Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study.

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

Rutaecarpine Ameliorates Murine N-Methyl-N'-Nitro-N-Nitrosoguanidine-Induced Chronic Atrophic Gastritis by Sonic Hedgehog Pathway.

CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream.

The relationship of intent to be COVID-19 vaccinated with depression, anxiety, insomnia, pain and smoking among Chinese patients with a pacemaker.

Background: This study examined the intent to be COVID-19 vaccinated and its correlates among patients with a pacemaker. Methods: This observational study was carried out between July 1, 2021, and May 17, 2022 in Beijing, China. Patients with a pacemaker were consecutively invited by a research physician to participate in the study. Intent to be COVID-19 vaccinated, depression, anxiety, insomnia, pain and smoking were measured with standard scales or questions. Results: Of the 206 participating patients, 72.82% (N = 150; 95% confidence interval [CI]: 66.74%-78.89%) expressed an intention to be COVID-19 vaccinated. Intent to be COVID-19 vaccinated was not significantly associated with severity of depression, anxiety, and insomnia. Multiple logistic regression analysis revealed that patients believing that COVID-19 vaccines provided protection and smokers were more likely to express an intention to receive COVID-19 vaccines. In contrast, older patients and those with higher level of physical pain were less likely to express an intention to be vaccinated against COVID-19. Conclusions: Specific vaccination promotion strategies should be implemented targeting this vulnerable segment of the population.

Prevalence, correlates, and network analysis of depression and its association with quality of life in survivors with myocardial infarction during the COVID-19 pandemic.

BACKGROUND: Depression is common among myocardial infarction (MI) survivors and is strongly associated with poor quality of life (QOL). The aim of this study was to examine the prevalence, correlates and the network structure of depression, and its association with QOL in MI survivors during the COVID-19 pandemic. METHODS: This cross-sectional study evaluated depression and QOL in MI survivors with the Chinese version of the nine-item Patient Health Questionnaire (PHQ-9) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF), respectively. Univariable analyses, multivariable analyses, and network analyses were performed. RESULTS: The prevalence of depression (PHQ-9 total score ≥ 5) among 565 MI survivors during the COVID-19 pandemic was 38.1 % (95 % CI: 34.1-42.1 %), which was significantly associated with poor QOL. Patients with depression were less likely to consult a doctor regularly after discharge, and more likely to experience more severe anxiety symptoms and fatigue. Item PHQ4 "Fatigue" was the most central symptom in the network, followed by PHQ6 "Guilt" and PHQ2 "Sad mood". The flow network showed that PHQ4 "Fatigue" had the highest negative association with QOL. CONCLUSION: Depression was prevalent among MI survivors during the COVID-19 pandemic and was significantly associated with poor QOL. Those who failed to consult a doctor regularly after discharge or reported severe anxiety symptoms and fatigue should be screened for depression. Effective interventions for MI survivors targeting central symptoms, especially fatigue, are needed to reduce the negative impact of depression and improve QOL.

Prevalence of depression and its association with quality of life in patients after pacemaker implantation during the COVID-19 pandemic: A network analysis.

Background: This study was designed to investigate the prevalence and predictors of depression in patients after pacemaker implantation during the COVID-19 pandemic in addition to identifying specific depressive symptoms associated with quality of life (QOL) using network analysis (NA). Methods: This cross-sectional, observational study was conducted in China between July 1, 2021, and May 17, 2022. Descriptive analysis was used to calculate depression prevalence. Univariate analyses were used to compare differences in demographic and clinical characteristics between depressed and non-depressed patients following pacemaker implantation. Binary logistic regression analysis was used to assess factors independently associated with depression. Network analysis "expected influence," and flow function indexes were used to identify symptoms central to the depression network of the sample and depressive symptoms that were directly associated with QOL, respectively. Network stability was examined using a case-dropping bootstrap procedure. Results: In total, 206 patients implanted with a pacemaker met the study entry criteria and completed the assessment. The overall prevalence of depression (PHQ-9 total score ≥ 5) was 39.92% [95% confidence interval (CI) = 29.37-42.47%]. A binary logistic regression analysis revealed that patients with depression were more likely to report a poor health status (p = 0.031), severe anxiety symptoms (p < 0.001), and fatigue (p < 0.001). In the network model for depression, "Sad mood," "Poor Energy," and "Guilt" were the most influential symptoms. "Fatigue" had the strongest negative association with QOL, followed by "Sad mood" and "Appetite". Conclusion: Depression is common among patients having undergone pacemaker implantation during the COVID-19 pandemic. Anxiety, central symptoms of depression (i.e., "Sad mood", "Poor Energy", and "Guilt") and depressive symptoms linked to QOL (i.e., "Sad mood", "Appetite", and "Fatigue") identified in this study are promising targets for interventions and preventive measures for depression in patients who have undergone pacemaker implants.

