Objective:To investigate the neuroprotective effect of vanillin on experimental autoimmune encephalomyelitis(EAE)rats by regulating C-X-C motif chemokine ligand 12(CXCL12)/chemokine(C-X-C motif)receptor(CXCR4)signaling path-way.Methods:A total of 50 rats were injected with 400 μl guinea pig spinal cord and water in oil mixture of complete Freund's adju-vant to establish EAE rat model,and were divided into model group,low-dose vanillin group(50 mg/kg),medium-dose vanillin group(100 mg/kg),high-dose vanillin group(200 mg/kg)and positive drug group(5 mg/kg prednisone acetate),another 10 rats were only injected with the mixture of the same amount of normal saline and complete Freud adjuvant as control group,since the first day of mod-eling,all rats were given corresponding drugs by gavage for 16 consecutive days,and after modeling,rats in each group were scored for neurological function every day;HE and LFB staining were used to observe the pathology and demyelination of spinal cord in rats;levels of serum TNF-α,IL-1β and IL-6 were detected by ELISA;immunohistochemistry was used to detect expressions of CD68 and Iba-1 in spinal cord of rats;Western blot was used to detect expressions of CXCL12 and CXCR4 proteins in spinal cord of rats.Results:Compared with control group,rats in model group showed obvious infiltration of inflammatory cells,a large number of inflammatory cells gathered around the small blood vessels,and the structure of myelin sheath in spinal cord of rats was abnormal,accompanied by a large number of myelin sheath loss,the neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,spinal cord CD68 and Iba-1 proteins,CXCL12 and CXCR4 proteins expressions in-creased obviously(P<0.05);compared with model group,inflammatory cell infiltration and myelin sheath loss of rats in low,medium and high doses groups and positive drug group were obviously alleviated,neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,and expressions of CD68 and Iba-1 proteins in spinal cord decreased obviously(P<0.05),while expressions of CXCL12 and CXCR4 proteins in spinal cord further increased(P<0.05).Conclusion:Vanillin inhibits inflammatory response and alleviates nerve injury in EAE rats,and its mechanism may be related to acti-vation of CXCL12/CXCR4 signaling pathway.

Objective:To investigate the neuroprotective effect of vanillin on experimental autoimmune encephalomyelitis(EAE)rats by regulating C-X-C motif chemokine ligand 12(CXCL12)/chemokine(C-X-C motif)receptor(CXCR4)signaling path-way.Methods:A total of 50 rats were injected with 400 μl guinea pig spinal cord and water in oil mixture of complete Freund's adju-vant to establish EAE rat model,and were divided into model group,low-dose vanillin group(50 mg/kg),medium-dose vanillin group(100 mg/kg),high-dose vanillin group(200 mg/kg)and positive drug group(5 mg/kg prednisone acetate),another 10 rats were only injected with the mixture of the same amount of normal saline and complete Freud adjuvant as control group,since the first day of mod-eling,all rats were given corresponding drugs by gavage for 16 consecutive days,and after modeling,rats in each group were scored for neurological function every day;HE and LFB staining were used to observe the pathology and demyelination of spinal cord in rats;levels of serum TNF-α,IL-1β and IL-6 were detected by ELISA;immunohistochemistry was used to detect expressions of CD68 and Iba-1 in spinal cord of rats;Western blot was used to detect expressions of CXCL12 and CXCR4 proteins in spinal cord of rats.Results:Compared with control group,rats in model group showed obvious infiltration of inflammatory cells,a large number of inflammatory cells gathered around the small blood vessels,and the structure of myelin sheath in spinal cord of rats was abnormal,accompanied by a large number of myelin sheath loss,the neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,spinal cord CD68 and Iba-1 proteins,CXCL12 and CXCR4 proteins expressions in-creased obviously(P<0.05);compared with model group,inflammatory cell infiltration and myelin sheath loss of rats in low,medium and high doses groups and positive drug group were obviously alleviated,neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,and expressions of CD68 and Iba-1 proteins in spinal cord decreased obviously(P<0.05),while expressions of CXCL12 and CXCR4 proteins in spinal cord further increased(P<0.05).Conclusion:Vanillin inhibits inflammatory response and alleviates nerve injury in EAE rats,and its mechanism may be related to acti-vation of CXCL12/CXCR4 signaling pathway.