Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

Objective The reference interval of venous whole blood red cells and related parameters of healthy children preschool stage 3 to 6 years in Panzhihua was established to provide practical experimental basis for pediatric clinical diagnosis and treatment.Methods From January to July 2023,1 467 eligible healthy children from 3 to 6 years old for physical examination were collected as study subjects,including 762 boys and 705 girls.Red blood cell(RBC),hemoglobin(Hb),hematocrit(HCT),mean red blood cell volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC)and red cell volume distribution width(RDW)were measured by Sysmex XN-1000 automatic blood analyzer.According to sex and age groups,the differences of the above indexes between different gender and age groups were compared,and the reference interval of venous whole blood red cells and related parameters of healthy children aged 3 to 6 years old in Panzhihua was established.At the same time,25 samples(including 13 boys and 12 girls)were selected to verify the newly established reference interval.Results HCT and RDW-SD reference intervals between boys and girls preschool stage 3～6 in the Panzhihua area,and the differences were not statistically significant(U=0.000,0.795,all P>0.05).The reference intervals for RBC,MCV,MCH and RDW-CV show statistically significant differences between boys and girls(U=2.829～5.753,all P＜0.05).There were gender and age differences in the reference intervals of Hb and MCHC(U=2.599,4.368,all P＜0.01).In the 3～6 years,the basal levels of RBC,HGB and HCT tended to increase gradually with age,while the overall base levels of RBC,HGB,MCHC,and RDW-CV in boys were higher than those in girls.And there were different degrees of difference with the reference range of industry standards.Also verify through the new reference interval.Conclusion With differences in RBC and related reference intervals of preschool stage children in different regions,it is necessary to establish a reference interval suitable for special population in Panzhihua.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective The reference interval of venous whole blood red cells and related parameters of healthy children preschool stage 3 to 6 years in Panzhihua was established to provide practical experimental basis for pediatric clinical diagnosis and treatment.Methods From January to July 2023,1 467 eligible healthy children from 3 to 6 years old for physical examination were collected as study subjects,including 762 boys and 705 girls.Red blood cell(RBC),hemoglobin(Hb),hematocrit(HCT),mean red blood cell volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC)and red cell volume distribution width(RDW)were measured by Sysmex XN-1000 automatic blood analyzer.According to sex and age groups,the differences of the above indexes between different gender and age groups were compared,and the reference interval of venous whole blood red cells and related parameters of healthy children aged 3 to 6 years old in Panzhihua was established.At the same time,25 samples(including 13 boys and 12 girls)were selected to verify the newly established reference interval.Results HCT and RDW-SD reference intervals between boys and girls preschool stage 3～6 in the Panzhihua area,and the differences were not statistically significant(U=0.000,0.795,all P>0.05).The reference intervals for RBC,MCV,MCH and RDW-CV show statistically significant differences between boys and girls(U=2.829～5.753,all P＜0.05).There were gender and age differences in the reference intervals of Hb and MCHC(U=2.599,4.368,all P＜0.01).In the 3～6 years,the basal levels of RBC,HGB and HCT tended to increase gradually with age,while the overall base levels of RBC,HGB,MCHC,and RDW-CV in boys were higher than those in girls.And there were different degrees of difference with the reference range of industry standards.Also verify through the new reference interval.Conclusion With differences in RBC and related reference intervals of preschool stage children in different regions,it is necessary to establish a reference interval suitable for special population in Panzhihua.

Objective:To compare the mechanical properties between our self-designed axially controlled compression spinal rod (ACCSR) and conventional spinal rod (CSR) for lumbar spondylolysis (LS).Methods:This study selected 36 ACCSRs (the ACCSR group) and 36 CSRs (the CSR group), both of which were in a diameter of 6.0 mm and manufactured in the same batch. They were subjected respectively to biomechanical tests of spinal rod and pedicle screw-rod internal fixation system. In spinal rod tests: the stiffness and yield load of the spinal rods were calculated using four-point bending tests ( n=7) and comparisons were made between the 2 groups; spinal rod fatigue tests ( n=8) recorded the successful compression loads after 2.5 million cycles of loading and compared them with the maximum force at the isthmus of a normal adult's unilateral lumbar spine (198.72 N). In tests of the pedicle screw-rod internal fixation system, the axial compression tests ( n=7) measured the axial gripping capacity, the axial torsion tests ( n=7) the torsional gripping capacity, and the lateral compression tests ( n=7) the stiffness and yield load of pedicle screws in the 2 groups respectively. Results:The stiffness [(1,543.37±61.41) N/mm] and yield load [1,338.57 (1,282.00, 1,353.80) N] of ACCSR group were significantly smaller than those of CSR group [(3,797.63±156.15) N/mm and 4,059.95 (3,813.80, 4,090.89) N] ( P<0.05). The spinal rod fatigue tests showed that the respective loads of CSR and ACCSR passing the 2.5 million fatigue tests were 640.00 N and 320.00 N, both larger than the maximum force at the unilateral lumbar isthmus of a normal adult (198.72 N). There were no significant differences between the ACCSR group and the CSR group in the axial gripping capacity and torsional gripping capacity, as well as in stiffness and yield load of screws between the 2 groups ( P>0.05). Conclusions:In fixation of LS, although the yield load, stiffness and fatigue resistance of ACCSR are inferior to those of CSR, the biomechanical properties of the two sets of pedicle screw-rod internal fixation system are comparable. The fatigue resistance of ACCSR can meet the stress requirements of the normal human isthmus.

Objective:To conduct evidence-based exercise training for patients with peripheral arterial disease, develop review indicators, analyze barriers and enablers in the evidence-based practice process, and develop change strategies.Methods:Guided by the clinical evidence application model of the Joanna Briggs Institute Evidence-Based Health Care Center, the study identified clinical nursing problems, formed the evidence-based practice team, systematically searched, evaluated, and summarized evidence of exercise training in patients with peripheral arterial disease, developed review indicators, and clarified review methods. The baseline review was conducted from October 1 to 31, 2022. The integrated-promoting action on research implementation in health services (i-PARIHS) framework was used to analyze the barriers and enablers of the baseline review results, and corresponding strategies were formulated.Results:A total of 20 best evidence were included, and 11 review indicators were developed, with only one indicator having a compliance rate of 100%. This study analyzed 22 barriers and 24 enablers, and formulated 14 change strategies.Conclusions:The review indicators constructed based on the best evidence are scientific, effective, appropriate, and feasible. The analysis of barriers and enablers, as well as the formulation of change strategies, can provide guarantees for promoting clinical practice of exercise training for patients with peripheral arterial diseases.

BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.