[First-Class Nursing Discipline Construction Spearheads the Cultivation of First-Class Talents].

Cultivating first-class talents is a key task of the Double First-Class Initiative, a national plan to build a number of world-class universities and disciplines in China by the end of 2050. On the basis of reviewing the history of the development of the nursing discipline, we analyzed, herein, opportunities and challenges of nursing professional training under the strategic guidance of the Double First-Class Initiative. We proposed suggestions on the cultivation of first-class nursing professionals of the future by considering the following aspects, constructing a theoretical system of ideological and political education for nursing education with Chinese characteristics, exploring for ways to develop a nursing knowledge system and personnel training model around the axis of a life-course approach to health, building "nursing plus" interdisciplinary clusters to cultivate innovative talents with interdisciplinary integrated abilities, enhancing efforts to recruit and cultivate scientific and technological talents, optimizing in an all-round way the composition of qualified nursing personnel, gaining the support of first-class research platforms, and creating incubation centers for innovative and outstanding nursing professionals.

Gut microbiota metabolic characteristics in coronary artery disease patients with hyperhomocysteine.

Hyperhomocysteine (HHcy) is known as a risk factor for coronary artery disease (CAD). Despite the knowledge that gut microbiota related metabolism pathway shares metabolites with that of Hcy, little has been shown concerning the association between HHcy and gut microbiota. To explore their relationship in the context of CAD, 105 patients and 14 healthy controls were recruited from one single medical center located in Beijing, China. Their serum and fecal samples were collected, with multi-omics analyses performed via LC/MS/MS and 16S rRNA gene V3-V4 region sequencing, respectively. Participants from the prospective cohort were divided into CAD, CAD & HHcy and healthy controls (HC) groups based on the diagnosis and serum Hcy concentration. The results revealed significant different metabolic signatures between CAD and CAD & HHcy groups. CAD patients with HHcy suffered a heavier atherosclerotic burden compared to CAD patients, and the difference was closely associated to betaine-homocysteine S-methyltransferase (BHMT)-related metabolites and trimethylamine N-oxide (TMAO)-related metabolites. Dimethylglycine (DMG) exhibited a strong positive correlation with serum total Hcy (tHcy), and TMAO and trimethylysine (TML) were associated with heavier atherosclerotic burden. Multiple other metabolites were also identified to be related to distinct cardiovascular risk factors. Additionally, Clostridium cluster IV and Butyricimonas were enriched in CAD patients with elevated tHcy. Our study suggested that CAD patients with elevated tHcy were correlated with higher atherosclerotic burden, and the impaired Hcy metabolism and cardiovascular risk were closely associated with BHMT-related metabolites, TMAO-related metabolites and impaired gut microbiota homeostasis.

Correlation between bone volume fraction in posterior implant area and initial implant stability.

OBJECTIVE: Bone volume fraction (BV/TV) was used as a quantitative indicator of bone mineral density (BMD) in the posterior dental implant area, and the relationship between it and the initial stability of the implant was analyzed. METHODS: 53 patients with posterior dental implantation were selected. Remove the bone fragments from the planting area and put them in the formalin solution. Then, the implant was placed after the operator prepared the hole step by step. Peak Insertion torque value (ITV) and Implant stability quotient (ISQ) were recorded. The BV/TV of the bone fragments was measured by Image pro Plus6.0. The correlation between it and ITV and ISQ was analyzed. RESULTS: BV/TV was correlated with ITV and ISQ in the posterior dental planting area (r=0.862, r=0.832, P < 0.05). The correlation of the parameters in the posterior part of maxilla was higher than that in the mandible. There were significant differences in BV/TV, ITV, and ISQ between the mandible and maxilla, and the implant area of the mandible was higher than that of the maxilla. CONCLUSION: BV/TV can provide an objective index for BMD in the implant area, which has an important influence on the evaluation of the initial stability of the implant.

Artificial intelligence applications in pathological diagnosis of gastric cancer.