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To examine the relationships between perceived organizational support in job resources, self-efficacy in personal resources, and teaching commitment based on the job requirement-resource model, and to explore the path of influencing clinical teachers' teaching commitment.Methods:Using the convenience sampling method, 463 clinical teachers from 16 university-affilicated hospitals in Shandong Province, China were selected as the study subjects. Surveys were conducted using the Perceived Organizational Support Scale, Self-efficacy Scale, and Teaching Commitment Scale. A statistical analysis was performed using SPSS 26.0. A structural equation model was constructed using AMOS 26.0 to test the mediation effect.Results:①The level of teaching commitment of clinical teachers was relatively high, with a total score of (45.25±9.21) points. The total score of perceived organizational support was (38.22±9.75) points, and the total score of self-efficacy was (112.27±17.30) points. ②Perceived organizational support and self-efficacy were positively correlated with teaching commitment ( r=0.59, r=0.65, both P<0.01). ③ Perceived organizational support had significant and direct positive effects on teaching commitment and self-efficacy ( β=0.36, β=0.51, both P<0.01). Self-efficacy significantly and positively affected teaching commitment ( β=0.47, P<0.01). Self-efficacy played a significant and partial mediating role in the effect of perceived organizational support on teaching commitment (standardized mediating effect value of 0.239, P<0.01), and the mediating effect percentage was 39.83%. Conclusions:Perceived organizational support not only directly predicts clinical teachers' teaching commitment, but also indirectly affects teaching commitment through self-efficacy. University-affiliated hospital administrators should pay attention to clinical teachers' perceived organizational support to improve their self-efficacy and teaching commitment, thereby ensuring teaching quality.

BACKGROUND:Graphene oxide,with its excellent physical and chemical properties and biocompatibility,can promote the differentiation of osteoblasts and inhibit the proliferation of bacteria,which will hopefully improve the success rate of implant restoration.OBJECTIVE:To summarize the research progress of graphene oxide in the field of dental implant restoration.METHODS:The related articles published by CNKI,WanFang Database,ScienceDirect,and PubMed from January 2000 to June 2024 were searched by computer.The keywords were"graphene oxide,dental implantation,biocompatibility,antibacterial mechanism,osteoblasts,mechanical properties,chemical properties"in Chinese and English.By reading the titles and abstracts,we preliminarily screened out the documents irrelevant to the topic of the article.According to the inclusion and exclusion criteria,65 documents were finally included for analysis.RESULTS AND CONCLUSION:Graphene oxide can increase the innate immune protection response of the body through its own antibacterial and drug-loaded antibacterial abilities,thus inhibiting the occurrence and development of periimplant inflammation.Graphene oxide can promote the proliferation and differentiation of bone marrow mesenchymal stem cells,enhance the proliferation of osteoblasts and vascular endothelial cells,inhibit the proliferation of osteoclasts,increase the rate of bone bonding between implants and alveolar bones,and contribute to the formation and stability of bone around implants.Graphene oxide can promote the combination of implant and gingival tissue,and reduce the occurrence of inflammation.Graphene oxide has low toxicity,and its biological safety needs further study.Graphene oxide coating endows the surface of titanium implant with excellent physical and chemical properties,which can greatly reduce the occurrence of complications such as implant fracture and prolong the survival time of implant.

