OBJECTIVE: To observe the expression level of cytokines in patients with sepsis and its effect on prognosis. METHODS: The clinical data of sepsis patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were analyzed retrospectively, including gender, age, and acute physiology and chronic health evaluation II (APACHE II), blood routine, procalcitonin (PCT), C-reactive protein (CRP), and cytokines levels [interleukins (IL-2, IL-4, IL-6, IL-10, IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)] within 24 hours of admission to ICU. The 28-day prognosis of the patients was followed up. The patients were divided into survival group and death group according to the prognosis. The clinical data between the two groups of sepsis patients with different prognosis were compared. Binary Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of patients with sepsis, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each risk factor for the prognosis of patients with sepsis. RESULTS: (1) A total of 227 patients with sepsis were enrolled, including 168 patients in the survival group (survival rate 74.0%) and 59 patients in the death group (mortality 26.0%). There were no significant differences in age (years old: 55.97±2.13 vs. 54.67±1.11) and gender (male: 71.2% vs. 57.1%) between the death group and the survival group (both P > 0.05), indicating that the baseline data of the two groups were comparable. (2) The APACHE II (19.37±0.99 vs. 14.88±0.61, P < 0.001) and PCT (μg/L: 12.39±2.94 vs. 4.14±0.90, P < 0.001) in the death group were significantly higher than those in the survival group, while the platelet count [PLT (×10⁹/L): 144.75±12.50 vs. 215.99±11.26, P = 0.001] and thrombocytocrit [(0.14±0.01)% vs. (0.19±0.01)%, P = 0.001] were significantly lower than those in the survival group. (3) The level of IL-6 in the death group was significantly higher than that in the survival group (ng/L: 577.66±143.16 vs. 99.74±33.84, P < 0.001). There were no statistically significant differences in other cytokines, IL-2, IL-4, IL-10, TNF-α, IFN-γ and IL-17 between the death group and the survival group [IL-2 (ng/L): 2.44±0.38 vs. 2.63±0.27, P = 0.708; IL-4 (ng/L): 3.26±0.67 vs. 3.18±0.34, P = 0.913; IL-10 (ng/L): 33.22±5.13 vs. 39.43±2.85, P = 0.262; TNF-α (ng/L): 59.33±19.21 vs. 48.79±29.87, P = 0.839; IFN-γ (ng/L): 6.69±5.18 vs. 1.81±0.16, P = 0.100; IL-17 (ng/L): 2.05±0.29 vs. 2.58±0.33, P = 0.369]. (4) Binary Logistic regression analysis showed that APACHE II and IL-6 were independent risk factors affecting the prognosis of patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.050 (1.008-1.093) and 1.001 (1.000-1.002), P values were 0.019 and 0.026, respectively]. (5) ROC curve analysis showed that APACHE II and IL-6 had certain predictive value for the prognosis of patients with sepsis, the area under the ROC curve (AUC) was 0.754 (95%CI was 0.681-0.827) and 0.592 (95%CI was 0.511-0.673), P values were < 0.001 and 0.035, respectively. When the optimal cut-off value of APACHE II was 16.50 score, the sensitivity was 72.6% and the specificity was 69.9%. When the optimal cut-off value of IL-6 was 27.87 ng/L, the sensitivity was 67.2% and the specificity was 52.8%. CONCLUSIONS APACHE II score and IL-6 level have certain predictive value for the prognosis of patients with sepsis, the higher APACHE II score and IL-6 level, the greater the probability of death in patients with sepsis.
Humans ; Male ; Interleukin-10 ; Interleukin-17 ; Cytokines ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Retrospective Studies ; Interleukin-2 ; Interleukin-4 ; ROC Curve ; Sepsis/diagnosis* ; Prognosis ; Procalcitonin ; Interferon-gamma ; Intensive Care Units

