Objective To explore the relationship between cognitive function changes and leukoaraiosis(LA)and cerebrovascular reserve(CVR)in elderly patients with rheumatoid arthritis(RA).Methods A total of 160 elderly patients with RA were selected and their cognitive function were also evaluated.Based on the scoring results of Montreal cognitive assessment(MoCA),all patients were categorized into normal cognitive function group[non cognitive impairment(CI)group]and CI group,respectively.The general clinical information of the patients were recorded,LA via head MRI were evaluated,and CVR through breath holding index(BHI)were assessed,respectively.The relevant risk factors of the two groups of RA patients were analyzed,and univariate and multivariate logistic regression analyses were used to screen the independent risk factors for cognitive decline in elderly patients with RA,and the predictive efficacy of LA score and BHI in the two groups of patients were compared,respectively.Results There were significant differences in education level,coronary heart disease,diabetes,disease activity score(DAS28 score),BHI and LA score between the two groups(P＜0.05).Multivariate logistic regression results displayed that BHI and LA score were independent risk factors for cognitive decline.The receiver operating characteristic(ROC)curve suggested that BHI had a higher predictive value for cognitive decline in elderly RA patients.Conclusion The LA score of elderly RA patients with CI increases while BHI significantly decreases.BHI has a high diagnostic value in predicting cognitive decline in elderly RA patients.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

Objective:To compare and analyze the application efficacy of active surveillance versus passive surveillance in post-marketing safety monitoring of the group A and C meningococcal polysaccharide vaccine(MPSV-AC).Methods:Safety data for MPSV-AC from its market launch in November 2011 to June 2024 were collected from Beijing Zhifei Lyuzhu Biopharmaceutical Co., Ltd., and categorized into active and passive surveillance data based on acquisition methods. Active surveillance data were derived from adverse events cases observed in the company′s phase Ⅳ clinical trial. Passive surveillance data were carried out by the Pharmacovigilance Department through the drug adverse reaction direct reporting system, which downloaded all adverse events following immunization(AEFI) case reports. Cases of adverse events under active surveillance that were "definitely related", "probably related", "possibly related", or "possibly unrelated" were classified as adverse reaction cases, and cases of passive surveillance that were classified as "general reaction" or "abnormal reaction" were classified as adverse reaction cases, and were counted according to the number of cases. For cases where different clinical manifestations of adverse reactions or preferred terminology were present in the same one patient, the number was counted separately. Descriptive epidemiological methods were used to describe the incidence of adverse reaction reports, the distribution of clinical manifestations, adverse reactions recorded and not recorded in the instructions and adverse reactions outcomes of two monitoring methods. The differences in the incidence of reported adverse reactions between active and passive surveillance were compared and analysed.Results:A total of 922 patients with MPSV-AC adverse reaction reports were obtained through two monitoring modes, and 1 308 adverse reactions were occurred. In the active surveillance, the number of vaccination doses was 9 999, and 579 patients with adverse reactions were reported with 911 adverse reactions. In the passive surveillance, the number of vaccination doses was 4 185 800, and 343 patients with adverse reactions were reported with 397 adverse reactions. The incidence of reported adverse reactions in the passive surveillance was lower than in the active surveillance, and the difference was statistically significant [0.008% (343/4 185 800) vs. 5.791% (579/9 999), P<0.001]. The age range for active surveillance was ≥2 to<7 years old; the age range of passive surveillance was 0-15 years old, with the highest proportion of those aged ≥2 to<7 years old [79.30% (273/343)]. The clinical manifestation that topped the composition ratio of major adverse reactions for both surveillanceme thods was fever, but systemic symptoms such as malaise and anorexia were more frequently reported in active surveillance, whereas signs visible on the surface such as allergic rash, erythema and hard nodules were reported in passive surveillance. The proportion of serious adverse reactions from active surveillance was 0.22%(2/922), which were upper respiratory tract infection and febrile convulsions. Of the adverse reactions not included in the specification, those from active surveillance mainly involved infections and invasive diseases [77.32% (75/97)], and those from passive surveillance mainly involved diseases of the skin and subcutaneous tissues(6/12). All 579 patients in the active surveillance adverse reaction reports were monitored until cured; in the passive surveillance, 199 cases (50.13%, 199/397) were cured, 168 cases (42.32%, 168/397) were improved, and 30 cases (7.56%, 30/397) were unknown. Conclusions:Active surveillance is irreplaceable for postmarketing safety evaluation of vaccines, as it comprehensively captures safety signals, indicating good safety of MPSV-AC. A multi-source data integration platform could be established in the future.

