Based on the etiology and clinical diagnostic criteria of type 2 diabetes mellitus （T2DM）， identification and typing of treatment from the perspective of traditional Chinese and western medicine， the criteria for evaluating the clinical compatibility of traditional Chinese and western medicine in animal models of T2DM were set up. The literature was reviewed to sort out and analyze the existing commonly used modeling methods， summarize the mechanism， compare the advantages and disadvantages， and calculate the consistency between the animal model and the clinical symptoms， syndromes， and indicators from the perspective of traditional Chinese and western medicine. The authors found that spontaneous animal models and high-fat diets combined with multiple low-dose streptozotocin （STZ） induction models were more in line with modern medical pathogenesis of T2DM. However， it fails to form some special syndromes required for traditional Chinese medicine （TCM） research. In addition， there are many methods of combining the etiology and pathogenesis of TCM， which can be divided into three categories： intervention carried out by drug administration， behavioral stimulation， or environmental changes according to TCM， or use of hormones according to clinical evidence and combination of the two methods mentioned above. All of them can successfully establish different types of animal models. However， different methods of establishing syndrome models have their own advantages and disadvantages， and there is no unified standard for the stability and evaluation of syndrome models. As for the clinical consistency criteria of traditional Chinese and western medicine established in this paper， the animal model with 100% consistency has not been calculated due to the conditions of incomplete symptoms and syndromes described in the studies and different selection indicators. Consequently， the establishment of a simple， easy-to-use， and affordable T2DM animal model with both traditional Chinese and western medicine disease characteristics and the improvement of the Chinese and western medicine evaluation system for different evidence types are of great significance for the future development of TCM research on T2DM.

Based on the etiology and clinical diagnostic criteria of type 2 diabetes mellitus （T2DM）， identification and typing of treatment from the perspective of traditional Chinese and western medicine， the criteria for evaluating the clinical compatibility of traditional Chinese and western medicine in animal models of T2DM were set up. The literature was reviewed to sort out and analyze the existing commonly used modeling methods， summarize the mechanism， compare the advantages and disadvantages， and calculate the consistency between the animal model and the clinical symptoms， syndromes， and indicators from the perspective of traditional Chinese and western medicine. The authors found that spontaneous animal models and high-fat diets combined with multiple low-dose streptozotocin （STZ） induction models were more in line with modern medical pathogenesis of T2DM. However， it fails to form some special syndromes required for traditional Chinese medicine （TCM） research. In addition， there are many methods of combining the etiology and pathogenesis of TCM， which can be divided into three categories： intervention carried out by drug administration， behavioral stimulation， or environmental changes according to TCM， or use of hormones according to clinical evidence and combination of the two methods mentioned above. All of them can successfully establish different types of animal models. However， different methods of establishing syndrome models have their own advantages and disadvantages， and there is no unified standard for the stability and evaluation of syndrome models. As for the clinical consistency criteria of traditional Chinese and western medicine established in this paper， the animal model with 100% consistency has not been calculated due to the conditions of incomplete symptoms and syndromes described in the studies and different selection indicators. Consequently， the establishment of a simple， easy-to-use， and affordable T2DM animal model with both traditional Chinese and western medicine disease characteristics and the improvement of the Chinese and western medicine evaluation system for different evidence types are of great significance for the future development of TCM research on T2DM.

Objective: To investigate the effect of different volumes of isotonic washing solution (0.9% NaCl) on the quality of intraoperative autologous blood salvage in craniocerebral surgery. Methods: Thirty patients who underwent neurosurgical procedures with intraoperative salvaged blood volumes exceeding 800 mL between August 2022 and July 2024 were enrolled as study subjects. The salvaged blood was divided into four groups: group A, group B, group C, and group D. Group A was washed with 500 mL of isotonic solution (blood-to-washing solution ratio of 1∶2), group B with 1000 mL (ratio of 1∶4), and group C with 1 500 mL (ratio of 1∶6). After centrifugation, the washed blood was stored in designated blood bags (A, B, and C, respectively). Blood gas analysis was performed on 5 mL samples obtained from the centrifuged blood in groups A, B, and C, and from the unwashed blood in the reservoir of the control group (group D). Parameters including red blood cell (RBC) count, pH, hemoglobin (Hb), hematocrit (HCT), potassium ion (K ), sodium ion (Na ), and lactate levels were also measured using these samples. Additionally, blood samples from each group were examined microscopically to assess red blood cell morphology. Results: No significant differences were observed among groups A, B, and C in terms of RBC recovery rate, HCT, Na concentration, or lactate clearance rate (P>0.05). All three groups exhibited a reduction in pH, with group C showing a more pronounced decrease compared to groups A and B. Similarly, K clearance was achieved in all groups, with group C demonstrating superior efficiency. Microscopic analysis revealed a reduction in spiculated red blood cells across all groups, with group C achieving the highest clearance rate. Conclusion: Group C (washed with 1 500 mL solution) demonstrated optimal performance in reducing pH levels, clearing K , and removing spherocytes, while maintaining red blood cell recovery rate. Additionally, it did not significantly increase the risk of hypernatremia in critically ill neurosurgical patients, making it more suitable for craniocerebral surgeries.