Objective:To explore the relief effect and mechanism of electroacupuncture in rats with knee osteoarthritis (KOA) based on the NF-κB/NLRP3 signaling pathway.Methods:SD rats were divided into a blank control group, a model group, an electroacupuncture group, and an electroacupuncture+PMA group using a random number table method, with 10 rats in each group. Except for the blank control group, all other groups were used to prepare KOA models. After successful modeling, rats in the electroacupuncture group and electroacupuncture+PMA group were subjected to electroacupuncture stimulation on both sides of the "Yanglingquan"(GB34), "Neixiyan"(EX LE4), and "Waixiyan"(EX-LE5); the electroacupuncture+PMA group received intraperitoneal injection of 5 mg/kg PMA once a day for 11 consecutive days of intervention; the blank control group and model group did not receive any intervention. Thermal foot contraction latency (TWL) and mechanical foot contraction threshold (MWT) were detected. HE staining was used to observe the inflammation and damage of synovial tissue and knee articular cartilage tissue. ELISA was used to detect the levels of calcitonin gene-related peptide (CGRP), pain mediator substance P (SP) and IL-6 in serum. The expressions of CGRP, iNOS proteins in dorsal root ganglion were detected by immunofluorescence assay. The expressions of CGRP, iNOS, p-p65/p65, NLRP3, Caspase-1, ASC proteins in dorsal root ganglia were detected by Western blot.Results:Compared with the model group, the TWL and MWT of the rats in the electroacupuncture group (3, 6, 9 and 11 days) significantly increased ( P<0.05), the pathological damage of synovial tissue and knee articular cartilage tissue were reduced, serum CGRP, SP, IL-6 levels significantly decreased ( P<0.05), and the expressions of CGRP, iNOS, p-p65/p65, NLRP3, Caspase-1, ASC proteins in dorsal root ganglion significantly decreased ( P<0.05); PMA significantly inhibited the effect of electrolysis on KOA rats ( P<0.05). Conclusion:Electroacupuncture can alleviate pain symptoms in KOA rats, and the mechanism may be related to the inhibition of the activation of NF-κB/NLRP3 signaling pathway.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease primarily affecting the joints of the limbs. As the disease progresses, it can involve multiple organ systems. Interstitial lung disease (ILD) is the most common pulmonary manifestation of RA. Reported animal models of RA-ILD include adjuvant-induced arthritis (AA), collagen-induced arthritis (CIA), and transgenic mouse arthritis. However, the establishment criteria and evaluation methods for these models lack uniform standards, and they fail to fully replicate the clinicopathological characteristics of RA-ILD. This limitation significantly hinders research into the pathogenesis and development of therapeutic drugs for RA-ILD. Objective: The aim of the study was to review literature in China and abroad on RA-ILD animal models, analyze current research progress, identify existing issues, and propose research recommendations. Methods: Literature searches were conducted using the English keywords “rheumatoid arthritis, interstitial lung disease, model” and the Chinese keywords “(rheumatoid arthritis), (interstitial lung disease), (model)” or “(rheumatoid arthritis), (lung interstitial lesions), (model).” The search was performed in PubMed, Web of Science, CNKI, Wanfang Data, and VIP (China Science and Technology Journal Database) for articles published before November 2024. A total of 41 articles were included. Results and conclusions: The CIA model and the CIA model combined with bleomycin are commonly used due to their similarities to the histopathology and disease manifestations of human RA-ILD. Additionally, these models have appropriate cost and modeling duration, along with a high success rate, making them preferable choices. Transgenic animal models exhibit pathological features similar to the nonspecific interstitial pneumonia subtype of human RA-ILD and are useful for studying the genetic effects on RA-ILD. However, they have drawbacks such as high economic costs, long modeling durations, and a low success rate in some cases. The AA model is easy to establish, requires a short modeling period, and has low experimental costs. However, it lacks the chronic pathological development characteristic of human RA and exhibits a degree of self-limitation in lesion progression. Among other models, the comprehensive HLA-DQ8 transgenic mouse model can be used to study the combined effects of genetic and environmental factors on RA-ILD. The collagen autoantibody-induced arthritis model combined with bleomycin has a short modeling period, but it does not align well with the disease course of RA-ILD. These established animal models provide valuable insights into the pathogenesis of RA-ILD, the identification of novel biomarkers, and the development of new therapeutic approaches. Future research should focus on identifying an animal model that better replicates the physiological and pathological changes of clinical RA-ILD while being more convenient, cost-effective, and comprehensive in reflecting disease progression.

