Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT), intensity modulated radiation therapy (IMRT) and tomotherapy (TOMO) techniques applied in the irradiation of pediatric whole central nervous system tumors.Methods:Taking the target area of a 14-year-old pediatric patient clinically diagnosed with atypical teratoid/rhabdomyoid tumor, meningeal metastasis by Shandong Cancer Hospital and Institute, and undergoing craniospinal irradiation (CSI) as an example, IMPT, IMRT and TOMO plans were designed respectively based on the clinical prescription of the target area and the limit requirements of organs at risk (OARs). The conformal index (CI), homogeneity index (HI) and gradient index (GI) of each planning target volume, as well as the dose volume index of normal tissues, were evaluated to compare the dosimetric characteristics of the three types of plans.Results:The CI (0.71), HI (0.05) and GI (3.13) of the IMPT plan were comparable to those of IMRT plan (0.80, 0.08, 3.14). The HI (0.03) and GI (2.54) of the TOMO plan were excellent, which were all within the clinically acceptable range. The irradiation dose to parallel organs in the IMPT plan was lower than that in the IMRT and TOMO plan. In the IMPT plan, V 5 of lungs was 2.9%, IMRT plan was 37.6%, and TOMO plan was 43.5%. The D mean of liver in the IMPT plan was 0.01 Gy (RBE), IMRT plan was 6.12 Gy, and TOMO plan was 6.39 Gy. In the IMPT plan, none of the bladder, rectum, and femoral head received the dose, while there was low-dose radiation in both IMRT and TOMO plan. For serial organs adjacent to and within the target area, the D max of spinal cord and brainstem in IMPT plan was 39.89 and 39.88 Gy (RBE), respectively; in IMRT plan, they were 39.43 and 38.59 Gy, respectively; and in TOMO plan, they were 38.41 and 37.69 Gy, respectively. The low-dose area in the IMPT plan was significantly better than the photon radiotherapy plans. Among them, the absolute volume IMPT plan occupied by 10% of the prescribed dose area in the patient's body was reduced by 70.10% compared with IMRT plan and 76.96% compared with TOMO plan; the 30% prescribed dose volume IMPT plan was reduced by 53.49% compared with IMRT plan and 62.51% compared with TOMO plan; the 50% prescribed dose volume IMPT plan was reduced by 39.06% compared with IMRT plan and 42.23% compared with TOMO plan. Conclusions:The IMPT plan demonstrated significantly reduced low-dose exposure and lower doses to parallel OARs compared to both IMRT and TOMO plans in pediatric CSI. The CI, HI and GI of the three plans can all meet the clinical requirements. However, for serial organs adjacent to and within the target area, the D max of the IMPT plan may be higher than that of IMRT and TOMO plans.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.

A portable molecularly imprinted(MIP)surface-enhanced Raman scattering(SERS)chip was fabricated via a green electrochemical approach for highly selective detection of bisphenol A(BPA).This MIP-AuNP/UIO-66/SPE sensor was fabricated through a single-step co-deposition process.The process involved electropolymerization onto a UIO-66 modified screen-printed electrode(SPE),by usingo-phenylenediamine(OPD)as functional monomer and BPA as template,and simultaneously electro-reduction generated gold nanoparticles(AuNPs),which served as the SERS-active substrate.Ultimately,this one-step method formed a three-dimensional porous architecture on the electrode surface.Under 785 nm laser excitation,the sensing chip exhibited a highly sensitive SERS response towards BPA.The intensity of its characteristic peak at 850 cm-1 showed a good linear relationship with logarithm of BPA concentration in the range of 1.0×10-10 to 1.0×10-6 mol/L,with a detection limit of 1.0×10-12 mol/L.More importantly,the fabricated chips maintained highly selective binding affinity for BPA in water samples even in the presence of structural analogs bisphenol F(BPF)and bisphenol S(BPS).When the chip was applied to detection of BPA in water samples from plastic bottle and paper cup,the recovery rates ranged from 94.0%to 103.0%with relative standard deviations(RSD)less than 4.7%.The developed chip offered a highly sensitive and selective solution for detection of trace BPA in complex water samples.

