Imaging features and deep learning for prediction of pulmonary epithelioid hemangioendothelioma in CT images.

Background: Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumour, and its early diagnosis remains challenging. This study aims to comprehensively analyse the imaging features of PEH and develop a model for predicting PEH. Methods: Retrospective and pooled analyses of imaging findings were performed in PEH patients at our center (n=25) and in published cases (n=71), respectively. Relevant computed tomography (CT) images were extracted and used to build a deep learning model for PEH identification and differentiation from other diseases. Results: In this study, bilateral multiple nodules/masses (n=19) appeared to be more common with most nodules less than 2 cm. In addition to the common types and features, the pattern of mixed type (n=4) and isolated nodules (n=4), punctate calcifications (5/25) and lymph node enlargement were also observed (10/25). The presence of pleural effusion is associated with a poor prognosis in PEH. The deep learning model, with an area under the receiver operating characteristic curve (AUC) of 0.71 [95% confidence interval (CI): 0.69-0.72], has a differentiation accuracy of 100% and 74% for the training and test sets respectively. Conclusions: This study confirmed the heterogeneity of the imaging findings in PEH and showed several previously undescribed types and features. The current deep learning model based on CT has potential for clinical application and needs to be further explored in the future.

Psoriasis comorbid with atherosclerosis meets in lipid metabolism.

Psoriasis (PSO) is a common skin disease affecting approximately 1%-3% of the population, and the incidence rate is increasing yearly. PSO is associated with a dramatically increased risk of cardiovascular disease, the most common of which is atherosclerosis (AS). In the past, inflammation was considered to be the triggering factor of the two comorbidities, but in recent years, studies have found that lipid metabolism disorders increase the probability of atherosclerosis in patients with psoriasis. In this review, we discuss epidemiological studies, clinical treatment methods, risk factors, and lipid metabolism of psoriasis and atherosclerosis comorbidities.

Blastic Plasmacytoid Dendritic Cell Neoplasm Presenting as a Mammary Gland Tumor in a Pediatric Patient: A Case Report.

Emanating from a discrete category within the lympho-hematopoietic tumor system, as established by the World Health Organization in 2008, the blastic plasmacytoid dendritic cell neoplasm constitutes an uncommon malignant hematological disorder. It is routinely misidentified on account of its conspicuous dermatological manifestation, yet may insidiously permeate bone marrow and lymph nodes, involving peripheral blood and diverse extra-nodal tissues. Instances of mammary gland encroachment are extraordinarily infrequent. The current document delineates a case of a 14-year-old female patient contending with blastic plasmacytoid dendritic cell neoplasm, whose primary symptom was a mammary nodule, and whose breast and bone marrow/blood involvement were synchronous, in attempt to increase clinical vigilance.

Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation.

Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage-mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3-associated phagocytosis (LAP), a non-canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G-protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL-induced efferocytosis, anti-colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3-associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.

Promoter cloning and activities analysis of JmLFY, a key gene for flowering in Juglans mandshurica.

Juglans mandshurica (Manchurian walnut) is a precious timber and woody grain and oil species in Northeast China. The heterodichogamous characteristic phenomenon resulted in the non-synchronous flowering and development of male and female flowers, which limited the mating and the yield and quality of fruits. LFY is a core gene in the flowering regulatory networks, which has been cloned in J. mandshurica, and the function has also been verified preliminarily. In this study, the JmLFY promoter sequence with different lengths of 5'-deletion (pLFY1-pLFY6) were cloned and conducted bioinformatics analysis, the promoter activities were analyzed by detecting their driving activity to GUS gene in the tobacco plants that transformed with different promoter sequence stably or transiently. After that, the interaction between JmSOC1 and JmLFY gene promoter was also analyzed via yeast single-hybrid. The results showed that the promoter sequence contains core cis-acting elements essential for eukaryotic promoters, hormone response elements, defense- and stress-responsive elements, flowering-related elements, etc. Transgenic tobacco plants with pLFY1 were obtained by Agrobacterium infection using the pCAMBIA1301 expression vector, and the GUS gene driven by the JmLFY promoter was detected to express in the leaf, stem, flower, and root of the transformed tobacco plant, which indicated that the obtained JmLFY promoter had driving activity. GUS histochemical staining and enzyme activity detection showed that promoter fragments with different lengths had promoter activity and could respond to the induction of long photoperiod, low temperature, salicylic acid (SA), IAA, GA3, and methyl jasmonate (MeJA). The core regulatory region of JmLFY gene promoter in J. mandshurica was between -657 bp and -1,904 bp. Point-to-point validation of yeast single-hybrid confirmed the interaction between JmSOC1 and JmLFY gene promoter, which indicated that JmLFY gene is the downstream target of JmSOC1. These results reveal relevant factors affecting JmLFY gene expression and clarify the molecular mechanism of JmLFY gene regulation in the flower developmental partially, which will provide a theoretical basis for regulating the flowering time by regulating JmLFY gene expression in J. mandshurica.

