Hepatic ischemia-reperfusion injury (HIRI) has been considered as an inevitable process of liver transplantation. Hepatocyte ferroptosis is a key factor in HIRI development, yet precise mechanism and potential therapies are still unclear. Here, we demonstrated a strong correlation between hepatocyte ferroptosis and the downregulation of poly(rC)-binding protein (PCBP2), which compromised the stability of antiporter system Xc^- (consisted of SL3A2/SLC7A11). Besides, inhibiting PCBP2 contributed to facilitating cofactor p300 to enhance the transcriptional activity of HIF1α, leading to the expression and secretion of HMGB1. Then, released HMGB1 from ferroptotic hepatocytes worsened M1 macrophage recruitment and immune response during HIRI. Additionally, acteoside (ACT) was shown to assist PCBP2 in stabilizing the mRNA stability of Slc3a2 and Slc7a11, as well as enhance the binding affinity of PCBP2-system Xc^-. Beyond that, ACT also supported PCBP2 to limit HMGB1-induced M1 macrophage recruitment through imposing restrictions on p300 and HIF1α. Furthermore, specific knockdown of PCBP2 in hepatocytes directly interposed the therapeutic efficacy of ACT on HIRI mice. In conclusion, ACT alleviated hepatocyte ferroptosis and HIRI via promoting PCBP2 to maintain the stability of system Xc^- and limit HIF1α/p300-HMGB1 signaling. These findings highlight the therapeutic benefits of ACT in treating HIRI and offer insights into innovative therapeutic strategies.

Objective:This article analyzed the current situation, similarities and differences and main problems of the registration and management systems of innovative medical devices in China and the United States.Methods:This article summarized the requirements and policies for the registration management of innovative medical devices in China and the United States, as well as the development and differences of the registration of innovative medical devices in China and the United States, and the main problems in the registration management of innovative medical devices in China.Results:At present, the development level of medical device industry in China and the United States was different, facing different development problems, and there were differences in the access standards and management methods of innovative medical devices. The registration management system established for innovative medical devices in China was gradually improving, and to a certain extent, it had promoted the enthusiasm of innovative product research and development and registration applications, but there were also problems such as unclear innovation evaluation scales, insufficient early intervention of review resources, and insufficient utilization of post-marketing data.Conclusions:Drawing on the beneficial experience of breakthrough device registration management in the United States, we will improve the registration management system for innovative products and shorten the review and approval cycle by clarifying the identification criteria for innovative medical devices, promoting the placement of review resources in the R&D stage, and further strengthening the use of post-marketing data and regulatory scientific research.

Type I interferon (IFN) is considered as a bridge between innate and adaptive immunity. Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion, tumor cell proliferation, and overactive immune responses. Due to intricate and diverse chemical structures, natural products and their derivatives have become an invaluable source inspiring innovative drug discovery. In addition, some natural products have been applied in clinical practice for infection, cancer, and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted. However, whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated. In the current review, we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity, including both agonism/activation and antagonism/inhibition, and their potential application as therapies. Furthermore, the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified. In conclusion, natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection, cancer, and autoimmune diseases.
Biological Products/therapeutic use* ; Immunity, Innate ; Signal Transduction ; Interferon Type I/metabolism*

Nonalcoholic fatty liver disease (NAFLD) has become one of the most prominent causes of chronic liver diseases and malignancies. However, few therapy has been approved. Radix Bupleuri (RB) is the most frequently used herbal medicine for the treatment of liver diseases. In the current study, we aim to systemically evaluate the therapeutic effects of saikosaponin A (SSa) and saikosaponin D (SSd), the major bioactive monomers in RB, against NAFLD and to investigate the underlying mechanisms. Our results demonstrated that both SSa and SSd improved diet-induced NAFLD. Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes, like

