The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

ObjectiveTo explore new targets and herbal medicines of total ginsenosides in ameliorating alcoholic hepatitis （AH） by data mining and experimental validation and to provide new directions for the clinical treatment of AH. MethodGSE28619 was selected as the test set from the GEO database and GSE83148 and GSE103580 were selected as the validation sets. The limma package and weighted gene co-expression network analysis （WGCNA） were employed to identify the AH-related differentially expressed genes and modular genes， and Venny was used to extract the common genes. The protein-protein interaction （PPI） network was constructed and the enrichment analysis was carried out. The hub genes were further screened and evaluated for their diagnostic value. After validation with the datasets， new potential targets of AH and traditional Chinese medicine were predicted. Molecular docking between the targets and active ingredients of traditional Chinese medicine was performed， and the results were validated by experiments. Eight out of 48 SD rats were randomly selected into a blank group and received an equal amount of normal saline. The rest rats were subjected to modeling with ethanol by gavage and then randomized into low- （10 mg·kg^-1）， medium- （20 mg·kg^-1）， and high-dose （40 mg·kg^-1） total ginsenosides， model， and positive control （metadoxine， 117 mg·kg^-1） groups. After 3 weeks of gavage， serum samples were collected for the measurement of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） levels， and liver samples were collected for hematoxylin-eosin （HE） staining. Western blot and Real-time PCR were employed to determine the protein and mRNA levels， respectively， of potential targets in the liver tissue. ResultData mining predicted the potential genes： Proto-oncogene FOS and collagen type Ⅰ alpha 2 （COL1A2）. Experimental validation showed that the liver injury was alleviated after drug administration compared with that after modeling. The serum AST and ALT levels were reduced after drug administration. The protein and mRNA levels of FOS were significantly up-regulated， while those of COL1A2 were down-regulated after drug administration. ConclusionTotal ginsenosides ameliorate HA via FOS and COL1A2.

White-matter tracts play a pivotal role in transmitting sensory and motor information, facilitating interhemispheric communication and integrating different brain regions. Meanwhile, sensorimotor disturbance is a common symptom in patients with major depressive disorder (MDD). However, the role of aberrant sensorimotor white-matter system in MDD remains largely unknown. Herein, we investigated the topological structure alterations of white-matter morphological brain networks in 233 MDD patients versus 257 matched healthy controls (HCs) from the DIRECT consortium. White-matter networks were derived from magnetic resonance imaging (MRI) data by combining voxel-based morphometry (VBM) and three-dimensional discrete wavelet transform (3D-DWT) approaches. Support vector machine (SVM) analysis was performed to discriminate MDD patients from HCs. The results indicated that the network topological changes in node degree, node efficiency, and node betweenness were mainly located in the sensorimotor superficial white-matter system in MDD. Using network nodal topological properties as classification features, the SVM model could effectively distinguish MDD patients from HCs. These findings provide new evidence to highlight the importance of the sensorimotor system in brain mechanisms underlying MDD from a new perspective of white-matter morphological network.
Humans ; Depressive Disorder, Major/pathology* ; White Matter/pathology* ; Male ; Female ; Support Vector Machine ; Adult ; Magnetic Resonance Imaging ; Middle Aged ; Case-Control Studies ; Sensorimotor Cortex ; Brain

BACKGROUND: Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. METHODS: Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. RESULTS: A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04-1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03-1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99-5.38). CONCLUSIONS: Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors. REGISTRATION No. CRD42021259776 at PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ).
Pregnancy ; Infant, Newborn ; Female ; Humans ; Pregnancy Outcome ; Premature Birth/epidemiology* ; Stillbirth/epidemiology* ; Temperature ; Pregnancy Complications

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients’ quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