Physiological response mechanism of European birch (Betula pendula Roth) to PEG-induced drought stress and hydration.

Drought stress is also one of the important abiotic factors limiting plant growth and development, and the global temperature is rising year by year, resulting in a dry environment in most terrestrial forests, which will continue to affect the growth, development and reproduction of tree species in forests. European birch(Betula pendula Roth.) native to Europe, introduced to the mountains of eastern Liaoning in 1981 (annual precipitation of about 800mm), European birch relative to downy birch (B. pubescens)has strong adaptability and drought tolerance and cold tolerance, can grow normally in eastern Liaoning, but it is easy to be affected by drought at the seedling stage and cause death, many arid and semi-arid areas have no introduction and practical application of European birch, and there is less research on the drought resistance of European birch. This study used different concentrations of PEG-6000 treatment to simulate drought stress and clarify the changes of various growth physiological parameters and photosynthetic characteristics of European birch seedlings under drought stress, in order to investigate the physiological response mechanism of European birch under drought stress . This study used different concentrations of PEG-6000 treatment to simulate drought stress and clarify the changes of various growth physiological parameters and photosynthetic characteristics of European birch seedlings under drought stress, in order to investigate the physiological response mechanism of European birch under drought stress. The findings demonstrated that stress duration and increasing PEG concentration had a highly significant impact on the growth traits of European birch seedlings (p<0.01); With increasing stress concentration and stress time, antioxidant enzyme activity, membrane lipid peroxidation, and osmoregulatory substance concentrations increased significantly (p<0.01); With increasing stress concentration and duration, photosynthetic parameters and pigments decreased highly significantly (p<0.01); Under different PEG concentration treatments, the anatomical structure of seedling leaves changed more noticeably; there was a significant effect (p <0.05) on the change in mean stomatal length and a highly significant effect (p<0.01) on the change in mean stomatal structure. The study's findings serve as a foundation for the selection and breeding of new drought-tolerant European birch species, as well as a theoretical underpinning for the use of this species in landscaping and the promotion of new drought-tolerant species in China.

Immunotherapy in combination with neoadjuvant anthracycline­free chemotherapy for triple­negative early breast cancer: A case report.

Immunotherapy is a promising anticancer strategy. In the present report, the case of a 36-year-old female patient with pathologically diagnosed, left triple-negative breast cancer and axillary lymph node involvement is reported. The patient received immunotherapy in combination with neoadjuvant anthracycline-free chemotherapy for six cycles, before undergoing left mastectomy and left axillary lymph node dissection. The postoperative pathology was a complete response to treatment, involving eradication of tumor from both the breast and the relevant lymph nodes. However, thyroid dysfunction occurred after two cycles of neoadjuvant treatment. The clinical presentation of the thyroid disorder was transient hyperthyroidism for 4 weeks and subsequent hypothyroidism, which required hormone replacement therapy.

Anti-breast cancer-induced cardiomyopathy: Mechanisms and future directions.

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and ß receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy.

Myocardial injury: where inflammation and autophagy meet.

Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles, aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment. Activation of autophagy can be observed during myocardial injury, during which inflammatory responses are strongly triggered. Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria. In addition, autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue. In this paper, we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions, including myocardial ischemia, ischemia/reperfusion injury and sepsis cardiomyopathy.

Tongguan capsule for treating myocardial ischemia-reperfusion injury: integrating network pharmacology and mechanism study.

CONTEXT: Although Tongguan capsule (TGC) is used in the treatment of coronary atherosclerotic disease, the exact mechanism remains unclear. OBJECTIVE: Network pharmacology and experimental validation were applied to examine the mechanism of TGC for treating myocardial ischemia-reperfusion injury (MIRI). MATERIALS AND METHODS: The components and candidate targets were searched based on various databases such as TCMSP, TCMID, BATMAN-TCM. The binding ability was determined by molecular docking. The ischemia-reperfusion (I/R) model was constructed by ligating the left anterior descending (LAD) coronary artery. APOE-/- mice were divided into three groups (n = 6): Sham group, I/R group, and TGC group (1 g/kg/d). To further verification, HCAEC cells were subjected to hypoxia-reoxygenation (H/R) to establish in vitro model. RESULTS: The compounds, such as quercetin, luteolin, tanshinone IIA, kaempferol and bifendate, were obtained after screening. The affinity values of the components with GSK-3ß, mTOR, Beclin-1, and LC3 were all <-5 kcal/mol. In vivo, TGC improved LVEF and FS, reducing infarct size. In vitro, Hoechst 33258 staining result showed TGC inhibited apoptosis. Compare with the H/R model, TGC treatment increased the levels of GSK-3ß, LC3, and Beclin1, while decreasing the expression of mTOR and p62 (p < 0.05). DISCUSSION AND CONCLUSION: The findings revealed that TGC exerted a cardioprotective effect by up regulating autophagy-related proteins through the mTOR pathway, which may be a therapeutic option for MIRI. However, there are still some limitations in this research. It is necessary to search more databases to obtain information and further demonstrated through randomized controlled trials for generalization.

Mitochondria-Targeted Nanosystem with Reactive Oxygen Species-Controlled Release of CO to Enhance Photodynamic Therapy of PCN-224 by Sensitizing Ferroptosis.

The apoptosis-resistant mechanism of photodynamic therapy (PDT) usually results in limited therapeutic efficacy. The development of new strategies for sensitizing targeted ferroptosis that bypass apoptosis resistance is of great significance to improve the antitumor efficacy of PDT. In this study, a novel amphiphilic copolymer whose main chain contains reactive oxygen species (ROS)-responsive groups and the end of side chains contains triphenylphosphine is synthesized, to encapsulate porphyrinic metal-organic framework PCN-224 via self-assembly which are hydrothermally synthesized by coordination of zirconium (IV) with tetra-kis(4-caboxyphenyl) porphyrin, and loaded carbon monoxide releasing molecule 401 (CORM-401) by their hollow structures (PCN-CORM), and finally, surface-coated with hyaluronic acid. The nanosystem can sequentially localize to mitochondria which is an important target to induce apoptosis and ferroptosis in cancer cells. Upon excitation with near-infrared light, PCN-224 is activated to produce amounts of ROS, and simultaneously triggers the rapid intracellular release of CO. More importantly, the released CO can sensitize ferroptosis and promote apoptosis to significantly enhance the antitumor efficacy of PCN-224 both in vitro and in vivo. These results illustrate that the mitochondria-targeted drug delivery system combined PDT with CO leads to an effective antitumor efficacy, which maybe a promising way to enhance the treatment efficiency of PDT.

The influence of subjective well-being on mental health in nursing students: the role of student cynicism.

Previous studies have reported high rates of poor mental health among nursing students, but few studies focused on the internal pathway of mental health. This cross-sectional study was conducted at a vocational medical school and investigated 384 nursing students. Symptom Check List-90, Index of Well-Being Scale and Cynical Attitudes Toward College Scale were used to test mental health, subjective well-being (SWB) and cynicism of nursing students, respectively. Academic cynicism, social cynicism and institutional cynicism were negatively related to mental health. SWB not only directly had positive effect on mental health, but had an indirect effect on mental health through academic cynicism, social cynicism and institutional cynicism.

