In this study, high-performance liquid chromatography coupled with tantrum mass spectrometry (HPLC-MS/MS) technology was employed to determine milrinone nitrogen oxides in milrinone. An ACCHROM XCharge-C18 column (100 mm × 2.1 mm, 5 μm) was used with a mobile phase consisting of A phase (methanol) and B phase (5 mmol/L NH4FA, pH3 adjusted by formic acid). Agilent 6410B triple quadrupole mass spectrometer was used for HPLC-MS/MS analysis. Detection was performed using positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode to analyze the limit of milrinone nitrogen oxides in milrinone, and the quantitative transition for the ion pair was from m/z 228.01 to m/z 181.90. Experimental results showed that the method exhibited good specificity, and that neither blank solvent nor blank samples interfered with the determination of milrinone nitrogen oxides of milrinone. The method demonstrated high sensitivity, with a limit of quantitation (LOQ) of 0.0076 μg/mL and a limit of detection (LOD) of 0.0038 μg/mL. The linear range spanned from 20% to 200% of the LOQ concentration, and a good linear relationship between concentration and peak area was observed within this range. Additionally, the recovery rates were consistently within the range of 80% to 120%, and the RSD for repeatability tests was 12.0%. These results indicated that the precision and accuracy of this method meet the required standards. In summary, the method developed in this study can effectively and accurately determine the content of milrinone nitrogen oxides in milrinone.

OBJECTIVES: To analyze sex and age distribution of global disease burden of calcific aortic valve disease (CAVD) from 1990 to 2021. METHODS: CAVD data during 1990-2021 were obtained from the IHME website for Global Burden of Disease (GBD). The prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed by gender and age groups. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC). RESULTS: In 2021, there were 13.32 million CAVD patients and 142 000 deaths caused by CAVD globally. Age-standardized prevalence was higher in males (193.2/10⁵) than that in females (128.9/10⁵). Patients in 65-<85 age group accounted for 64.0% of total cases, while those ≥85 years old accounted for 16.1%. From 1990 to 2021, prevalence increased in both sexes with an AAPC of 0.72% for males and 0.57% for females, respectively. Prevalence grew fastest from 2000 to 2010, slowed thereafter, and declined from 2015 to 2021. In <65 years old, the mortality of males was 2.4 times higher than that of females, while in ≥85 years old, mortality of females (117.3/10⁵) exceeded that of males (99.1/10⁵). YLD rates increased with age, and were higher in males for all age groups. DALY rates decreased overall but increased in ≥85 years old, with a greater increase in females. CONCLUSIONS There are significant gender and age disparities in global disease burden of CAVD, with the elderly, especially super-elderly females deserving particular attention. It is recommended to develop personalized intervention strategies for these populations.
Humans ; Male ; Female ; Aged ; Calcinosis/mortality* ; Prevalence ; Global Burden of Disease ; Aged, 80 and over ; Middle Aged ; Aortic Valve/pathology* ; Aortic Valve Stenosis/epidemiology* ; Age Distribution ; Adult ; Disability-Adjusted Life Years ; Sex Distribution ; Global Health ; Aortic Valve Disease/epidemiology* ; Sex Factors

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Parkinson's disease(PD)is a common progressive neurodegenerative disease mainly affecting the motor system.Various genetic factors and cellular mechanisms underlying PD have recently been discovered.Emerging evidence suggests that epigenetic modifications play a very important role in the pathogenesis,prevention,and treatment of PD.Epigenetic modification mediates genetic and environmental interactions mainly through complex interactions of DNA methylation,histone modification,and non-coding RNA,thereby affecting expression in the absence of changes in DNA sequence.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.Recent studies have found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modifications in the treatment of PD.Traditional Chinese medicine benefits from its multi-level and multi-target regulatory effects,and various traditional Chinese medicine monomers,compound prescriptions,and techniques have been evaluated,confirming that this is a promising approach for improving symptoms in PD.This review summarizes the mechanisms by which epigenetic modifications contribute to P D,explores the role of traditional Chinese medicine,and provides new ideas for clinical treatment and drug development in PD through epigenetic intervention.

Parkinson's disease(PD)is a common progressive neurodegenerative disease mainly affecting the motor system.Various genetic factors and cellular mechanisms underlying PD have recently been discovered.Emerging evidence suggests that epigenetic modifications play a very important role in the pathogenesis,prevention,and treatment of PD.Epigenetic modification mediates genetic and environmental interactions mainly through complex interactions of DNA methylation,histone modification,and non-coding RNA,thereby affecting expression in the absence of changes in DNA sequence.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.Recent studies have found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modifications in the treatment of PD.Traditional Chinese medicine benefits from its multi-level and multi-target regulatory effects,and various traditional Chinese medicine monomers,compound prescriptions,and techniques have been evaluated,confirming that this is a promising approach for improving symptoms in PD.This review summarizes the mechanisms by which epigenetic modifications contribute to P D,explores the role of traditional Chinese medicine,and provides new ideas for clinical treatment and drug development in PD through epigenetic intervention.

