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

Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*

【Objective】 To explore the correlation between CSAG1 expression and the prognosis and tumor-infiltrating lymphocytes in renal clear cell carcinoma (RCCC), and to predict the survival and tumor progression. 【Methods】 The gene expression profiles and clinical information of CSAG1 were downloaded from the Cancer Genome Atlas (TCGA). Based on the differential mRNA expression, GO annotation and KEGG pathway analysis were performed. The relationship between CSAG1 and tumor immune infiltration was assessed with Tumor Immunoassay Resource (Timer 2.0) database. The mRNA expression of CSAG1 in human RCCC specimens was validated with qRT-PCR. 【Results】 CSAG1 expression was significantly higher in RCCC tissues than in normal tissues (P<0.05). The qRT-PCR results revealed that the mRNA level of CSAG1 was consistent with that predicted by bioinformatic analysis. The KEGG analysis and GO annotation indicated high GSAG1 expression in RCCC was related to transmembrane transport, tricarboxylic acid cycle and lysosome. CSAG1 expression was positively related to the infiltration of pDC, aDC, CD8⁺ T cells, cytotoxic cells, TFH, TH1 cells, Tem, NK CD56^dm cells, Treg and T cells, but negatively correlated with macrophage infiltration. 【Conclusion】 CSAG1 may be associated with poor prognosis of RCCC and become a potential immunotherapy target.

Objective:To investigate the influence of different degrees of facet joint arthropathy on the indirect decompression effect of crenel lumbar interbody fusion (CLIF), and the clinical outcomes of CLIF for the treatment of lumbar spinal stenosis with severe facet joint arthropathy (grade 3).Methods:This study reviewed a total of 269 surgical segments in 156 patients with lumbar spinal stenosis treated with CLIF technique from November 2016 to February 2020. According to preoperative CT images, the facet joint was graded according to Pathria classification. There are 19 segments with grade 0, 156 segments with grade 1, 67 segments with grade 2, and 27 segments with grade 3. Radiographic parameters included disc angle, anterior and posterior disc height, and bilateral intervertebral foramen height on CT, and the midsagittal canal diameter and axial central canal area. In 30 patients with at least one segment of grade 3, the clinical efficacy was assessed using visual analogue scale (VAS) and Oswestry disability index (ODI).Results:The average the anterior and posterior intervertebral space height, intervertebral space angle, height of bilateral intervertebral foramina, spinal canal sagittal diameter and spinal canal area were significantly improved after the operation of grade 3 facet joint degeneration segment compared to preoperation. The preoperative mean spinal canal sagittal diameter and spinal canal area of grade 3 facet joint degeneration segment were significantly less than grade 1 and grade 2. The average change of spinal canal area after grade 3 articular degeneration was significantly less than that of grade 1 and 2, but there was no significant difference with that of grade 0. The posterior decompression rate was 55.56% (15/27) for grade 3, 35.82% (24/67) for grade 2, 16.03% (25/156) for grade 1, and 21.05% (4/19) for grade 0. The posterior decompression rate of grade 3 articular process degeneration was significantly higher than that of other grades ( P<0.001). Severe lateral recess stenosis and 24.24% of severe intervertebral foraminal stenosis were found in 81.48% of grade 3 degenerative segment. The 23 patients were followed up with an average of 21.62±6.52 months, and the average improvement of ODI was 24.10%±11.09%; the average VAS for leg pain and back pain were improved significantly. Conclusion:The degrees of facet joint degeneration do not prevent intervertebral space distraction of CLIF. However, because segments with severe facet joint arthropathy were usually associated with severe spinal canal stenosis, CLIF had a high rate of second-stage posterior decompression in the treatment of lumbar spinal stenosis with severe facet joint arthropathy.

Methamphetamine (MA) has the characteristics of neurotoxicity and strong psychological dependence. At present, there is a lack of effective intervention for MA dependence. Aiming at the brain pathological damage and clinical characteristics of MA dependence, new multi-dimensional evaluation instruments were developed including virtual reality craving evaluation system, cognitive and impulsive damage assessment, and SWOT (strengths, weaknesses, opportunities and threats) analysis. Rehabilitation interventions were also investigated and developed including computerized cognitive addiction therapy, precise neuroregulatory intervention aimed at reducing craving, music therapy, and community-based addiction rehabilitation electronic system. On this basis, On this basis, we propose to establish a whole course and accurate intervention model based on repeatedly measurement-based assesments for MA dependence, or WARM model. The WARM model focuses on the difficulties of MA dependence at different stages and is committed to multi-dimensional rehabilitation of MA patients. The WARM model will further be explored with the assistance of artificial intelligence.

