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Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively character-izing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear time-invariant dynamical model.It is shown that the transition matrices of dynamical cell systems signifi-cantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.
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Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
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The immune system plays a pivotal role in the pathogenesis and progression of diseases. Lipid peroxidation, as a key effector molecule in the execution of ferroptosis, exerts critical effects on the functionality and survival of various immune cells and is involved in the pathological processes of multiple diseases. There is accumulating evidence suggesting the presence of ferroptosis in immune cells as well. Lipid peroxidation is closely associated with immune cell function. Accumulation of lipid peroxidation products in immune cells can lead to ferroptosis, directly impacting immune cell function. Non-immune cells, through lipid peroxidation-mediated cell death, release signaling molecules that regulate immune cell function. They jointly influence the body's homeostasis. This article provides a comprehensive review of the latest research progress on the regulatory role of lipid peroxidation in immune function. It analyzes the relationship between lipid peroxidation and immune cells, and provides a theoretical foundation for potential strategies targeting cellular lipid peroxidation and immunotherapy in the treatment of diseases.
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In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg-1·day-1) and high dose (64 g·kg-1·day-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.
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Objective:To study the risk factors of early postoperative portal vein thrombosis (PVT) after salvage devascularization for failed endoscopic therapy.Methods:A retrospective analysis was conducted on the clinical data of 525 cirrhotic patients who underwent pericardial devascularization for portal hypertension and esophagogastric variceal bleeding at the Department of General Surgery, Beijing Ditan Hospital, Capital Medical University from January 2012 to January 2022. There were 435 males and 90 females, aged 47(37, 58) years old. These patients were divided into two groups based on whether PVT occurred after devascularization: the PVT group ( n=225) and the non-PVT group ( n=300). Clinical data including gender, age, portal vein diameter and postoperative platelet elevation level (PPEL) were studied and the related factors of PVT were analyzed by univariate analysis. Factors with statistically significant differences were included in logistic regression analysis. Results:Univariate analysis showed that the significant risk factors of PVT were the scores of the model of end-stage liver disease, platelets, portal vein diameter, endoscopic therapy, operation duration, surgical bleeding volume, intraoperative blood transfusion and PPEL on the first and third postoperative days (all P<0.05). Multivariate analysis showed that portal vein diameter ≥13 mm ( OR=6.000, 95% CI: 3.418-10.533), endoscopic injection ( OR=1.894, 95% CI: 1.196-2.998), operation duration ≥ 180 min ( OR=8.520, 95% CI: 5.333-13.554), PPEL ≥ 20×10 9/L on the first postoperative day ( OR=2.125, 95% CI: 1.306-3.456) and PPEL≥50×10 9/L on the third postoperative day ( OR=1.925, 95% CI: 1.192-3.109) increased the risk of PVT (all P<0.05). Conclusion:The diameter of portal vein, endoscopic treatment, operation duration and PPEL on the first and third days after operation were independent risk factors of early postoperative PVT development.
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Objective To investigate the incidence rate of pulmonary infection after laparoscopic surgery and related risk factors in patients with hepatocellular carcinoma (HCC) comorbid with liver cirrhosis and portal hypertension (PHT). Methods A retrospective analysis was performed for the clinical data of 105 HCC patients with liver cirrhosis and PHT who underwent laparoscopic surgery in Beijing Ditan Hospital, Capital Medical University, from January 2017 to February 2022. A total of 30 factors that might cause pulmonary infection were recorded, including general information, disease factors, surgical factors, and postoperative factors. Postoperative recovery was observed and the occurrence of pulmonary infection was recorded. The chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups, and the multivariate logistic regression analysis was used to investigate the independent risk factors for pulmonary infection. Results Among the 105 patients, 66 underwent laparoscopic devascularization combined with hepatectomy and 39 underwent laparoscopic devascularization combined with radiofrequency ablation (RFA). The surgery was successful for all patients, with no case of conversion to laparotomy or unscheduled reoperation. No death was observed within 30 days after surgery and during hospitalization, with a median length of hospital stay of 20 days (range 14-25 days). The incidence rate of pulmonary infection was 25.71% (27/105). Smoking (odds ratio [ OR ]=3.362, 95% confidence interval [ CI ]: 1.282-8.817, P =0.014), MELD score ( OR =3.801, 95% CI : 1.007-14.351, P =0.049), tumor location ( OR =1.937, 95% CI : 1.169-3.211, P =0.010), surgical procedure ( OR =0.006, 95% CI : 0.001-0.064, P =0.000), intraoperative infusion volume ( OR =4.871, 95% CI : 1.211-19.597, P =0.026), and postoperative pleural effusion ( OR =9.790, 95% CI : 1.826-52.480, P =0.008) were independent risk factors for pulmonary infection. Conclusion There is a relatively high risk of pulmonary infection in HCC patients with liver cirrhosis and PHT undergoing laparoscopic surgery. Postoperative pleural effusion is the high risk factor for pulmonary infection, and devascularization combined with RFA can significantly reduce the risk of pulmonary infection. It is recommended to strengthen preoperative rehabilitation, perioperative liver function maintenance, intraoperative damage control, and goal-oriented fluid therapy and reduce postoperative fluid accumulation in the third space, so as to reduce the incidence rate of pulmonary infection.
