ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Objective:To determine the prevalence of self-reported food allergies among children in the grasslands of North China and to analyze its associated risk factors.Methods:In this study, a cross-sectional epidemiological survey method was used to select children under 14 years old by multi-stage, stratified and random cluster sampling in the grassland ecological area of Zhangbei County, Hebei Province, China from May to July 2018. Face-to-face questionnaires were administered to gather food allergy-related information from the participants. Multivariate logistic regression analysis was used to analyze the risk factors associated with self-reported food allergy.Results:A total of 2 086 children completed the survey. The prevalence of self-reported food allergies was 22.0%(459/2 086). The prevalence of multiple food allergies (≥3 types) was 3.1%(64/2 086) versus 16.3% (341/2 086) for a single food allergy among all children. Mango allergy (6.1%, 127/2 086) was the most common, followed by peach allergy (4.1%, 85/2 086). Children who reported food allergies had a significantly higher prevalence of all 4 atopic disorders (eczema, asthma, allergic rhinitis, and allergic conjunctivitis than those without food allergies(35.73% vs. 20.65%, 5.88% vs. 2.77%, 17.86% vs. 7.38%, 16.78% vs. 10.45%, χ2 =44.663 1, 10.434 3, 45.038 3, 13.728 4, all P<0.001).Significantly associated risk factors of food allergy were found to be pollen allergy ( OR: 2.29; 95% CI: 1.80-2.92) and drug allergy ( OR: 1.53; 95% CI: 1.12-2.09). Conclusions:The prevalence of self-reported food allergies among children in the Zhangbei County area of the North China Grassland was relatively high. Pollen allergy and drug allergy are major risk factors.

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

Objective:To explore the longitudinal effect of learning stress on learning burnout in vocational college students, and the mediating role of academic procrastination.Methods:A total of 1 212 vocational college students were selected, and two follow-up surveys were conducted at 12-week intervals in September (T1) and November (T2) of 2024 using the basic situation questionnaire, the burnout inventory-student survey, the learning pressure questionnaire and the brief academic procrastination scale. SPSS 26.0 software was used to compare the demographic characteristics of students' depersonalization using t test and single factor analysis of variance. Bootstrap was used to analyze the relationship among learning stress, academic procrastination and learning burnout. Results:The scores of learning stress at T1 and T2 for vocational college students were 14.47±3.52 and 14.52 ±3.50, the scores of academic procrastination at T1 and T2 were 27.14±9.07 and 27.21±9.04, and the scores of learning burnout T1 and T2 were 39.38±8.76 and 39.69±8.79.The t-test showed that the score of learning burnout at T1 of students aged 18 and below (36.70±8.72) was lower than students aged 18 above (40.15±8.63, t=-5.81, P<0.01). The score of learning burnout for liberal arts students at T1(40.82±8.54) was higher than that of science students (37.68±8.72, t=6.31, P<0.01). Single factor analysis of variance showed that the score of learning burnout for grade 1 students at T1(35.19±8.45) was lower than that of grade 2 students (41.33±7.98) and grade 3 students (38.92±9.88), and learning burnout score of grade 2 students at T1 was higher than that of grades 3 students ( F=61.59, P<0.01). The score of learning burnout for high-achieving students at T1(36.23±8.34) was lower than that of middle-achieving students (39.82±8.52) and low-achieving students (45.42±9.14), and the score of learning burnout for middle-achieving students at T1 were lower than that of low-achieving students ( F=36.53, P<0.01). Bootstrap test showed that academic procrastination T2 played a partial mediating role in the relationship between learning stress T1 and learning burnout T2 (effect size=0.04, 95% CI=0.03-0.07). Academic procrastination T1 played a partial mediating role in the relationship between learning stress T1 and learning burnout T2 (effect size=0.05, 95% CI=0.04-0.07). Conclusion:Learning stress can directly affect learning burnout in vocational college students, and also can indirectly affect learning burnout through the mediating effect of academic procrastination.

