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.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To investigate whether there is a synergistic pathogenic effect between triglyceride glucose index(TyG)and C-reactive protein(CRP)on new-onset nonalcoholic fatty liver disease(NAFLD)by observing the influence of combinations of TyG and CRP at different levels,and to provide a basis for identifying the high-risk population of NAFLD.Methods A total of 31 935 employees in Kailuan Group who participated in physical examination in 2006-2007 were enrolled as the observation cohort,and they had no history of drinking,fatty liver disease,cardiovascular disease,or malignant tumor and did not take antidiabetic or lipid-lowering drugs.According to the median of TyG and CRP at baseline,the subjects were divided into TyG<8.42 and CRP<0.60 mg/L group,TyG<8.42 and CRP≥0.60 mg/L group,TyG≥8.42 and CRP<0.60 mg/L group,and TyG≥8.42 and CRP≥0.60 mg/L group.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and an analysis of variance was used for comparison of continuous data with skewed distribution between groups after logarithmic transformation;the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to calculate the cumulative incidence rate of NAFLD in different combinations of CRP and TyG levels,and the multivariate Cox regression model was used to investigate the influence of different combinations of TyG and CRP on the incidence rate of NAFLD.Results After a mean follow-up time of 7.59 years,a total of 16 592 employees developed NAFLD.The cumulative incidence rate of NAFLD in the TyG<8.42 and CRP<0.60 mg/L group,TyG<8.42 and CRP≥0.60 mg/L group,TyG≥8.42 and CRP<0.60 mg/L group,and TyG≥8.42 and CRP≥0.60 mg/L group were 59.5%,67.1%,73.8%,and 80.8%,respectively(P<0.001).After adjustment for confounding factors,compared with the TyG<8.42 and CRP<0.60 mg/L group,the TyG≥8.42 and CRP≥0.60 mg/L group had the highest risk of developing NAFLD(hazard ratio[HR]=1.54,95%confidence interval[CI]:1.47-1.61),followed by the TyG≥8.42 and CRP<0.60 mg/L group(HR=1.43,95%CI:1.36-1.49)and the TyG<8.42 and CRP≥0.60 mg/L group(HR=1.17,95%CI:1.12-1.22).Conclusion With elevated TyG and CRP levels,the cumulative incidence of NAFLD increased,and rising levels of these markers significantly augmented the risk of NAFLD development.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.