Alzheimer's disease （AD） is a common type of dementia， primarily characterized by cognitive and behavioral impairments as well as deficits in learning and memory. The progression of AD has imposed a significant economic burden on society and families. However， its exact pathogenesis has not yet been fully elucidated. Currently， available therapeutic drugs are limited and are often accompanied by serious adverse effects. Traditional Chinese medicines （TCMs） and their extracts are mostly natural products and possess advantages such as multi-pathway regulation and relatively few adverse reactions. Experimental studies have shown that TCMs exhibit great potential in the prevention and treatment of AD. For example， Huanglian Jieduang， Danggui Shaoyaosan， Kaixin San， Liuwei Dihuangwan， Buyang Huanwutang， as well as Ginseng Radix et Rhizoma， Astragali Radix， Uncariae Ramulus cum Uncis， Coptidis Rhizoma， Gardeniae Fructus， Ginkgo Folium， Salviae Miltiorrhizae Radix et Rhizoma， and Curcumae Longae Rhizoma， can reduce β-amyloid deposition， inhibit excessive Tau protein phosphorylation， restore mitochondrial function， alleviate oxidative stress， suppress neuroinflammation and apoptosis， repair synaptic function， and improve gut microbiota. This article mainly summarizes the effects of several TCMs and compound prescriptions on AD， aiming to provide a reference for subsequent TCM-based treatment of AD.

ObjectiveTo dynamically observe and evaluate the damage to the pulmonary air-blood barrier in mice during the inflammatory cancer transformation process of ulcerative colitis （UC） based on the "lung-intestine correlation" theory. MethodsSixty-five C57BL/6 mice were divided into a normal group （n=25） and a model group （n=40） using a random number table. Azoxymethane/dextran sodium sulfate （DSS） method was used to establish a mouse model of UC inflammation cancer transformation in the modeling group. According to the tissue collection time points at 5， 8， 11， 13， and 15 weeks， the normal group mice were randomly divided into the normal 5w， 8w， 11w， 13w， and 15w groups. The model group mice， 10 mice of which died after the first cycle of DSS administration， were randomly divided into model 5w， 8w， 11w， 13w， and 15w groups. During the experiment， the general condition of the mice was observed daily， and their body weight was measured weekly. At the corresponding tissue collection time points， the colon length of each group was measured. Histopathology of mouse lung and colon tissues was examined using HE staining. Immunofluorescence was used to detect changes in the positive expression of tight junction protein （ZO-1）， vascular endothelial cadherin （VE-cadherin）， and cytoskeletal protein （F-actin） in lung and colon tissues. RT-PCR was used to detect the mRNA expression of apoptosis regulatory proteins B-cell lymphoma-2 （Bcl-2）， BCL2-associated X protein （Bax）， and Cysteine aspartic acid protease-3 （Caspase-3） in lung tissues. Western Blot was employed to measure protein levels of ZO-1， VE-cadherin， and F-actin in lung tissues. ResultsCompared to the normal group at the same time point， the mice in the model group at each time point generally had poorer conditions， with weight loss and shortened colon length （P＜0.05 or P＜0.01）. In the model 5w group， there was significant inflammatory cell infiltration in the colon tissue； in the model 8w group， there was mild atypical hyperplasia； in the model 11w group， the crypt structure was disordered， and moderate to severe atypical hyperplasia occurred； in the model 13w and 15w groups， tumors appeared. Pulmonary interstitial lesions， inflammation， vasculitis， and fibrosis were observed at all stages of UC inflammation cancer transformation. The protein levels of ZO-1， VE-cadherin， and