Globally, gastric cancer is the third leading cause of death from tumors. Prevention and individualized treatment are considered to be the best options for reducing the mortality rate of gastric cancer. Artificial intelligence (AI) technology has been widely used in the field of gastric cancer, including diagnosis, prognosis, and image analysis. Eligible papers were identified from PubMed and IEEE up to April 13, 2022. Through the comparison of these articles, the application status of AI technology in the diagnosis of gastric cancer was summarized, including application types, application scenarios, advantages and limitations. This review presents the current state and role of AI in the diagnosis of gastric cancer based on four aspects: 1) accurate sampling from early diagnosis (endoscopy), 2) digital pathological diagnosis, 3) molecules and genes, and 4) clinical big data analysis and prognosis prediction. AI plays a very important role in facilitating the diagnosis of gastric cancer; however, it also has shortcomings such as interpretability. The purpose of this review is to provide assistance to researchers working in this domain.

Blood lead level in Chinese adults with and without coronary artery disease.

BACKGROUND: The Trial to Assess Chelation Therapy study found that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced the incidence of cardiac events in stable post-myocardial infarction patients, and a body of epidemiological data has shown that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. However, limited studies have focused on the relationship between angiographically diagnosed coronary artery disease (CAD) and lead exposure. This study compared blood lead level (BLL) in Chinese patients with and without CAD. METHODS: In this prospective, observational study, 450 consecutive patients admitted to Beijing Anzhen Hospital with suspected CAD from November 1, 2018, to January 30, 2019, were enrolled. All patients underwent coronary angiography, and an experienced heart team calculated the SYNTAX scores (SXscore) for all available coronary angiograms. BLLs were determined with atomic absorption spectrophotometry and compared between patients with angiographically diagnosed CAD and those without CAD. RESULTS: In total, 343 (76%) patients had CAD, of whom 42% had low (0-22), 22% had intermediate (23-32), and 36% had high (≥ 33) SXscore. BLLs were 36.8 ± 16.95 µg/L in patients with CAD and 31.2 ± 15.75 µg/L in those without CAD (P = 0.003). When BLLs were categorized into three groups (low, middle, high), CAD prevalence increased with increasing BLLs (P < 0.05). In the multivariate regression model, BLLs were associated with CAD (odds ratio (OR): 1.023, 95% confidence interval (CI): 1.008-1.039; P = 0.0017). OR in the high versus low BLL group was 2.36 (95% CI: 1.29-4.42,P = 0.003). Furthermore, BLLs were independently associated with intermediate and high SXscore (adjusted OR: 1.050, 95% CI: 1.036-1.066; P < 0.0001). CONCLUSION: BLLs were significantly associated with angiographically diagnosed CAD. Furthermore, BLLs showed excellent predictive value for SXscore, especially for complex coronary artery lesions.

[Automatic Segmentation of Digital Pathology Slides Based on Unsupervised Learning].

OBJECTIVE: To segment images through an unsupervised method as an alternative to manual labeling. METHODS: A total of 100 whole slide image (WSI) data of HE stained and Pap stained slides were selected as the research and test objects, including 70 breast slides, 20 lung slides and 10 thyroid slides. In order to ensure the diversity of data, the breast slides included those of normal tissue, inflammation and tumor, the lung slides were mainly neoplasms in the lower lobe, including those of inflammation and tumor, and the thyroid slides were of cells, all benign, obtained through fine needle aspiration. The maximum total magnification (original magnification) of each image was 400 times, and the file format was NDPI. Each WSI was manually labeled, and the labeled area of each WSI was more than 10 fields of vision. The labeled information was to be used for validity verification. An unsupervised image segmentation technique based on superpixel and fully convolution neural network algorithms was constructed and used to segment any region of interest (ROI) of unlabeled WSI. In comparison with the region adjacency graph merging method, the segmentation effect of the two methods was assessed with the under segmentation error, the boundary recall and the mean Intersection-over-Union, and the efficiency of the two methods was also compared. In the comparison of execution efficiency, the test process included the preprocessing time of superpixel, and excluded the time of loading the deep learning engine. RESULTS: Unsupervised automatic segmentation was implemented for any ROI region of WSI according to the texture and color. The results of the breast slides, lung slides and thyroid slides showed slight differences, and multiple tests yielded stable results. However, the performance of this method in differentiating inflammation and tumor was average. The under-segmentation error, the boundary recall and the mean Intersection-over-Union were 19.10%, 82.06% and 45.06%, respectively. The under segmentation error, the boundary recall and the mean Intersection-over-Union for the region adjacency graph merging method were 21.52%, 78.39% and 44.81%, respectively. The average time consumption of the whole process was 0.27 s in GPU mode and 1.30 s in CPU mode. The average time consumption of the region adjacency graph merging method was 10.5 s in CPU mode because the method of region adjacency graph merging was not realized in the GPU mode. CONCLUSION: This method produced ideal pixel level labeling results through simple human-computer interaction, which could effectively reduce the cost of digital pathology slide data labeling. Compared with the region adjacency graph merging method, this method had better performance in processing image texture and had faster processing speed.