Corrigendum: Combination effect of three main constituents from Sarcandra glabra inhibits oxidative stress in the mice following acute lung injury: a role of MAPK-NF-κB pathway.

[This corrects the article DOI: 10.3389/fphar.2020.580064.].

Direct medical costs of tuberculosis patients and its influencing factors in Hainan Province / 中国热带医学

@#Abstract： Objective　To investigate and analyze the factors influencing the direct medical costs of tuberculosis patients in Hainan Province, so as to provide scientific reference for reducing the medical burden of patients and adjusting the medical insurance reimbursement policies in the local area. Methods　Using the total health expenditure accounting data of Hainan Province in 2020, including the outpatient and inpatient data of 14 provincial medical institutions, 235 city and county level medical institutions, and other relevant data from the 2020 Hainan Statistical Yearbook and Health Financial Yearbook, the direct medical costs of tuberculosis patients in the province in that year were calculated, and the influencing factors were explored using single factor analysis and multivariate generalized linear model. Results　The final number of cases included in this study was 11 979, including 7 526 males (62.83%) and 4 453 females (37.17%). The total direct medical costs of patients were 43.207 3 million yuan, of which the total outpatient costs were 2.733 9 million yuan (6.32%) and the total inpatient costs were 40.473 4 million yuan (93.67%). In the cost composition analysis, the drug cost was 17.971 million yuan (41.44%), the examination cost was 8.854 7 million yuan (20.49%), other costs were 16.445 5 million yuan (38.06%), and the median (quartile) M(P25,P75) direct medical cost of each patient was 177.50 (66.73,764.89) yuan. The multivariate generalized linear model analysis showed that hospitalization, new rural cooperative medical insurance (NRCMI) and urban employee medical insurance were the influencing factors of the increase in direct medical costs of tuberculosis patients the median (quartile) M(P25,P75) of direct medical costs are 10 425.04 (6 560.87,17 374.9), 10 246.5 (5 871.28,17 220.33), 3 177.2 (293.09,7 730.23) yuan respectively; the OR(95%CI) values were -3.505 (-3.499- -3.517), 1.559 (1.551-1.569) and 2.191 (2.188-2.207) respectively. Conclusions　The direct medical costs of tuberculosis patients in Hainan Province are high. Hospitalization, the new rural cooperative medical insurance and the medical insurance for urban workers are the influencing factors of the increase in costs.

Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors.

The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circulation and diffusion of drugs. To overcome these obstacles, hydrogels formed in situ at the tumor site have been proposed to promote drug accumulation, retention, and long-lasting release. We developed a thiolated chitosan (CSSH) hydrogel with a gelation point of 37°C. Due to the pH-sensitive characteristics of disulfides, the prepared hydrogel facilitated drug release in the acidic tumor environment. A drug release system composed of hydrophilic doxorubicin (Dox) and hydrophobic liposome-encapsulated curcumin (Cur-Lip) was designed to enhance the long-lasting therapeutic impacts and reduce adverse side effects. These composite gels possess a suitable gelation time of approximately 8-12 min under physiological conditions. The cumulative release ratio was higher at pH = 5.5 than at pH = 7.4 over the first 24 h, during which approximately 10% of the Dox was released, and Cur was released slowly over the following 24-120 h. Cell assays indicated that the Cur-Lip/Dox/CSSH gels effectively inhibited the growth of cancer cells. These in situ-formed Cur-Lip/Dox gels with long-term drug release capabilities have potential applications for tumor suppression and tissue regeneration after surgical tumor resection.

PCSK9 Inhibition: From Current Advances to Evolving Future.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson's disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.

Cu-Hemin Nanosheets and Indocyanine Green Co-Loaded Hydrogel for Photothermal Therapy and Amplified Photodynamic Therapy.

