Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Baoshan District, Shanghai from 2017 to 2024, so as to provide an evidence-based reference for optimizing prevention and control strategies. MethodsData on pertussis cases were collected from the China Disease Prevention and Control Information System, Shanghai Integrated Management and Immunization Service Information System, and follow-up epidemiological investigations. Descriptive epidemiological analyses were performed to analyze the epidemiological characteristics, clinical manifestations, and vaccine effectiveness. Joinpoint regression analyses were used to examine the temporal trends in incidence rates, and a Poisson model was constructed for spatiotemporal scan analyses. ResultsA total of 1 634 pertussis cases were reported in Baoshan District from 2017 to 2024, with a male-to-female ratio of 1.08∶1. More cases were observed in males than in females, with the age ranged from 20 days to 81 years. Among them, 59.92% were in the 6‒<11 years age group, and 63.34% were students. Low-level sporadic incidence persisted during 2017‒2023, followed by a sharp increase in 2024 (71.37/100 000). Starting in January 2024, the incidence rate showed an upward trend, peaking in May before declining. The majority of cases occurred between April and June. The trend in reported pertussis incidence rates in Baoshan District from 2017 to 2023 showed no statistically significant change (APC=10.039%, t=2.586, P=0.150). Incidence rate rose from January 2024, peaked in May (APC=133.641%, t=3.841, P=0.006), then declined significantly (APC=-47.816%, t=2.586, P<0.001). The 12 subdistricts of Baoshan District were divided into low, medium, and high population density areas, with an average annual reported incidence rate of 6.09/100 000, 8.19/100 000 and 11.96/100 000, respectively. The reported incidence rate increased with an increase in population density. Spatiotemporal scan analyses showed that cases clustered in the southwest and northeast of Baoshan District. Epidemiological follow-up investigations of 1 520 cases revealed that the main clinical symptoms were cough (97.63%) and sputum production (41.58%), and 98.13% of the cases were confirmed by positive nucleic-acid test results. Among the 1 475 cases with immunization records, 83.53% had completed the four-dose pertussis vaccine before onset. The complication incidence rates, from high to low, were in the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group. The duration of cough, from long to short, was observed in the the 0-dose vaccination group, 1‒3-dose vaccination group and 4-dose vaccination group, correspondingly. ConclusionIt is recommended to improve the pertussis surveillance system in medical institutions and establish an active monitoring network, prioritizing deployment in school settings and areas with high population density. Enhancing diphtheria-tetanus-pertussis (DTP) vaccination coverage among 6-year-old children and further optimizing the pertussis immunization strategies are essential to prevent and reduce the risk of pertussis among school-aged children.

Objective To investigate the expression of T cell subsets in the spleen of BTBR T+Itpr3tf autistic mouse at 4,8,and 12 weeks of age,and to determine the optimal age for studying the relationship between immune abnormalities and autism in BTBR autistic mice.Methods It randomly selected 5～6 male BTBR mouse at 4 weeks,8 weeks,and 12 weeks of age and C57BL/6J mouse of the same gender at corresponding ages for the three-box social interaction test,the self-grooming test,and the marble-burying test;Single cell suspensions were prepared from the spleens of mouse at 8 and 12 weeks of age,and flow cytometry was used to detect 8 subsets of T cells(TH 1,TH2,TH17,TC1,TC2,TC17,TFH,and Treg).Results Compared with C57BL/6J mouse of the same age,BTBR mouse at 4 weeks,8 weeks,and 12 weeks of age showed a decrease in social time(P＜0.001),an increase in grooming time(P＜0.01,P＜0.001),and an increase in the number of marbles buried(P＜0.01,P＜0.001)in BTBR mouse at 8 weeks and 12 weeks of age.As well,the expression of TH 1(P＜0.001),TH2(P＜0.01),TC 1(P＜0.05),TC2(P＜0.001),and TFH(P＜0.01)cells in 8-week-old BTBR mouse were significantly increased,while the expression of Treg(P＜0.001)cells were significantly decreased;The expression of TH 1(P＜0.01),TH2(P＜0.01),TH 17(P＜0.05),TC1(P＜0.01),TC2(P＜0.001),TC 17(P＜0.01),and TFH(P＜0.001)increased in 12-week-old BTBR mouse,while the expression of Treg(P＜0.05)cells decreased.At different age stages(P＜0.050)the ratio of TH 1/Treg and TC 1/Treg in 8-week-old BTBR mouse were significantly higher than those in 12 week old mouse,while the TC 17/Treg ratio decreased.Conclusions BTBR mouse at different developmental stages exhibit varying degrees of abnormal increase in Teff/Treg ratio.Based on result of behavioral test,it is recommended to use 8-week-old BTBR mice for research on autism and immune abnormalities.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

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.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Microvascular invasion is one of the critical factors influencing the prognosis of patients with hepatocellular carcinoma.Accurate preoperative prediction for its occurrence holds pivotal significance for the formulation of clinical individualized treatment decisions.Traditional diagnosis primarily relies on the evaluation of postoperative histopathological results,which exhibits a certain degree of lag.However,the emergence of radiomics features and biomarkers offers new insights for the preoperative prediction of mi-crovascular invasion.The preoperative prediction model based on radiomics and biomarkers is capable of precisely analyzing and efficiently predicting the occurrence risk of microvascular invasion from both macro-scopic imaging features and microscopic molecular levels,thereby providing multi-dimensional and precise scientific evidence for clinical decision-making.