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Objective:Three-dimensional simulation modeling technology was used to conduct three-dimensional reconstruction, classification and measurement for the anatomic structures of colorectal canal, tumor and key blood vessels in patients with rectal cancer before operation. And the accuracy of the data and information obtained for the prediction of anastomotic tension, important types of vascular variant, positioning of anatomical landmarks, etc. in laparoscopic-assisted radical resection of rectal cancer, and the guiding effect of operation was evaluated.Methods:The clinical data of 50 patients with laparoscopic-assisted radical resection of rectal cancer treated in the General Surgery Department, Beijing Ditan Hospital Capital Medical University from January 2019 to February 2021 were analyzed retrospectively, including 31 males and 19 females, aged from 42 to 83 years old, with an average age of (62.72 ±15.21) years. The patients were divided into two groups according to whether the patients underwent three-dimensional simulation reconstruction before operation. The patients who underwent abdomen pelvic enhancement CT and further three-dimensional reconstruction before surgery were taken as reconstruction group ( n=24), and the patients who were only routinely performed abdomen pelvic enhancement CT before operation were taken as control group ( n=26). For the patients in the reconstruction group, the CT images were modeled by Mimics software before operation, and the key data such as the length of colorectal and tumor, the correlation length of rigid structure of pelvic wall, the length of inferior mesenteric artery (IMA) from the bifurcation point of left and right arteria iliaca communis, the type and proportion of IMA variation, the length of left colonic artery (LCA) from the beginning of IMA and the distance between LCA and IMV were measured, and the consistency correlation coefficient (CCC) was analyzed with the actual data obtained during operation. And then the accuracy of three-dimensional simulation modeling technology for surgical guidance was evaluated. MedCalc 19.0 software was used for statistical analysis. Results:In the reconstruction group, regarding the data of each dimension of the model (intestinal tract, pelvic cavity, blood vessels) and the corresponding structural measurements during the operation, the consistent correlation coefficient (CCC) evaluation was more than 0.9. One case was predicted to have free splenic flexure of colon and one case actually had free splenic flexure of colon. The prediction accuracy was 100%. The IMA variants in the reconstruction group were divided into 4 types, all of which were verified by operation. Compared with the control group, the operation time ( P=0.011) and the location time (IMA, P=0.043; LCA, P=0.007; IMV, P=0.034) of each vessel in the reconstruction group were shorter, and the amount of intraoperative blood loss was less ( P=0.017). Conclusion:The application of three-dimensional simulation modeling technology before operation is helpful for the operator to accurately predict the intraoperative anastomotic tension, the type of IMA variation and the related diameter length, based on which the accurate operation plan can be made to guide the operation.
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Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.
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Humans , Thyroid Nodule/pathology , Biopsy, Fine-Needle , Cyclin D1 , Immunohistochemistry , Thyroid Neoplasms/pathology , Retrospective StudiesABSTRACT
Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. About a quarter of the world's population were infected with Mycobacterium tuberculosis in 2020, and the majority of them were latently infected. Approximately 5%-10% of the population with latent tuberculosis infection may progress to active TB disease. Identifying latent TB infection from active TB by biomarkers and screening people with latent TB infection at high risk of progression for preventive treatment by biomarkers that can reliably predict the progression is one of the most effective strategies to control TB. This article reviews the progress of research on transcriptional and immunological biomarkers for identifying TB infection and predicting the progression from latent infection to active TB, with the aim of providing new ideas for tuberculosis control.
