Objective:To investigate the effect of PD-1/PD-L1 inhibitor BMS-1 on LPS-induced inflammation in mouse microg-lia cells(BV-2 cells).Methods:Bv-2 cells were divided into Control group,LPS group and LPS+BMS-1 group.Bv-2 cells in Control group were cultured in DMEM medium for 78 hours,cells in LPS group were stimulated with 100 ng/ml LPS for 6 hours after 72 hours of normal culture,Bv-2 cells in LPS+BMS-1 group were treated with 50 nmol/ml BMS-1 for 72 hours and then stimulated with 100 ng/ml LPS for 6 hours.Expressions of PD-1 and iNOS mRNA in each group were detected by RT-qPCR,and expressions of PD-1 and iNOS protein in microglia were detected by Western blot.Flow cytometry was used to detect cell apoptosis in each group.Levels of inflamma-tory cytokines IL-1β,IL-6,TNF-α and IL-10 were detected by ELISA.Results:RT-qPCR and Western blot results showed that com-pared with Control group,LPS group had significantly increased expression of PD-1 and iNOS(P<0.05).Compared with LPS group,LPS+BMS-1 group had significantly decreased expression of PD-1(P<0.05)and significantly increased expression of iNOS(P<0.05).Flow cytometry showed that compared with Control group,LPS group had a significantly increased in apoptosis of microglia(P<0.000 1).Compared with LPS group,LPS+BMS-1 group had a significantly increased in apoptosis of microglia(P<0.000 1).ELISA results showed that compared with Control group,LPS group had no significantly increased in pro-inflammatory factors IL-1β and IL-6(P>0.05),while significantly increased in TNF-α(P<0.000 1)and anti-inflammatory factor IL-10(P<0.000 1).Pro-inflammatory cyto-kine IL-1β in LPS+BMS-1 group was significantly higher than that in LPS group(P=0.000 1),IL-6 and TNF-α were also significantly higher than those in LPS group(P<0.000 1),while anti-inflammatory cytokine IL-10 in LPS+BMS-1 group was significantly lower than that in LPS group(P<0.000 1).Conclusion:BMS-1 can promote LPS-induced inflammatory response or impede the recovery of inflammation,and increase apoptosis of microglia.PD-1/PD-L1 pathway may be a potential therapeutic target for neuroinflammation.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To investigate the effect of PD-1/PD-L1 inhibitor BMS-1 on LPS-induced inflammation in mouse microg-lia cells(BV-2 cells).Methods:Bv-2 cells were divided into Control group,LPS group and LPS+BMS-1 group.Bv-2 cells in Control group were cultured in DMEM medium for 78 hours,cells in LPS group were stimulated with 100 ng/ml LPS for 6 hours after 72 hours of normal culture,Bv-2 cells in LPS+BMS-1 group were treated with 50 nmol/ml BMS-1 for 72 hours and then stimulated with 100 ng/ml LPS for 6 hours.Expressions of PD-1 and iNOS mRNA in each group were detected by RT-qPCR,and expressions of PD-1 and iNOS protein in microglia were detected by Western blot.Flow cytometry was used to detect cell apoptosis in each group.Levels of inflamma-tory cytokines IL-1β,IL-6,TNF-α and IL-10 were detected by ELISA.Results:RT-qPCR and Western blot results showed that com-pared with Control group,LPS group had significantly increased expression of PD-1 and iNOS(P<0.05).Compared with LPS group,LPS+BMS-1 group had significantly decreased expression of PD-1(P<0.05)and significantly increased expression of iNOS(P<0.05).Flow cytometry showed that compared with Control group,LPS group had a significantly increased in apoptosis of microglia(P<0.000 1).Compared with LPS group,LPS+BMS-1 group had a significantly increased in apoptosis of microglia(P<0.000 1).ELISA results showed that compared with Control group,LPS group had no significantly increased in pro-inflammatory factors IL-1β and IL-6(P>0.05),while significantly increased in TNF-α(P<0.000 1)and anti-inflammatory factor IL-10(P<0.000 1).Pro-inflammatory cyto-kine IL-1β in LPS+BMS-1 group was significantly higher than that in LPS group(P=0.000 1),IL-6 and TNF-α were also significantly higher than those in LPS group(P<0.000 1),while anti-inflammatory cytokine IL-10 in LPS+BMS-1 group was significantly lower than that in LPS group(P<0.000 1).Conclusion:BMS-1 can promote LPS-induced inflammatory response or impede the recovery of inflammation,and increase apoptosis of microglia.PD-1/PD-L1 pathway may be a potential therapeutic target for neuroinflammation.