[Application Test of the AI-Automatic Diagnostic System for Ki-67 in Breast Cancer].

OBJECTIVE: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results. METHODS: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient ( ICC) was used to evaluate the correlation. RESULTS: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal. CONCLUSION: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.

Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy found globally. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play critical roles in HCC. However, the function of lncRNA in HCC remains poorly understood. AIM: To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms. METHODS: We measured the expression of lncRNA W42 in HCC tissues and cells (Huh7 and SMMC-7721) by quantitative reverse transcriptase polymerase chain reaction. Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression. HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42. Cell functions were detected by cell counting Kit-8 (CCK-8), colony formation, flow cytometry and Transwell assays. The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays. An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo. The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC. RESULTS: In this study, we identified a novel lncRNA (lncRNA W42), and investigated its biological functions and clinical significance in HCC. LncRNA W42 expression was upregulated in HCC tissues and cells. Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC, and inhibited cell apoptosis. LncRNA W42 directly bound to DBN1 and activated the downstream pathway. LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo. The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times. CONCLUSION: In vitro and in vivo results suggested that the novel lncRNA W42, which is upregulated in HCC, may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.

Skewed CD39/CD73/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B.

BACKGROUND: The mechanisms underlying B-cell hyperactivation in patients with chronic hepatitis B virus (HBV) infection remain largely undefined. The present study assessed the clinical characteristics of the CD39/CD73/adenosine pathway in patients with chronic hepatitis B (CHB). METHODS: We examined CD39 and CD73 expression and adenosine production by B-cells from 202 HBV-infected patients. B-cell-activation phenotypes were assessed by flow cytometry after CpG+CD40 ligand stimulation with or without blockade and activation of the adenosine pathway. RESULTS: CD39 and CD73 expression on circulating B-cells was decreased in CHB patients with high HBV DNA, HBeAg positivity, high HBsAg levels, and active liver inflammation, and was hierarchically restored in complete responders according to HBeAg seroconversion or HBsAg reduction. However, CD39 and CD73 expression on activated memory and tissue-like memory B-cell subsets in complete responders was not increased despite effective antiviral treatments. Furthermore, CD39 and CD73 expression on intra-hepatic B-cells was decreased in inflammatory livers. In vitro, B-cells from CHB patients showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine and expressed increased levels of activation markers after adenosine-production blockade. Contrastingly, metformin significantly reduced activation-marker expression via regulating AMP-activated protein kinase. CONCLUSIONS: The skewed CD39 and CD73 expression on B-cells was associated with a high viral burden, liver inflammation, and antiviral efficacy in CHB patients, and the skewed CD39/CD73/adenosine pathway contributed to B-cell hyperactivation. Regulation of the CD39/CD73/adenosine pathway using metformin may represent a therapeutic option to reverse HBV-induced immune pathogenesis.

Therapeutic effects of Aconiti Lateralis Radix Praeparata combined with Zingiberis Rhizoma on doxorubicin-induced chronic heart failure in rats based on an integrated approach.

OBJECTIVES: This study was aimed to explore the mechanism of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats by integrated approaches. METHODS: Effects of ALRP and ZR on cardiac function, serum biochemical indicators and histopathology in rats were analysed. Moreover, UHPLC-Q-TOF/MS was performed to identify the potential metabolites affecting the pathological process of CHF. Metabolomics and network pharmacology analyses were conducted to illustrate the possible pathways and network in CHF treatment. The predicted gene expression levels in heart tissue were verified and assessed by RT-PCR. KEY FINDINGS: ALRP-ZR demonstrated remarkable promotion of hemodynamic indices and alleviated histological damage of heart tissue. Metabolomics analyses showed that the therapeutic effect of ALRP and ZR is mainly associated with the regulation of eight metabolites and ten pathways, which may be responsible for the therapeutic efficacy of ALRP-ZR. Moreover, the results of RT-PCR showed that ALRP-ZR could substantially increase the expression level of energy metabolism-related genes, including PPARδ, PPARγ, Lpl, Scd, Fasn and Pla2g2e. CONCLUSIONS: The results highlighted the role of ALRP-ZR in the treatment of CHF by influencing the metabolites related to energy metabolism pathway via metabolomics and network pharmacology analyses.