BACKGROUND: Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy of population-based screening studies primarily assessing baseline LDCT screening for lung cancer. METHODS: MEDLINE, Excerpta Medica Database, and Web of Science were searched for articles published up to April 10, 2022. According to the inclusion and exclusion criteria, the data of true positives, false-positives, false negatives, and true negatives in the screening test were extracted. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the literature. A bivariate random effects model was used to estimate pooled sensitivity and specificity. The area under the curve (AUC) was calculated by using hierarchical summary receiver-operating characteristics analysis. Heterogeneity between studies was measured using the Higgins I2 statistic, and publication bias was evaluated using a Deeks' funnel plot and linear regression test. RESULTS: A total of 49 studies with 157,762 individuals were identified for the final qualitative synthesis; most of them were from Europe and America (38 studies), ten were from Asia, and one was from Oceania. The recruitment period was 1992 to 2018, and most of the subjects were 40 to 75 years old. The analysis showed that the AUC of lung cancer screening by LDCT was 0.98 (95% CI: 0.96-0.99), and the overall sensitivity and specificity were 0.97 (95% CI: 0.94-0.98) and 0.87 (95% CI: 0.82-0.91), respectively. The funnel plot and test results showed that there was no significant publication bias among the included studies. CONCLUSIONS Baseline LDCT has high sensitivity and specificity as a screening technique for lung cancer. However, long-term follow-up of the whole study population (including those with a negative baseline screening result) should be performed to enhance the accuracy of LDCT screening.
Humans ; Adult ; Middle Aged ; Aged ; Lung Neoplasms/diagnostic imaging* ; Early Detection of Cancer ; Sensitivity and Specificity ; Mass Screening ; Tomography, X-Ray Computed

Background: Red blood cell distribution width/platelet count ratio (RPR) is a reliable prognostic assessment indicator for numerous diseases. However, no studies to date have examined the relationship between RPR and the prognosis of diffuse large B-cell lymphoma (DLBCL).Therefore, this study aimed to investigate the correlation between RPR and the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma. Methods: We retrospectively studied 143 patients with newly diagnosed DLBCL and used the median value as the RPR threshold. We also investigated the correlation of pretreatment RPR level with clinical characteristics and its impact on DLBCL prognosis. Results: Using the median value as the cut-off, patients with DLBCL were divided into a low RPR group (＜0.0549) and a high RPR group (≥0.0549). Patients in the high RPR group were older, had a later Ann Arbor stage, were prone to bone marrow invasion, and had a higher National Comprehensive Cancer Network International Prognostic Index score (P ＜ 0.05). A survival analysis showed that progression-free survival (PFS) (P =0.003) and overall survival (OS) (P ＜0.0001) were significantly shorter in the high versus low RPR group. A multifactorial Cox analysis showed that bone marrow invasion and elevated lactate dehydrogenase (LDH) were separate risk factors for PFS (P ＜0.05), while an RPR ≥0.0549 and elevated LDH were separate risk factors for OS (P ＜0.05). Conclusion A high RPR (≥0.0549) in patients with newly diagnosed DLBCL is an independent risk factor for a poor prognosis.

Objective:To analyze the changes of metabolic indexes and other characteristics in patients with primary aldosteronism (PA) and improve the understanding of PA.Methods:From January 2017 to August 2020, 91 PA patients who were clearly diagnosed and met the inclusion conditions in Tangshan workers Hospital, Hebei Medical University were selected as the observation object (PA group), and 112 patients diagnosed as essential hypertension (EH) in the same period were included as the control (EH group). A retrospective case-control study was conducted to compare the differences of blood glucose, blood lipid, homocysteine, blood potassium, creatinine, uric acid, aldosterone, renin, plasma aldosterone to renin ratio (ARR), blood pressure and waist circumference between the two groups. The measurement data of normal distribution were compared by independent sample t-test. The non normal distribution data are represented by M (Q 1, Q 3), and the rank sum test is used for inter group comparison. Comparison of counting data χ2 inspection. Logistic regression was used in multivariate analysis. Results:Univariate analysis showed that serum potassium, renin and ARR were (3.37±0.39) mmol/L, 1.61 (0.34, 7.23) ng/L and 96.85 (26.06, 506.10) in PA group and (3.91±0.59) mmol/L, 12.81 (1.90, 82.45) ng/L and 13.22 (1.06, 54.63) in EH group ( t=3.35, z=6.24, z=55.40, all P<0.001). In PA group, systolic blood pressure was (190.80±20.30) mmHg, diastolic blood pressure was (117.70±12.89) mmHg, waist circumference was (91.67±9.38) cm, and in EH group, systolic blood pressure was (177.01±12.89) mmHg, diastolic blood pressure was (101.39±9.34) mmHg, waist circumference was (86.59±9.07) cm. There were significant differences between the two groups ( t=5.88, 10.44, 3.90; all P<0.001). Multivariate logistic regression analysis showed that waist circumference (OR=1.065, 95% CI 1.007-1.118, P<0.001), systolic blood pressure (OR=1.053, 95% CI 1.034-1.077, P<0.001), diastolic blood pressure (OR=1.054, 95% CI 1.031-1.077, P<0.001), and ARR (OR=1.170, 95% CI 1.115-1.228, P<0.001) were the risk factors for PA. Conclusion:Compared with essential hypertension, PA patients have higher blood pressure, ARR and waist circumference, lower blood potassium and renin levels. Systolic blood pressure, diastolic blood pressure, ARR and waist circumference are the risk factors of PA. Strengthening the screening and treatment of PA in high-risk groups is helpful to better avoid the risk of target organ damage.

