Metabolic score tool for personalized acute pancreatitis prognosis: A multicenter analysis.

Increasing evidence suggests that body composition is associated with the development of acute pancreatitis (AP). This study aimed to investigate the applicability of body composition in predicting AP severity. Data of 213 patients with AP from Affiliated Hospital of Putian University (AHOPTU) were included in this study, whilst data of 173 patients with AP from Fujian Medical University Union Hospital (FMUUH) were used for external validation. Patients were classified into the non-severe and severe groups according to AP severity. After seven days of treatment, in patients from AHOPTU, the difference in skeletal muscle index before and after treatment (ΔSMI) was significantly higher (P = 0.002), while the skeletal muscle radiodensity before treatment (PreSMR) was significantly lower (P = 0.042) in the non-severe group than in the severe group. The multivariate logistic regression model also revealed that the ΔSMI and PreSMR were independent risk factors for AP severity. The optimal cut-off values of ΔSMI and PreSMR were 1.0 and 43.7, respectively. The following metabolic score (SMS) was established to predict AP severity: 0: ΔSMI < 1.0 and PreSMR < 43.7; 1: ΔSMI ≥ 1.0 and PreSMR < 43.7 or ΔSMI < 1.0 and PreSMR ≥ 43.7; 3: ΔSMI ≥ 1.0 and PreSMR ≥ 43.7. In patients from AHOPTU and FMUUH, the areas under the curves (AUC) for this model were 0.764 and 0.741, respectively. ΔSMI and PreSMR can accurately predict AP severity. It is recommended to routinely evaluate the statuses of patients with AP using the predictive model presented in this study for individualized treatment.

Neutrophil extracellular traps in central nervous system (CNS) diseases.

Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.

Acute pancreatitis: A review of diagnosis, severity prediction and prognosis assessment from imaging technology, scoring system and artificial intelligence.

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by the severity of the disease. Diagnosis, severity prediction, and prognosis assessment of AP typically involve the use of imaging technologies, such as computed tomography, magnetic resonance imaging, and ultrasound, and scoring systems, including Ranson, Acute Physiology and Chronic Health Evaluation II, and Bedside Index for Severity in AP scores. Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity, while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications. Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild, moderate, or severe categories, guiding treatment decisions, such as intensive care unit admission, early enteral feeding, and antibiotic use. Despite the central role of imaging technologies and scoring systems in AP management, these methods have limitations in terms of accuracy, reproducibility, practicality and economics. Recent advancements of artificial intelligence (AI) provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data. AI algorithms can analyze large amounts of clinical and imaging data, identify scoring system patterns, and predict the clinical course of disease. AI-based models have shown promising results in predicting the severity and mortality of AP, but further validation and standardization are required before widespread clinical application. In addition, understanding the correlation between these three technologies will aid in developing new methods that can accurately, sensitively, and specifically be used in the diagnosis, severity prediction, and prognosis assessment of AP through complementary advantages.

Prostaglandin F2α synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F2α-dependent and F2α-independent mechanism.

BACKGROUND: Oxaliplatin (Oxa) is the first-line chemotherapy drug for colorectal cancer (CRC), and Oxa resistance is crucial for treatment failure. Prostaglandin F2α synthase (PGF2α) (PGFS), an enzyme that catalyzes the production of PGF2α, is involved in the proliferation and growth of a variety of tumors. However, the role of PGFS in Oxa resistance in CRC remains unclear. AIM: To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC. METHODS: The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels. Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance (HCT116-OxR and HCT8-OxR) and their parental cell lines (HCT116 and HCT8) to assess its influence on cell proliferation, chemoresistance, apoptosis, and DNA damage. For determination of the underlying mechanisms, CRC cells were examined for platinum-DNA adducts and reactive oxygen species (ROS) levels in the presence of a PGFS inhibitor or its products. RESULTS: Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues. Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dose-dependent manner. Furthermore, overexpression of PGFS in parental CRC cells significantly attenuated Oxa-induced proliferative suppression, apoptosis, and DNA damage. In contrast, knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells (HCT116-OxR and HCT8-OxR) accentuated the effect of Oxa treatment in vitro and in vivo. The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa. Treatment with the PGFS-catalyzed product PGF2α reversed the effect of PGFS knockdown on Oxa sensitivity. Interestingly, PGFS inhibited the formation of platinum-DNA adducts in a PGF2α-independent manner. PGF2α exerts its protective effect against DNA damage by reducing ROS levels. CONCLUSION: PGFS promotes resistance to Oxa in CRC via both PGF2α-dependent and PGF2α-independent mechanisms.