Methamphetamine (MA) has the characteristics of neurotoxicity and strong psychological dependence. At present, there is a lack of effective intervention for MA dependence. Aiming at the brain pathological damage and clinical characteristics of MA dependence, new multi-dimensional evaluation instruments were developed including virtual reality craving evaluation system, cognitive and impulsive damage assessment, and SWOT (strengths, weaknesses, opportunities and threats) analysis. Rehabilitation interventions were also investigated and developed including computerized cognitive addiction therapy, precise neuroregulatory intervention aimed at reducing craving, music therapy, and community-based addiction rehabilitation electronic system. On this basis, On this basis, we propose to establish a whole course and accurate intervention model based on repeatedly measurement-based assesments for MA dependence, or WARM model. The WARM model focuses on the difficulties of MA dependence at different stages and is committed to multi-dimensional rehabilitation of MA patients. The WARM model will further be explored with the assistance of artificial intelligence.

Objective:To investigate whether nursing students face the transition shock problems in the stage of clinical practice, and analyze the performance in the dimensions of physical, emotional, intellectual, sociocultural and developmental, and provide reference for formulating clinical intern training programs for nursing students.Methods:A cross-sectional survey of nursing students on the impact of transition shock and its influencing factors were conducted using the General Survey Form and the Transition Shock of Newly Graduated Nurses Scale.Results:The transition shock score of nursing students was 64.49±16.33. The score of physical dimension was 15.73±5.22, intellectual dimension was 13.13±3.80, emotional dimension was 19.15±5.32, sociocultural and developmental dimension was 16.47±5.41. The proposed academic qualifications ( F value was 5.96, P<0.01), the reason for choosing nursing profession ( F value was 7.28, P<0.01), family support level ( t value was -2.75, P=0.01), first internship department ( F value was 5.22, P<0.01), and internship intention ( F value was 3.43, P=0.03) cause the differences in the transition shock of nursing students. Conclusions:Nursing students will face the transition shock problems in the stage of clinical practice, and the impact of physical dimension is the most obvious. In the development of clinical internship training programs, hospitals and institutions should take into account the transition shock of nursing students, as earlier as possible perceive and prevent the occurrence and intensification of nursing students' clinical transformation problems, and assist them to successfully pass the transitional impact stage.

Objective: To explore the optimal method of microelectrode implantation that can produce efficient mouth closure with microelectrode for orbicularis oris muscle (OOM) in rhesus monkeys with unilateral peripheral facial paralysis (UPFP) in order to provide basis for the research and development of artificial facial nerve prosthesis (AFNP). Methods: Right lateral peripheral facial paralysis model on four healthy rhesus monkeys (two males and two femles, aged 5-6 years, weighed 2.0-3.0 kg) were prepared. AFNP electric stimulation was used to induce closed-mouth reaction of the affected OOM with a one-way rectangular pulse, 50 Hz frequency and 0.2 ms pulse width in vitro. Around the affected lateral OOM, four stimulus electrodes implantation positions were selected at the upper lip (position A), the lower lip (position B), the connection with the corner of the mouth to the ipsilateral tragus (position C), and the horizontal line of the mouth angle (position D). According to the different implantation positions of three stimulation electrodes on the stimulation side of AFNP and the results of our previous study, six groups of microelectrode implantation methods were designed. In Group A, two microelectrodes were implanted at position A and one microelectrode was implanted at position B; in Group B, one microelectrode was implanted at position A, B and C respectively; in Group C, one microelectrode was implanted at position A and two microelectrodes were implanted at position B; in Group D, one microelectrode was implanted at position A, B and D respectively; in Group E, one microelectrode was implanted at position A, C and D respectively; in Group F, one microelectrode was implanted at position B, C and D respectively. The minimum stimulating current (threshold current) required for effective mouth closure were recorded. The threshold and peak current values were compared using one-way ANOVA and LSD-t multiple comparisons. Results: The microelectrodes of the AFNP stimulating side in Group E and F failed to induce a smooth mouth closure. The microelectrodes in A, B, C and D group induced smooth mouth closure. The threshold current value of OOM contraction on affected side in the Group A, B, C, and D were (1.35±0.05), (1.02±0.04), (1.40±0.04) and (1.10±0.02) mA, respectively (F=295.302, P<0.001), with the lowest value in Group B and there was significant difference between the current value in Group B and those in the other groups (all P<0.05). The peak current value of OOM contraction on affected side in the four groups were (3.95±0.02), (2.95±0.03), (3.99±0.05) and (3.51±0.01) mA, respectively (F=1 014.985, P<0.001). Group B showed the best lip-closure morphology observed with naked eyes. Conclusions When three output microelectrode of the AFNP stimulated side are separately imbedded into the upper lip, the lower lip and the connection with the corner of the mouth to the ipsilateral tragus, AFNP can sufficiently induce closed-mouth reaction. These positions are suitable as priority options microelectrodes implantation positions for the microelectrodes of the AFNP stimulated side.