OBJECTIVE: To explore the characteristics of changes in peripheral blood lymphocyte subsets in patients with sepsis in intensive care unit (ICU) and analyze their predictive value for prognosis. METHODS: The clinical data of sepsis patients admitted to the surgical intensive care unit (SICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were analyzed retrospectively. The patients met the diagnostic criteria of Sepsis-3 and were ≥ 18 years old. Peripheral venous blood samples were collected from all patients on the next morning after admission to SICU for routine blood test and peripheral blood lymphocyte subsets. According to the 28-day survival, the patients were divided into two groups, and the differences in immune indexes between the two groups were compared. Logistic regression analysis was used to analyze the risk factors of immune indexes that affect prognosis. RESULTS: (1) A total of 279 patients with sepsis were enrolled in the experiment, of which 198 patients survived at 28 days (28-day survival rate 71.0%), and 81 patients died (28-day mortality 29.0%). There were no significant differences in age (years old: 57.81±1.71 vs. 54.99±1.05) and gender (male: 60.5% vs. 63.6%) between the death group and the survival group (both P > 0.05), and the baseline data was comparable.(2) Acute physiology and chronic health evalution II (APACHE II: 22.06±0.08 vs. 14.08±0.52, P < 0.001), neutrophil percentage [NEU%: (88.90±1.09)% vs. (84.12±0.77)%, P = 0.001], procalcitonin [PCT (μg/L): 11.97±2.73 vs. 5.76±1.08, P = 0.011], platelet distribution width (fL: 16.81±0.10 vs. 16.57±0.06, P = 0.029) were higher than those in the survival group, while lymphocyte percentage [LYM%: (6.98±0.78)% vs. (10.59±0.86)%, P = 0.012], lymphocyte count [LYM (×10⁹/L): 0.70±0.06 vs. 0.98±0.49, P = 0.002], and platelet count [PLT (×10⁹/L): 151.38±13.96 vs. 205.80±9.38, P = 0.002], and thrombocytocrit [(0.15±0.01)% vs. (0.19±0.07)%, P = 0.012] were lower than those in the survival group. (3) There was no statistically significant difference in the percentage of lymphocyte subsets between the death group and the survival group, but the absolute value of LYM (pieces/μL: 650.24±84.67 vs. 876.64±38.02, P = 0.005), CD3⁺ absolute value (pieces/μL: 445.30±57.33 vs. 606.84±29.25, P = 0.006), CD3⁺CD4⁺ absolute value (pieces/μL: 239.97±26.96 vs. 353.49±18.59, P = 0.001), CD19⁺ absolute value (pieces/μL: 111.10±18.66 vs. 150.30±10.15, P = 0.049) in the death group was lower than those in the survival group. Other lymphocyte subsets in the death group, such as CD3⁺CD8⁺ absolute value (pieces/μL: 172.40±24.34 vs. 211.22±11.95, P = 0.112), absolute value of natural killer cell [NK (pieces/μL): 101.26±18.15 vs. 114.72±7.64, P = 0.420], absolute value of natural killer T cell [NKT (pieces/μL): 33.22±5.13 vs. 39.43±2.85, P = 0.262], CD4^-CD8^- absolute value (pieces/μL: 41.07±11.07 vs. 48.84±3.31, P = 0.510), CD4⁺CD8⁺ absolute value (pieces/μL: 3.39±1.45 vs. 3.47±0.36, P = 0.943) were not significantly different from those in the survival group. (4)Logistic regression analysis showed that lymphocyte subsets were not selected as immune markers with statistical significance for the prognosis of sepsis. CONCLUSIONS The changes of immune indexes in sepsis patients are closely related to their prognosis. Early monitoring of the above indexes can accurately evaluate the condition and prognosis of sepsis patients.
Humans ; Male ; Adolescent ; Retrospective Studies ; ROC Curve ; Sepsis/diagnosis* ; Lymphocyte Count ; Lymphocyte Subsets ; Prognosis ; Killer Cells, Natural

