1.Intermittent hypoxia aggravates asthma inflammation via NLRP3/IL-1β-dependent pyroptosis mediated by HIF-1α signalling pathway.
Ling ZHOU ; Huojun ZHANG ; Lu LIU ; Fengqin ZHANG ; Lingling WANG ; Pengdou ZHENG ; Zhenyu MAO ; Xiaoyan ZHU ; Guisha ZI ; Lixiang CHEN ; Xiaojing CAI ; Huiguo LIU ; Wei LIU
Chinese Medical Journal 2025;138(14):1714-1729
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*
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Humans
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Asthma/metabolism*
;
Animals
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Pyroptosis/physiology*
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Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
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Mice
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Signal Transduction/physiology*
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Male
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Hypoxia/metabolism*
;
Female
;
Interleukin-1beta/metabolism*
;
Adult
;
Inflammation/metabolism*
;
Middle Aged
;
Mice, Inbred C57BL
2.Predictive value of pre-radiotherapy maximum tumor diameter and peripheral blood NLR for esophageal fistula in esophageal squamous carcinoma patients
Xiaowei WU ; Ge HU ; Li CHEN ; Xiaotao QIAN ; Xiangli CUI ; Fengqin ZHU
Journal of International Oncology 2025;52(1):38-42
Objective:To investigate the predictive value of maximum tumor diameter and the peripheral blood neutrophil to lymphocyte ratio (NLR) before radiotherapy for the occurrence of esophageal fistula after radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) .Methods:A total of 98 patients with ESCC who underwent radiotherapy in Hefei Cancer Hospital, Chinese Academy of Sciences from February 2017 to February 2021 were selected, and the patients were divided into esophageal fistula group (13 cases) and no esophageal fistula group (85 cases) according to whether esophageal fistula occurred during the follow-up process. The prognostic nutritional index (PNI) , NLR, and systemic inflammatory response index (SIRI) were calculated. Univariate and multivariate logistic regression were used to analyze the influencing factors of esophageal fistula, and the predictive value of each indicator was evaluated by using the receiver operator characteristic (ROC) curve.Results:There were no statistically significant differences in age, smoking history, diabetes mellitus history, gender, concurrent chemotherapy and alcohol history between the esophageal fistula group and the no esophageal fistula group (all P>0.05) , while there were statistically significant differences in PNI ( t=2.24, P=0.041) , NLR ( t=3.75, P=0.001) , SIRI ( t=2.68, P=0.015) . Univariate analysis showed that tumor length ( OR=1.16, 95% CI: 1.01-1.35, P=0.043) , maximum tumor diameter ( OR=1.63, 95% CI: 1.11-2.39, P=0.012) , PNI ( OR=0.83, 95% CI: 0.71-0.98, P=0.023) , NLR ( OR=1.94, 95% CI: 1.20-3.12, P=0.007) and SIRI ( OR=1.82, 95% CI: 1.03-3.24, P=0.041) were related to esophageal fistula. Multivariate analysis showed that maximum tumor diameter ( OR=2.17, 95% CI: 1.02-4.94, P=0.033) and NLR ( OR=2.40, 95% CI: 1.89-6.59, P=0.018) were independent influencing factors for the development of esophageal fistula in patients with ESCC after radiotherapy. ROC curve analysis showed that the area under the curve of maximum tumor diameter before radiotherapy combined with NLR for predicting esophageal fistula in patients with esophageal squamous cell carcinoma after radiotherapy was 0.83 (95% CI: 0.74-0.90) , which was greater than that of maximum tumor diameter before radiotherapy (0.71, 95% CI: 0.63-0.81, Z=1.80, P=0.039) and NLR (0.74, 95% CI: 0.67-0.85, Z=1.64, P=0.046) alone. Conclusions:The maximum tumor diameter before radiotherapy and NLR are closely related to the occurrence of esophageal fistula in ESCC after radiotherapy, and these factors are expected to serve as key predictors of the occurrence of esophageal fistula.
3.Research progress of SGK1 in digestive system diseases
Xixi BIAN ; Dehuai JING ; Guangxi ZHOU ; Fengqin ZHU
Journal of Chinese Physician 2024;26(9):1433-1437
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.
4.Research progress on the mechanism of hypoxia-inducible factor-1α in inflammatory bowel disease
Leilei CHEN ; Dehuai JING ; Yaowen ZHANG ; Yan WANG ; Wei YU ; Zongjing HU ; Fengqin ZHU ; Guangxi ZHOU
Chinese Journal of Inflammatory Bowel Diseases 2024;08(2):174-180
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.
5.Research progress on the mechanism of hypoxia-inducible factor-1α in inflammatory bowel disease
Leilei CHEN ; Dehuai JING ; Yaowen ZHANG ; Yan WANG ; Wei YU ; Zongjing HU ; Fengqin ZHU ; Guangxi ZHOU
Chinese Journal of Inflammatory Bowel Diseases 2024;08(2):174-180
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.