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Humans , Latent Tuberculosis/diagnosis , Tuberculosis/diagnosis , Mycobacterium tuberculosis/genetics , BiomarkersABSTRACT
The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC50 = 16.94 μg·mL-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.
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Objectives: To establish a newly-designed scoring system for breast imaging-reporting and data system (BI-RADS) 4 and 5 breast lesions only visible on MRI, and to examine their clinical pathway of biopsy. Methods: The BI-RADS 4 and 5 breast lesions only visible on MRI but not suspected on mammograms or ultrasound between June 2007 and December 2021 at Beijing Hospital were evaluated retrospectively. A total of 209 lesions from 184 patients were finally included. All patients were female, aged (50±11) years (range: 27 to 76 years). All lesions were confirmed by pathology and divided into malignancy and non-malignancy. The lesions were divided into mass and non-mass type using BI-RADS. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the new scoring system. Four types of pathology-obtaining pathway were used: biopsy guided by second-look ultrasound, local excision guided by lesion position information on MRI, intraductal lesion excision guided by methylene blue stain and mastectomy. The data between mass and non-mass lesions were compared by Mann-Whitney U test, χ2 test or Fisher exact test,respectively. Results: There were 124 malignant and 85 non-malignant lesions, while 100 mass and 109 non-mass lessions. The sizes between mass and non-mass lesions showed significant difference(M(IQR)) (7.0 (3.0) mm vs. 25.0 (25.0) mm, U=568.000, P<0.01) and their BI-RADS diagnostic accuracy had no significant difference (53.0% (53/100) vs. 65.1% (71/109), χ2=3.184, P=0.074). The areas under ROC curve of the new scoring system for evaluating mass and non-mass were 0.841 and 0.802, respectively. When taking Score 3 as threshold, it can potentially avoid 14.0% (14/100) and 4.6% (5/109) of biopsies in mass and non-mass, respectively. As to pathway of obtaining pathology, second-look ultrasound succeeded more easily in mass than non-mass (41.0% (41/100) vs.26.6% (29/109), χ2=4.851, P=0.028). More MRI-guided local excisions were performed in non-mass than mass (52.3% (57/109) vs. 34.0% (34/100), χ2=7.100, P=0.008). Conclusions: For suspicious breast lesions detected by MRI but not suspected on X-ray or ultrasound, the new scoring system can further increase diagnostic accuracy. The second-look ultrasound plays an important role for obtaining pathology, especially for mass-type lesion.
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Humans , Female , Male , Retrospective Studies , Breast Neoplasms/diagnostic imaging , Mastectomy , Radiography , Magnetic Resonance ImagingABSTRACT
The modern surgical treatment of cervical degenerative disc disease can be traced back to the advent of anterior cervical decompression and fusion.With the emergence of fusion-related complications,different scholars have promoted the gradual transformation of cervical degenerative disc diseases from "fusion fixation" to "non-fusion reconstruction" through in-depth fusion with materials science,engineering mechanics and other disciplines.The innovation of this treatment concept is consistent with the original intention of "structural remodeling,functional reconstruction,maximum repair and reconstruction of the morphology and function of skeletal muscle system" in orthopedic bionic treatment,which is essentially in line with the "bionic alternative therapy" in orthopedic bionic therapy.This paper focuses on the surgical treatment of cervical degenerative disc diseases,reviews the development history of artificial cervical disc replacement,analyzes the evolution from orthopedic biomimetic therapy,and explores a new direction for the design of artificial cervical disc prostheses and the treatment of cervical degenerative disc diseases in the future.