Objective:To investigate the correlation between EOS level and hormone therapy effect and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:From January 2016 to June 2018, 120 patients with AECOPD were selected in the Fifth People's Hospital of Datong.According to EOS levels, all patients were divided into two groups, including EOS ≥2% group(56 cases) and EOS<2% group(64 cases). The general clinical data and treatment related indicators of patients with different EOS levels were compared, and the clinical value of EOS level in predicting the risk of severe AECOPD recurrence and death of patients were evaluated.Results:The levels of WBC, N%, NLR and CRP of the EOS≥2% group were significantly lower than those of the EOS<2% group[(6.89±1.16)×10 9/L, (69.08±12.79)%, (3.54±1.16), (5.30±1.18)mg/L vs.(8.45±1.85)×10 9/L, (76.42±16.58)%, (6.08±1.42), (7.43±1.77)mg/L]( t=5.27, 4.81, 4.65, 2.58, all P<0.05). The used time of antibiotics of the EOS≥2% group was significantly shorter than that of the EOS<2% group[8.0(6.0, 10.0)d vs.9.0(7.0, 11.0)d]( U=2.46, P<0.05). The time of hormone therapy and hospitalization time of the EOS≥2% group were significantly shorter than those of the EOS<2% group[9.0(7.0, 11.0)d, 10.0(9.0, 12.0)d vs.11.0(7.0, 13.0)d, 12.0(10.0, 13.0)d]( U=2.79, 2.56, all P<0.05). The proportion of CAT score decreased ≥2 points at 7d after treatment of the EOS≥2% group was significantly higher than that of the EOS<2% group[86.84% vs.68.18%](χ 2=2.84, P<0.05). Logistic regression analysis showed that EOS≥2% was the independent risk factor for severe AECOPD recurrence and death( OR=2.84, 95% CI: 1.49~5.03, P<0.05). There was no relationship between EOS level and death risk ( P>0.05). Conclusion:Serum EOS level can independently predict the clinical effect of hormone therapy and prognosis in patients with AECOPD, and clinicians can make more reasonable clinical treatment plan accordingly.

Objective To investigate the occurrence of common symptoms in breast cancer patients in different chemotherapy periods and to analyze the relationship with the chemotherapy periods. Methods A total of four hundred and fifty?six breast cancer patients receiving chemotherapy in Tangshan Cancer Hospital from August 2016 to August 2017 were investigated via common symptom questionnaire among breast cancer patients. The results of the investigation were statistically analyzed, and the relationship between chemotherapy related symptoms and chemotherapy periods was analyzed by multiple Logistic regression analysis. Results In terms of the 20 kinds of chemotherapy symptoms, among the patients whose incidence rate was >50％ had 9 kinds of symptoms. Multivariate Logistic regression analysis showed that alopecia (95％ CI=5. 820～562. 784,P=0. 001) ,skin allergy ( 95％ CI=0. 002～0. 157,P<0. 001) ,cancer caused insomnia( 95％ CI=1. 179～25. 638, P=0. 030) ,dry mouth ( 95％ CI=0. 008～0. 470,P=0. 007) ,vaginal dryness or burning heat ( 95％ CI=13. 368～647. 615 P<0. 001) ,oral ulcer ( 95％CI=0. 026～0. 654,P=0. 013) ,abnormal defecation ( 95％ CI=0. 025～0. 749,P=0. 022),memory loss (95％CI=1. 065～19. 415,P=0. 041),distal phalanges numbness (95％ CI=0. 004～0. 421,P=0. 007),poor appetite (95％ CI=1. 189～65. 964,P=0. 033),local skin irritation /ulceration ( 95％ CI=0. 003～0. 143, P<0. 001 ) were associated with the chemotherapy, the difference was statistically significant. The above symptoms can be divided into 3 symptom groups by factor analysis,and they were respectively medicine side effect symptom cluster, neuropsychiatric symptom cluster and mucocutaneous symptom cluster. Conclusion There are many symptom clusters that affect the life and rehabilitation level in patients with breast cancer during chemotherapy, and are closely related with the chemotherap cycle. Doctors should adopt a scientific model of symptom management and take measures to improve the survival state of the patients.

Oxidative stress is an important factor that can cause aging body, tissue damage and diseases.FoxO3a transcription factor is critical for the regulation of oxidative stress.Recently, there are some reports on the quite complex role of FoxO3a in regulating oxidative stress.Not only can it promote the survival of cells, but also induce cell apoptosis at some oxidative stress conditions.In this paper, the role of FoxO3a in oxidative stress, the possible signal pathway and the potential effect of target FoxO3a for oxidative stress diseases treatment are reviewed.