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

OBJECTIVE: To investigate the effect of liver X receptor(LXR)-adenosine triphosphate-binding cassette transporter A1(ABCA1) signaling pathway on the free silica(SiO_2)-induced foaming of macrophages. METHODS: Human histiocytic lymphoma U937 cells were induced to differentiate into macrophages by phorbol myristate acetate. The macrophages at logarithmic growth phase were randomly divided into 4 groups: the cells in the control group received no treatment, the cells in the SiO_2 stimulation group were stimulated with SiO_2 suspension at a dose of 50 mg/L, and the cells in the oxidized low-density lipoprotein(ox-LDL) group were treated with ox-LDL at the dosed 50 mg/L, the cells in the combination group were simultaneously stimulated with SiO_2 suspension and ox-LDL at a dose of 50 mg/L. Cells were collected after 48 hours of culture. Macrophage foaming was observed by oil red O staining. The levels of total cholesterol(TC), free cholesterol(FC), cholesteryl ester(CE) and CE specific gravity(CE%) in macrophages were detected using a microplate reader. The expression of LXR and ABCA1 was detected using Western blotting. RESULTS: The results of the oil red O staining showed that all the macrophages in the SiO_2 stimulation group, ox-LDL group and the combination group had foaming changes. The degree of foaming in the macrophages in the combination group was higher than that in the other two groups. The levels of TC, FC, CE and CE% in macrophages increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), in SiO_2 stimulation group, ox-LDL group and combination group compared with the control group. The macrophages in the combination group were transformed into foam cells. The levels of TC, FC, CE and CE% in macrophages of the combination group increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), compared with the SiO_2 stimulation group and the ox-LDL group. CONCLUSION:sFree SiO_2 can induce foaming of macrophages, and ox-LDL in combination with SiO_2 has a synergistic effect on the formation of foaming of macrophages.The process of macrophage foaming may be achieved by inhibiting the LXR-ABCA1 signaling pathway.

OBJECTIVE: To investigate the preventive effect of rock salt aerosol on the development of silicosis in rats. METHODS: The specific pathogen free adult male SD rats were randomly divided into normal control group, rock salt control group, silicosis model group and rock salt intervention group, 18 rats in each group. Rats in the silicosis model group and the salt rock intervention group were treated with silica dust at the concentration of 2 000.0 mg/m~3 by dynamic dusting method for 3 hours daily. Rats in the rock salt control group and the rock salt intervention group inhaled the rock salt aerosols with the mass concentration of 20.0 mg/m~3 for 30 minutes daily. The normal control group was not treated with the dust or rock salt aerosol. At the time points of 14, 28 and 56 days after exposure to dust or rock salt aerosol, 6 rats were randomly selected from each group and samples were collected. The pathological change of lung was observed, the total cell count in the bronchoalveolar lavage fluid(BALF) was performed, the enzyme-linked immunosorbent assay was used to detect the change of transforming growth factor-β(TGF-β) in BALF, surfactant D(SP-D) and superoxide dismutase(SOD) in lung tissue. RESULTS: The results of hematoxylin-eosin and Masson staining showed that the inflammatory changes of lung tissue and the pulmonary interstitial fibrosis in the rock salt intervention group were less severer than that in the silicosis model group. At 14, 28, and 56 days after dust exposure, the total cell counts in BALF and SP-D levels in lung tissue of rats in silicosis model group and rock salt intervention group were higher(P<0.05), the SOD activities in lung tissue were lower(P<0.05), as well as the TGF-β levels in BALF in silicosis model group were higher(P<0.05),compared with the normal control group and rock salt control group. The total cell counts and TGF-β levels in BALF, and SP-D levels in lung tissue of rock salt intervention group were lower(P<0.05), the SOD activities in lung tissue were higher(P<0.05), compared with the silicosis model group. CONCLUSION: Rock salt aerosol intervention may delay the pathogenesis of silicosis by improving the inflammatory response, regulating oxidative stress and reducing interstitial fibrosis of lungs.

Objective:To explore benefit finding in patients receiving combined heart-lung transplantation (CHLT) , and provide a reference for improving clinical nursing work.Methods:From September to October 2019, totally 6 patients who survived after CHLT in the Department of Cardiac Surgery at the First Affiliated Hospital of Guangzhou Medical University were selected by purposive sampling for semi-structured interviews in terms of their benefit finding using phenomenological methods. Colaizzi's seven-step analysis was used to organize and analyze the interview results.Results:The patients undergoing CHLT showed a sense of benefit finding, which could be summarized into four themes, namely, changes in mental quality (learning to be grateful and contented, understanding the meaning of life, learning to be open-minded and optimistic) , improved learning initiative (actively learning drug-related knowledge, the knowledge of rehabilitation and exercise, the knowledge of diet and nutrition, and the knowledge of prevention of complications) , perceiving social support (family members changed life habits, family members actively learned disease knowledge, improved communication between patients and family members and friends) , and actively planning future life.Conclusions:The patients receiving CHLT can experience a sense of benefit finding in the rehabilitation after organ transplantation. Medical staff should understand the sense of benefit finding in patients receiving CHLT, promote the early generation of benefiting finding, and provide targeted guidance to patients.