Purpose To investigate the clinical significance of Gasdermin B(GSDMB)in ovarian cancer and its relationship with immune infiltration,aiming to explore novel biomarkers for immunotherapy.Methods Gene expres-sion matrix,somatic mutations,somatic copy number alterations(SCNA),and clinical data were obtained from the The Cancer Genome Atlas(TCGA)database.Copy number variation(CNV)analysis was performed using the GISTIC algorithm,and the CIBERSORT algorithm was applied to quantify the relative abundance of 22 immune cell types in the tumor microenvironment.Protein-protein interaction(PPI)network analysis was conducted to identify GSDMB-associ-ated interacting proteins.Additionally,multiplex immunofluorescence was used to verify the spatial distribution differ-ences of GSDMB protein in clinical ovarian cancer samples with different immune phenotypes and its interaction with immune cells.Results The expression level of the GSDMB gene was significantly higher in adjacent non-cancerous tissues than in tumor tissues(P＜0.001).Patients with high GSDMB expression exhibited elevated levels of immune chemokines(such as CXCL9 and CXCL10,P＜0.01)and tumor-killing lymphocytes(the proportion of CD8+T cell was significantly higher in the high-expression group than in the low-expression group,P＜0.001).CNV analysis re-vealed that GSDMB copy number alterations significantly influenced immune cell infiltration:patients with GSDMB cop-y number amplification had decreased infiltration levels of CD4+T cells and dendritic cells(P＜0.05),while those with deep deletion of GSDMB had significantly reduced infiltration levels of CD8+T cells and neutrophils(P＜0.01).PPI network analysis indicated that GSDMB might interact with key immune molecules,including IL-37,IL-18BP,IL-33,and IL-2(Pearson correlation coefficient r＞0.6,P＜0.001).Multiplex immunofluorescence analysis demonstra-ted that tumors with high GSDMB expression were more likely to exhibit an immune-inflamed phenotype(52.6％),while tumors in the low-expression group were predominantly immune-desert type(47.3％).Immunotherapy cohort a-nalysis suggested that GSDMB could serve as a potential predictive biomarker for immunotherapy responsiveness,with high predictive efficacy in multiple immune checkpoint inhibitor therapy cohorts targeting PD-1,PD-L1,and CTLA4(AUC＞0.8).Conclusion GSDMB plays a crucial role in reshaping the tumor microenvironment in ovarian cancer and may serve as a novel sensitizing target for immunotherapy.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

This study aimed to investigate the therapeutic effect of Yindan Pinggan capsules (YDPG) on intrahepatic cholestasis (IHC) through animal experiments, while utilizing network pharmacology and molecular docking techniques to explore its potential mechanisms. Initially, the therapeutic effect of YDPG on an α-naphthylisothiocyanate (ANIT)-induced IHC mouse model was assessed through liver function tests, routine blood tests, and liver pathology analysis. Subsequently, network pharmacology tools were employed to predict the active components, core targets, and signaling pathways of YDPG. Molecular docking technology was employed to verify the binding activity of key active components of YDPG with core targets, followed by protein immunoblotting to validate the key targets. Results showed that YDPG significantly improved liver function abnormalities and hepatocyte damage in IHC mice. Network pharmacology analysis revealed that 94 active components in YDPG were associated with 396 targets for the treatment of IHC, and were significantly enriched in pathways such as the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, lipid metabolism, and bile secretion. Molecular docking results showed good binding activity between key active components of YDPG and core targets of the PI3K-AKT signaling pathway. Further protein immunoblotting confirmed that YDPG could reduce the phosphorylation levels of PI3K and AKT proteins, core targets of the PI3K-AKT pathway in liver tissue. These findings suggest that YDPG may alleviate biological processes such as oxidative stress and inflammatory responses by regulating the PI3K-AKT signaling pathway, thereby improving liver damage in IHC mice and exerting a therapeutic effect on IHC. This experiment has been approved by the Animal Experiment Ethics Committee of Jinan University (ethical approval number: IACUC-20241011-09).