To explore the optimal method of microelectrode implantation that can produce efficient mouth closure with microelectrode for orbicularis oris muscle (OOM) in rhesus monkeys with unilateral peripheral facial paralysis (UPFP) in order to provide basis for the research and development of artificial facial nerve prosthesis (AFNP). Methods Right lateral peripheral facial paralysis model on four healthy rhesus monkeys (two males and two femles, aged 5-6 years, weighed 2.0-3.0 kg) were prepared. AFNP electric stimulation was used to induce closed?mouth reaction of the affected OOM with a one?way rectangular pulse, 50 Hz frequency and 0.2 ms pulse width in vitro. Around the affected lateral OOM, four stimulus electrodes implantation positions were selected at the upper lip (position A), the lower lip (position B), the connection with the corner of the mouth to the ipsilateral tragus (position C), and the horizontal line of the mouth angle (position D). According to the different implantation positions of three stimulation electrodes on the stimulation side of AFNP and the results of our previous study, six groups of microelectrode implantation methods were designed. In Group A, two microelectrodes were implanted at position A and one microelectrode was implanted at position B; in Group B, one microelectrode was implanted at position A, B and C respectively; in Group C, one microelectrode was implanted at position A and two microelectrodes were implanted at position B; in Group D, one microelectrode was implanted at position A, B and D respectively; in Group E, one microelectrode was implanted at position A, C and D respectively; in Group F, one microelectrode was implanted at position B, C and D respectively. The minimum stimulating current (threshold current) required for effective mouth closure were recorded. The threshold and peak current values were compared using one?way ANOVA and LSD-t multiple comparisons. Results The microelectrodes of the AFNP stimulating side in Group E and F failed to induce a smooth mouth closure. The microelectrodes in A, B, C and D group induced smooth mouth closure. The threshold current value of OOM contraction on affected side in the Group A, B, C, and D were (1.35±0.05), (1.02±0.04), (1.40±0.04) and (1.10± 0.02) mA, respectively (F=295.302, P<0.001), with the lowest value in Group B and there was significant difference between the current value in Group B and those in the other groups (all P<0.05). The peak current value of OOM contraction on affected side in the four groups were (3.95±0.02), (2.95±0.03), (3.99±0.05) and (3.51 ± 0.01) mA, respectively (F=1 014.985, P<0.001). Group B showed the best lip?closure morphology observed with naked eyes. Conclusions When three output microelectrode of the AFNP stimulated side are separately imbedded into the upper lip, the lower lip and the connection with the corner of the mouth to the ipsilateral tragus, AFNP can sufficiently induce closed?mouth reaction. These positions are suitable as priority options microelectrodes implantation positions for the microelectrodes of the AFNP stimulated side.

Objective? To investigate the feasibility and safety of vacuum modelling pad for patients with lateral position in thoracic surgery to improve the convenience and comfortable experience for medical staff and patients. Methods? From May 2017 to March 2018, 100 patients who underwent thoracic surgery under general anesthesia with lateral position in the operating room of Sun Yat-sen University Cancer Center were randomly selected and divided into observation group(n=50) and control group (n=50) according to random number table. The polyurethane vacuum modelling pad was used for to secure the patients' position in the observation group, while the sand bag baffle was used to secure the patient's position in the control group. Position placement time and skin pressure blisters were recorded in both groups. Questionnaires were sent out after operation to collect the satisfaction of medical staff with this position. The patients' comfort was followed up within 24 hours after operation. Results? The position placement time in the observation group was (183.56±10.36) s, shorter than the control group with (290.80±14.71)s and the difference was statistically significant(P＜ 0.01); there were 11 cases of skin reddening under pressure and 2 cases of blister in the observation group, which is statistically different from the control group with 24 cases of skin reddening under pressure and 9 cases of blister(P＜ 0.05). Patients' comfort score was(6.72±0.39) in the observation group, higher than the control group with (6.02±0.44) and the difference was statistically significant(P＜ 0.01). In terms of the 4 items of "the convenient operation", "comfortable standing position", "patient safety" and"overall evaluation", the observation group scored higher than the control group with statistical differences (P＜0.01); in terms of the "surgical field exposure" and "fasten effects", there was no statistical difference (P＞0.05). Conclusions? The use of modelling pad for patient lateral position in thoracic surgery can not only prevent organ and skin damage and ensure patient safety, but also simplify the operation procedure, improve the comfort of standing position and the working efficiency and satisfaction of the medical staff.