BACKGROUND:Multiple studies and observations have indicated a close relationship between inflammation,metabolites,and osteoporosis.However,it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process.OBJECTIVE:To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process.METHODS:Summary data from genome-wide association studies(GWAS)were used,with osteoporosis data sourced from the Fengenn database,and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies.The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships.Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis,and two-step Mendelian randomization was used to discover potential mediating metabolites.Sensitivity analyses were then performed to further validate the robustness of the results.Cochran's Q test was used to assess heterogeneity,and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.RESULTS AND CONCLUSION:The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship.Artemin(odds ratio[OR]=0.895,95%confidence interval[CI]:0.819-0.979,P=0.015)was negatively associated with osteoporosis,whereas chemokine(C-X-C Motif)ligand 1(OR=1.100,95%CI:1.002-1.209,P=0.046),chemokine(C-X-C Motif)ligand 11(OR=1.150,95%CI:1.043-1.268,P=0.005),interleukin 17C(OR=1.087,95%CI:1.004-1.176,P=0.040),and tumor necrosis factor-like weak inducer of apoptosis(OR=1.108,95%CI:1.002-1.226,P=0.046)were positively associated with osteoporosis.Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects.Subsequently,we conducted a two-step Mendelian randomization to discover potential mediating metabolites.This study showed that 1-palmitoyl-gpc(16:0)increased the negative effect of Artemin on osteoporosis.5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 1 and chemokine(C-X-C Motif)ligand 11.The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11 and interleukin-17C.Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11.12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C.The sulfate level of piperine metabolite C16H19NO3(3)and adenosine 3',5'-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis.In conclusion,the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis,both positively and negatively,and some of these effects are mediated by plasma metabolites.This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis.

Under the background of breaking the " five only" evaluation criteria, continuously optimizing the scientific research performance evaluation system of hospitals to mobilize the enthusiasm and creativity of scientific researchers and guide the direction of scientific research development plays an important role in enhancing the overall scientific research capability of hospitals. Through literature analysis and expert consultation, a certain hospital has constructed a personal scientific research performance evaluation index system for medical staff in tertiary public hospitals, oriented towards innovation quality and member contributions, and began to implement it throughout the hospital in 2021. This index system included four categories of scientific research performance: vertical scientific research projects, academic influence, science and technology awards, and transformation of achievements, with a total of 20 indicators. The annual scientific research performance score of an individual would serve as the basis for the distribution of year-end scientific research performance and an important reference for applying for key and major projects within the hospital. After the application of this evaluation index system, the enthusiasm of medical staff for scientific research has been effectively stimulated. The average individual scientific research performance score increased from 0.974 in 2020 to 1.220 in 2023. All scientific research indicators involved in the evaluation system have shown growth, with a significant increase in high-quality results. This evaluation system can provide a reference for the scientific research performance evaluation of public hospitals under the background of breaking the " five only" evaluation criteria.

BACKGROUND:Multiple studies and observations have indicated a close relationship between inflammation,metabolites,and osteoporosis.However,it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process.OBJECTIVE:To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process.METHODS:Summary data from genome-wide association studies(GWAS)were used,with osteoporosis data sourced from the Fengenn database,and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies.The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships.Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis,and two-step Mendelian randomization was used to discover potential mediating metabolites.Sensitivity analyses were then performed to further validate the robustness of the results.Cochran's Q test was used to assess heterogeneity,and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.RESULTS AND CONCLUSION:The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship.Artemin(odds ratio[OR]=0.895,95%confidence interval[CI]:0.819-0.979,P=0.015)was negatively associated with osteoporosis,whereas chemokine(C-X-C Motif)ligand 1(OR=1.100,95%CI:1.002-1.209,P=0.046),chemokine(C-X-C Motif)ligand 11(OR=1.150,95%CI:1.043-1.268,P=0.005),interleukin 17C(OR=1.087,95%CI:1.004-1.176,P=0.040),and tumor necrosis factor-like weak inducer of apoptosis(OR=1.108,95%CI:1.002-1.226,P=0.046)were positively associated with osteoporosis.Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects.Subsequently,we conducted a two-step Mendelian randomization to discover potential mediating metabolites.This study showed that 1-palmitoyl-gpc(16:0)increased the negative effect of Artemin on osteoporosis.5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 1 and chemokine(C-X-C Motif)ligand 11.The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11 and interleukin-17C.Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11.12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C.The sulfate level of piperine metabolite C16H19NO3(3)and adenosine 3',5'-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis.In conclusion,the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis,both positively and negatively,and some of these effects are mediated by plasma metabolites.This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis.

