OBJECTIVES: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism. METHODS: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced via intracellular transfection of lipopolysaccharide (LPS). Western blotting was used to detect the secretory protein markers of NLRP3 inflammasome activation and assess pyroptosis, and the levels of inflammatory cytokines in cell culture supernatant were determined with ELISA. In a mouse model of LPS-induced septic shock, the effect of avitinib treatment on the levels of inflammatory cytokines in serum and peritoneal lavage fluid were examined with ELISA, and survival curves of the mice were plotted using the Kaplan-Meier method. RESULTS: Avitinib significantly inhibited NLRP3 inflammasome activation in multiple cell types, and dose-dependently reduced IL-1β secretion and caspase-1 cleavage while suppressing GSDMD-mediated pyroptosis without obviously affecting IL-6 or TNF-α levels. In the mouse models of LPS-induced septic shock, avitinib significantly lowered IL-1β levels in serum and peritoneal fluid and extended survival time of the mice. CONCLUSIONS Avitinib suppresses NLRP3 inflammasome activation and alleviates septic shock in mice.
Animals ; Shock, Septic/metabolism* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes/drug effects* ; Humans ; Macrophages/metabolism* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides

The emerging and re-emerging arthropod-borne infectious diseases pose a serious threat to global public health security. Field and laboratory studies of arthropods of medical importance are essential and critical for the prevention and control of arthropod-borne infectious diseases. Various institutions or universities in China have been conducting research in the field or laboratory study of arthropods of medical importance, but up to 2023, it is still lacking detailed biosafety guidelines or recommendations that can guide the related work for arthropods of medical importance. In order to proactively address potential biosafety issues in the field or laboratory activities related to arthropods of medical importance, improve the standardization of arthropod biosafety classification, operations, and protection, and ensure the safety of practitioners, an expert consensus on the biosafety recommendation of arthropods of medical importance in field and laboratory has been developed, aiming to guide the future work of arthropods and ensure the national biosafety and biosecurity of China.

Objective To explore the clinical application of ultrasound-guided transabdominal villus and amniocentesis in the prenatal diagnosis of thalassemia,and to find a suitable method for the prenatal diagnosis of thalassemia in Qinzhou.Methods A total of 531 high-risk pregnant women with severe or intermediate thalassemia during single pregnancy who were treated in the Department of Medical Genetics and Prenatal Diagnosis,Qinzhou Maternal and Child Health Hospital from March 2021 to April 2022 were selected for the study.According to different sampling methods,they were divided into control group(amniocentesis,n=415)and study group(transabdominal villus puncture,n=116).The success rate,complication rate of the two groups were compared.Results The success rate of puncture in the control group was 100％,2 cases were aborted within 2 weeks after surgery,17 cases were diagnosed with severe alpha-thalassemia,10 cases with severe β-thalassemia and 64 cases with intermediate thalassemia,48 cases with moderate and severe thalassemia induced labor.The success rate of puncture in the research group was 100％,10 cases were diagnosed with severe alpha-thalassemia,4 cases with severe β-thalassemia and 17 cases with intermediate thalassemia,and 26 cases with moderate severe thalassemia were induced labor.There was no significant difference in puncture success rate and abortion rate between the two methods(P>0.05).Conclusion Both methods are safe and effective.Transabdominal villus sampling can detect fetal thalassemia in early pregnancy,and it is worth promoting and applying in clinical practice.

