The excessive accumulation of advanced glycosylation end products(AGEs), the end products of non-enzymatic glycosylation reactions, can be involved in the pathological processes of various ocular diseases through mechanisms such as oxidative stress, inflammatory responses and apoptosis. In this paper, we systematically reviewed the key role of AGEs in diabetic keratopathy, cataract, glaucoma, age-related macular degeneration(ARMD)and diabetic retinopathy(DR). It was found that AGEs activate signalling pathways such as NADPH oxidase, MAPK and NF-κB by binding to the receptor RAGE, leading to reactive oxygen species(ROS)generation, release of inflammatory factors, and vascular endothelial dysfunction, which in turn induces delayed corneal healing, cross-linking of lens proteins, optic nerve degeneration, formation of choroidal neovascularisation(CNV), and blood-retinal barrier(BRB)disruption. For example, in diabetic keratopathy, AGEs delay wound healing via the ROS/NLRP3 inflammatory vesicle axis; in cataract, ascorbic acid-mediated cross-linking of lens proteins due to AGEs directly impairs lens transparency; and in DR, AGEs exacerbate microvascular damage by regulating vasucular endothelial growth factor(VEGF)expression and pericyte apoptosis. In addition, this article discusses the advances and limitations of AGEs detection techniques, such as the potential application of lens AGEscan fluorescence assay in screening for diabetic complications, and the need to develop tissue-specific assays for aqueous humour and vitreous. For therapeutic strategies, the research directions of inhibiting AGEs production, blocking RAGE signalling pathway and developing anti-glycosylation drugs are proposed to emphasise their clinical value in delaying disease progression. This review not only integrates the molecular mechanisms and clinical associations of AGEs in ocular diseases, but also provides a theoretical basis for targeted interventions, which is of great significance in exploring novel diagnostic and therapeutic strategies.

Non-human primate animal models are core tools for the study of highly pathogenic microorganisms and are irreplaceable in the fields of pathology and drug discovery.However,anatomical sampling of non-human primate infection models in high-level biosafety laboratories carries potential risk and related risk assessment and control measures require clarification.Based on biosafety regulations and practical experience,we systematically discuss the risk control strategies of anatomical operations with respect to personal protection,instrument selection,anatomical specifications,documentation,and personnel training.Our review will help to improve the management of high-level biosafety laboratories,reduce the risk of pathogen escape and human infection,and provide support for the safe research of highly pathogenic microorganisms.

ObjectiveExploring the formula rules of commonly used traditional Chinese medicines（TCMs） for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining， providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched， and the contents such as source， dynasty， author， diagnosis， formula name， therapeutic method and efficacy， and composition of medicines from each article that met the inclusion criteria were extracted. Then， an Excel standardized database was established， and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis， Pearson correlation analysis， and association rule analysis. ResultsA total of 1 595 formulas were included， involving 558 TCMs. The efficacy of these medicines could be classified into two categories， namely， expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis， high-frequency medicines were mainly detoxification， Fu-organ dredging， aromatization and promoting blood circulation， followed by the medicines with the effect of treating the lungs， such as clearing the lungs and resolving phlegm， clearing heat and purging the lungs， relieving cough and asthma， and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba， and the core acrid-cold herb was mainly Forsythiae Fructus， resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history， the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi"， focusing on the treatment of the causes and characteristics of epidemics through detoxification， Fu-organ dredging， and aromatization， emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ， eliminate toxins and pathogens， and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness， diagnose and treatment according to syndrome differentiation was performed.

ObjectiveExploring the formula rules of commonly used traditional Chinese medicines（TCMs） for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining， providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched， and the contents such as source， dynasty， author， diagnosis， formula name， therapeutic method and efficacy， and composition of medicines from each article that met the inclusion criteria were extracted. Then， an Excel standardized database was established， and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis， Pearson correlation analysis， and association rule analysis. ResultsA total of 1 595 formulas were included， involving 558 TCMs. The efficacy of these medicines could be classified into two categories， namely， expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis， high-frequency medicines were mainly detoxification， Fu-organ dredging， aromatization and promoting blood circulation， followed by the medicines with the effect of treating the lungs， such as clearing the lungs and resolving phlegm， clearing heat and purging the lungs， relieving cough and asthma， and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba， and the core acrid-cold herb was mainly Forsythiae Fructus， resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history， the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi"， focusing on the treatment of the causes and characteristics of epidemics through detoxification， Fu-organ dredging， and aromatization， emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ， eliminate toxins and pathogens， and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness， diagnose and treatment according to syndrome differentiation was performed.

Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

ObjectiveTo investigate the seroprevalence of Japanese encephalitis virus (JEV) IgG antibodies among the healthy individuals in Huzhou City, Zhejiang Province, so as to provide a scientific basis for the development of prevention and control strategies for Japanese B encephalitis (JE). MethodsA cross-sectional study was conducted from 2023 to 2024. Serum samples were collected from healthy individuals across 12 age groups (<8 months, 8 months‒<2 years, 2‒<4 years, 4‒<6 years, 6‒<8 years, 8‒<10 years, 10‒<15 years, 15‒<20 years, 20‒<30 years, 30‒<40 years, 40‒<50 years, 50‒ years) and tested for JEV IgG antibody to determine positivity rates. ResultsThe overall JEV IgG antibody seroprevalence rate was 57.75 % among the healthy individuals in Huzhou City. The positivity rates for the age groups of <8 months, 8 months‒<2 years, 2‒<4 years, 4‒<6 years, 6‒<8 years, 8‒<10 years, 10‒<15 years, 15‒<20 years, 20‒<30 years, 30‒<40 years, 40‒<50 years, and 50‒ years were 10.14%, 23.76%, 77.31%, 66.88%, 73.87%, 58.33%, 41.67%, 55.06%, 47.00%, 61.00%, 62.00%, and 92.00%, respectively, with a statistically significant difference observed in different age groups (χ²=243.996, P<0.001). Seroprevalence rates also differed significantly between males and females (χ²=9.999, P=0.002). Among subjects vaccinated with 0,1 or 2 doses of live attenuated Japanese encephalitis virus vaccine (JEV-L), the IgG antibody seroprevalence rate was 4.76%, 27.27% and 72.33%, respectively (χ²=108.568, P<0.001). Within the 2 doses group, the IgG antibody seroprevalence rate at <1 year, 1 year, 2 years and 3‒5 years after immunization were 80.85%, 77.36%, 66.67% and 65.45%, respectively, indicating a declining trend with time increased since vaccination (Z=-2.024, P=0.043). ConclusionAdults aged 50‒ years maintain high antibody levels, whereas levels are lower among the age groups of <2 years and 8‒<30 years and wane with time since vaccination in Huzhou City. It is recommended to maintain the routine JE vaccination schedule while exploring booster vaccination strategies for the age groups of 8‒<30 years, in order to enhance population immunity against JEV.

OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.

Objective To translate the English version of communicative effectiveness index(CETI)into Chinese and validate its reliability and validity for use in the elderly population.Methods The English version of CETI was translated into Chinese and back-translated using the Brislin translation model.After adjustments and pilot testing,a Chinese version of CETI was created.Between January and March 2024,a total of 395 elderly individuals aged 60 years and over were recruited from Jiangsu and Henan Provinces via convenience sampling.A total of 30 elderly people were retested with the Chinese version of CETI after two weeks of primary test to assess the reliability and validity of the scale.Results The Chinese version of CETI comprised two dimensions:conversational comprehensibility(5 items)and conversational initiative(4 items).The Cronbach α coefficient of the scale was 0.831with the split-half reliability 0.785 and the test-retest reliability 0.909.The Cronbach α coefficients of each dimension ranged from 0.641 to 0.778.The test-retest reliability of each dimension ranged from 0.889 to 0.936.The KMO value of exploratory factor analysis was 0.893,Bartlett's sphericity test valueχ 2=583.291(P<0.01),and the total explanatory rate of variation was 63.305%.Conclusion The Chinese version of CETI has good reliability and validity.It is suitable to be used in the assessment of the status of verbal communicative function in the elderly.

Non-human primate animal models are core tools for the study of highly pathogenic microorganisms and are irreplaceable in the fields of pathology and drug discovery.However,anatomical sampling of non-human primate infection models in high-level biosafety laboratories carries potential risk and related risk assessment and control measures require clarification.Based on biosafety regulations and practical experience,we systematically discuss the risk control strategies of anatomical operations with respect to personal protection,instrument selection,anatomical specifications,documentation,and personnel training.Our review will help to improve the management of high-level biosafety laboratories,reduce the risk of pathogen escape and human infection,and provide support for the safe research of highly pathogenic microorganisms.