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.

Objective:To explore the influencing factors for pneumonia occurrence within three months in patients undergoing partial laryngectomy combined with radiotherapy, and to construct a nomogram prediction model for the risk of pneumonia occurrence.Methods:A total of 165 patients with laryngeal squamous cell carcinoma who underwent partial laryngectomy combined with postoperative radiotherapy in the Affiliated Cancer Hospital of Zhengzhou University from 2017 to 2023 were divided into three groups: a group without pneumonia, a low risk pneumonia group, and a medium to high risk pneumonia group according to the occurrence of pneumonia. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values of the mean dose to the larynx (Larynx-Dmean) and the mean dose to the pharyngeal constrictor muscles (PCM-Dmean) for predicting the occurrence of pneumonia. Logistic regression analysis was used to screen out the influencing factors of pneumonia within three months after partial laryngectomy combined with radiotherapy, and a nomogram prediction model was constructed.Results:Among the 165 patients, 59 were in the group without pneumonia, 60 were in the group with a low risk of pneumonia, and 46 were in the group with a medium to high risk of pneumonia. The overall incidence of pneumonia was 64.2% (106/165). ROC curve analysis showed that the area under the curve (AUC) of the Larynx-Dmean for predicting the occurrence of pneumonia was 0.876, and the optimal cutoff value was 60.8 Gy. When the Larynx-Dmean was >60.8 Gy, the incidence of pneumonia was 96.7%. The AUC of the PCM-Dmean for predicting the occurrence of pneumonia was 0.747, and the optimal cutoff value was 54.6 Gy. When the PCM-Dmean was >54.6 Gy, the incidence of pneumonia was 74.7%. The AUC of the Larynx-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.987, and the optimal cutoff value was 68.2 Gy. When the Larynx-Dmean was >68.2 Gy, the incidence of medium to high risk pneumonia was 100.0%. The AUC of the PCM-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.850, and the optimal cutoff value was 58.7 Gy. When the PCM-Dmean was >58.7 Gy, the incidence of medium to high risk pneumonia was 85.2%. Multivariate logistic regression analysis showed that the incidence of pneumonia was higher in patients with a history of smoking ( OR=1.54, 95% CI: 1.02-1.74), a higher smoking index ( OR=2.43, 95% CI: 1.16-7.59), a higher Larynx-Dmean ( OR=3.79, 95% CI: 1.25-6.49), and a higher PCM-Dmean ( OR=2.44, 95% CI: 1.53-3.16). A nomogram prediction model for the risk of pneumonia and medium to high risk pneumonia within three months after partial laryngectomy combined with radiotherapy was successfully constructed, with C indices of 0.78 and 0.98, respectively, which had good predictive performance and clinical efficacy. Conclusions:When the Larynx-Dmean was >60.8 Gy and the PCM-Dmean was >54.6 Gy for postoperative radiotherapy after partial laryngectomy, the possibility of pneumonia occurrence in patients within three months increased significantly. Smoking history, smoking index, Larynx-Dmean, and PCM-Dmean were independent influencing factors for the occurrence of pneumonia. The nomogram prediction model constructed based on this can guide clinicians to take intervention measures to prevent the occurrence of pneumonia in patients with laryngeal cancer.

Objective:To investigate the inhibitory effect of tripartite motif-containing 25 (TRIM25) on the replication of Japanese encephalitis virus (JEV) in cells and its molecular mechanism.Methods:Human glioma cells (U251 cells) and Kunming mice were infected with JEV, and then the cells and brain tissue samples were collected. The transcription levels of six TRIM genes were detected by real-time PCR, and the expression of TRIM25 in cells was detected by Western blot. U251 and A549 cells overexpressed with TRIM25 and U251 cells knocked out with TRIM25 gene were constructed. Cells were infected with JEV, and the replication of JEV was detected by viral plaque assay, real-time PCR and Western blot. The interaction of TRIM25 with viral proteins was investigated by co-immunoprecipitation (Co-IP) and indirect immunofluorescence assay. The expression of IFN-β in overexpressed TRIM25 cells was detected by real-time PCR and ELISA.Results:JEV infection promoted the expression of TRIM25 in cells and mouse brain tissues. TRIM25 overexpression restricted JEV replication in U251 and A549 cells, while TRIM25 knockout enhanced JEV replication. TRIM25 overexpression upregulated the level of IFN-β in cells. TRIM25 interacted with JEV capsid protein and promoted the degradation of capsid protein.Conclusion:TRIM25 can inhibit the replication of JEV in cells by upregulating IFN-β and promoting the degradation of JEV C protein.