ObjectiveBased on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway， this study explores the protective effect and mechanism of Taohong Siwutang against retinal vasculitis （RV） from the perspective of angiogenesis. MethodsSPF-grade C57BL/6J mice were used to establish a RV model induced by experimental autoimmune uveitis （EAU）， and the protective effect of Taohong Siwutang on RV was investigated. Fifty mice were randomly assigned to a blank group， model group， and low-， medium-， and high-dose Taohong Siwutang groups （3.315、6.63、13.26 g·kg^-1，10 mice in each group）. After modeling， gavage administration was performed for 20 consecutive days. A small-animal retinal imaging system and fluorescein sodium angiography were used to observe pathological changes in the retinal tissue and vessels. Hematoxylin-eosin （HE） staining was used to assess retinal histopathological changes. Immunohistochemistry was performed to evaluate CD31-positive expression. Western blot was used to detect the protein expression levels of JAK2， phosphorylated （p）-JAK2， STAT3， p-STAT3， and vascular endothelial growth factor receptor 2 （VEGFR2） in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the relative expression level of VEGFR2 mRNA in retinal vessels. ResultsCompared with the blank group， the model group showed relative optic disc swelling， multiple areas of inflammatory cell infiltration around retinal veins with partial vascular occlusion， vessel thickening and morphological alterations， uneven retinal thickness， wrinkling and bending of inner and outer layers， vascular dilation， and disordered cellular arrangement. Compared with the model group， the Taohong Siwutang groups showed markedly reduced CD31-positive expression and effectively improved perivascular inflammatory infiltration， vascular tortuous dilation， angiogenesis， vascular occlusion， and hemorrhage. Western blot results showed that compared with the model group， the expression of VEGFR2 and the phosphorylation levels of JAK2 and STAT3 were significantly decreased in the Taohong Siwutang groups （P0.01）. Real-time PCR results indicated that VEGFR2 mRNA expression was significantly decreased in the Taohong Siwutang groups compared with the model group （P0.05）. ConclusionTaohong Siwutang can effectively alleviate angiogenesis in RV and， through the JAK2/STAT3 signaling pathway， reduce angiogenesis and improve retinal pathological injury， thereby exerting a protective effect on retinal vessels.

ObjectiveBased on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway， this study explores the protective effect and mechanism of Taohong Siwutang against retinal vasculitis （RV） from the perspective of angiogenesis. MethodsSPF-grade C57BL/6J mice were used to establish a RV model induced by experimental autoimmune uveitis （EAU）， and the protective effect of Taohong Siwutang on RV was investigated. Fifty mice were randomly assigned to a blank group， model group， and low-， medium-， and high-dose Taohong Siwutang groups （3.315、6.63、13.26 g·kg^-1，10 mice in each group）. After modeling， gavage administration was performed for 20 consecutive days. A small-animal retinal imaging system and fluorescein sodium angiography were used to observe pathological changes in the retinal tissue and vessels. Hematoxylin-eosin （HE） staining was used to assess retinal histopathological changes. Immunohistochemistry was performed to evaluate CD31-positive expression. Western blot was used to detect the protein expression levels of JAK2， phosphorylated （p）-JAK2， STAT3， p-STAT3， and vascular endothelial growth factor receptor 2 （VEGFR2） in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the relative expression level of VEGFR2 mRNA in retinal vessels. ResultsCompared with the blank group， the model group showed relative optic disc swelling， multiple areas of inflammatory cell infiltration around retinal veins with partial vascular occlusion， vessel thickening and morphological alterations， uneven retinal thickness， wrinkling and bending of inner and outer layers， vascular dilation， and disordered cellular arrangement. Compared with the model group， the Taohong Siwutang groups showed markedly reduced CD31-positive expression and effectively improved perivascular inflammatory infiltration， vascular tortuous dilation， angiogenesis， vascular occlusion， and hemorrhage. Western blot results showed that compared with the model group， the expression of VEGFR2 and the phosphorylation levels of JAK2 and STAT3 were significantly decreased in the Taohong Siwutang groups （P0.01）. Real-time PCR results indicated that VEGFR2 mRNA expression was significantly decreased in the Taohong Siwutang groups compared with the model group （P0.05）. ConclusionTaohong Siwutang can effectively alleviate angiogenesis in RV and， through the JAK2/STAT3 signaling pathway， reduce angiogenesis and improve retinal pathological injury， thereby exerting a protective effect on retinal vessels.

OBJECTIVE To explore and predict the quality markers （Q-markers） of Compound xiebai capsules for the treatment of chronic obstructive pulmonary disease （COPD） by constituents analysis combined with network pharmacology and molecular docking studies， and to establish the quality standard of Compound xiebai capsules. METHODS UHPLC-TOF-MS was used for qualitative analysis of Compound xiebai capsules， and the candidate Q-markers of Compound xiebai capsules were screened by combining network pharmacology and molecular docking technology. Further， HPLC was applied to establish the fingerprints of 15 batches of Compound xiebai capsules and to conduct quantitative analysis of the main components. RESULTS A total of 51 components were identified from Compound xiebai capsules. Among them， 15 components， namely oxyberberine， methylworenine， coptisine， tetrahydroberberine， epiberberine， berberine， magnoflorine， gandensin， cucurbitacin D， hydroxygenkwan， jatrorrhizine， columbamine， quercetin， cucurbitacin R， and palmatine， were determined as the candidate Q-markers for Compound xiebai capsules in the treatment of COPD. A total of 13 common peaks were calibrated in the fingerprints of 15 batches of Compound xiebai capsules for COPD treatment， with similarity values ranging from 0.976 to 0.999 compared to the reference fingerprint. Seven components were identified among these peaks， namely peak 5 （magnoflorine）， peak 8 （jatrorrhizine）， peak 9 （epiberberine）， peak 10 （columbamine）， peak 11 （coptisine）， peak 12 （palmatine）， and peak 13 （berberine）. Their respective contents were （0.267±0.048）， （0.453±0.084）， （0.572±0.160）， （0.392±0.074）， （1.076±0.273）， （1.477±0.271）， and （6.664±1.249） mg/g （ n ＝3）. CONCLUSIONS This study predicted 15 candidate Q-markers of Compound xiebai capsules in the treatment of COPD and established the fingerprint along with a quantitative determination method for seven major components.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

Bronchial asthma （abbreviated as asthma） is one of the common chronic airway inflammatory diseases in the respiratory system， which is difficult to cure. Airway mucus hypersecretion （AMH） is an important factor leading to acute asthma attacks. Traditional Chinese medicine （TCM） possesses therapeutic advantages characterized by multiple pathways， multiple targets， and multiple links， and its mechanism of action in intervening in AMH has gradually drawn attention. TCM can effectively alleviate the symptoms of patients by intervening in asthma through methods such as eliminating phlegm and eliminating fluid retention. This review finds that the pathogenesis of asthma-associated AMH is correlated with decreased mucociliary clearance function and enhanced mucus secretion function； single TCM （such as Platycodon grandiflorum）， effective components of TCM （such as pinellia polysaccharides）， and compound prescriptions （mainly heat-clearing and phlegm-resolving prescriptions， etc.） can improve asthma-associated AMH by regulating the PI3K/Akt and JAK/STAT signaling pathways， inhibiting airway inflammatory responses， oxidative stress， and recovering the water-salt ratio of the mucus layer itself.