Objective:To examine the relationships between perceived organizational support in job resources, self-efficacy in personal resources, and teaching commitment based on the job requirement-resource model, and to explore the path of influencing clinical teachers' teaching commitment.Methods:Using the convenience sampling method, 463 clinical teachers from 16 university-affilicated hospitals in Shandong Province, China were selected as the study subjects. Surveys were conducted using the Perceived Organizational Support Scale, Self-efficacy Scale, and Teaching Commitment Scale. A statistical analysis was performed using SPSS 26.0. A structural equation model was constructed using AMOS 26.0 to test the mediation effect.Results:①The level of teaching commitment of clinical teachers was relatively high, with a total score of (45.25±9.21) points. The total score of perceived organizational support was (38.22±9.75) points, and the total score of self-efficacy was (112.27±17.30) points. ②Perceived organizational support and self-efficacy were positively correlated with teaching commitment ( r=0.59, r=0.65, both P<0.01). ③ Perceived organizational support had significant and direct positive effects on teaching commitment and self-efficacy ( β=0.36, β=0.51, both P<0.01). Self-efficacy significantly and positively affected teaching commitment ( β=0.47, P<0.01). Self-efficacy played a significant and partial mediating role in the effect of perceived organizational support on teaching commitment (standardized mediating effect value of 0.239, P<0.01), and the mediating effect percentage was 39.83%. Conclusions:Perceived organizational support not only directly predicts clinical teachers' teaching commitment, but also indirectly affects teaching commitment through self-efficacy. University-affiliated hospital administrators should pay attention to clinical teachers' perceived organizational support to improve their self-efficacy and teaching commitment, thereby ensuring teaching quality.

Objective:To investigate effect of andrographolide(AG)on neuroinflammation in young epileptic rats by regulating cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response element binding protein(CREB)signaling pathway.Methods:SPF grade young SD rats were randomly divided into Control group,Model group,low-dose AG group(AG-L,125 mg/kg),high-dose AG group(AG-H,250 mg/kg)and high-dose AG+PKA inhibitor H-89 group(AG-H+H-89,250 mg/kg AG+2 mg/kg H-89),with 12 rats in each group.Epilepsy model of young rats was established by intraperitoneal injection of kainic acid(KA).Morris water maze test was used to detect learning and memory functions of rats.ELISA was used to detect levels of TNF-α,IL-10,malondialdehyde(MDA),superoxide dismutase(SOD)and cAMP in hippocampus of rats in each group.Histomorphology of hippo-campus was detected by Nissl staining.TUNEL test was usd to determine apoptosis rate of neurons in rat hippocampus.PKA and CREB mRNA expressions in hippocampus of rats in each group were detected by RT-qPCR.Western blot was used to detect protein expressions of PKA,Bax,Caspase-3,CREB,p-CREB and brain derived neurotrophic factor(BDNF)in hippocampus of rats in each group.Results:Compared with control group,escape latency,TNF-α and MDA levels in hippocampus,apoptosis rate of nerve cells,Bax and Caspase-3 protein expressions in Model group were obviously increased(P<0.05),target quadrant residence time,SOD,IL-10,cAMP levels,PKA,CREB mRNA and protein expressions,BDNF protein expression in hippocampus were decreased obviously(P<0.05),hippocampal tissue showed pathological damage and a large number of Nissl bodies were lost.Compared with Model group,cor-responding indexes of rats in AG-H group were contrary to the above(P<0.05),loss of Nissl corpuscles was reduced.H-89 alleviated improvement of AG on neuroinflammation in young epileptic rats.Conclusion:AG may reduce neuroinflammation in young epileptic rats by activating cAMP/PKA/CREB signaling pathway.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.