Brain computed tomography reading of stroke patients by resident doctors from different medical specialities: An eye-tracking study.

BACKGROUND: Using the eye-tracking technique, our work aimed to examine whether difference in clinical background may affect the training outcome of resident doctors' interpretation skills and reading behaviour related to brain computed tomography (CT). METHODS: Twelve resident doctors in the neurology, radiology, and emergency departments were recruited. Each participant had to read CT images of the brain for two cases. We evaluated each participant's accuracy of lesion identification. We also used the eye-tracking technique to assess reading behaviour. We recorded dwell times, fixation counts, run counts, and first-run dwell times of target lesions to evaluate visual attention. Transition entropy was applied to assess the temporal relations and spatial dynamics of systematic image reading. RESULTS: The eye-tracking results showed that the image reading sequence examined by transition entropy was comparable among resident doctors from different medical specialties (p = 0.82). However, the dwell time of the target lesions was shorter for the resident doctors from the neurology department (4828.63 ms, p = 0.01) than for those from the resident doctors from the radiology (6275.88 ms) and emergency (5305.00 ms) departments. The eye-tracking results in individual areas of interest only showed differences in the eye-tracking performance of the first-run dwell time (p = 0.05) in the anterior cerebral falx. DISCUSSION: Our findings demonstrate that resident doctors from different medical specialties may achieve similar imaging reading patterns for brain CT. This may mitigate queries regarding the influence of different backgrounds on training outcomes.

Macrophage-derived exosomes promote intestinal mucosal barrier dysfunction in inflammatory bowel disease by regulating TMIGD1 via mircroRNA-223.

BACKGROUND & AIM: Exosomes are effective mediators of cell-to-cell interactions and transport several regulatory molecules, including microRNAs (miRNAs), involved in diverse fundamental biological processes. The role of macrophage-derived exosomes in the development of inflammatory bowel disease (IBD) has not been previously reported. This study investigated specific miRNAs in macrophage-derived exosomes in IBD and their molecular mechanism. METHODS: A dextran sulfate sodium (DSS)-induced IBD mouse model was established. The culture supernatant of murine bone marrow-derived macrophages (BMDMs) cultured with or without lipopolysaccharide (LPS) was used for isolating exosomes, which were subjected to miRNA sequencing. Lentiviruses were used to alter miRNA expression and investigate the role of macrophage-derived exosomal miRNAs. Both mouse and human organoids were co-cultured with macrophages in a Transwell system to model cellular IBD in vitro. RESULTS: LPS-induced macrophages released exosomes containing various miRNAs and exacerbated IBD. Based on miRNA sequencing of macrophage-derived exosomes, miR-223 was selected for further analysis. Exosomes with upregulated miR-223 expression contributed to the exacerbation of intestinal barrier dysfunction in vivo, which was further verified using both mouse and human colon organoids. Furthermore, time-dependent analysis of the mRNAs in DSS-induced colitis mouse tissue and miR-223 target gene prediction were performed to select the candidate gene, resulting in the identification of the barrier-related factor Tmigd1. CONCLUSION: Macrophage-derived exosomal miR-223 has a novel role in the progression of DSS-induced colitis by inducing intestinal barrier dysfunction through the inhibition of TMIGD1.

Endoscopic management of pancreatic fluid collections with disconnected pancreatic duct syndrome.

Disconnected pancreatic duct syndrome (DPDS) is an important and common complication of acute necrotizing pancreatitis. Endoscopic approach has been established as the first-line treatment for pancreatic fluid collections (PFCs) with less invasion and satisfactory outcome. However, the presence of DPDS significantly complicates the management of PFC; besides, there is no standardized treatment for DPDS. The diagnosis of DPDS presents the first step of management, which can be preliminarily established by imaging methods including contrast-enhanced computed tomography, ERCP, magnetic resonance cholangiopancreatography (MRCP), and EUS. Historically, ERCP is considered as the gold standard for the diagnosis of DPDS, and secretin-enhanced MRCP is recommended as an appropriate diagnostic method in existing guidelines. With the development of endoscopic techniques and accessories, the endoscopic approach, mainly including transpapillary and transmural drainage, has been developed as the preferred treatment over percutaneous drainage and surgery for the management of PFC with DPDS. Many studies concerning various endoscopic treatment strategies have been published, especially in the recent 5 years. Nonetheless, existing current literature has reported inconsistent and confusing results. In this article, the latest evidence is summarized to explore the optimal endoscopic management of PFC with DPDS.