Near-infrared (NIR) organic small molecule indocyanine green (ICG) could respond well to 808 nm laser to promote local high temperature and ROS generation for realizing photothermal therapy (PTT)/photodynamic therapy (PDT). However, the high content of GSH in the tumor microenvironment (TME) limited the further therapeutic performance of ICG. Herein, injectable agarose in situ forming NIR-responsive hydrogels (CIH) incorporating Cu-Hemin and ICG were prepared for the first time. When CIH system was located to the tumor tissue through local injection, the ICG in the hydrogel could efficiently convert the light energy emitted by the 808 nm laser into thermal energy, resulting in the heating and softening of the hydrogel matrix, which releases the Cu-Hemin. Then, the over-expressed GSH in the TME could also down-regulated by Cu-Hemin, which amplified ICG-mediated PDT. In vivo experiments validated that ICG-based PDT/PTT and Cu-Hemin-mediated glutathione depletion could eliminate cancer tissues with admirable safety. This hydrogel-based GSH-depletion strategy is instructive to improve the objective response rate of PDT.

Extracellular vesicles in pancreatic cancer immune escape: Emerging roles and mechanisms.

Pancreatic cancer (PC) is the most lethal malignancy worldwide due to its delayed diagnosis and limited treatment options. Despite great progress in clinical trials of immunotherapies for various cancers, their effectiveness in PC is very low, indicating that immune evasion is still a major obstacle to immunotherapy in PC. However, the mechanism of immune escape in PC is not fully understood, which substantially restricts the development of immunotherapy. As an important component of intercellular communication networks, extracellular vesicles (EVs) have attracted increasing attention in relation to immune escape. This review aims to provide a better understanding of the roles of EVs in tumor immune escape and the potential to expand their application in cancer immunotherapy. The relationship between PC and the tumor immune microenvironment is briefly introduced. Then, the mechanism by which EVs are involved in immune regulation is summarized, and the latest progress in determining the role of EVs in regulating PC immune escape is highlighted.

Satisfaction as a Mediator and Its Interaction With Adherence to Labor Analgesia Protocols: A Cross-Sectional Survey of Chinese Medical Personnel.

Background: Although the Chinese promotion of labor analgesia began in 2018 to improve maternal health, high-quality medical care is difficult to provide to pregnant women when medical staff cannot implement standard labor analgesia procedures. This study aims to examine medical personnel's adherence to labor analgesia protocols and to explore the relationships among adherence, satisfaction, and other factors. Methods: The data were from a national cross-sectional dataset (N = 13,944) of the 2020 Chinese Labor Analgesia Pilot Evaluation Project. Mediating and moderating effects analyses were used to examine the role of satisfaction as a mediator between support measures and adherence. Results: There were differences in adherence between different types of medical personnel. Support measures and satisfaction had a positive association with adherence to labor analgesia protocols. Satisfaction had a significant mediating and moderating effect on the relationship between support measures and adherence to labor analgesia standards. Moderating effects of professional titles and attitudes were also observed. Conclusion: Primary health care policies worth considering include comprehensive incentives for medical institutions to improve the use of labor analgesia by medical personnel. It is also worth considering providing more training opportunities for the staff in anesthesiology departments.

Engineered extracellular vesicles and their mimetics for cancer immunotherapy.

Extracellular vesicles (EVs) are heterogeneous membranous vesicles secreted by living cells that are involved in many physiological and pathological processes as intermediaries for intercellular communication and molecular transfer. Recent studies have shown that EVs can regulate the occurrence and development of tumors by transferring proteins, lipids and nucleic acids to immune cells as signaling molecules. As a new diagnostic biomarker and drug delivery system, EVs have broad application prospects in immunotherapy. In addition, the breakthrough of nanotechnology has promoted the development and exploration of engineered EVs for immune-targeted therapy. Herein, we review the uniqueness of EVs in immune regulation and the engineering strategies used for immunotherapy and highlight the logic of their design through typical examples. The present situation and challenges of clinical transformation are discussed, and the development prospects of EVs in immunotherapy are proposed. The goal of this review is to provide new insights into the design of immune-regulatory EVs and expand their application in cancer immunotherapy.