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.

Objective To investigate the effect and underlying mechanism of serine and arginine rich splicing factor 1(SRSF1)on the replication of hepatitis B virus(HBV).Methods The effects of SRSF1 on HBV replication were investigated in different HBV replicating cell models by Southern blotting,Northern blotting and ELISA.Quantitative PCR,luciferase reporter assay and chromatin immunoprecipitation(ChIP)were applied to determine the effects of SRSF1 on the activities of HBV core promoter/enhancer in HepG2 cells.The relationship between SRSF1 and P53 was explored with Western blotting and ubiquitination assay.The effects of P53 on HBV replication were verified in different HBV replicating cell models,and the role of P53 in SRSF1 inhibition of HBV was clarified.Results Overexpression of SRSF1 significantly inhibited HBV DNA and HBV RNA and reduced HBsAg and HBeAg secretion levels in a variety of HBV replicative cell models(P<0.0001).SRSF1 also inhibited the activity of HBV core promoter,although this inhibition was regulated by indirect mechanisms.In addition,SRSF1 enhanced P53 stability by protecting P53 from ubiquitination and subsequent proteasomal degradation.Meanwhile,the regulatory effect of overexpression or knockdown of P53 on HBV was validated in different cell models(P<0.0001).Conclusion Overexpression of splicing factor SRSF1 significantly inhibits HBV replication in a variety of cell models,and this inhibitory effect is mediated by its enhancement of P53 stability.

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*

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.

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.

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 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 explore the value of coronary computed tomography angiography(CCTA)in assessing the relationship between the fat volume around coronary plaque and the abnormal coronary hemodynamics.Methods:A total of 218 hospitalized patients admitted to Cangzhou People's Hospital from June 2022 to September 2023 were selected.In these patients,108 patients without coronary heart disease(CHD)were included in the control group,and 110 CHD patients were included in the observation group.All patients underwent CCTA examination to compare the CT imaging values(FFRCT)of the fat volume around heart and blood flow reserve fraction between the two groups.Receiver operating characteristic(ROC)curve was performed to analyze the efficacy of the fat volume around heart and FFRCT values in predicting coronary artery plaques.Additionally,Pearson's method was used to analyze the correlation between fat volume around heart and FFRCT.Results:The fat volume around heart in the observation group was(168.70±38.16)cm3,which was significantly higher than(98.75±21.19)cm3 in the control group,and the FFRCT value(0.78±0.11)of the observation group was lower than(0.89±0.10)in the control group,with statistically significant differences(t=16.688,8.041,P<0.05),respectively.In the observation group,89 patients occurred plaque,and 21 patients did not occur plaque.In the observation group,the fat volume around heart in patients with plaques was(176.63±34.15)cm3,which was significantly higher than(133.52±36.85)cm3 in patients without plaques,and the FFRCT value in patients with plaques was(0.76±0.10),which was significantly lower than(0.85±0.11)in patients without plaques,with statistically significant differences(t=4.945,3.815,P<0.05),respectively.According to Pearson's analysis,there was a negative correlation between the fat volume around heart and FFRCT value.According to Spearman's analysis,with or without plaques appeared positive correlation with the fat volume around heart in CHD patients,and they appeared negative correlation with FFRct value.According to ROC curve analysis,the area under curve(AUC)values of fat volume around heart,FFRCT,and the combination of them were respectively 0.777,0.726 and 0.930 in predicting the plaques of CHD patients.Conclusion:Hemodynamics and fat volume around heart that is measured by CCTA can predict coronary plaque,and there is a certain of relationship between coronary hemodynamics and the fat volume around coronary artery plaques,which appears negative correlation.