[Comparative study of 3D printing implant guide in different implant surgeries in anterior tooth defect area].

OBJECTIVE: To study the accuracy of 3D printing implant-guided anterior tooth implantation under flap or flapless surgery. METHODS: Twenty-one cases (32 teeth) with missing teeth were divided into two groups: tooth implantation on the maxillary models under flap surgery (FP group) and tooth implantation on the maxillary models under flapless surgery (FPS group). A dental implant guide was designed and used in the two groups. The actual position of the dental implants in the two groups was compared with the preplanned deviation values of implant top, bottom, vertical distance, and angle deviation. SPSS 19.0 software was used for statistical analysis. RESULTS: The deviation values of implant top, bottom, vertical distance, and angle were significantly lower in the FP group than in the FPS group (P<0.05). CONCLUSIONS: High accuracy of tooth implantation can be realized by using the 3D printing implant guide. The different surgical methods influence the precision of tooth implantation. Clinicians can choose the surgery reasonably depending on the actual situation.

Comparison of integrated PET/MRI with PET/CT in evaluation of endometrial cancer: a retrospective analysis of 81 cases.

BACKGROUND: The objective of this study was to compare the diagnostic value of integrated PET/MRI with PET/CT for assessment of regional lymph node metastasis and deep myometrial invasion detection of endometrial cancer. METHODS: Eighty-one patients with biopsy-proven endometrial cancer underwent preoperative PET/CT (n = 37) and integrated PET/MRI (n = 44) for initial staging. The diagnostic performance of PET/CT and integrated PET/MRI for assessing the extent of the primary tumor and metastasis to the regional lymph nodes was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. McNemar's test was employed for statistical analysis. RESULTS: Integrated PET/MRI and PET/CT both detected 100% of the primary tumors. Integrated PET/MRI proved significantly more sensitivity and specificity than PET/CT in regional lymph node metastasis detection (P = 0.015 and P < 0.001, respectively). The overall accuracy of myometrial invasion detection for PET/CT and Integrated PET/MRI was 45.9% and 81.8%, respectively. Integrated PET/MRI proved significantly more accurate than PET/CT (P < 0.001). CONCLUSION: Integrated PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for the assessment of the lymph node metastasis and myometrial invasion in patients with endometrial cancer.

Plasma levels of receptor interacting protein kinase-3 correlated with coronary artery disease.

BACKGROUND: Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity. METHODS: A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models. RESULTS: Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04-11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05). CONCLUSIONS: Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.

Novel effects of sphingosylphosphorylcholine on the apoptosis of breast cancer via autophagy/AKT/p38 and JNK signaling.

Sphingosylphosphorylcholine (SPC), an important lipid mediator in blood, inhibits the proliferation and migration of various cancer cells. However, its effect as a cell-specific sphingolipid in breast cancer cells is still unknown. Here, we showed that SPC promoted autophagy and apoptosis in triple-negative breast cancer MDA-MB-231 cells. Autophagy worked as a negative regulator of apoptosis-induced by SPC. Mechanistically, SPC mediated apoptosis via activating c-Jun N-terminal kinase (JNK). Meanwhile, p38MAPK (p38) and protein kinase B (PKB or AKT) signaling pathways were also activated to inhibit apoptosis, suggesting that SPC could evoke multiple signaling pathways to modulate cell apoptosis. In addition, the crosstalk between autophagy, p38, AKT and JNK is that autophagy, p38, and AKT attenuated the JNK. AKT and p38 were in the downstream of autophagy, which is autophagy/AKT/p38 signaling evoked by SPC to antagonize JNK signaling and subsequent apoptosis. Although the pathways that antagonize apoptosis were evoked, the cells eventually reached apoptosis by SPC. Therefore, the combination with pharmacological autophagy inhibitors would be a more effective therapeutic strategy for eliminating breast cancer cells by SPC.