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*

Objective To evaluate the safety and effectiveness of excessive dynamic airway collapse(EDAC)treated by laser.Methods 13 patients with EDAC confirmed by bronchoscopy from January 2018 to August 2022 were selected and divided into a simple EDAC group(6 cases)and an EDAC combined with tracheobronchomalacia(TBM)group(7 cases)based on whether they were combined with TBM.All patients underwent laser tracheobronchoplasty under bronchoscope.Symptoms,airway collapse,oxygenation index,modified version of British Medical Research Council dyspnoea scale(mMRC)and 6 min walking test before and after treatment were compared to evaluate the therapeutic effect.Results 13 patients underwent 17 times of laser tracheobronchoplasty with laser power of 8～15 W,and 4 patients underwent 2 times of laser tracheobronchoplasty.After treatment,the clinical symptoms of cough,sputum,shortness of breath and dyspnea were improved in all patients.1 week post-treatment,the EDAC group showed a significant improvement in airway lumen stenosis,with a significant statistical difference(P<0.05),1 month post-treatment,enhancements were observed in airway stenosis,oxygenation index,FEV1%,6-minute walk test,and mMRC,which remained stable over a 6 month follow-up.In the EDAC + TBM group,significant enhancements in airway stenosis,oxygenation index,and mMRC were noted 1 week post-treatment,with statistical significance(P<0.05).Between 8 d～6 months post-treatment,some patients exhibited a recurrence of airway stenosis,necessitating comprehensive interventions like balloon dilation,cryotherapy,and stent insertion.Local necrosis and granuloma occurred in some patients after laser therapy,and no serious complications associated with laser intervention were found in all patients.Conclusion Laser tracheobronchoplasty is a safe and effective technique for the treatment of EDAC.For patients with EDAC alone,the therapeutic effect is good,but for patients with EDAC combined with TBM,the long-term effect is not good.

Objective:To investigate the levels of microRNA (miR) -106b-5p and miR-760 in the serum of early lung cancer patients, and the clinical value of the combination of them and low-dose spiral CT in the diagnosis of early lung cancer.Methods:Ninety early lung cancer patients (lung cancer group) who underwent treatment in Cangzhou People's Hospital of Hebei Province from January 2022 to March 2023 were collected as research subjects, meantime, 90 patients with benign pulmonary lesions (benign pulmonary nodules) diagnosed by pathology were selected as the control group. The levels of miR-106b-5p and miR-760 in the serum of two groups were compared, the results of low-dose spiral CT examination were analyzed; receiver operating characteristic curve was drawn to determine the optimal cut-off values of serum miR-106b-5p and miR-760; four grid table method was applied to analyze the diagnostic efficacy of serum miR-106b-5p, miR-760 combined with low-dose spiral CT for early lung cancer.Results:The level of miR-106b-5p in lung cancer group was higher than that in control group (1.39±0.31 vs. 1.04±0.30), serum miR-760 level was lower than that in control group (0.75±0.24 vs. 1.02±0.26), with statistically significant differences ( t=7.70, P<0.001; t=7.24, P<0.001). The area under curve (AUC) of miR-106b-5p, miR-760 and low-dose spiral CT in the diagnosis of early lung cancer was 0.83, 0.81 and 0.82, the accuracy was 76.67%, 77.22% and 81.67%, the sensitivity was 84.44%, 81.11% and 76.67%, and the specificity was 68.89%, 73.33% and 86.67%, respectively. The AUC, accuracy, sensitivity, and specificity of serum miR-106b-5p, miR-760 combined with low-dose spiral CT in diagnosing early lung cancer were 0.96, 90.00%, 94.44%, and 85.56%, respectively. The accuracy of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 and low-dose spiral CT ( χ2=11.52, P=0.001; χ2=10.72, P=0.001; χ2=5.14, P=0.023), the sensitivity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 and low-dose spiral CT ( χ2=4.77, P=0.029; χ2=7.46, P=0.006; χ2=11.51, P=0.001), the specificity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 ( χ2=7.11, P=0.008; χ2=4.12, P=0.042) . Conclusion:The serum level of miR-106b-5p is significantly increased in early lung cancer patients, while the serum level of miR-760 is significantly reduced. The combination of miR-106b-5p, miR-760 and low-dose spiral CT has high diagnostic value for early lung cancer.

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.

Parkinson's disease is a neurodegenerative disease associated with abnormal copper metabolism in the brain,which leads to misfolding and aggregation of α-synuclein-copper complexes,which is an important pathological sign of Parkinson's disease.Copper metabolism,i.e.,cellular metabolic processes involving copper ions,is closely related to the pathogenesis of α-synuclein aggregation,dopamine metabolism,mitochondrial dysfunction,oxidative stress,and ferroptosis in Parkinson's disease.In this review,we summarize the molecular metabolic mechanism of copper toxicity by studying the pathological role of copper metabolism in Parkinson's disease,to support our further understanding of the mechanism of action and drug development.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.