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

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.

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.

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.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

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.

Yersiniosis is one of the "other infectious diarrhea" of the notifiable infectious diseases and also an important food-borne disease. However, it lacked the basis or standard for diagnosis. The Chinese Preventive Medicine Association coordinated experienced researchers from National Institute for Communicable Disease Control and Prevention, China CDC and other institutes to produce the group standard entitled "Diagnosis of Yersiniosis" (T/CPMA 005-2019). Based on the principle of "legality, scientificity, advancement, and feasibility" , the standard gives a clear definition for Yerisiniosis, stipulates diagnosis basis, principles and main differential diagnosis and provides two informative appendixes for epidemiological and clinical characteristics and a normative appendix for laboratory detection. The standard provides accurate basis and methods of Yersiniosis diagnosis for hospitals and CDCs at all levels in China. It will solve the problems that Yersiniosis cannot be clearly diagnosed for clinical cases and in the outbreaks.

Objective To investigate the protective mechanism of MEK1/2 inhibitor PD98059 on ox-LDL induced injury of human umbilical vein endothelial cells (HUVEC),and its influence on the expression of LOX-1.Methods HUVEC damage models were established by using ox-LDL and were treated with PD98059 later,divided into the negative control group,the ox-LDL group,the positive control group and the PD98059+ox-LDL group.The effect of inhibition of MEK1/2 on ox-LDL induced HUVEC damage was measured.Results Compared with the negative control group,the levels in the ox-LDL group of LOX-1,pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were increased significantly,the proliferations of HUVEC and the productions of NO were decreased (P＜0.05).Compared with the ox-LDL group,the levels in the positive control group and the PD98059+ox-LDL group of pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were decreased,the proliferation of HUVEC and the production of NO were increased (P＜0.05).Conclusion PD98059 inhibit the MEK1/2 signaling pathway to suppress the ox-LDL induced damage of HUVEC by decreasing the expression of LOX-1.

Objective To compare predictive power for deep vein thrombosis among hip and knee joint replacement patients using Autar scale and Wells scale.Methods Convenience sampling method was used.Totally 331 patients from ten tertiary hospitals receiving hip and knee joint replacement were recruited.General information questionnaire,Autar scale and Wells scale were used to collect data.Telephone follow-up was performed at 2 weeks,1 month and 3 months after hospital discharge.The primary endpoint of follow-up was occurrence of DVT,and the secondary endpoint was no occurrence of DVT within 3 months after hospital discharge.Results The Cronbach's α coefficients of Autar scale ranged from 0.716 to 0.762 for scores 24h before operation,24h after operation and at the day of discharge,and those of Wells scale ranged from 0.580 to 0.603.The area under the ROC curve of Autar scale ranged from 0.726 to 0.798.The area under the ROC curve of Wells scale ranged from 0.568 to 0.628.Conclusion The predictive power of Autar scale was higher than that of Wells scale which enabled Autar scale to better predict deep vein thrombosis for patients receiving hip and knee joint replacement.

OBJECTIVE To study the clinical efficacy of voice training on voice recovery in patients with vocal cord polyps during perioperative period.METHODS A total of 72 patients with vocal cord polyp were chosen in this study and they were randomly divided into study group and control group. After operation, the control group received routine treatment, and the study group received voice training on the basis of routine treatment. The results of voice acoustic analysis in the two groups were compared at 8 weeks after operation.RESULTS After 8 weeks, the maximum phonation time(MPT), dysphonia severity index (DSI) and the highest frequency(F0-High) of the study group were significantly higher than that of control group (P<0.05). The fundamental frequency perturbation(Jitter) of the study group was markedly lower than that of the control group(P<0.05). There was no statistical difference in the fundamental frequency(F0), the lowest intensity(I-Low) and amplitude perturbation(Shimmer) between the two group (P>0.05).CONCLUSION Voice training in the early postoperative period of vocal cord polyps was helpful to the recovery of the voice.