Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.

Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.

Objective:To survey the availability status of pharmaceutical and medical device for venous thromboembolism (VTE) prevention and the awareness among healthcare workers in community health service centers in Shanghai.Methods:This cross-sectional study was conducted by online questionnaire survey among doctors, nurses, and pharmacists from 20 community health service centers in Shanghai from June 2023 to April 2024. The survey covered participants′ demographic information, VTE prevention and management practices at their centers, the knowledge of VTE prevention, and related training or education. The assessment of VTE prevention and management status was completed by department heads of pharmacy, medical equipment, nursing, and inpatient units.Results:A total of 864 healthcare professionals participated in the survey, including 587(67.9%) doctors, 246(28.5%) nurses, and 31(3.6%) pharmacists, and 675(78.1%) were females. Among the 20 centers, 19 stocked VTE prevention medications, while only 8 had VTE prevention devices. Of the 864 participants, 145(16.8%) reported conducting VTE risk assessments for all patients, and 279(32.3%) correctly identified VTE as comprising deep vein thrombosis and pulmonary embolism. While 664(76.9%) believed that VTE risk assessment for hospitalized patients was necessary, only 11(1.3%) were familiar with and routinely used VTE risk assessment tools. Over 85% recognized advanced age, body mass index (BMI)>30 kg/m2, recent major surgery, prolonged immobilization, stroke, and varicose veins as VTE risk factors. A majority (837(96.9%)) agreed that bleeding risk assessment should precede pharmacological VTE prevention, and 549(63.5%) preferred oral antiplatelet agents as the first choice. Convenience (730(84.5%)) and safety (719(83.2%)) were key considerations in drug selection, while 710(82.2%) expressed concern about bleeding risks during medication. Only 258(29.9%) had received VTE-related training.Conclusions:Community health service centers in Shanghai face shortages in VTE prevention devices and medications, and healthcare professionals′ awareness of VTE needs to be improved. Enhanced training and education on VTE prevention are warranted.

Objective:To survey the availability status of pharmaceutical and medical device for venous thromboembolism (VTE) prevention and the awareness among healthcare workers in community health service centers in Shanghai.Methods:This cross-sectional study was conducted by online questionnaire survey among doctors, nurses, and pharmacists from 20 community health service centers in Shanghai from June 2023 to April 2024. The survey covered participants′ demographic information, VTE prevention and management practices at their centers, the knowledge of VTE prevention, and related training or education. The assessment of VTE prevention and management status was completed by department heads of pharmacy, medical equipment, nursing, and inpatient units.Results:A total of 864 healthcare professionals participated in the survey, including 587(67.9%) doctors, 246(28.5%) nurses, and 31(3.6%) pharmacists, and 675(78.1%) were females. Among the 20 centers, 19 stocked VTE prevention medications, while only 8 had VTE prevention devices. Of the 864 participants, 145(16.8%) reported conducting VTE risk assessments for all patients, and 279(32.3%) correctly identified VTE as comprising deep vein thrombosis and pulmonary embolism. While 664(76.9%) believed that VTE risk assessment for hospitalized patients was necessary, only 11(1.3%) were familiar with and routinely used VTE risk assessment tools. Over 85% recognized advanced age, body mass index (BMI)>30 kg/m2, recent major surgery, prolonged immobilization, stroke, and varicose veins as VTE risk factors. A majority (837(96.9%)) agreed that bleeding risk assessment should precede pharmacological VTE prevention, and 549(63.5%) preferred oral antiplatelet agents as the first choice. Convenience (730(84.5%)) and safety (719(83.2%)) were key considerations in drug selection, while 710(82.2%) expressed concern about bleeding risks during medication. Only 258(29.9%) had received VTE-related training.Conclusions:Community health service centers in Shanghai face shortages in VTE prevention devices and medications, and healthcare professionals′ awareness of VTE needs to be improved. Enhanced training and education on VTE prevention are warranted.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To study the cyclic peptides from sponge Reniochalina sp. under the guidance of mass spectrometry. Methods Mass spectrometry-guided procedural separation methods were used to track and isolate the cyclic peptides from the sponge genus Reniochalina. The structures of compounds were elucidated by the determination of physicochemical parameters and comparison of spectroscopic data. The preliminary cytotoxic activity of compounds was assessed by the Cell Counting Kit-8 (CCK-8) method. Results Three cyclic peptides were isolated from the sponge Reniochalina sp. and identified as stylopeptide 1 (1), hymenamide D (2) and axinastatin 2 (3). Compound 1 exhibited cytotoxicity against six human cancer cell lines with IC₅₀ values ranging from 6.09 to 17.26 μmol/L. Conclusion Compound 1 - 3 were isolated from Reniochalina sp. for the first time, and compound 1 was a cytotoxic cyclic heptapeptide.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective To study the chemical constituents of Aspergillus terreus from sponge epiphytic fungal. Methods Sephadex LH-20 column chromatography, silica gel column chromatography and high performance liquid chroma-tography were used to separate and purify the compounds. The structures of compounds were identified by spectroscopic data. The α-glucosidase inhibitory activity and antioxidant activity of the compounds were tested by PNPG and DPPH methods, respectively. Results Eight compounds were isolated from Aspergillus terreus and identified as methyl-3,4,5-trimethoxy-2-(2-(nicotinamido) benzamido) benzoate (1), terrelumamide A (2), emeheterone (3), (8R,9S)-dihydroisoflavipucine (4), (8S,9S)-dihydroisoflavipucine (5), cyclo(S-Pro-S-Phe) (6), brevianamide F (7), terrein (8). Compound 3 showed strong inhibitory activity against α-glucosidase and the IC₅₀ value was 14.28 μmol/L. Conclusion Compounds 3, 4, 5, and 7 were obtained from Aspergillus terreus for the first time.