OBJECTIVE T o explore the distribution of pathogens and risk factors for hospital-associated infections in the laryngeal cancer patients undergoing tracheotomy so as to provide theoretical bases for reasonable clinical use of antibiotics.METHODS Totally 118 laryngeal cancer and tracheotomy patients who were complicated with infec-tions and treated in otolaryngology head and neck surgery department of The First Medical Center of Chinese PLA General Hospital from Oct.2021 to Oct.2024 were retrospectively assigned as the infection group,meanwhile,the 118 patients who were not complicated with infections were chosen as the no infection group.The distribution and drug susceptibility rates of the pathogens isolated from clinical specimens of the patients with infections were observed,and the risk factors for the hospital-associated infections were explored.RESULTS Totally 168 strains of pathogens were isolated from the 118 patients with infections,107 of which were gram-negative bacteria,51 were gram-positive bacteria,and 10 were fungi.The result of multivariate logistic regression analysis showed that age(OR=2.435,95％CI:1.052 to 5.634),duration of tracheotomy(OR=3.525,95％CI:1.871 to 14.259),length of hospital stay(OR=2.829,95％CI:1.099 to 7.276)and complication with diabetes mellitus(OR=4.807,95％CI:1.704 to 13.557)were the risk factors for the hospital-associated infections in the laryngeal cancer pa-tients undergoing tracheotomy(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the laryngeal cancer and tracheotomy patients with hospital-associated infections.The age,duration of tracheotomy,length of hospital stay and complication with diabetes mellitus are the risk factors for the hospital-associated infections in the laryngeal cancer patients undergoing tracheotomy.It is necessary to formulate the prevention and control measures based on the above factors so as to reduce the incidence of infec-tions.

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.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

Cleidocranial dysplasia, a rare genetic disorder primarily caused by Runt-related transcription factor 2 (RUNX2) heterozygous mutation, serves as a representative model for investigating regulatory mechanisms of RUNX2 in bone remodeling and tooth eruption. As a master transcription factor governing mineralized tissue development, RUNX2 orchestrates bone remodeling and tooth eruption through diverse regulatory networks. It drives alveolar bone formation via transcriptional activation, integration of multiple signaling cascades, and epigenetic modifications, thereby generating the biomechanical force for tooth eruption. Concurrently, RUNX2 promotes osteoblastic secretion of osteoclastogenic factors and directly regulates osteoclast precursor differentiation, facilitating bone resorption at the coronal aspect of dental follicles to estavlish the eruption pathway. Furthermore, RUNX2 modulates eruption progression by participating in stress-induced biological signal transduction within dental follicle cells (DFCs), remodeling the DFCs microenvironment, and regulating DFCs senescence. RUNX2 also influences root development via the NOTUM-Wnt axis, providing auxiliary biomechanical conditions conducive to eruption. This review systematically delineates the pivotal role of RUNX2 in coordinating bone remodeling and tooth eruption. Future studies should leverage organoid models and multi-omics technologies to further elucidate the spatiotemporal regulatory networks of RUNX2, potentially advancing precision diagnostics and therapeutics for rare skeletal-dental developmental disorders.

Alzheimer's disease(AD)is an age-related neurodegenerative disease that mainly manifests clinically as progressive functional impairments in cognition,memory,and language.With the accelerated transition toward an older population in China,the number of people suffering from AD in China is increasing.The exact pathogenesis of AD remains unclear,with current therapeutic strategies mainly limited to symptomatic treatments.Animal models are important tools for preclinical research,enabling explorations of molecular mechanisms,behavioral functions,and treatment strategies of diseases.Future mechanistic research and drug development of AD should involve the establishment of animal models that are consistent with clinical pathological characteristics.This review summarizes the AD animal models commonly used in research,providing details on the strains,age,modeling method and doses.It also discusses research on traditional Chinese medicine(TCM)components and their pharmacodynamic mechanisms in related AD animal models,aiming to provide references for the development of new animal models and in-depth exploration of the specific pharmacological activities,targets,metabolic pathways,and clinical applications of each TCM component.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