6.Application research of situation comedy teaching combined with peer teaching in clinical practice teaching of undergraduate nursing students
Zhengyun ZHU ; Zhehao ZHANG ; Fengqin XU ; Xiaohuan JIN
Chinese Journal of Medical Education Research 2023;22(2):310-314
Objective:To explore the application effect of situation comedy teaching combined with peer teaching in clinical practice teaching of undergraduate nursing students.Methods:A total of 96 undergraduate nursing students who practiced in a first-class hospital at grade 3 in 2019 were randomly divided into the observation group and the control group, with 48 nursing students in each group. The control group adopted clinical teaching mode, including group theory teaching and group operation demonstration. On the basis of this, the observation group additionally adopted the clinical teaching mode of situation comedy teaching combined with peer teaching. The differences between the two groups in the assessment of nursing knowledge and skills assessment, independent learning ability and teaching satisfaction were observed. SPSS 20.0 software was used for t-test. Results:After the implementation of clinical teaching, the scores of nursing comprehensive ability of nursing students in the observation group (87.71 ± 5.11) were higher than those in the control group (78.47±6.24) ( P < 0.05). The independent learning ability of nursing students in the observation group (98.80±10.61) was significantly higher than that in the control group (74.47±9.83), and the difference was statistically significant ( P < 0.05). The score of teaching satisfaction in the observation group (2.83±7.07) was significantly higher than that in the control group (50.17±6.75), and the difference was statistically significant ( P < 0.05). Conclusion:The application of situation domedy teaching combined with peer teaching in the clinical teaching of undergraduate nursing students can improve their independent learning ability and clinical practice ability. Meanwhile, the process of teachers and students participating in situational experience and peer analysis and discussion can increase the teacher-student interaction, and improve the satisfaction of nursing students with clinical teaching.
7.Construction of quality evaluation index system for postoperative rehabilitation in children with developmental dislocation of the hip
Yunyun WANG ; Jihong FANG ; Ying YIN ; Jiali FAN ; Fengqin WU ; Yumei XIAO ; Shujuan ZUO ; Jing ZHU
Chinese Journal of Modern Nursing 2023;29(28):3836-3841
Objective:To construct a quality evaluation index system for postoperative rehabilitation in children with developmental dislocation of the hip (DDH) .Methods:From August to November 2021, a quality evaluation index system for postoperative rehabilitation in children with DDH was established through literature review, group discussion, and Delphi expert consultation. The analytic hierarchy process was used to determine the weights of various indicators. The positive coefficient of experts was expressed by the effective response rate of the questionnaire. The authority level of experts was represented by the authority coefficient ( Cr) , which was determined by the expert judgment coefficient ( Ca) and the expert familiarity level ( Cs) . The degree of coordination of expert opinions was represented by the Kendall harmony coefficient (Kendall's W) . The degree of concentration of expert opinions was represented by the average score of importance assignment, coefficient of variation, and full score rate. Results:The effective response rates of the two rounds of expert consultation questionnaires were 90.00% and 100.00%, respectively. The Cr of experts in two rounds were 0.785 and 0.815, and the Kendall harmony coefficients were 0.098-0.193 and 0.147-0.212 ( P<0.05) . In the second round of expert consultation, the average scores of importance assignment for all levels of indicators were≥4.0, with coefficients of variation of 0-0.24 and a full score rate of ≥50%. The final quality evaluation index system for postoperative rehabilitation in children with DDH included 3 first-level indicators, 9 second-level indicators, and 37 third-level indicators. In the consistency test results of each indicator at all levels, all of the CI were <0.001, and all of the CR were<0.001. Conclusions:The construction process of the quality evaluation index system for postoperative rehabilitation in children with DDH is scientific, and the weight distribution of the indicators is reasonable, which can be used as an effective tool for evaluating the postoperative rehabilitation quality of DDH children.
8.Research progress of regulated cell death in inflammatory bowel disease
Xizhuang GAO ; Yonghong YANG ; Wei YU ; Fengqin ZHU ; Guangxi ZHOU
Chinese Journal of Inflammatory Bowel Diseases 2023;07(4):365-370
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.
9.Research progress of regulated cell death in inflammatory bowel disease
Xizhuang GAO ; Yonghong YANG ; Wei YU ; Fengqin ZHU ; Guangxi ZHOU
Chinese Journal of Inflammatory Bowel Diseases 2023;07(4):365-370
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.
10.Traditional Chinese Medicine Prevention and Treatment Strategy of Cognitive Impairment Secondary to Cardiovascular Disease and Simultaneous Treatment of Heart and Brain
Fenglan LIU ; Mengmeng ZHU ; Qing WANG ; Shihan XU ; Yanfei LIU ; Yue LIU ; Fengqin XU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):179-184
Cognitive impairment secondary to cardiovascular disease is a common complication in the elderly population, which seriously threatens the health of patients and affects the long-term quality of life. Cardiovascular diseases can lead to vascular endothelial injury, cerebral hypoperfusion, and brain lesions, and then cause cognitive impairment. Cardiovascular risk factors also increase the risk of secondary cognitive impairment in patients. It is particularly important to seek for early diagnosis and traditional Chinese medicine (TCM) and western medicine prevention and treatment. Based on the "holistic concept", TCM puts forward the theory of "the connection of heart and brain". The heart and brain are connected and both are in charge of mental activities. Heart injury affects the brain, resulting in abnormal consciousness, which is considered to be the pathogenesis of cognitive impairment secondary to cardiovascular disease in TCM. Later generations of doctors propose the theory of "simultaneous treatment of the heart and the brain" on the basis of "treating different diseases with the same treatment" and "the connection of heart and brain". The theory contains two meanings. One is that different diseases can be treated by the same method because of the same etiology and pathogenesis. The other is the coexistence of different diseases and the treatment should be targeted to the same risk factors. This paper systematically discussed the TCM pathogenesis of cognitive impairment secondary to cardiovascular disease and the prevention and treatment strategy of "simultaneous treatment of the heart and the brain". In this paper, the deficiency of qi and blood was the foundation, and the interaction of blood stasis and poison and the obstruction of the pulse and the loss of the body were the key factors. Activating blood, detoxifying arteries, and connecting the orifices were the main treatment method for the disease. This paper is expected to enrich the connotation of "simultaneous treatment of the heart and the brain", and provide new ideas for the prevention and treatment of cognitive impairment secondary to the cardiovascular disease with TCM.

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