To explore the relationship between plasma amyloid?β (Aβ) and cognitive decline during 2 year follow?up in a population?based cohort in Xi′an rural areas. Methods The study was conducted in Qubao village in Xi′an suburbs cognitively normal residents over 40 years old were recruited from October 2014 to March 2015 and given a face?to?face standardized interview. Mini?mental state examination (MMSE) was employed to evaluate the global cognitive function, and quantification of plasma Aβ was measured by sandwich enzyme?linked immunosorbent assay (ELISA) at baseline. Two years later, MMSE was tested at the end of study. Then logistic regression was performed to analyze the relationship between baseline Aβ and cognitive change during 2 year follow?up. Results A total of 1 020 participants completed the study, among whom 223 subjects (21.9%) presented MMSE scores decline (defined as MMSE scores decreased≥2 points). Compared with those without decline, participants in the MMSE decline group were older (P<0.001) and had lower education level (P<0.001), while gender, hypertension, hyperlipemia, diabetes mellitus and APOE genotype were not significantly different between two groups. One?way analysis of variance (ANOVA) showed that the MMSE score decline was slighter in the lower tertile of baseline Aβ1?40 compared with middle tertile (P=0.012), while MMSE decline were similar between different A β 1?42 level groups and A β 1?42/A β 1?40 ratio groups (P=0.758, P=0.671, respectively). Multivariable logistic regression analysis showed that MMSE scores in the lower baseline plasma A β 1?40 level declined more slowly (OR=0.565, 95%CI 0.379-0.845, P=0.005). However, the MMSE decline were also similar among different baseline plasma Aβ1?42 levels groups and Aβ1?42/Aβ1?40 ratio groups. Conclusion Population with lower level of baseline plasma Aβ1?40 manifests lower cognitive decline during 2 years, however further investigation on dynamics of plasma Aβ and long term follow up are needed.

Objective: To explore the relationship between plasma amyloid-β (Aβ) and cognitive decline during 2 year follow-up in a population-based cohort in Xi′an rural areas. Methods: The study was conducted in Qubao village in Xi′an suburbs cognitively normal residents over 40 years old were recruited from October 2014 to March 2015 and given a face-to-face standardized interview. Mini-mental state examination (MMSE) was employed to evaluate the global cognitive function, and quantification of plasma Aβ was measured by sandwich enzyme-linked immunosorbent assay (ELISA) at baseline. Two years later, MMSE was tested at the end of study. Then logistic regression was performed to analyze the relationship between baseline Aβ and cognitive change during 2 year follow-up. Results: A total of 1 020 participants completed the study, among whom 223 subjects (21.9%) presented MMSE scores decline (defined as MMSE scores decreased ≥2 points). Compared with those without decline, participants in the MMSE decline group were older (P<0.001) and had lower education level (P<0.001), while gender, hypertension, hyperlipemia, diabetes mellitus and APOE genotype were not significantly different between two groups. One-way analysis of variance (ANOVA) showed that the MMSE score decline was slighter in the lower tertile of baseline Aβ₁-40 compared with middle tertile (P=0.012), while MMSE decline were similar between different Aβ₁-42 level groups and Aβ_1-42/Aβ_1-40 ratio groups (P=0.758, P=0.671, respectively). Multivariable logistic regression analysis showed that MMSE scores in the lower baseline plasma Aβ_1-40 level declined more slowly (OR=0.565, 95%CI 0.379-0.845, P=0.005). However, the MMSE decline were also similar among different baseline plasma Aβ_1-42 levels groups and Aβ_1-42/Aβ_1-40 ratio groups. Conclusion Population with lower level of baseline plasma Aβ_1-40 manifests lower cognitive decline during 2 years, however further investigation on dynamics of plasma Aβ and long term follow up are needed.