Objective : To evaluate the coverage and spatial clustering of 13-valent pneumococcal conjugate vaccine(PCV13) among the 2017—2023 birth cohorts in Anhui Province. Methods : Obtained vaccination data of PCV13 for children born in 2017—2023 from the Anhui Immunization Information Management System.We estimated coverage levels and described characteristics of coverage.The spatial autocorrelation analysis of coverage was conducted. Results : Cumulative coverage,cumulative primary immunization coverage and cumulative full-series coverage of PCV13 were 17.19%,12.12% and 9.09% among the 2017—2023 birth cohort in Anhui Province.The coverage of PCV13 increased from 1.14% in the 2017 birth cohort to 41.59% in the 2022 birth cohort.The first dose of PCV13 at ages under 3,3—6,7—11,12—23 and not less than 24 months were 45.35%,29.84%,5.52%,10.75% and 8.53%,respectively.There were significant differences in the ages of the first dose between children of different years of born and kinds of PCV13(P<0.001).Significant differences were also observed in the cumulative coverage,cumulative primary immunization coverage,cumulative full-series coverage of PCV13 and ages of the first dose among children from various residence regions(P<0.001).From 2018 to 2023 birth cohort,the coverage of PCV13 in Anhui Province showed obvious positive spatial autocorrelation.Local spatial autocorrelation analysis showed that the "high-high" agglomeration areas were concentrated in the central area of Anhui. Conclusion The coverage of PCV13 was low in Anhui Province with significant regional differences.

Objective To investigate the relationship between 9 immunoinflammatory indicators derived from complete blood count and the severity of Mycoplasma pneumoniae pneumonia(MPP)in children of different ages.Methods Totally 2 132 children with MPP who were hospitalized in the Department of Pediatrics of The First Affiliated Hospital of Naval Medical University from Jul.1,2023,to Dec.31,2024 were enrolled,and were assigned to severe MPP(SMPP)or non-severe MPP(NSMPP)groups.According to age and gender 1∶1 matching,the children were assigned to 2 subgroups according to age(1-6 years old and＞6-16 years old).The basic data,laboratory examination and immunoinflammatory indicators from complete blood count of each group were collected and compared.The influencing factors of SMPP were analyzed by univariate and multivariate Cox proportional hazards regression models.Receiver operating characteristic curves were used to analyze the predictive value of indicators that showed statistically significant differences for SMPP.Results There were 220 patients with SMPP,accounting for 10.3%of MPP.In children aged 1-6 years,compared with the NSMPP group,the SMPP group had a longer hospital stay,higher platelet(PLT)count,platelet-to-lymphocyte ratio(PLR),neutrophil-to-lymphocyte ratio,derived neutrophil-to-lymphocyte ratio and systemic immune-inflammation index(all P＜0.05).PLR was an independent risk factor for SMPP(odds ratio=1.010,95%confidence interval[CI]1.003-1.018,P=0.007).The area under curve predicted by PLR for SMPP was 0.635(95%CI 0.560-0.711,P＜0.001),the best cut-off value was 125.04,and the corresponding sensitivity and specificity were 57.7%and 70.2%,respectively.All the children were assigned to low PLR group or high PLR group using the best cut-offvalue as the boundary,and the severe disease rate in the high PLR group was significantly higher than that in the low PLR group(65.9%[60/91]vs 37.6%[44/117],P＜0.001).All the children were assigned to Q1-Q4 groups by quartile,and the severe disease rate of the Q4 group(71.2%,37/52)was significantly higher than that of the Q1-Q3 group(all P＜0.05).In children aged＞6-16 years,compared with the NSMPP group,the PLT and PLR in the SMPP group were higher(both P＜0.05),but neither was an independent risk factor.All the children were assigned to low PLR group or high PLR group using the best cut-offvalue(137.03)as the boundary,and the severe disease rate in the high PLR group was significantly higher than that in the low PLR group(57.0%[77/135]vs 40.2%[39/97],P=0.011).All the children were assigned to Q1-Q4 groups by quartile,and the severe disease rate of the Q4 group(65.5%,38/58)was significantly higher than that of the Q1-Q3 group(all P＜0.05).Conclusion The immunoinflammatory indicators derived from complete blood count,especially PLR,have certain application value in predicting the severity of MPP children in different ages.

Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

Objective To understand the pathogenic molecular characteristics of the latest prevalent Group A Streptococcus(GAS)in a suburban area of Beijing.Methods Throat swab specimens from children suspected of GAS infection in the outpatient setting of a sentinel surveillance hospital in a suburban area of Beijing from January 2023 to June 2025 were collected.GAS strains were detected and cultured.Antimicrobial susceptibility testing on 12 antimicrobial agents were performed,and molecular epidemiological characteristics of GAS strains was further ana-lyzed by whole genome sequencing technique.Results Data of 326 children suspected of GAS infection in outpatient setting were collected.A total of 41 GAS strains were detected and cultured,with a detection rate of 12.58％.The proportions of children with anterior cervical lymph node enlargement,tonsil congestion,and jaw congestion in the GAS positive group were all higher than those in the GAS negative group,and differences were all statistically sig-nificant(all P＜0.05).All 41 GAS strains carried both erm(B)and tet(M)resistance genes and exhibited a struc-tural type(cMLS)resistance phenotype.All of the emm12 strains were ST36,and emm1 strains were ST28.A to-tal of 6 emm12 subtypes and 1 emm1 subtype were detected,namely emm12.2,emm12.95,emm12.69,emm12.17,emm12.19,emm12.149,and emm1.12.Among them,emm12.149 was a newly discovered subtype.Nucleobase at the 175 100 locus in gene sequence had undergone an A→ T mutation.A total of 5 bacteriophages and 6 superanti-gens were detected.There were statistically significant differences in multi-nucleotide polymorphisms(MNPs)and insertion numbers in the genomes of emm12.0 and emm12 subtypes(both P＜0.05).The phylogenetic tree presen-ted a highly clonal group of 23 GAS strains in this area,accounting for 57.50％.Conclusion The prevalent GAS strain in this area is emm12.emm12.149 is a new subtype.The resistance genes and phenotypes are erm(B),tet(M),and structural type(cMLS).The genome has plenty genetic polymorphism,and the genome sequences of multiple GAS strains are highly cloned,indicating the possibility of clone transmission.This suggests that the sur-veillance of GAS in sentinel hospitals should continue to be strengthened,so as to provide theoretical basis for the prevention and control of GAS epidemics.

To analyze the relationship between serum non-HDL-C levels and cardiovascular disease (CVD) mortality in community populations. A retrospective cohort study was conducted using the Yuecheng District Health Information Platform in Shaoxing City, Zhejiang Province. The study cohort included individuals aged 40 years or older with no prior history of CVD who underwent physical examinations at Yuecheng District healthcare institutions between January and December 2019. A total of 39 038 participants were included, including 19 085 males (48.9%) and 19 953 females (51.1%), with a mean age of (73.64±9.10) years. The mean follow-up duration was 52.3 months. During follow-up, 1 227 CVD death events occurred. The results indicated a significant overall association between non-HDL-C levels and the risk of CVD mortality, including coronary heart disease (CHD) and stroke. Cox models indicated that, using the ideal level of non-HDL-C as the reference, the hazard ratios (HRs) for risk of CVD death in the suitable level, borderline elevated level and elevated level groups were 1.24 (95% CI: 1.08-1.42), 1.57 (95% CI: 1.34-1.85) and 2.31 (95% CI: 1.87-2.86), respectively. The corresponding HRs for CHD death were 1.39 (95% CI: 1.10-1.76), 1.69 (95% CI: 1.28-2.12) and 2.53 (95% CI: 1.76-3.64), respectively. Subgroup analysis revealed significant interaction effects between non-HDL-C and sex, smoking, alcohol consumption, and diabetes (all P interaction<0.05). Sensitivity analyses confirmed that results were consistent with the primary findings regarding the association between non-HDL-C and CVD mortality risk. In conclusion, increasing non-HDL-C levels are associated with higher risks of death from cardiovascular diseases, including stroke and CHD. The risk of CVD death associated with elevated non-HDL-C is greater among males, individuals with a history of diabetes, smokers or drinkers. In the future, attention should be paid to the monitoring of non-HDL-C in community health management, and the intensive and personalized management of blood lipids in high-risk population should be strengthened.

AIM To study the chemical constituents from the bark of Toona sinensis(A.Juss.)Roem and their anti-inflammatory activity.METHODS Silica gel,RP-18 reverse phase silica gel and HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activity were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as(9Z)-18-hydroxyo-ctadec-9-en-4,6-diyn-3-one(1),toonapolyyne C(2),(9S,10E,16R)-octadec-10-ene-12,14-diyne-1,9,16-triol(3),(9S,10E,16R)-9,16-dihydroxyoctadec-10-ene-12,14-diy-n-1-yl acetate(4),toonapolyyne A(5),toonasindiyne B(6),scopoletin(7),sco-parone(8),3-O-acetyl(-)-epicatechin(9),p-ethoxyacetanilide(10),kulonic acid(11),β-sitosterol-3-O-β-D-glucopyranoside(12),vanillic acid(13),cleomiscosin A(14),(-)-isolariciresinol(15),resveratrol(16).The IC50 values of compounds 3-4,6,11-13 for NO were 6.90,10.49,20.03,9.49,18.34,24.36 μmol/L,respectively.CONCLUSION Compound 1 is a new polyacetylene,8-16 are isolated from T.sinensis for the first time.Compounds 3-4,6,11-13 have good anti-inflammatory activity.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.