BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Objective:To summarize the ultrasonographic features and prognosis of fetal persistent vitelline artery.Methods:The prenatal ultrasound features, genetic testing results, and prognosis of a fetus with an isolated persistent vitelline artery that was diagnosed in our hospital in December 2021 were retrospectively analyzed. Relevant articles were retrieved from CNKI, VIP, Wanfang, Yiigle, PubMed, Embase, and UpToDate databases using the terms "persistent vitelline artery", "type Ⅱ single umbilical artery", and "prenatal ultrasound" in both Chinese and English. Prenatal ultrasound features and prognosis of the persistent vitelline artery in fetuses were summarized using descriptive statistical analysis.Results:(1) Case report: In this case, ultrasound at 23 gestational weeks showed that an abnormally large blood vessel deriving from the celiac artery near the superior mesenteric artery entered the placenta through the umbilical opening in parallel with the umbilical vein. Color Doppler showed a blood flow spectrum like that in the umbilical artery. The transverse section image showed that bilateral umbilical arteries were not observed in the bladder and the free segment of the umbilical cord was in the shape of the Chinese character "Lyu". No obvious other structural abnormalities and a negative result of genetic testing were observed in the fetus. Followed up to one year old, the patient showed normal growth and development. (2) Literature review: A total of five articles involving four cases were retrieved (three in English and two in Chinese). Among the five cases, including the present case, one was terminated due to left renal agenesis and abnormal heart arteries ratio revealed by prenatal ultrasound, and the remaining four cases without obvious structural abnormalities in the prenatal ultrasound were born and developed well. Histopathological examination of the umbilical cord was performed in three cases, of which two with persistent vitelline artery had a distinct internal elastic lamina, and one with remained vitelline duct.Conclusions:The prenatal ultrasound of fetal persistent vitelline artery is typically characterized by an abnormal vessel that is derived from the abdominal aorta or superior mesenteric artery and plays the function of the umbilical artery. The prognosis of the isolated persistent vitelline artery is good, but a better understanding of such embryonic abnormalities is needed as there are few relevant reports at home and abroad.

The development of inflammatory bowel diseases (IBD) is associated with genetics, environment, immune abnormalities, and intestinal flora, including ulcerative colitis (UC) and Crohn′s disease (CD). Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that promotes the expression of multiple genes in response to the hypoxic environment, and its roles in regulating intestinal barrier function, intestinal metabolism, and inflammatory and immune responses are research hotspots. This article reviews the role of HIF-1α in IBD by analyzing the relationships between HIF-1α and intestinal epithelial barrier and inflammatory response to provide new ideas for the clinical treatment of IBD.

Serum and glucocorticoid-inducible kinases (SGKs) are serine threonine protein kinases involved in the regulation of multiple signal transduction pathways in vivo. SGKs include SGK1, SGK2 and SGK3. SGK1 plays a crucial role in the development of diseases such as digestive inflammation and tumors by regulating inflammatory and immune responses through phosphorylation. This article briefly introduces the structure and function of SGK1, and describes the research progress and clinical significance of SGK1 in digestive diseases.

The development of inflammatory bowel diseases (IBD) is associated with genetics, environment, immune abnormalities, and intestinal flora, including ulcerative colitis (UC) and Crohn′s disease (CD). Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that promotes the expression of multiple genes in response to the hypoxic environment, and its roles in regulating intestinal barrier function, intestinal metabolism, and inflammatory and immune responses are research hotspots. This article reviews the role of HIF-1α in IBD by analyzing the relationships between HIF-1α and intestinal epithelial barrier and inflammatory response to provide new ideas for the clinical treatment of IBD.

Diabetic cardiomyopathy refers to dysfunction of cardiac muscle in patients with diabetes that cannot be directly ascribed to hypertension， coronary heart disease or other defined cardiac abnormalities. Imbalance in metabolic flexibility is the underlying cause of diabetic cardiomyopathy， which is manifested as distorted nutrient sensing， slow substrate switching， and impaired energy homeostasis. In the case of diabetes/insulin resistance， cardiac fatty acid oxidation increases while glucose oxidation decreases， resulting in the imbalance in cardiac metabolic flexibility. Thus， the heart fails to switch substrates depending on the changes （taking food/fasting， rest/exercise） and the energy production in cardiomyocytes reduced， causing cardiac dysfunction. Moreover， the excessive cardiac fatty acid fails to be degraded by the mitochondrial β oxidation， triggering cardiac lipid accumulation and reduction in glucose oxidation. Therefore， the glucose in the pentose phosphate （PPP） and the hexosamine biosynthetic pathway （HBP） increases and the production of advanced glycation end products rises， inducing glycolipotoxicity. The intermediates of abnormal substrate metabolism cause oxidative stress， inflammation， mitochondrial dysfunction and further result in impaired myocardial function. Qi and blood are the main functional substances for the normal functioning of the body. Qi and blood harmonize and work together to defend against external pathogen， while disharmony of blood and Qi will induce the production of various pathological products that lead to the occurrence of diseases. The function and regulation of Qi-Blood movement are similar to those of metabolism. Qi deficiency and blood stasis， Qi stagnation and blood stasis， and other "blood-Qi disharmony" types run through the whole process of diabetic cardiomyopathy， and "blood-Qi disharmony" will affect systemic substrate metabolism and lead to impaired energy metabolism. By systematically explaining the relationship between "blood-Qi disharmony" and "metabolic flexibility" in diabetic cardiomyopathy， we provide scientific research and clinical formulation ideas for targeting "metabolic flexibility" in the prevention of diabetic cardiomyopathy with Qi-replenishing and Blood-activating medicinals.