To analyze the prevalence, drug resistance and whole genome characteristics of Mycoplasma pneumoniae (MP) in respiratory throat swab samples of hospitalized children with pneumonia in Suzhou City from 2023 to 2024. Throat swab samples of hospitalized children aged 0-14 years old with pneumonia in Suzhou were collected from September 2023 to September 2024. Real-time fluorenscence quantitative PCR technology was used to detect MP nucleic acid. The results showed that the positive rate of MP in 3 235 samples was 22.44% (726/3 235), with a rate of 55.00% in week 47 of 2023. The positive rate of MP increased with age ( χ2=45.842, P<0.001). The study selected MP nucleic acid test positive samples from week 20 (5.13-5.19) to week 23 (6.3-6.9) of 2024 for isolation, culture and resistance phenotype detection. About 31 MP strains were successfully isolated and cultured, all of which were resistant to macrolides. The next-generation sequencing technology and nanopore sequencing technology were used for genome sequencing. All 31 strains carried the A2063G mutation, with the main prevalent genotype being the P1-1, and the main mlST type being the ST3. Despite the overall genomic similarity between strains being over 99%, there were significant differences between the P1-1 and P1-2 strains in the P1 gene region. In summary, from 2023 to 2024, the main MP type prevalent in Suzhou City is the P1-1 genotype. All isolated MP strains carry an A2063G resistance site mutation and are resistant to macrolides, requiring continuous monitoring and further research.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Aim To investigate the effect of Zhenwu decoction on inflammation,oxidative stress and apopto-sis of human glomerular epithelial cells(HGEC)in-duced by lipopolysaccharide(LPS)based on Nrf2/HO-1 signaling pathway,and to explore the underlying mechanism.Methods HGEC were treated with LPS(1.0 mg·L-1)for 24 h to construct an oxidative damage model.On this basis,2.5％,5％and 10％Zhenwu decoction-containing serum were added to the low,medium and high dose groups of Zhenwu decoc-tion,and a normal group was set up.The changes of cell activity were assessed by MTT method and LDH method.The contents of TNF-α,IL-6,IL-10,SOD,CAT,GSH-Px,ROS and MDA in each group were de-tected by ELISA.The apoptosis of each group was de-tected by flow cytometry.The mRNA and protein ex-pressions of Bax,Bcl-2,caspase-3,caspase-9 and Nrf2/HO-1 pathway were detected by RT-qPCR and Western blot,respectively.Results Compared to the normal group,the model group of HGEC exhibited increased levels of inflammatory cytokines,enhanced oxidative stress response and aggravated apoptosis;after inter-vention with various doses of Zhenwu decoction,the in-flammatory levels in HGEC were reduced,oxidative damage and apoptosis were effectively ameliorated,and the mRNA and protein expression levels of the Nrf2/HO-1 signaling pathway were upregulated.Conclu-sions Zhenwu decoction can protect HGEC from LPS-induced inflammation and oxidative damage and im-prove apoptosis.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

This article reports the clinical features and gene mutation types of a large family with Nascimento form of syndromic X-linked intellectual developmental disorder (MRXSN), involving 9 individuals across 3 generations, and a literature review was conducted. In this family, 9 individuals had similar manifestations including mental retardation and unusual facies, and 4 of them had passed away. Genetic testing showed that the proband had the deletion of exons 2-3 of the UBE2A gene, which was inherited from the mother. Fluorescent quantitative polymerase chain reaction showed that the proband and his uncle had the deletion of exons 2-3 of the UBE2A gene; the proband's mother, grandmother, and great-aunt had a heterozygous deletion of exons 2-3 of the UBE2A gene; the proband's father, sister, and aunt had a normal copy number of exons 2-3 of the UBE2A gene. The 34 patients reported in the literature had diverse clinical phenotypes, and UBE2A gene mutations (22/34, 65%) and large fragment deletions (12/34, 35%) were the main mutation types. Moderate to severe mental retardation (34/34, 100%), speech and language impairment (33/34, 97%), and unusual facies (32/34, 94%) were the main clinical manifestations of MRXSN patients. The disease has obvious phenotypic heterogeneity, and early diagnosis facilitates optimal prenatal and postnatal management to improve reproductive outcomes.
Humans ; Male ; Ubiquitin-Conjugating Enzymes/genetics* ; Female ; X-Linked Intellectual Disability/genetics* ; Gene Deletion ; Child ; Pedigree ; Child, Preschool ; Adult

AIM:To investigate the effect and mechanism of panax notoginseng saponins(PNS)inhibiting the proliferation of pulmonary artery smooth muscle cells(PASMCs)in rats under the ef-fect of monocrotaline(MCT).METHODS:PASMCs cultured in vitro were randomly divided into the normal control(Control)group,the monocrotaline(MCT)group,the panax notoginseng saponins(PNS)group,the knockdown(M+Si ADAM10)group,the knockdown postconditioning(M+P+Si ADAM10)group,the overexpression(M+OE AD-AM10)group,and the overexpression postcondi-tioning(M+P+OE ADAM10)group.After the model was constructed,the cell viability of each group was measured using the CCK-8 assay,along with Western blot utilized to detect the expression of proliferating cell nuclear antigen(PCNA),disinteg-rin metalloproteinase 10(ADAM10),and notch ho-mology protein-3(Notch3)at the cellular neurogen-ic locus,respectively.RESULTS:Under the effect of MCT,the viability of PASMCs was significantly en-hanced(P<0.05 or P<0.01);0-400 mg/L PNS was not toxic to the viability of normal cells,and 100 mg/L PNS could significantly inhibit the MCT-in-duced viability(P<0.01).After the knockdown of ADAM10,the viability of PASMCs significantly de-clined(P<0.01),and the expression of PCNA protein was significantly decreased(P<0.05),evidently in the M+P+Si ADAM10 group.Meanwhile,the ex-pression of ADAM10 and Notch3 protein was signif-icantly decreased(P<0.05 or P<0.01),evidently in the M+P+Si ADAM10 group.After overexpression of ADAM10,the viability of PASMCs was significant-ly enhanced(P<0.01),the expression of PCNA pro-tein was significantly increased(P<0.01),the PCNA value was slightly higher(P>0.05),and the expres-sion of ADAM10 and Notch3 protein was signifi-cantly elevated(P<0.05)in the M+P+OE ADAM10 group.Additionally,PASMCs overexpressing AD-AM10 with concomitant PNS exhibited a significant decrease in the expression of PCNA protein com-pared with PASMCs knocking down ADAM10(P<0.01),and the expression of ADAM10 and Notch3 protein declined to varying degrees(P>0.05).CON-CLUSION:Panax notoginseng saponins can mitigate MCT-induced PASMCs proliferation in rats by inhib-iting the ADAM10/Notch3 signaling pathway.