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 analyze the imaging features of testicular conventional ultrasonography（US），shear wave elastography（SWE），and contrast-enhanced ultrasonography（CEUS）in subtypes of spermatogenic dysfunction（focal，arrest，and exhausted），and to evaluate the diagnostic efficacy of testicular multimodal ultrasound.Methods:A prospective study enrolled 310 spermatogenic dysfunction patients（focal type group： n=77，arrest type group： n=20，exhaustive type group： n=213）and 30 healthy volunteers（control group）at Shanghai General Hospital between October 2023 and December 2024. All patients underwent preoperative testicular US，SWE，and CEUS examinations，followed by microdissection testicular sperm extraction. Ultrasound parameters were compared among groups，and receiver operating characteristic（ROC）curves were plotted to assess the diagnostic efficacy of multimodal ultrasound for different subtypes. Results:①Testicular volume：The arrest group exhibited significantly greater volume compared to the focal group and the exhausted group（all P<0.05）. No statistically significant difference was observed between the arrest group and the normal group（ P>0.05）. ②Mean Young's modulus（Emean）：The arrest group exhibited significantly lower Emean compared with both the focal and exhausted groups（all P<0.05），but showed no significant difference versus the normal group（ P>0.05）. ③CEUS quantitative parameters：The arrival time（AT）and time to peak（TTP）in the exhausted group were higher than those in the normal group，while the peak intensity（PI）and area under the time-intensity curve（AUC）were lower（all P<0.05）. No significant differences were found in AT，TTP，or AUC among the three spermatogenic dysfunction subgroups（all P>0.05）. ④CEUS perfusion patterns：The focal group predominantly exhibited a mottled pattern（70.13%，54/77）. Both the arrest group（90.00%，18/20）and the normal group（93.33%，28/30）predominantly exhibited an rich pattern. The exhausted group predominantly exhibited a sparse pattern（56.34%，120/213）. ⑤ROC curve analysis showed that for differentiating the arrest group from the focal type group and the exhaustive type group，the combination of Emean，testicular volume，and CEUS perfusion pattern yielded an AUC of 0.931，with a sensitivity of 95.00% and specificity of 85.86%. For differentiating the focal type group from the exhaustive type group，the combination of testicular echogenicity，CEUS perfusion pattern，and Emean yielded an AUC of 0.833，with a sensitivity of 81.82% and specificity of 75.12%. Conclusions:Multimodal ultrasonography can comprehensively characterize the imaging features of different subtypes of spermatogenic dysfunction，holding promise as a noninvasive predictive tool.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

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 explore the association between circadian syndrome (CircS), metabolic syndrome (MetS) and mild cognitive impairment (MCI) in elderly rural adults in China.Methods:From March to September 2018, totally 5 765 participants aged 60 years or older from 52 villages in Yanlou Town, Yanggu County, Shandong Province were selected. The data included demographic, underlying disease and neuropsychological data were collected by questionaire survey. Having ≥3 of the following components was defined as MetS: elevated waist circumference, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure and elevated fasting glucose. Having ≥4 of the following components was defined as CircS: short sleep (<6 h/d), depression and five other components which were used to define MetS, with elevated waist circumference as a mandatory item. MCI was diagnosed according to Petersen's criteria and further classified into amnestic MCI (aMCI) and non-amnestic MCI (naMCI) based on whether the memory domains impaired.Data were analyzed using multivariable Logistic regression and general linear regression models by R statistical software.Results:In the total sample ( n=4 898), 1 280 participants were diagnosed with MCI, of which 1 075 were aMCI and 205 were naMCI.Compared to the normal group, CircS alone was significantly associated with increased risks of MCI ( B=0.695, P=0.039) and aMCI ( B=0.782, P=0.024), as well as lower verbal fluency scores ( B=-0.244, P=0.045). No significant associations were found between MetS alone or both MetS and CircS and cognitive impairment( P>0.05). At the component level, short sleep and depression were associated with increased risks of MCI ( B=0.167, P=0.025; B=0.605, P<0.001) and aMCI ( B=0.185, P=0.020; B=0.600, P<0.001). Conclusion:Individuals with CircS are at a higher risk of cognitive impairment, CircS is more strongly associated with cognitive impairment than MetS, with short sleep duration and depressive symptoms potentially playing key roles.

Objective To explore the relationship between cognitive function changes and leukoaraiosis(LA)and cerebrovascular reserve(CVR)in elderly patients with rheumatoid arthritis(RA).Methods A total of 160 elderly patients with RA were selected and their cognitive function were also evaluated.Based on the scoring results of Montreal cognitive assessment(MoCA),all patients were categorized into normal cognitive function group[non cognitive impairment(CI)group]and CI group,respectively.The general clinical information of the patients were recorded,LA via head MRI were evaluated,and CVR through breath holding index(BHI)were assessed,respectively.The relevant risk factors of the two groups of RA patients were analyzed,and univariate and multivariate logistic regression analyses were used to screen the independent risk factors for cognitive decline in elderly patients with RA,and the predictive efficacy of LA score and BHI in the two groups of patients were compared,respectively.Results There were significant differences in education level,coronary heart disease,diabetes,disease activity score(DAS28 score),BHI and LA score between the two groups(P＜0.05).Multivariate logistic regression results displayed that BHI and LA score were independent risk factors for cognitive decline.The receiver operating characteristic(ROC)curve suggested that BHI had a higher predictive value for cognitive decline in elderly RA patients.Conclusion The LA score of elderly RA patients with CI increases while BHI significantly decreases.BHI has a high diagnostic value in predicting cognitive decline in elderly RA patients.