PADs and NETs in digestive system: From physiology to pathology.

Peptidylarginine deiminases (PADs) are the only enzyme class known to deiminate arginine residues into citrulline in proteins, a process known as citrullination. This is an important post-translational modification that functions in several physiological and pathological processes. Neutrophil extracellular traps (NETs) are generated by NETosis, a novel cell death in neutrophils and a double-edged sword in inflammation. Excessive activation of PADs and NETs is critically implicated in their transformation from a physiological to a pathological state. Herein, we review the physiological and pathological functions of PADs and NETs, in particular, the involvement of PAD2 and PAD4 in the digestive system, from inflammatory to oncological diseases, along with related therapeutic prospects.

Oral presentation assessment and image reading behaviour on brain computed tomography reading in novice clinical learners: an eye-tracking study.

BACKGROUND: To study whether oral presentation (OP) assessment could reflect the novice learners' interpretation skills and reading behaviour on brain computed tomography (CT) reading. METHODS: Eighty fifth-year medical students were recruited, received a 2-hour interactive workshop on how to read brain CT, and were assigned to read two brain CT images before and after instruction. We evaluated their image reading behaviour in terms of overall OP post-test rating, the lesion identification, and competency in systematic image reading after instruction. Students' reading behaviour in searching for the target lesions were recorded by the eye-tracking technique and were used to validate the accuracy of lesion reports. Statistical analyses, including lag sequential analysis (LSA), linear mixed models, and transition entropy (TE) were conducted to reveal temporal relations and spatial complexity of systematic image reading from the eye movement perspective. RESULTS: The overall OP ratings [pre-test vs. post-test: 0 vs. 1 in case 1, 0 vs. 1 in case 2, p < 0.001] improved after instruction. Both the scores of systematic OP ratings [0 vs.1 in both cases, p < 0.001] and eye-tracking studies (Case 1: 3.42 ± 0.62 and 3.67 ± 0.37 in TE, p = 0.001; Case 2: 3.42 ± 0.76 and 3.75 ± 0.37 in TE, p = 0.002) showed that the image reading behaviour changed before and after instruction. The results of linear mixed models suggested a significant interaction between instruction and area of interests for case 1 (p < 0.001) and case 2 (p = 0.004). Visual attention to the target lesions in the case 1 assessed by dwell time were 506.50 ± 509.06 and 374.38 ± 464.68 milliseconds before and after instruction (p = 0.02). However, the dwell times in the case 2, the fixation counts and the frequencies of accurate lesion diagnoses in both cases did not change after instruction. CONCLUSION: Our results showed OP performance may change concurrently with the medical students' reading behaviour on brain CT after a structured instruction.

Neutrophil-Epithelial Crosstalk During Intestinal Inflammation.

Neutrophils are the most abundant leukocyte population in the human circulatory system and are rapidly recruited to sites of inflammation. Neutrophils play a multifaceted role in intestinal inflammation, as they contribute to the elimination of invading pathogens. Recently, their role in epithelial restitution has been widely recognized; however, they are also associated with bystander tissue damage. The intestinal epithelium provides a physical barrier to prevent direct contact of luminal contents with subepithelial tissues, which is extremely important for the maintenance of intestinal homeostasis. Numerous studies have demonstrated that transepithelial migration of neutrophils is closely related to disease symptoms and disruption of crypt architecture in inflammatory bowel disease and experimental colitis. There has been growing interest in how neutrophils interact with the epithelium under inflammatory conditions. Most studies focus on the effects of neutrophils on intestinal epithelial cells; however, the effects of intestinal epithelial cells on neutrophils during intestinal inflammation need to be well-established. Based on these data, we have summarized recent articles on the role of neutrophil-epithelial interactions in intestinal inflammation, particularly highlighting the epithelium-derived molecular regulators that mediate neutrophil recruitment, transepithelial migration, and detachment from the epithelium, as well as the functional consequences of their crosstalk. A better understanding of these molecular events may help develop novel therapeutic targets for mitigating the deleterious effects of neutrophils in inflammatory bowel disease.