Under the background of breaking the " five only" evaluation criteria, continuously optimizing the scientific research performance evaluation system of hospitals to mobilize the enthusiasm and creativity of scientific researchers and guide the direction of scientific research development plays an important role in enhancing the overall scientific research capability of hospitals. Through literature analysis and expert consultation, a certain hospital has constructed a personal scientific research performance evaluation index system for medical staff in tertiary public hospitals, oriented towards innovation quality and member contributions, and began to implement it throughout the hospital in 2021. This index system included four categories of scientific research performance: vertical scientific research projects, academic influence, science and technology awards, and transformation of achievements, with a total of 20 indicators. The annual scientific research performance score of an individual would serve as the basis for the distribution of year-end scientific research performance and an important reference for applying for key and major projects within the hospital. After the application of this evaluation index system, the enthusiasm of medical staff for scientific research has been effectively stimulated. The average individual scientific research performance score increased from 0.974 in 2020 to 1.220 in 2023. All scientific research indicators involved in the evaluation system have shown growth, with a significant increase in high-quality results. This evaluation system can provide a reference for the scientific research performance evaluation of public hospitals under the background of breaking the " five only" evaluation criteria.

Objective:To analyze the effect of chlorpyrifos on the expression of autophagy related proteins in rat hippocampal neurons, and to explore the role of autophagy in central nerve injury caused by acute chlorpyrifos poisoning.Methods:In October 2018, 35 male clean grade SD rats were randomly divided into 7 groups according to the observation time point, namely 0.5 d, 1 d, 2 d, 3 d, 5 d and 7 d groups and the control group, with 5 rats in each group. Each observation group was given 81.5 mg/kg chlorpyrifos by gavage, and the control group was given olive oil by gavage. The general conditions and poisoning symptoms of rats were observed continuously after exposure. The expressions of autophagy related proteins Beclin1, P62/SQSTM1 and LC3 in hippocampus were detected by Western blot. The cell morphology and LC3 expression in brain were observed by immunohistochemical staining.Results:Western blot results showed that compared with the control group, the expression of Beclin1 protein in hippocampal neurons of rats in the 1 d, 2 d, and 3 d groups increased, while the expression of P62/SQSTM1 protein in the 0.5 d, 1 d, and 2 d groups decreased, and the expression of LC3 protein was decreased in the 2 d group, and the differences were statistically significant ( P<0.05) . The results of immunohistochemistry showed that the hippocampal neurons of rats in the 5 d group were arranged disorderly, and some nuclei contours disappeared, especially in the 7 d group. The LC3 protein was expressed in the cytoplasm, and the expression level gradually increased, reaching a peak on the second day. Conclusion:The early activation of autophagy in rats with acute chlorpyrifos poisoning may be involved in chlorpyrifos induced hippocampal neuronal injury.

Objective:To analyze the effect of chlorpyrifos on the expression of autophagy related proteins in rat hippocampal neurons, and to explore the role of autophagy in central nerve injury caused by acute chlorpyrifos poisoning.Methods:In October 2018, 35 male clean grade SD rats were randomly divided into 7 groups according to the observation time point, namely 0.5 d, 1 d, 2 d, 3 d, 5 d and 7 d groups and the control group, with 5 rats in each group. Each observation group was given 81.5 mg/kg chlorpyrifos by gavage, and the control group was given olive oil by gavage. The general conditions and poisoning symptoms of rats were observed continuously after exposure. The expressions of autophagy related proteins Beclin1, P62/SQSTM1 and LC3 in hippocampus were detected by Western blot. The cell morphology and LC3 expression in brain were observed by immunohistochemical staining.Results:Western blot results showed that compared with the control group, the expression of Beclin1 protein in hippocampal neurons of rats in the 1 d, 2 d, and 3 d groups increased, while the expression of P62/SQSTM1 protein in the 0.5 d, 1 d, and 2 d groups decreased, and the expression of LC3 protein was decreased in the 2 d group, and the differences were statistically significant ( P<0.05) . The results of immunohistochemistry showed that the hippocampal neurons of rats in the 5 d group were arranged disorderly, and some nuclei contours disappeared, especially in the 7 d group. The LC3 protein was expressed in the cytoplasm, and the expression level gradually increased, reaching a peak on the second day. Conclusion:The early activation of autophagy in rats with acute chlorpyrifos poisoning may be involved in chlorpyrifos induced hippocampal neuronal injury.