F-actin， as well as Bcl-2 mRNA expression in lung tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period， while the expressions of Bax and Caspase-3 mRNA increased； the expressions of ZO-1， VE-cadherin， and F-actin proteins in colon tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period （P＜0.01 or P＜0.05）. Compared to the model 5w group， the ZO-1 and F-actin protein levels and Bcl-2 mRNA expression in lung tissue in the other model groups increased in the atypical hyperplasia period and canceration period， while the expressions of Bax and Caspase-3 mRNA decreased； the expression of ZO-1 protein in colon tissue increased in the canceration period， and the expression of VE-cadherin protein decreased in the atypical hyperplasia period （P＜0.01 or P＜0.05）. ConclusionIn the process of "inflammatory response-atypical hyperplasia-carcinogenesis" in UC inflammatory cancer transformation mice， there were damage to air-blood barrier.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

OBJECTIVE To prepare polyethylene glycol （PEG）-modified flower lactose （FL） loaded Curcumin （Cur） solid lipid nanoparticle （SLN） inhalable micropowder （referred to as “PEG-Cur-FL”）. METHODS PEG-Cur-FL was prepared by the solvent emulsification diffusion low-temperature solidification method， and its encapsulation efficiency， drug loading capacity， powder properties， aerodynamic particle size， in vitro deposition properties， and in vitro release characteristics were characterized. The mice were divided into Cur-SLN-FL （unmodified with PEG） group and PEG-Cur-FL group， with 55 mice in each group. Both groups of mice were given a single inhalation of 5 mg/kg （calculated as Cur） of the corresponding drug micropowder through an air tube. At 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24， 48 and 72 hours after administration， eyeballs were removed to collect blood and tracheal， lung， liver and kidney tissues were separated. The mass concentration of Cur in mouse plasma and various tissue samples was measured， and the tissue distribution and retention of the drug were analyzed. RESULTS The encapsulation efficiency and drug loading capacity of PEG-Cur-FL were （86.2±1.8）% and （4.2±0.2）%， respectively； the bulk density and tap density were （0.24±0.01） g/cm3 and （0.30±0.01） g/cm3， respectively； the aerodynamic particle size was （2.74±0.64） μm； the in vitro effective site deposition rate （secondary drug deposition rate） was （45.07±2.79）%. Compared with Cur raw materials， Cur-SLN- FL and PEG-Cur-FL had sustained release effects under both leakage and non-leakage conditions， and PEG-Cur-FL had a smoother sustained release in artificial lung fluid， with release characteristics consistent with the Weibull model. The results of in vivo distribution showed that the drug concentration in the lung tissue of PEG-Cur-FL group was significantly lower than that of Cur- SLN-FL group during the same period after 1 hour of administration， while the drug concentration in the lung tissue at 4 to 48 hours was significantly higher than that of Cur-SLN-FL group during the same period （P＜0.05）； the plasma drug concentrations of the PEG-Cur-FL group at all time points from 0.25 to 12 hours were significantly lower than those of the Cur-SLN-FL group during the same period （P＜0.05）， and the drug concentrations in liver and kidney tissues were also lower than those of the Cur-SLN-FL group during the same period （P＜0.05）. CONCLUSIONS PEG-Cur-FL is prepared successfully； the inhalable micropowder has good inhalability and release performance； after administration through the trachea， the effective concentration of Cur in lung tissue can be increased， while reducing its plasma drug concentration and drug distribution concentration in non-target organs.

OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Objective:To detect the biological markers related to Alzheimer's disease(AD)in the peripheral blood of AD patients,and to explore the activities and levels of the antioxidant function indexes and the expressions of related genes and proteins in the blood of AD patients and the changes after intervention of selenium-rich food.Methods:The Mini-Mental State Examination(MMSE)combined with electroencephalogram or brain CT and clinician diagnosis were used for screening AD.Fifty-six elderly patients with AD aged 75-90 years old were selected.Among them,28 cases were selected as normal diet group for AD(AD group),and 28 cases were selected as dietary selenium intervention group(Se-AD group).The patients in Se-AD group were given daily dietary selenium supplementation(increaseing dietary selenium by 15-20 μg per day)for 3 months.Meanwhile,30 people with the same age were selected as healthy control group.The activities of serum superoxide dismutase(SOD),cholinesterase(CHE),and glutathione peroxidase(GSH-Px)and the levels of serum malondialdehyde(MDA),homocysteine(Hcy),and nitric oxide(NO)as well as reagent kit the levels of serum β-amyloid protein(Aβ),and microtubule-associated protein(Tau)and phosphorylated microtubule-associated protein(p-Tau)of the subjects in various groups were detected by and enzyme-linked immunosorbent assay(ELISA)method;the expression levels of apolipoprotein E4(ApoE4),presenilin 1(PS1),presenilin 2(PS2),cysteinyl aspartate specific proteinase 3(Caspase3),sorting associated protein receptor 1(SORL1),β-site amyloid precursor protein cleaving enzyme 1(BACE1),hypoxia-inducible factor 1(HIF1),nuclear factor-kappa B(NF-κB),β-amyloid precursor protein(APP),protein kinase C(PKC),and Aβ mRNA in peripheral blood of the subjects various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with healthy control group,the serum SOD activities of the patients in Se-AD group and AD group were significantly decreased(P＜0.05),while serum CHE activity and the levels of MDA and Hcy were significantly increased(P＜0.05);the serum GSH-Px activity of the patients in AD group was significantly decreased(P＜0.05),and the level of NO was significantly increased(P＜0.05).Compared with Se-AD group,serum CHE activity and the level of Hcy of the patients in AD group were significantly increased(P＜0.05).The expression levels of ApoE4,PS1,Caspase3,BACE1,NF-κB and APP mRNA of the patients in Se-AD group and AD group were significantly increased(P＜0.05),and the expression levels of PKC mRNA were significantly decreased(P＜0.05);the expression level of PS2 mRNA of the patients in AD group was significantly increased(P＜0.05),and the expression levels of Aβ mRNA of the patients in Se-AD group and AD group were significantly increased(P＜0.05).Conclusion:The activities of serum SOD,GSH-Px and CHE and the levels of MDA,Hcy and NO,the levels of Aβ,Tau and p-Tau proteins,and the expression levels of ApoE4,PS1,Caspase3,BACE1,NF-κB,PKC,PS2,Aβ and APP mRNA in peripheral blood of the AD patients may vary and can be used for clinical diagnosis of the AD patients.Selenium-rich food can improve AD to some extent,and its mechanism is related to reducing the oxidative damage of brain tissue and decreasing the expression of AD related genes PS2 and Aβ.

Objective:To explore the mechanism of modified Shaoyao Decoction with Astragali Radix and Houttuynize Herba in regulating PI3K/Akt/NF-κB pathway against intestinal mucosal barrier injury in ulcerative colitis (UC) rats.Methods:Totally 72 Wistar rats were randomly divided into a blank control group, a model group, a mesalazine group, and modified Shaoyao Decoction high-, medium-, and low-dose groups using a random number table method. After successful modeling, the mesalazine group was given 0.2 g/kg of mesalazine suspension by gavage, while modified Shaoyao Decoction high-, medium-, and low-dose groups were given 44.5, 22.3, and 11.1 g/kg of modified Shaoyao Decoction by gavage, once a day, for a total of 4 weeks. The pathological changes of colon tissue were observed using HE staining; immunofluorescence assay was used to detect the expressions of tight junction protein (ZO-1), cytoskeletal protein (F-actin), and vascular endothelial cadherin (VE cadherin) in colon tissue; Western blot was used to detect the protein expressions of PI3K, Akt, NF-κB, VEGF, and cyclooxygenase (COX-2) in colon tissue; QRT PCR was used to detect the expressions of PI3K and Akt mRNA in colon tissue; ELISA method was used to detect the levels of serum TNF-α and endothelin (ET).Results:Compared with the model group, the DAI scores of the mesalazine group and modified Shaoyao Decoction high-dosage group decreased significantly on the 7th, 14th, 21st and 28th day after modeling ( P<0.05 or P<0.01). In mesalazine group and modified Shaoyao Decoction high-, medium-, and low-dose groups, the pathological injury score of colon tissue decreased ( P<0.01), the immunofluorescence intensity of ZO-1, F-actin and VE-cadherin protein expression in colon tissue increased ( P<0.05 or P<0.01), and the expressions of PI3K, Akt, NF-κB and VEGF protein decreased ( P<0.01). The expression of COX-2 protein and the levels of PI3K mRNA and Akt mRNA decreased in the mesalazine group and modified Shaoyao Decoction high- and medium groups ( P<0.05 or P<0.01). Conclusion:Modified Shaoyao Decoction can antagonize the intestinal barrier injury of UC by inhibiting PI3K/Akt/NF-κB pathway and promote the healing of intestinal mucosal ulcer.