Corticotropin releasing hormone promotes inflammatory bowel disease via inducing intestinal macrophage autophagy.

Psychosocial stress is a vital factor contributing to the pathogenesis and progression of inflammatory bowel disease (IBD). The contribution of intestinal macrophage autophagy to the onset and development of IBD has been widely studied. Herein, we investigated the underlying mechanism of psychosocial stress in an IBD mouse model pertaining to macrophage autophagy. Corticotropin releasing hormone (CRH) was peripherally administrated to induce psychosocial stress. For in vivo studies, dextran sulfate sodium (DSS) was used for the creation of our IBD mouse model. For in vitro studies, lipopolysaccharide (LPS) was applied on murine bone marrow-derived macrophages (BMDMs) as a cellular IBD-related challenge. Chloroquine was applied to inhibit autophagy. We found that CRH aggravated the severity of DSS-induced IBD, increasing overall and local inflammatory reactions and infiltration. The levels of autophagy in intestinal macrophages and murine BMDMs were increased under these IBD-related inflammatory challenges and CRH further enhanced these effects. Subsequent administration of chloroquine markedly attenuated the detrimental effects of CRH on IBD severity and inflammatory reactions via inhibition of autophagy. These findings illustrate the effects of peripheral administration of CRH on DSS-induced IBD via the enhancement of intestinal macrophage autophagy, thus providing a novel understanding as well as therapeutic target for the treatment of IBD.

Using a 360° Virtual Reality or 2D Video to Learn History Taking and Physical Examination Skills for Undergraduate Medical Students: Pilot Randomized Controlled Trial.

BACKGROUND: Learning through a 360° virtual reality (VR) or 2D video represents an alternative way to learn a complex medical education task. However, there is currently no consensus on how best to assess the effects of different learning materials on cognitive load estimates, heart rate variability (HRV), outcomes, and experience in learning history taking and physical examination (H&P) skills. OBJECTIVE: The aim of this study was to investigate how learning materials (ie, VR or 2D video) impact learning outcomes and experience through changes in cognitive load estimates and HRV for learning H&P skills. METHODS: This pilot system-design study included 32 undergraduate medical students at an academic teaching hospital. The students were randomly assigned, with a 1:1 allocation, to a 360° VR video group or a 2D video group, matched by age, sex, and cognitive style. The contents of both videos were different with regard to visual angle and self-determination. Learning outcomes were evaluated using the Milestone reporting form. Subjective and objective cognitive loads were estimated using the Paas Cognitive Load Scale, the National Aeronautics and Space Administration Task Load Index, and secondary-task reaction time. Cardiac autonomic function was assessed using HRV measurements. Learning experience was assessed using the AttrakDiff2 questionnaire and qualitative feedback. Statistical significance was accepted at a two-sided P value of <.01. RESULTS: All 32 participants received the intended intervention. The sample consisted of 20 (63%) males and 12 (38%) females, with a median age of 24 (IQR 23-25) years. The 360° VR video group seemed to have a higher Milestone level than the 2D video group (P=.04). The reaction time at the 10th minute in the 360° VR video group was significantly higher than that in the 2D video group (P<.001). Multiple logistic regression models of the overall cohort showed that the 360° VR video module was independently and positively associated with a reaction time at the 10th minute of ≥3.6 seconds (exp B=18.8, 95% CI 3.2-110.8; P=.001) and a Milestone level of ≥3 (exp B=15.0, 95% CI 2.3-99.6; P=.005). However, a reaction time at the 10th minute of ≥3.6 seconds was not related to a Milestone level of ≥3. A low-frequency to high-frequency ratio between the 5th and 10th minute of ≥1.43 seemed to be inversely associated with a hedonic stimulation score of ≥2.0 (exp B=0.14, 95% CI 0.03-0.68; P=.015) after adjusting for video module. The main qualitative feedback indicated that the 360° VR video module was fun but caused mild dizziness, whereas the 2D video module was easy to follow but tedious. CONCLUSIONS: Our preliminary results showed that 360° VR video learning may be associated with a better Milestone level than 2D video learning, and that this did not seem to be related to cognitive load estimates or HRV indexes in the novice learners. Of note, an increase in sympathovagal balance may have been associated with a lower hedonic stimulation score, which may have met the learners' needs and prompted learning through the different video modules. TRIAL REGISTRATION: ClinicalTrials.gov NCT03501641; https://clinicaltrials.gov/ct2/show/NCT03501641.