Objective:To analyze the research status of umbrella review by bibliometric methods.Methods:The citation search was performed via Web of Science Core Collection database to obtain studies on umbrella review from inception to December 31, 2021. VOSviewer1.6.16 was used to extract the included authors, countries, institutions and keywords, and generate the cooperative network graph of high-productivity authors, countries, institutions, and clustering graph of high-frequency keywords. CiteSpace5.7.R5W was used to detect burst terms.Results:A total of 755 articles or reviews were included. The quantity of studies had been increasing over time. The United Kingdom was the country with the most published papers (297), and the University of College London was the institution with the most published papers (77). A total of 3 863 authors participated in the umbrella review research, of which Solmi M had the largest number of papers with 28 papers published. The main authors formed three groups, with little cooperation between the groups. Research hotspots focused on chronic diseases such as cardiovascular disease, diabetes, cancer, mental health and its health management. Besides, diabetes, heart failure and Mediterranean diet were the frontier fields.Conclusions:Umbrella review is in the development stage, and the amount of studies is increasing. The United Kingdom is in a leading position in this field. The members of each team work closely together, but there is a lack of cross-team cooperation. Chronic diseases and their management are currently research hotspots and key research contents.

Objective:To evaluate the reporting quality of diagnostic radiological imaging case reports published in Chinese science citation database (CSCD) imaging journals.Methods:This study was a cross-sectional survey. We searched CSCD to include imaging journals from 2021 to 2022, from which we retrieved diagnostic radiological imaging case reports published in 2020, and evaluated their reporting quality using case reports (CARE) reporting criteria.Results:A total of five imaging CSCD journals were searched, with 161 final diagnostic imaging case reports included. The median and interquartile range reporting rate of the included studies was 33.5% (7.5%, 93.3%), and patient perspective and informed consent were not reported in all studies. Items with reporting rates below 10% included 3a (abstract-introduction), 3c (abstract-diagnoses, therapeutic interventions, and outcomes), 8b (diagnostic challenges), and 8d (prognosis where applicable), with reporting rates of 2.5% (4/161), 0.6% (1/161), 0.6% (1/161), and 4.3% (7/161), respectively. Reporting rates for items between 10% and 50% included 3b (abstract-main symptoms and/or important clinical findings), 4 (introduction), 5c (medical, family, and psycho-social history), 7 (timeline), 10 (follow-up and outcomes), and 11a (a scientific discussion of the strengths and limitations), with reporting rates of 16.8% (27/161), 30.4% (49/161), 34.2% (55/161), 24.8% (40/161), 32.9% (53/161), and 31.7% (51/161), respectively; The reporting rates for item 1 (title), item 2 (keywords), item 5a (identified patient specific information), item 5b (primary concerns and symptoms of the patient), item 8a (diagnostic testing), and item 11c (the scientific rationale for any conclusions) were all over 90%. Moreover, the number of authors as well as the number of disciplines were not associated with the quality of diagnostic imaging case reports.Conclusions:The overall adherence to CARE items in radiographic diagnostic case reports published in the CSCD imaging journals is low. Editors of the imaging journals, radiologists and the researchers of the reporting standard should emphasize the guidelines for drafting case reports and improve the quality of reporting of case reports.