Objective:To discuss the effect of Compound Rehmannia Granules on intestinal flora of the pneumonia model rats induced by Streptococcus pneumoniae(Spn)through 16s rRNA sequencing technology,and to clarify its potential mechanism.Methods:A total of 30 rats were randomly divided into control group(normal rats),model group(Spn-induced pneumonia rat models),low dose of Compound Rehmannia Granules group(pneumonia rat models administered 1.75 g·kg-1 Compound Rehmannia Granules by gavage),medium dose of Compound Rehmannia Granules group(pneumonia rat models administered 3.50 g·kg-1 Compound Rehmannia Granules by gavage),and high dose of Compound Rehmannia Granules group(pneumonia rat model administered 7.00 g·kg-1 Compound Rehmannia Granules by gavage),with 6 rats in each group.The wet/dry weight(W/D)ratio of lung tissue and blood gas indexes were measured;HE staining was used to observe the pathomorphology and the degree of lung injury in lung tissue of the rats in various groups were assessed;kit assay was used to detect the bacterial load level and the levels of interleukin(IL)-6,IL-8,and IL-10 in bronchoalveolar lavage fluid(BALF)of the rats in various groups;16s rRNA intestinal flora sequencing analysis was performed.Results:Compared with control group,the arterial partial pressure of carbon dioxide(PaCO2)of the rats in model group was significantly increased(P<0.05),and the arterial partial pressure of oxygen(PaO2)and oxygen saturation(SaO2)were significantly decreased(P<0.05);compared with model group,the PaCO2 of the rats in low,medium,and high doses of Compound Rehmannia Granules groups was significantly decreased(P<0.05),and the PaO? and SaO?were significantly increased(P<0.05),showing a dose-dependent manner.The HE staining results showed no significant injury in lung tissue of the rats in control group;the cells in lung tissue of the rats in model group were arranged disorderly with massive inflammatory cell infiltration,and the alveolar wall capillaries were significantly dilated;compared with model group,the morphological damage of lung tissue of the rats in low,medium,and high doses of Compound Rehmannia Granules groups was improved.Compared with control group,the W/D value and pathological score of lung tissue of the rats in model group were significantly increased(P<0.05);compared with model group,the W/D value and pathological scores of lung tissue of the rats in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased(P<0.05),showing a dose-dependent manner.Compared with control group,the bacterial load level in BALF of the rats in model group was significantly increased(P<0.05);compared with model group,the bacterial load level in BALF of the rats in low,medium,and high doses of Compound Rehmannia Granules groups was significantly decreased(P<0.05),showing a dose-dependent manner.Compared with control group,the levels of IL-6 and IL-8 in BALF of the rats in model group were significantly increased(P<0.05),and the IL-10 level was significantly decreased(P<0.05);compared with model group,the levels of IL-6 and IL-8 in BALF of the rats in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased(P<0.05),and the IL-10 level was significantly increased(P<0.05),showing a dose-dependent manner.Compared with control group,the microbial abundance indicator(Chao1),microbial diversity and evenness indicator(Shannon),microbial dominance indicator(Simpson),and observed species indicator(observed_species)of the rats in model group were significantly decreased(P<0.05);compared with model group,the Chao1,Shannon,Simpson,and(observed_species)indices of the rats in low,medium,and high doses of Compound Rehmannia Granules groups were significantly increased(P<0.05),showing a dose-dependent manner.Compared with control group,the relative abundance of Bacteroidetes in model group was decreased,the relative abundance of Firmicutes was increased,and the Firmicutes/Bacteroidetes ratio was significantly increased(P<0.05);compared with model group,the relative abundances of Bacteroidetes in low,medium,and high doses of Compound Rehmannia Granules groups were increased,the relative abundance of Firmicutes was decreased,and the Firmicutes/Bacteroidetes ratio was significantly decreased(P<0.05),showing a dose-dependent manner.At the family level,compared with control group,the relative abundances of Corynebacteriaceae,Staphylococcaceae,and Moraxellaceae in model group were significantly increased,while the relative abundances of Lactobacillaceae,Lachnospiraceae,and Akkermansiaceae were significantly decreased;compared with model group,the relative abundances of Corynebacteriaceae,Staphylococcaceae,and Moraxellaceae in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased,and the relative abundances of Lactobacillaceae,Lachnospiraceae,and Akkermansiaceae were significantly increased.At the genus level,compared with control group,the relative abundances of Desulfovibrio and Facklamia in model group were significantly increased,and the relative abundances of Bifidobacterium and Ruminococcaceae were significantly decreased;compared with model group,the relative abundances of Desulfovibrio and Facklamia in low,medium,and high doses of Compound Rehmannia Granules groups were significantly decreased,and the relative abundances of Bifidobacterium and Ruminococcaceae were significantly increased.Conclusion:Compound Rehmannia Granules can alleviate inflammation and lung injury in Spn-induced pneumonia rats,which may be related to the increase in the abundance and diversity of intestinal flora.