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Humans , Bionics , Cervical Vertebrae/surgery , Diskectomy , Follow-Up Studies , Intervertebral Disc/surgery , Intervertebral Disc Degeneration/surgery , Spinal Fusion , Total Disc Replacement , Treatment OutcomeABSTRACT
Objective: To analyze the epidemiological characteristics of anthrax in China from 2017 to 2019 and molecular typing of Bacillus anthracis isolated from some provinces (autonomous regions). Methods: Surveillance data of anthrax cases reported from 2017 to 2019 in the Infectious Disease Surveillance information System of China Disease Prevention and Control and the Public Health Emergency Reporting and Management Information System were collected, and descriptive epidemiological methods were used to analyze the epidemic characteristics, including the temporal, geographic and demographic distribution of this disease. A total of 47 strains of Bacillus anthracis isolated from 2017 to 2019 were analyzed by canSNP and MLVA15. Results: A total of 951 cases of anthrax were reported from 2017 to 2019, of which 938 were cutaneous anthrax, representing 98.63% of the total number reported. It was mainly distributed in the west and northeast of China, and the three provinces with the highest number of cases were Gansu (215), Sichuan (202) and Qinghai (191). Cases had been reported throughout the year, more cases occurred in the summer and autumn, and August was the month with the most cases,66.35% (211/318), 72.32% (243/336) and 68.01% (202/297) of cases were reported during June to September. The age distribution was mainly between 20 and 59 years old, accounting for more than 80% of all cases. The number of male cases was significantly higher than that of female cases, the ratio of male to female was about 3∶1. The occupations were mainly herdsmen and farmers, accounting for 49.70% to 58.18% and 31.45% to 36.70%, respectively. Public health events occurred every year, and 29 events had been reported from 2017 to 2019. canSNP analysis showed that 37 of the 47 strains belonged to the A.Br.001/002 subgroup and 10 belonged to the A.Br.Ames subgroup. MLVA15 analysis showed that there were 17 genotypes, of which 10 genotypes contained only one strain. Conclusion: Cutaneous anthrax was the predominant clinical type in China from 2017 to 2019.The seasonal, geographic and demographic distribution characteristics were evident.Molecular typing methods such as canSNP and MLVA15 can be used to trace the source of infectious diseases and provide technical support for anthrax prevention and control.
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Adult , Female , Humans , Male , Middle Aged , Young Adult , Anthrax/prevention & control , Bacillus anthracis/genetics , China/epidemiology , Molecular Typing , Polymorphism, Single Nucleotide , Skin Diseases, BacterialABSTRACT
The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.
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The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.
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Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.
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In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.
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In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.
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The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.
ABSTRACT
Objective To investigate the significance of the three-dimensional visualization ablation planning system in radiofrequency ablation for liver cancer. Methods A total of 71 patients who received radiofrequency ablation for hepatocellular carcinoma in Beijing Ditan Hospital, Capital Medical University from July 2017 to December 2020 were enrolled as subjects. The 34 patients in the three-dimensional group used the three-dimensional visualization ablation planning system for radiofrequency protocol planning before surgery and the 37 patients in the two-dimensional group used the two-dimensional image for radiofrequency protocol planning before surgery. The two groups were compared in terms of the indices such as the first-attempt success rate of puncture, complete tumor ablation rate, and tumor-free survival. The Fisher's exact test, the chi-square test of continuous correction, or the Pearson chi-square test was used for comparison of categorical data between two groups; the t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank (Mantel-Cox) test was used for comparison of tumor recurrence and survival; the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for tumor-free survival. Results Compared with the two-dimensional group, the three-dimensional group had a significantly higher first-attempt success rate of puncture (94.12% vs 75.68%, Pearson χ 2 =4.183, P =0.041) and a significantly shorter median time of puncture (5 minutes vs 7 minutes, Z =-2.407, P =0.013). There was no significant difference in complete ablation rate between the three-dimensional group and the two-dimensional group (97.06% vs 91.89%, continuous correction χ 2 =0.183, P =0.669). There were significant differences in the 1-, 2-, and 4-year cumulative tumor-free survival rates between the three-dimensional group and the two-dimensional group (90.8%/78.8%/72.8% vs 61.5%/55.9%/44.7%, χ 2 =5.073, P =0.024). The multivariate Cox regression analysis showed that preoperative planning method, complete or incomplete ablation, and alpha-fetoprotein at 1 month after surgery were independent influencing factors for the tumor-free survival of patients with liver cancer after radiofrequency ablation (all P < 0.05). Conclusion Radiofrequency ablation planning via the three-dimensional visualization ablation planning system can ensure the therapeutic effect of radiofrequency ablation, reduce the recurrence rate of liver cancer, and prolong the tumor-free survival of patients.