Objective:To investigate the relationship between serum retinol binding protein (RBP), stromal cell derived factor-1 (SDF-1) and renal function in patients with diabetic nephropathy (DKD).Methods:The patients with type 2 diabetes mellitus (T2DM) admitted to Yantai Affiliated Hospital of Binzhou Medical College from October 2017 to October 2020 were prospectively selected, 438 patients were divided into simple T2DM group ( n=276)and DKD group( n=162) according to the presence or absence of DKD, according to the ratio of urinary albinin/creatinine (UACR) were divided into normal( n=25), microalbuminuria ( n=75) and macroalbuminuria group ( n=62), according to the estimated glomerular filtration rate (eGFR) were divided into G1 stage ( n=28), G2 stage ( n=27), G3A + G3B stage ( n=35), G4 stage ( n=39)and G5 stages( n=33). The relationship between RBP, SDF-1 and renal function index UACR, serum uric acid (UA), blood urea nitrogen (BUN), β 2-microglobulin (β 2-MG) and serum creatinine (Scr) was analyzed. Measurement data of normal distribution were expressed as Mean± standard deviation ( Mean± SD). Independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups.Chi-square test was used to compare the enumeration data between groups. Receiver operating characteristic curve (ROC) was used to analyze the discriminant value of RBP and SDF-1 for DKD. Pearson was used for correlation analysis among indicators. Multivariate linear regression analysis was used to analyze the influencing factors of RBP. Results:In the DKD group, the duration of diabetes was longer, the levels of RBP, UACR, UA, BUN, β 2-MG, Scr were high, SDF-1 and eGFR were lower, with statistically significant differences compared with the simple T2DM group( P<0.05).The areas under the curve of RBP and SDF-1 to distinguish DKD were 0.903 and 0.868, and the optimal cut-off values was 70.71 mg/L and 5.69 ng/mL. With the increase of urinary albumin and clinical stage, the levels of RBP, UACR, UA, BUN, β 2-MG, Scr increased gradually, while SDF-1 and eGFR decreased gradually, and the differences were statistically significant ( P<0.05).RBP was positively correlated with UACR, UA, BUN, β 2-MG and Scr in DKD patients ( r=0.764, 0.787, 0.693, 0.577, 0.801, P<0.000 1), and negatively correlated with EGFR ( r=-0.782, P<0.000 1). SDF-1 was negatively correlated with UACR, UA, BUN, β 2-MG and Scr ( r=-0.744, -0.794, -0.666, -0.605, -0.820, P<0.000 1), and positively correlated with EGFR ( r=0.767, P<0.000 1). The multiple linear regression equation was RBP=29.852+ 0.007UACR+ 0.101UA+ 0.497BUN+ 0.034Scr-0.083eGFR ( P<0.001). Conclusion:RBP and SDF-1 have certain discriminant value for DKD patients in T2DM population, and the degree of DKD renal function injury is positively correlated with RBP and negatively correlated with SDF-1, the increase of UACR, UA, BUN, Scr and the decrease of eGFR are risk factors for the increase of RBP.

Objective: To establish the Wistar rat model of acute diquat poisoning and observe the pathological damage of main target organs. Methods: Thirty-six Wistar rats were randomly divided into six groups (n=6) , including one normal saline control group and five treatment groups which were separately given single-dose of intragastric administration at the doses of 46.2 mg/kg, 77.0 mg/kg, 115.5 mg/kg, 231.0 mg/kg and 346.5 mg/kg. The pathological changes of lung, liver and kidney were observed by hematoxylin and eosin (HE) and Masson staining. The optimal dose was determined according to the general situation and pathological changes. Thirty-six Wistar rats were randomly divided into five treatment groups and one normal saline control group. Treatment groups were given single-dose of intragastric administration according to the optimal dose. The rats were sacrificed at 1st, 3rd, 7th, 11th and 14th day after exposed, respectively. The activity of serum glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) were measured by chemical colorimetry. The pathological changes of lung, liver and kidney were observed by HE and Masson staining. Results: According to 14 d survival rate, the toxic symptoms and pathological changes, 115.50 mg/kg was determined the best dose. Given single-dose of intragastric administration at the doses of 115.50 mg/kg, it was found that the serum AST and ALT activity of rats on the first and third day of exposure was significant higher than those in control group. The results of pathological examination exhibited that in 115.50 mg/kg group, the pathological changes of lung, liver and kidney began to appear on the first day of exposure, the pathological changes were the most serious on the third day, and then gradually alleviated. On the 14th day, the alveolar septum was slightly widened, with inflammatory cell infiltration, local alveolar cavity became narrow, atrophy, peripheral alveolar compensation, bronchi and alveolar septum collagen fiber proliferation; The local renal tubular epithelial cells were enlarged and necrotic; the central vein surrounding hepatic cells showed vacuolar degeneration with punctate necrosis. Conclusion The rat model of acute diquat poisoning can be successfully induced by single-dose of intragastric administration. The condition of wistar rats and the pathological damage of the main target organs could be observed during the whole course of 115.50 mg/kg administration.

Objective: To investigate the clinical and laboratory features of Aeromonas bacteremia in patients with hematological diseases, and provide evidence for the prevention and treatment of Aeromonas infection. Methods: A retrospective study of patients with bloodstream infection of Aeromonas in our hospital from January 2014 to December 2018 was carried out. The clinical characteristics, antimicrobial susceptibility, infection seasons, antimicrobial therapy and evolution were analyzed. Results: A total of 42 patients with hematological diseases had Aeromonas bloodstream infection within 5 years. Among them, 39 cases (92.9%) of bloodstream infection occurred in the stage of neutropenia. The median time of fever was 4 (1-27) d, 22 (52.4%) patients only had fever, 6 (14.3%) with gastrointestinal symptoms (abdominal pain, diarrhea, nausea, upper gastrointestinal bleeding) , 8 (19.0%) with pulmonary infection, 13 (31.0%) with skin and soft tissue infections. Seven patients (16.7%) died with skin and soft tissue infection. The resistance of Aeromonas to carbapenems was 68.3%-70.7%, while the resistance rate to cephalosporins, quinolones and aminoglycosides were less than 10%. Conclusions Aeromonas bacteremia in patients with hematological diseases mainly occur in the neutropenia stage, usually with symptom like fever. The mortality is increased when accompanied by skin and soft tissue infection. Antibiotic use should be based on susceptibility results, and avoid the use of carbapenems.