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.

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.

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.

Objective In order to obtain small molecule compounds with novel structure and good biological activity, the secondary metabolites of polar sponge-symbiotic Streptomyces sp. LHW11-07 were studied. Methods The fermentation product of Streptomyces sp. LHW11-07 was isolated and purified by gel column chromatography, silica gel column chromatography, reversed-phase medium pressure column chromatography and high performance liquid chromatography. The structures of the monomeric compound were identified by modern spectroscopic methods such as mass spectrometry, nuclear magnetic resonance and related literature reports. Results A total of nine compounds were isolated from the fermentation of this strain, which were cyclo-(L-Tyr-L-Trp) (1), cyclo-(L-Trp-L-Ser) (2), cyclo-(D-Tyr-D-Pro) (3), cyclo-(L-Tyr-L-Phe) (4), cyclo-(L-Tyr-L-Leu) (5), albaflavenol B (6), β-adenosine (7), N-formylantimyic acid methyl ester (8) and conglobatin A (9). Conclusion Compounds 1 and 2 were isolated from Streptomyces sp. for the first time.

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.

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 discover the medicinal active molecules from the fermentation extract of sponge-symbiotic Streptomyces sp. LHW2432. Methods Compounds were isolated and purified from the fermentation extract of LHW2432 by silica gel, ODS chromatographic columns, and HPLC. The structures of the compounds were elucidated based on the analyses of modern spectrum technologies and the related literatures research. Through plate coating method and broth microdilution method, the antimicrobial activities were tested by the indicator strains of Bacillus mycoides, methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium smegmatis, Candida Albicans, and Escherichia coli. Results Five compounds were discovered and their structures were identified as descycloavandulyl-lavanduquinocin (1), N-acetyltyramine (2), phomapyrone C (3), germicidin A (4), and germicidin I (5). Compound 1 showed inhibitory activities against MRSA (MIC, 100 μg/ml) and M. smegmatis (MIC, 64 μg/ml), respectively. Conclusion Five compounds were discovered from LHW2432, among which compound 1 was a new natural product and could be used as a precursor of the tricyclic carbazole alkaloids with neuroprotective activity. Moreover, compound 1 showed weak inhibitory activities against gram-positive pathogenic bacteria.