Objective To analyze the differences between the semi-quantitative RT-PCR and real time quantitative fluorescence RT-PCR assays for detecting XDH/XO mRNA expression in various organ tissues of rhesus monkey, and provide useful reference in methodology of experimental studies.Total RNA was extracted from the myocardium, kidney, testis, skin, and liver tissues, respectively, for detecting XDH/XO mRNA expression in rhesus monkey by semi-quantitative RT-PCR and real time quantitative fluorescence RT-PCR assays.The sensitivity and specificity of the two assays were compared with each other using the same primer sequences and reference genes.Results The expression of XDH/XO mRNA in different organ tissues were detected by both the two PCR assays.The sensitivity of quantitative fluorescence real-time RT-PCR for the XDH/XO mRNA expression in the liver tissue was 39 times higher than that by semi-quantitative RT-PCR.Conclusions Both the quantitative and semi-quantitative fluorescence RT-PCR assays can be used to detect the expression of XDH/XO mRNA in different organ tissues of rhesus monkey.The sensitivity of quantitative fluorescence real-time PCR assay is more sensitive than that of the semi-quantitative RT-PCR assay.

Objective To explore the clinical features,risk factors and gender differences of silent cerebral infarction (SCI),and provide the clinical basis for the primary and secondary preventions.Methods Three hundred and fifty-six patients without previous history of stroke and neurological signs,admitted to our hospital from January 2010 to January 2013,were selected and divided to 2 groups:an observation group (n=138,having SCI) and a control group (n=218,not having SCI).Age,gender,levels of blood pressure,blood glucose,triglyceride,low density lipoprotein (LDL) and total cholesterol,smoking history,drinking history,family history of stroke,and coronary heart disease history were analyzed by single and multiple factor Logistic analysis.SCI patients were divided into male SCI group and female SCI group to compare the differences of high risk factors.Results SCI lesions mainly located in the basal ganglia and crown areas of radiation,which were mainly multiple lesions.Logistic regression analysis showed that independent risk factors were age,hypertension,coronary heart disease history,diabetes history,high triglyceride and high LDL levels,and smoking history.The incidences of diabetes and coronary heart disease in female SCI patients were significantly higher than those in male SCI patients (P＜0.05),and those of high triglyceride and smoking in SCI female patients were statistically lower than those in male SCI patients (P＜0.05).Conclusion Risk factors of SCI include age,hypertension,coronary heart disease history,diabetes,high triglyceride and high LDL levels,and smoking;and gender differences exist in these risk factors.

OBJECTIVETo investigate the role of NLRP3 inflammasome in imiquimod-induced psoriasis-like inflammation in mice and the therapeutic effects of mustard seed (Sinapis Alba Linn).

METHODSThirty BALB/c mice were randomized equally into blank control group (fed with normal forage and treated with vehicle), model group (fed with normal forage and treated with 5% imiquimod cream), and experimental group (fed with 5% mustard seed forage and treated with 5% imiquimod cream). RT-PCR was used to detect the mRNA expression of NLRP3, ASC, caspase-1, and caspase-11. Immunohistochemistry was performed to determine the expression and distribution of ASC and caspase-1. ELISA was used to test the serum levels of interleukin-1β (IL-1β) and IL-18.

RESULTSCompared with the blank control group, the mice with imiquimod-induced psoriasis-like inflammation showed significantly increased NLRP3, ASC, caspase-1, and caspase-11 mRNA expressions, ASC and caspase-1 protein expressions , and serum levels of IL-1β and IL-18 (P<0.05). These changes were obviously attenuated by feeding the mice with mustard seed.

CONCLUSIONNLRP3 inflammasome is involved in imiquimod-induced psoriasis-like inflammation in mice, and mustard seed may suppress the inflammation induced by IL-1β and IL-18 through down-regulating the expression of NLRP3 inflammasome.

Aminoquinolines ; adverse effects ; Animals ; Carrier Proteins ; metabolism ; Caspase 1 ; metabolism ; Female ; Inflammasomes ; metabolism ; Inflammation ; drug therapy ; pathology ; Interleukin-18 ; metabolism ; Interleukin-1beta ; metabolism ; Mice ; Mice, Inbred BALB C ; Mustard Plant ; chemistry ; NLR Family, Pyrin Domain-Containing 3 Protein ; Phytotherapy ; Psoriasis ; chemically induced ; drug therapy ; metabolism ; Seeds ; chemistry