Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Objective:To investigate the effect of safflower yellow pigment injection combined with alprostadil on patients after coronary artery bypass grafting(CABG).Methods:A total of 92 patients with coronary heart disease who received CABG in Department of Cardiovascular Surgery,Handan Central Hospital between September 2018 and September 2020 were selected.According to order of admission,they were divided into control group(n=46,from September 2018 to Sep-tember 2019,routine therapy+alprostadil after CABG)and study group(n=46,from October 2019 to September 2020,safflower yellow pigment injection based on control group),both groups were treated for 28d.On 3d after drug withdraw-al,therapeutic effect,cardiac function indexes,four myocardial enzyme spectrum and perioperative indexes were compared between two groups.Results:On 3d after drug withdrawal,compared with control group,patients in study group had sig-nificant higher total effective rate(73.9％vs.91.3％),left ventricular ejection fraction(LVEF)[(55.77±4.48)％vs.(62.18±4.21)％](P=0.028,＜0.001),and significant lower left atrial diameter(LAD)[(36.83±3.45)mm vs.(32.09±3.23)mm],left ventricular end-diastolic diameter(LVEDd)[(49.04±4.65)mm vs.(43.83±5.24)mm],levels of creatine kinase(CK)[(125.13±14.21)U/L vs.(62.56±8.42)U/L],lactate dehydrogenase(LDH)[(203.58±31.63)U/L vs.(156.07±22.26)U/L],aspartate aminotransferase(AST)[(44.25±12.98)U/L vs.(35.41±12.37)U/L]and creatine kinase isoenzyme MB(CK-MB)[(28.11±9.84)U/L vs.(17.59±7.41)U/L](P＜0.001 all).Conclusion:The combination of safflower yellow pigment injection and alprostadil can improve the thera-peutic effect and heart function,and reduce myocardial injury in patients after CABG.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective To observe the value of contrast-enhanced mammography(CEM)for differentiating benign and malignant breast lesions with calcifications.Methods Data of 116 female patients with 132 breast imaging reporting and data system(BI-RADS)category 4 to 5 lesions were retrospectively analyzed.The lesions were divided into malignant group(n=86)and benign group(n=46)according to the pathologic results.The morphological manifestations of calcification and their distributions were classified into high or low risk,and the combined risk typing of calcifications was assessed according to these two.Finally,an overall risk typing of CEM was obtained through combining the combined risk type of calcifications and accompanied enhancement or not.Then receiver operating characteristic(ROC)curves were drawn,the area under the curves(AUC)were calculated,and the efficacy of the above indexes for differentiating benign and malignant breast lesions with calcifications were evaluated and compared.Results Significant differences of morphology,distribution and accompanied enhancement were found between groups(all P＜0.05).The AUC of morphology risk,distribution risk,the combined risk of calcification,accompanied enhancement and CEM overall risk for differentiating benign and malignant breast lesions with calcifications was 0.709,0.678,0.774,0.800 and 0.875,respectively,of CEM overall risk was higher than that of the others(all P＜0.05).Conclusion CEM overall risk type obtained through integrating morphology and distribution manifestations of calcifications and enhancement type could improve the efficiency of CEM for differentiating benign and malignant breast lesions with calcifications.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Shwachman-Diamond Syndrome ; Myelodysplastic Syndromes/therapy* ; Transplantation, Homologous ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning

Objective: To study the correlation between ceramic and chronic obstructive pulmonary disease (COPD), and explore its related risk factors. Methods: In January 2021, five representative ceramic enterprises were selected from Chancheng District, Nanhai District, Gaoming District and Sanshui District of Foshan City. The ceramic workers who came to Chancheng Hospital of Foshan First People's Hospital for physical examination from January to October 2021 were selected as the research objects, and 525 people were included. Conduct questionnaire survey and pulmonary function test. Logistic regresion was performed to analyze the influencing facters of COPD among ceramic workers. Results: The subjects were (38.51±1.25) years old, 328 males and 197 females, and the detection rate of COPD was 9.52% (50/525). The incidence of respiratory symptoms such as dyspnea, chronic cough, wheezing and chest tightness, the detection rates of abnormal lung age, abnormal lung function and COPD in males were higher than those in females (P<0.05). The logistic regression analysis showed that male, age, working years, smoking status and family history of COPD were the risk factors for COPD among ceramic workers (P<0.05) . Conclusion: The ceramic workers are the high risk population of COPD. We should do a good job in health education, and do a regular physical examination to find the changes of lung function in time, and prevent the occurrence of COPD as soon as possible.
Female ; Humans ; Male ; Adult ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Ceramics ; Health Education ; Hospitals ; Physical Examination

OBJECTIVE: To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. METHODS: Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. RESULTS: Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05). CONCLUSION BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.
Animals ; Mice ; Abortion, Habitual/prevention & control* ; Signal Transduction ; Down-Regulation ; Disease Models, Animal

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Multiparametric Magnetic Resonance Imaging ; Magnetic Resonance Imaging/methods* ; Prostate/pathology* ; Image-Guided Biopsy/methods*