Objective To explore the value of high-resolution CT combined with serum epidermal growth factor receptor(EGFR)and metastasis associated gene l(MTA1)in distinguishing multiple primary lung adenocarcinoma and lung adenocarcinoma with intrapulmonary metastasis.Methods From October 2020 to October 2022,56 patients with multiple primary lung adenocarcinoma accepted by our hospital were regarded as the multiple primary lung adenocarcinoma group,47 patients with lung adenocarcinoma and intrapulmonary metastasis admitted to our hospital were as the lung adenocarcinoma and intrapulmonary metastasis group,and 50 healthy individuals were as the control group.The basic data of multiple primary lung adenocarcinoma patients and lung adenocarcinoma patients with intrapulmonary metastasis were collected,organized,and compared;the serum EGFR and MTA1 levels were compared between the control group,multiple primary lung adenocarcinoma patients,and lung adenocarcinoma patients with intrapulmonary metastasis;the imaging matching types of multiple primary lung adenocarcinoma patients and lung adenocarcinoma patients with intrapulmonary metastasis were compared;the imaging features of the main and accompanying lesions in the two groups were compared;receiver operating characteristic(ROC)curve was applied to analyze the value of high-resolution CT combined with serum EGFR and MTA1 in distinguishing multiple primary lung adenocarcinoma and lung adenocarcinoma with intrapulmonary metastasis.Results There was no significant difference in age between patients with multiple primary lung adenocarcinoma and those with lung adenocarcinoma with intrapulmonary metastasis(P＞0.05),however,the proportion of males and those with a history of smoking in lung adenocarcinoma and intrapulmonary metastasis group was obviously higher than that in multiple primary lung adenocarcinoma group(P＜0.05);the levels of serum EGFR and MTA1 in patients with lung adenocarcinoma and intrapulmonary metastasis were obviously higher than those in the multiple primary lung adenocarcinoma group and control group(P＜0.05);in the imaging matching types,there were significant differences between multiple primary lung adenocarcinoma group and lung adenocarcinoma with intrapulmonary metastasis group in pure ground glass nodules,mixed ground glass nodules,solid nodules,pure ground glass nodules+mixed ground glass nodules,pure ground glass nodules+solid nodules,and mixed ground glass nodules+solid nodules(P＜0.05);there was a significant difference in the presence or absence of ground glass components and vacuoles in the main lesion between the group of multiple primary lung adenocarcinoma and the group of lung adenocarcinoma with intrapulmonary metastasis(P＜0.05),the shape,clear boundary,presence or absence of ground glass components,lobulation,and vacuoles in the accompanying lesions of patients in two groups had a significant impact on the accompanying lesions(P＜0.05);ROC curve showed that the area under the curve(AUC)of high-resolution CT,serum EGFR,and MTA1 for distinguishing multiple primary lung adenocarcinoma and lung adenocarcinoma with intrapulmonary metastasis was 0.819,0.778,0.826,and 0.908,respectively,the combined identification value of the three was superior to individual identification(Zthree combination-high-resolution Ct=3.026,P=0.003,Zthree combination-EGFR=3.057,P=0.002,Zthree combination-MTAI=2.361,P=0.018).Conclusion Serum EGFR and MTA1 levels,and high-resolution CT have certain clinical reference value for distinguishing multiple primary lung adenocarcinoma and lung adenocarcinoma with intrapulmonary metastasis,and the combination of the three has a good differentiation effect.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To develop an Oral Frailty Assessment Scale for Elderly Inpatients and test its reliability and validity.Methods:Through literature review, qualitative interview, expert consultations and pre-investigation, the preliminary draft of Oral Frailty Assessment Scale for Elderly Inpatients was formed. Using the convenient sampling method, a total of 300 elderly patients who were hospitalized in Geriatrics Department of Zhongnan Hospital of Wuhan University from April to June 2023 were selected as the research subjects. The reliability and validity of the scale were tested using item analysis, exploratory factor analysis, confirmatory factor analysis and reliability analysis.Results:A total of 300 questionnaires were distributed in this study, and 274 valid questionnaires were collected, with an effective response rate of 91.33% (274/300). The Oral Frailty Assessment Scale for Elderly Inpatients included four dimensions of teeth, dry mouth, swallowing and chewing, with a total of 11 items. The exploratory factor analysis extracted four common factors, and the cumulative variance contribution rate was 69.059%. The Cronbach's α coefficient for the scale was 0.76, the split-half reliability coefficient was 0.67, and the retest reliability coefficient was 0.98.Conclusions:The Oral Frailty Assessment Scale for Elderly Inpatients has good reliability and validity, which is suitable for evaluating oral frailty in elderly inpatients.