The results indicated that the expression of the PCV2 capsid protein CAP was significantly decreased after pretreatment with Bacillus amyloliquefaciens B10. Then, the effects of the Bacillus amyloliquefaciens B10 pretreatment on the type I interferon, antiviral protein and the antiviral signal pathway cGAS-STING was further investigated. The findings displayed that the expression of the type I interferon and antiviral protein were increased, while the IL-10 were decreased after pretreatment with Bacillus amyloliquefaciens B10. The inhibition of DON on the cGAS-STING signal pathway was relieved. Furthermore, it was found that this intervention effect was produced by inhibiting autophagy. In summary, Bacillus amyloliquefaciens B10 can mitigate the immunosuppressive effects of PCV2 and DON by inhibiting the production of autophagy.

Carbohydrate-based quality consistency evaluation of Saposhnikoviae Radix / 中国中药杂志

This study aims to evaluate the quality consistency of Saposhnikoviae Radix based on carbohydrates, and explore the potential of carbohydrates as the internal quality control indicators of Saposhnikoviae Radix. The total polysaccharides were quantified by UV-Vis spectrophotometry and the molecular weight range of the polysaccharides was determined by high performance gel-permeation chromatography-evaporative light scattering detection(HPGPC-ELSD). The monosaccharides in polysaccharides and the free monosaccharides were quantified by high performance liquid chromatography-UV detection(HPLC-UV), and the oligosaccharides and fructose were quantified by high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD). The carbohydrate-based quality of Saposhnikoviae Radix was compared among 45 batches of commercial samples and 13 batches of self-collected samples. The results showed that the molecular weight distribution, monosaccharide composition, oligosaccharide, and free monosaccharide composition were similar in the 58 batches of samples. The average content of total polysaccharides, oligosaccharides, and total free monosaccharides in commercial samples were 39.66, 148.79, and 68.62 mg·g~(-1), respectively. The content showed significant differences among batches, with the highest differences of 3.51, 1.75, and 2.58 times, respectively. The RSD of the relative ratios of monosaccharides in the polysaccharides in commercial samples reached 28%-45%. The average content of total polysaccharides, oligosaccharides, and total free monosaccharides in self-collected samples were 68.07, 145.76, and 42.04 mg·g~(-1), respectively, with the inter-region differences of 2.88, 1.88, and 1.07 times, respectively. The RSD of the relative ratios of monosaccharides in polysaccharides in self-collected samples ranged from 8.2% to 59%. The total polysaccharides and total free monosaccharides in self-collected samples were 1.72 times higher and 1.63 times lower, respectively, than those in commercial samples. The content of oligosaccharides was similar between self-collected samples and commercial samples. To sum up, carbohydrates are one of the material bases for the internal quality consistency of Saposhnikoviae Radix. The qualitative characteristics of polysaccharides and the quantitative characteristics of polysaccharides and oligosaccharides are related to the origin of medicinal materials. Moreover, the quantitative characteristics of polysaccharides and free monosaccharides may be related to the storage conditions. Carbohydrates are potential indicators for the quality control of Saposhnikoviae Radix and deserve attention.

Risk factors for acute cholangitis after endoscopic retrograde cholangiopancreatography and construction of the nomogram / 中华消化内镜杂志

Objective:To investigate the risk factors for acute cholangitis after endoscopic retrograde cholangiopancreatography (ERCP) and to construct its nomogram.Methods:Clinical data of patients who underwent ERCP for common bile duct stones in the First Hospital of Lanzhou University from January 2014 to December 2019 were retrospectively analyzed. A total of 95 patients with acute cholangitis after the operation (the acute cholangitis group) were included and 285 patients without acute cholangitis after the operation (the non-acute cholangitis group) were selected by random sampling at 1∶3 via the software. Logistic regression analysis was used to evaluate the risk factors for acute cholangitis after ERCP. A nomogram model was established to predict the incidence of acute cholangitis after ERCP based on the results of multivariate analysis.Results:Univariate analysis showed that there were significant differences in age, combination with diabetes, levels of alanine aminotransferase, alkaline phosphatase and glucose, roughness in gallbladder wall, bile duct diameter, stenosis in lower bile duct, proportion of patients who underwent endoscopic retrograde biliary drainage and endoscopic nasobiliary drainage between the two groups ( P<0.05). Logistic multivariate regression analysis showed that advanced age ( OR=1.108, 95% CI:1.079-1.138, P<0.001), combination with diabetes ( OR=4.524, 95% CI:1.299-15.758, P=0.018), roughness in gallbladder wall ( OR=2.495, 95% CI:1.106-5.630, P=0.028), increased bile duct diameter ( OR=1.303, 95% CI:1.181-1.437, P<0.001), and stenosis in lower bile duct ( OR=4.192, 95% CI:2.508-7.005, P<0.001) were independent risk factors for acute cholangitis after ERCP. Based on the results of multivariate analysis, the nomogram of acute cholangitis after ERCP was established. The area under the receiver operator characteristic curve was 0.887. Conclusion:Advanced age, combination with diabetes, rough gallbladder wall, increased diameter of bile duct and stenosis in lower bile duct are independent risk factors for acute cholangitis after ERCP. Clinicians can make clinical intervention based on the nomogram of risk factors above to improve the prognosis of patients.

Clinical characteristics of choledocholithiasis combined with periampullary diverticulum and influencing factor analysis for difficult cannulation of endoscopic retrograde cholangiopan-creatography: a report of 1 920 cases / 中华消化外科杂志

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Application of the CRISPR/Cas System in Pathogen Detection: A Review.

Early and rapid diagnosis of pathogens is important for the prevention and control of epidemic disease. The polymerase chain reaction (PCR) technique requires expensive instrument control, a special test site, complex solution treatment steps and professional operation, which can limit its application in practice. The pathogen detection method based on the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated protein (CRISPR/Cas) system is characterized by strong specificity, high sensitivity and convenience for detection, which is more suitable for practical applications. This article first reviews the CRISPR/Cas system, and then introduces the application of the two types of systems represented by Type II (cas9), Type V (cas12a, cas12b, cas14a) and Type VI (cas13a) in pathogen detection. Finally, challenges and prospects are proposed.

Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy.

Quercetin, as a flavonol compound found in plants, has a variety of biological activities. It is widely present in nature and the human diet, with powerful oxidative properties and biological activities. In this review, the antioxidant mechanism and broad-spectrum antibacterial properties of quercetin are revealed; the intervention effects of quercetin on pesticide poisoning and the pathway of action are investigated; the toxic effects of main mycotoxins on the collection and the detoxification process of quercetin are summarized; whether it is able to reduce the toxicity of mycotoxins is proved; and the harmful effects of heavy metal poisoning on the collection, the prevention, and control of quercetin are evaluated. This review is expected to enrich the understanding of the properties of quercetin and promote its better application in clinical practice.