Establishment and validation of a computer-assisted colonic polyp localization system based on deep learning.

BACKGROUND: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.

Y-box binding protein 1 augments sorafenib resistance via the PI3K/Akt signaling pathway in hepatocellular carcinoma.

BACKGROUND: Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Y-box binding protein 1 (YB-1) is closely correlated with tumors and drug resistance. However, the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown. AIM: To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC. METHODS: The protein expression levels of YB-1 were assessed in human HCC tissues and adjacent nontumor tissues. Next, we constructed YB-1 overexpression and knockdown hepatocarcinoma cell lines with lentiviruses and stimulated these cell lines with different concentrations of sorafenib. Then, we detected the proliferation and apoptosis in these cells by terminal deoxynucleotidyl transferase dUTP nick end labeling, flow cytometry and Western blotting assays. We also constructed a xenograft tumor model to explore the effect of YB-1 on the efficacy of sorafenib in vivo. Moreover, we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing (DGE-seq). RESULTS: YB-1 protein levels were found to be higher in HCC tissues than in corresponding nontumor tissues. YB-1 suppressed the effect of sorafenib on cell proliferation and apoptosis. Consistently, the efficacy of sorafenib in vivo was enhanced after YB-1 was knocked down. Furthermore, KEGG pathway enrichment analysis of DGE-seq demonstrated that the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was essential for the sorafenib resistance induced by YB-1. Subsequently, YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway (Akt1 and PIK3R1) as shown by searching the BioGRID and HitPredict websites. Finally, YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib, and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance. CONCLUSION: Overall, we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene, which is of great significance for the application of sorafenib in advanced-stage HCC.

[Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances].

This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.

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.

Activated carbon derived from waste tangerine seed for the high-performance adsorption of carbamate pesticides from water and plant.

This research presents the tangerine seed activated carbon (TSAC), obtained from food waste (tangerine seed) by one-step pyrolysis method and applied to remove carbamate pesticides (CMs) from complex solutions. The effects of carbonization temperature and time on adsorption performance were studied. Structural properties of TSAC were determined by Fourier Transform Infrared Spectrometer, X-ray diffraction analysis, Raman spectroscopy, scanning electron microscope and nitrogen adsorption/desorption methods and compared with that of tangerine seed. The TSAC exhibited a specific surface area of 659.62 m2/g, a total pore volume of 0.6203 cc/g and a pore diameter of 1.410 nm. The influences of initial pesticide concentration, adsorption temperature and contact time were investigated through batch experiments. Pseudo-second-order kinetic model and Langmuir isotherm model were more suitable for CMs adsorption process onto TSAC. Furthermore, the thermodynamic research indicated that this adsorption process was spontaneous and exothermic.

Incidence and risk factors for post-ERCP pancreatitis in pancreas divisum patients without chronic pancreatitis.

Aims: The studies on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in pancreas divisum (PD) patients without chronic pancreatitis (CP) are rare. In this study, we aimed to evaluate the incidence of PEP in PD patients without CP and the risk and protective factors for PEP.Methods: Consecutive patients with symptomatic PD that underwent ERCP from January 2005 to December 2017 were retrospectively analyzed. The patients were divided into PD without CP group and CP group. The basic information and medical records of patients were collected. The risk and protective factors for PEP in PD patients without CP were analyzed by univariate logistic analysis.Results: A total of 89 ERCP procedures were performed in 51 PD patients without CP, and 249 procedures in 136 patients with CP. The incidence of PEP was significantly higher in PD patients without CP than those with CP (15.7% vs. 5.6%, p = .005). Female gender were independent risk factors for PEP, while dorsal duct stent placement was a protective factor.Conclusion: CP may be a protective factor against PEP in PD patients. Female was a risk factor for PEP in PD patients and dorsal duct stent placement was a preventive factor that reduced the incidence of PEP in PD patients without CP.