Objective:To investigate the association of nonalcoholic fatty liver disease (NAFLD) and obesity with risk of atherosclerotic cardiovascular disease (ASCVD).Methods:A total of 1 486 individuals, including 1 051 males and 635 women aged (56.0±9.0) years, who underwent health check-up at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from January 2020 to November 2021 were enrolled. The participants were divided into non-NAFLD group ( n=564), NAFLD without obesity group ( n=689), and NAFLD with obesity group ( n=233) according to the presence of NAFLD and body mass index. The general information, smoking history, alcohol consumption, medical history and results of physical examination, laboratory tests and liver ultrasound of participants were collected from the electronic medical record system. Body mass index≥28.0 kg/m 2 was defined as obesity, fatty liver was diagnosed by ultrasonography, and ASCVD risk was assessed according to the criteria of the Chinese guideline on the primary prevention of cardiovascular diseases( 2020). Multivariate logistic regression model was used to analyse the relationship of NAFLD and obesity with risk of ASCVD. Results:The proportions of individuals at high risk for ASCVD in the non-NAFLD group, the NAFLD without obesity group and the NAFLD with obesity group were 27.5%(155/564), 50.1%(345/689) and 61.8%(144/233), respectively, and the proportions of individuals at high ASCVD risk in the NAFLD without obesity group and the NAFLD with obesity group were higher than that in the non-NAFLD group (all P<0.05), and the proportion in the NAFLD with obesity group was higher than the NAFLD without obesity group ( P<0.05). Multivariate logistic regression analysis showed that NAFLD was significantly associated with a higher risk of ASCVD after correction for sex, alcohol consumption and alanine aminotransferase, and the association was stronger in the NAFLD with obesity, and the results were unchanged after further correction for uric acid, fasting glucose and systolic blood pressure (all P<0.001). Conclusion:NAFLD is strongly associated with the risk of ASCVD with or without obesity, and obesity may strengthen this association.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease, mainly including ulcerative colitis (UC) and Crohn′s disease (CD). With the in-depth study of the role of regulated cell death (RCD) in IBD, more and more evidences show that autophagy, ferroptosis, pyroptosis, apoptosis and necroptosis are closely related to the progress and prognosis of IBD. This article reviews the pathogenesis and therapeutic prospects of RCD represented by autophagy in IBD, providing a reference for the treatment of IBD.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease, mainly including ulcerative colitis (UC) and Crohn′s disease (CD). With the in-depth study of the role of regulated cell death (RCD) in IBD, more and more evidences show that autophagy, ferroptosis, pyroptosis, apoptosis and necroptosis are closely related to the progress and prognosis of IBD. This article reviews the pathogenesis and therapeutic prospects of RCD represented by autophagy in IBD, providing a reference for the treatment of IBD.

Objective:To study the ultrasonographic characteristics of embryos/fetuses with normal or abnormal central nervous system (CNS) from 7 to 13 +6 weeks of gestation using high resolution two-dimensional ultrasound combined with HD-live silhouette technology and provide a reference for early diagnosis of CNS abnormalities. Methods:Eighty normal embryos/fetuses during 7-13 +6 weeks and 41 fetuses with CNS malformations in early pregnancy during 11-13 +6 weeks were selected to observe the ultrasonographic features of embryos/fetuses with normal or abnormal CNS using transvaginal high resolution two-dimensional ultrasound and HD-live silhouette technology. Descriptive analysis was performed on the results. Results:From seven weeks of gestational age, high resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically show the prosencephalon, mesencephalon and rhombencephalon. The rhombencephalon changed the most in the brain development of embryos. At nine weeks of gestation, cleared structures of pons curvature, the fourth ventricle and cisterna magna were observed. The developing cerebellum and the original Blake pouch cyst were seen at 10 weeks of gestation. From 11 to 13 +6 weeks, the most remarkable change was the choroid plexus of the fourth ventricle changed from perpendicular to parallel to the long axis of the neural tube. Of the 41 fetuses with CNS malformation, 16 (39.0%) were exencephaly, 11 (26.8%) were holoprosencephaly, five (12.2%) were encephalocele, four (9.7%) were anencephaly, three (7.3%) were fourth ventricle dilatation, and two (4.9%) were open spina bifida. Conclusions:High resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically display the morphological changes in embryonic embryos/fetuses with development of normal CNS at 7-13 +6 weeks, which is helpful to better understand the origin of CNS embryonic abnormalities and provide diagnostic clues for the early detection of CNS abnormalities.