Objective:To determine the prevalence of self-reported food allergies among children in the grasslands of North China and to analyze its associated risk factors.Methods:In this study, a cross-sectional epidemiological survey method was used to select children under 14 years old by multi-stage, stratified and random cluster sampling in the grassland ecological area of Zhangbei County, Hebei Province, China from May to July 2018. Face-to-face questionnaires were administered to gather food allergy-related information from the participants. Multivariate logistic regression analysis was used to analyze the risk factors associated with self-reported food allergy.Results:A total of 2 086 children completed the survey. The prevalence of self-reported food allergies was 22.0%(459/2 086). The prevalence of multiple food allergies (≥3 types) was 3.1%(64/2 086) versus 16.3% (341/2 086) for a single food allergy among all children. Mango allergy (6.1%, 127/2 086) was the most common, followed by peach allergy (4.1%, 85/2 086). Children who reported food allergies had a significantly higher prevalence of all 4 atopic disorders (eczema, asthma, allergic rhinitis, and allergic conjunctivitis than those without food allergies(35.73% vs. 20.65%, 5.88% vs. 2.77%, 17.86% vs. 7.38%, 16.78% vs. 10.45%, χ2 =44.663 1, 10.434 3, 45.038 3, 13.728 4, all P<0.001).Significantly associated risk factors of food allergy were found to be pollen allergy ( OR: 2.29; 95% CI: 1.80-2.92) and drug allergy ( OR: 1.53; 95% CI: 1.12-2.09). Conclusions:The prevalence of self-reported food allergies among children in the Zhangbei County area of the North China Grassland was relatively high. Pollen allergy and drug allergy are major risk factors.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Objective:To explore the longitudinal effect of learning stress on learning burnout in vocational college students, and the mediating role of academic procrastination.Methods:A total of 1 212 vocational college students were selected, and two follow-up surveys were conducted at 12-week intervals in September (T1) and November (T2) of 2024 using the basic situation questionnaire, the burnout inventory-student survey, the learning pressure questionnaire and the brief academic procrastination scale. SPSS 26.0 software was used to compare the demographic characteristics of students' depersonalization using t test and single factor analysis of variance. Bootstrap was used to analyze the relationship among learning stress, academic procrastination and learning burnout. Results:The scores of learning stress at T1 and T2 for vocational college students were 14.47±3.52 and 14.52 ±3.50, the scores of academic procrastination at T1 and T2 were 27.14±9.07 and 27.21±9.04, and the scores of learning burnout T1 and T2 were 39.38±8.76 and 39.69±8.79.The t-test showed that the score of learning burnout at T1 of students aged 18 and below (36.70±8.72) was lower than students aged 18 above (40.15±8.63, t=-5.81, P<0.01). The score of learning burnout for liberal arts students at T1(40.82±8.54) was higher than that of science students (37.68±8.72, t=6.31, P<0.01). Single factor analysis of variance showed that the score of learning burnout for grade 1 students at T1(35.19±8.45) was lower than that of grade 2 students (41.33±7.98) and grade 3 students (38.92±9.88), and learning burnout score of grade 2 students at T1 was higher than that of grades 3 students ( F=61.59, P<0.01). The score of learning burnout for high-achieving students at T1(36.23±8.34) was lower than that of middle-achieving students (39.82±8.52) and low-achieving students (45.42±9.14), and the score of learning burnout for middle-achieving students at T1 were lower than that of low-achieving students ( F=36.53, P<0.01). Bootstrap test showed that academic procrastination T2 played a partial mediating role in the relationship between learning stress T1 and learning burnout T2 (effect size=0.04, 95% CI=0.03-0.07). Academic procrastination T1 played a partial mediating role in the relationship between learning stress T1 and learning burnout T2 (effect size=0.05, 95% CI=0.04-0.07). Conclusion:Learning stress can directly affect learning burnout in vocational college students, and also can indirectly affect learning burnout through the mediating effect of academic procrastination.

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and r df_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, l mb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.