Objective:To analyze the value of the modified 5-factor frailty index in assessing postoperative complications and mortality in elderly hip fracture patients.Methods:In this retrospective study, clinical data were collected of hip fracture patients aged 60 years and above surgically treated at Beijing Luhe Hospital affiliated to Capital Medical University between January 2015 and December 2019.Patients' group assignment was based on whether the modified frailty index score was ≤1 or ≥2, and a post-surgery follow-up was conducted for survival at 30 days, 1 year, 2 years, and 4 years, which was analyzed by the Kaplan-Meier method.Multivariate Cox regression analysis was used to identify factors affecting death in elderly patients.Results:A total of 1 208 patients were included, with 890 in the group with the index score ≤1 and 318 in the group with the index score ≥2.There was no difference in mortality at 30 days(1.6% or 14/890 vs.1.9% or 6/318, P=0.707), 1-year(11.3% or 99/874 vs.11.6% or 36/310, P=0.917), 2-years(19.7% or 168/852 vs.24.3% or 73/300, P=0.099)and 4-years(44.0% or 238/541 vs.51.5% or 106/206, P=0.071). The incidence of postoperative complications in the group with the score ≥2 was higher(14.8% or 47/318 vs.9.7% or 86/890, P=0.012), including the incidence of stroke(6.3% or 20/318 vs.1.8% or 16/890, P<0.001)and the incidence of postoperative pneumonia(6.0% or 19/318 vs.3.1% or 28/890, P=0.029), and the differences were statistically significant.Multivariate Cox regression analysis showed that age, being female, the Charlson comorbidity index score and low hemoglobin at admission were risk factors for 1-year, 2-year and 4-year mortality post-surgery(all P<0.05), while the modified frailty index score had no correlation with postoperative mortality. Conclusions:A modified frailty index ≥2 is predictive of increased risk of postoperative pneumonia and stroke in patients with hip fractures, but is not correlated with the risk of postoperative mortality.

Air lock module pressure control is a necessary step to balance the pressure inside and outside the spacecraft cabin and achieve the transfer of materials or personnel inside and outside the spacecraft cabin.The two main functions of the air lock module pressure control system are to reduce the pressure when leaving the chamber and increase the pressure when returning to the chamber.There are some methods such as releasing the gas in the chamber to vacuum or storing the gas in the chamber using containers.The control equipment for releasing gas is simple,but the gas is wasted.Gas storage requires temperature control and gas compressing equipment,but the gas is saved.There are some methods such as releasing gas from high-pressure vessels or releasing gas from nearby chamber.This article theoretically analyzes airlock module pressure controlling and provides several technical solutions for designing module pressure control systems.Releasing the gas to vacuum is suitable for spacecraft with a single sealed cabin while storing the gas is suitable for spacecraft with multi sealed cabins.Combined methods are also used in specific conditions.

Juvenile open angle glaucoma(JOAG)is a subtype of primary open angle glaucoma(POAG)that severely affects the quality of life of young patients and has a high disability rate. While JOAG is commonly considered an autosomal dominant disease, it has been found to have a diverse mode of inheritance, including autosomal recessive inheritance in specific populations. The variable genetic predisposition of JOAG may be attributed to the co-regulation of several key disease-causing genes, such as MYOC, CYP1B1, and CPAMD8. Mutations in these genes are closely associated with various biological processes in ocular tissues, including cellular metabolic regulation, oxidative stress response, and abnormal induction of programmed death. Therefore, a comprehensive study of the causative genes associated with JOAG is crucial to understanding the specific genetic background of disease onset, progression, and clinical phenotype. This knowledge will provide a strong foundation for early identification and screening of high-risk populations. The objective of this review is to focus on the genetic characterization and genetic studies of JOAG. Through a systematic review of the relevant literature, we summarize the causative genes and their mutations associated with JOAG and explore their potential applications and value in advancing research in the field, aiming to provide valuable insights for the diagnosis and treatment of JOAG.

The technologies such as deep learning and machine learning enable the rapid screening for potential drug candidate molecules and the prediction of their interactions with biological targets.Additionally,artificial intelligence exhibits great potential in drug design,synthesis pathway planning and clinical trial data analysis,and is expected to shorten the time from laboratory to market for new drugs and reduce research and development costs.Herein the study reviews the application of artificial intelligence technology in new drug research and development,explores the challenges it faces,and discusses the future development directions.

Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.