Objective:To investigate immunological non-responders (INRs) and immunological responders (IRs) during long-term antiretroviral therapy (ART), and study the dynamics of HIV reservoir and α4β7 cells in INRs and IRs and their correlation.Methods:Twenty-six patients with chronic HIV infection who received ART for 5 years were included. They were divided into INRs (CD4 + T cell counts≤350 cells/μl, n=9) and IRs (CD4 + T cell counts≥500 cells/μl, n=17) based on immune reconstitution outcomes. The percentages and numbers of α4β7 cells in both groups at baseline, ART 1, 3, and 5 years were detected by flow cytometry, and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods. HIV viral decay, α4β7 cells dynamics, and their correlations with T cells were compared at baseline, ART 1, 3 and 5 years between the two groups. Results:Over 5 years of ART, INRs exhibited higher HIV reservoir levels compared to IRs, but the decline trend was not slow. The counts of α4β7 cell were lower and the growth trend was slow in INRs ( P<0.05). α4β7 cell counts were strongly positively correlated with CD4 + T cell counts at all timepoints (Year 1: r=0.887; Year 3: r=0.878; Year 5: r=0.887; P all <0.001), while showing significantly negative correlations with activated CD38 + HLA-DR + CD4 + T cells (Year 1: r=-0.619, P=0.001), CD38 + HLA-DR + CD8 + T cells (Year 1: r=-0.517; Year 5: r=-0.532; P all <0.01), and PD-1 + CD4 + T cells (Year 1: r=-0.476, Year 5: r=-0.390, P all <0.05). Conclusions:During long-term ART, INRs maintained higher HIV reservoir and lower α4β7 cell counts compared with IRs, and decreased α4β7 cells may be associated with disease progression.

Strategic management of tributary veins including concomitant versus staged intervention during endovenous thermal ablation for truncal varicose veins remains debated. Concomitant procedures mainly involves thermal ablation with ultrasound-guided foam sclerotherapy or phlebectomy. Staged strategies include initial truncal ablation followed by deliberated tributary management. Major venous disease guidelines exhibit substantial divergence,Japanese Society of Phlebology guidelines in 2019 contraindicate concomitant procedures, European Society for Vascular Surgery 2022 Clinical Practice Guidelines and Chinese frameworks endorse individualized decision-making,while American Vein and Lymphatic Society guidelines in 2023 prioritize concomitant procedures. Systematic literature review reveals that concomitant procedures do not uniformly translate into reduced reintervention rates or improved early Venous Clinical Severity Scores, yet consistently incur elevated complication risks and postoperative pain. Conversely, staged strategies offer superior tolerability with minimized complications. Hemodynamic principles indicate that most competent tributaries undergo partial or complete regression within 6 weeks to 6 months post-ablation and hemodynamic studies demonstrate that staged approaches preserve the drainage function of tributaries, preventing edema in their respective drainage territories and reducing tributary intervention rates. Future multicenter randomized controlled trials are imperative to delineate comparative outcomes between concomitant and staged management of truncal and tributary veins.