Objective:To analyze the level and influencing factors of nurses′ proactive career behavior, problem-solving coping strategies and organizational identification, and to explore the relationship among them.Methods:This was a cross-sectional survey. A total of 536 nurses from Cangzhou Central Hospital, Luanzhou People′s Hospital, the Second Affiliated Hospital of Xingtai Medical College, People′s Hospital of Qiu County, Hebei Province in November 2023 were selected by convenience sampling method and investigated by general data questionnaire, Proactive Career Behavior Scale, Career Coping Strategies Scale and Organizational Identification Scale. The mediation effect was analyzed by AMOS 24.0 structural equation model.Results:Finally, 495 valid questionnaires were collected. There were 432 females and 63 males, 170 cases aged<31 years old, 256 cases aged 31-40 years old, and 69 cases aged>40 years old. The score of nurses′ proactive career behavior was (51.28 ± 9.86) points, problem-solving coping strategies was (16.25 ± 2.81) points, and organizational identification was (19.00 ± 4.84) points. The results of single factor analysis showed that nurses′ proactive career behavior was affected by age, title, department and salary satisfaction( F values were 2.20-24.44, all P<0.05), problem-solving coping strategies was affected by title, department and salary satisfaction ( F=5.72, 2.75, 21.30, all P<0.01), organizational identification was affected by salary satisfaction ( F=23.22, P<0.01). Problem-solving coping strategies, organizational identification were positively associated with proactive career behavior( r=0.786, 0.722, both P<0.01). Problem-solving coping strategies had a partial mediating effect between organizational identification and proactive career behavior( β=0.432, P<0.01), and the mediating effect accounted for 64.48% of the total effect. Conclusions:There is still room for improvement of nurses′ proactive career behavior, problem-solving strategies, and organizational identification. Nursing managers should pay attention to nurses′ job advantage of different age, title and department, and improve salary satisfaction to stimulate their work potential, and improve their organizational identification, guide them to adopt problem-solving strategies in coping with occupational stress, so as to promote the development of proactive career behavior.

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

Severe asthma is "asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled’ or which remains 'uncontrolled’ despite this therapy." The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. This phenotype has been associated with a Type-2 (T2) inflammatory profile with expression of interleukin (IL)-4, IL-5, and IL-13. Molecular phenotyping has also revealed non-T2 inflammatory phenotypes such as Type-1 or Type-17 driven phenotypes. Antibody treatments targeted at the T2 targets such as anti-IL5, anti-IL5Rα, and anti-IL4Rα antibodies are now available for treating severe eosinophilic asthma, in addition to anti-immunoglobulin E antibody for severe allergic asthma. No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.

AIM: To investigate the effect of telmisartan on intestinal flora and metabolite TMAO in atherosclerosis. METHODS: Seventeen ApoE

Objective To investigate the selective targeting ability of a novel folate-modified nanobubbles with two-fold amount of folate [(FOL)2-NBs] . Methods DSPE-PEG2000-AD-(FOL)2with two-fold of folate per DSPE-PEG2000 chain was synthesized and then tested by 1 H nuclear magnetic resonance (1H NMR) . The novel (FOL)2-NBs was prepared using the mechanical shaking method based on lipid-stabilized perfluoropropane . The bubble size was measured by Malvern laser particle size analyzer and the contrast enhancement ability was also detected with imaging machine using a self-made agarose mold . The experiment of selective targeting ability was also carried out in human breast cancer MCF-7 cell with over-expression of folate receptor ( FR) using fluorescence activated cell sorting ( FACS) . Results The result of 1H NMR proved that DSPE-PEG2000-AD-( FOL )2was successfully synthesized ,and the purity reached up to 90% . The novel prepared ( FOL) 2-NBs showed superior contrast enhancement ability with a particle size of ( 286 .87 ± 22 .96) nm . Compared with the conventional NBs ,the novel ( FOL) 2-NBs exhibited improved selective cellular targeting ability proven by FACS . Conclusions A novel nanobubble with improved selective targeting ability is successfully prepared and shows great potential in extravascular imaging and curation in FR overexpressed tumors .

Refined-JQ (JQ-R) is a mixture of refined extracts from(Ranunculaceae),(Leguminosae) and(Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKmice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKmice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-B p65), inhibitor of NF-B (IB), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKmice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.