1.Overview of host-directed antiviral targets for future research and drug development.
Xiaoxia GU ; Mengzhu ZHENG ; Ya GAO ; Shuang LIN ; Xiaotian ZHANG ; Chunmei CHEN ; Hucheng ZHU ; Weiguang SUN ; Yonghui ZHANG
Acta Pharmaceutica Sinica B 2025;15(4):1723-1751
Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.
2.Amoenucles A-F, novel nucleoside derivatives with TNF-α inhibitory activities from Aspergillus amoenus TJ507.
Yeting ZHANG ; Zhengyi SHI ; Chunhua ZHAO ; Lanqin LI ; Ming CHEN ; Yunfang CAO ; Fengqing WANG ; Bo TAO ; Xinye HUANG ; Jieru GUO ; Changxing QI ; Weiguang SUN ; Yonghui ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):111-118
Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry*
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Tumor Necrosis Factor-alpha/antagonists & inhibitors*
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Molecular Structure
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Nucleosides/isolation & purification*
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Crystallography, X-Ray
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Animals
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Humans
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Mice
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Magnetic Resonance Spectroscopy
3.Structurally diverse sesquiterpenoids with anti-MDR cancer activity from Penicillium roqueforti.
Shuyuan MO ; Nanjin DING ; Zhihong HUANG ; Jun YAO ; Weiguang SUN ; Jianping WANG ; Yonghui ZHANG ; Zhengxi HU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(4):504-512
Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC50) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L-1, which was 65-fold more potent than PTX alone (IC50 3.26 μmol·L-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry*
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Humans
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Sesquiterpenes/isolation & purification*
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Cell Line, Tumor
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Molecular Structure
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Drug Resistance, Neoplasm/drug effects*
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Antineoplastic Agents/pharmacology*
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Drug Resistance, Multiple/drug effects*
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Molecular Docking Simulation
4.(±)-Talapyrones A-F: six pairs of dimeric polyketide enantiomers with unusual 6/6/6 and 6/6/6/5 ring systems from Talaromycesadpressus.
Meijia ZHENG ; Xinyi ZHAO ; Chenxi ZHOU ; Hong LIAO ; Qin LI ; Yuling LU ; Bingbing DAI ; Weiguang SUN ; Ying YE ; Chunmei CHEN ; Yonghui ZHANG ; Hucheng ZHU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(8):932-937
(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C8 poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification*
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Talaromyces/chemistry*
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Stereoisomerism
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Molecular Structure
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Circular Dichroism
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Pyrones/chemistry*
5.Comparison of the efficacy of continuous VA chemotherapy and I/HDAC consolidation in postremission therapy for acute myeloid leukemia fit for standard chemotherapy
Li SUN ; Pengpeng ZHANG ; Simei REN ; Nan ZHOU ; Liyuan LI ; Zhenzhen WANG ; Weiguang CUI ; Fan YANG ; Jianmin LUO ; Lin YANG
Chinese Journal of Hematology 2025;46(4):343-348
Objective:To compare the efficacy and safety of continuous venetoclax combined azacitidine (VA) chemotherapy and intermedium/high-dose cytarabine (I/HDAC) consolidation in patients with acute myeloid leukemia (AML) fit for standard chemotherapy (transform from UNFIT) .Methods:Clinical data of patients who were fit for standard chemotherapy were collected among those with AML who underwent VA induction in the Department of Hematology, the Second Hospital of Hebei Medical University. The overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), and incidence of adverse events were analyzed retrospectively.Results:This study enrolled 69 patients, consisting of 46 cases in the VA group and 23 cases in the I/HDAC group. We revealed the following. ① The median OS, RFS, EFS were 26.18, 24.69, 20.34 months in the VA group, and 34.14, 30.99, 28.42 months in the I/HDAC group, respectively, with no statistically significant difference (all P>0.05). Median OS of patients who underwent I/HDAC consolidation with European Leukemia Net (ELN) favorable-risk, positive measurable residual disease (MRD), wild type FLT3, or IDH1/2 mutation was significantly longer than those who received VA ( P<0.05). ②Adverse events rate of grade 3 - 4 neutropenia, grade 3 - 4 thrombocytopenia, and bacteremia were significantly lower in the VA group than in the I/HDAC group ( P<0.05) . Conclusions:I/HDAC consolidation was more likely to help get survival benefits for patients with ELN favorable-risk, positive MRD, wild type FLT3, or IDH1/2 mutation. Continuous VA chemotherapy exhibited superior safety than I/HDAC consolidation.
6.Value of half-dose 18F-FDG deep-inhaled breath-hold total-body PET/CT in improvement of poor alignment of tumor lesions in thoracic and upper abdominal regions
Jin JIA ; Keqing YUAN ; Meng LIU ; Yingying HU ; Wei FAN ; Chao ZHOU ; Weiguang ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(5):281-287
Objective:To evaluate the value of deep-inhaled breath-hold (DIBH)-30s scanning with total-body PET/CT under half-dose injection mode in improving the poor alignment of thoracic and upper abdominal tumors.Methods:Forty-six patients (28 males, 18 females, age (57.3±11.4) years) who underwent half-dose 18F-FDG total-body DIBH-30s PET/CT examination because of suspect or confirmed thoracic and upper abdominal tumors in Sun Yat-Sen University Cancer Center between October 2022 and February 2023 were analyzed retrospectively. SUV, standard deviation (SD) and signal-to-noise ratio (SNR) of the liver and mediastinal blood pool in free breath (FB)-8min, FB-30s and DIBH-30s PET images were measured; SUV of lesions, metabolic tumor volume (MTV) and tumor-to-background ratio (TBR) in DIBH-30s and FB-8min images were also measured; maximum diameter of contraposition offset and offset rate in coronal, transverse and sagittal directions of lesions in DIBH-30s and FB-8min images were calculated. Five-point Likert scale was used to score the overall image quality, image noise level and diagnostic confidence of fused images. Kruskal-Wallis rank sum test, Nemenyi test or Mann-Whitney U test was used to compare the parameters of different groups. Results:Among the 46 patients, 38 successfully completed breath-holding collection, and 80 lesions were detected, including 37 in the lungs and 43 in the livers. The liver SUV max (3.40(3.15, 3.63), 3.44(3.06, 3.70)) and SD (0.36(0.32, 0.41), 0.35(0.30, 0.40)) in DIBH-30s group and FB-30s group were higher than those (SUV max: 2.73(2.45, 2.92), SD: 0.15(0.13, 0.17)) in FB-8min group ( H values: 49.79, 85.27, χ2 values: 3.26-3.65, all P<0.001). The SUV max and the SD of mediastinal blood pool in DIBH-30s group and FB-30s group were also higher ( H values: 9.31, 59.73, χ2 values: 2.13-2.75, all P<0.01), while SNR liver and SNR med in those 2 groups were lower ( H values: 87.90, 54.11, χ2 values: 3.36-5.47, all P<0.001). The image noise scores of DIBH-30s group and FB-30s group were lower than the score of FB-8min group (3(3, 3) vs 3(3, 4) vs 5(5, 5); H=93.02, χ2 values: 2.13, 2.23, all P<0.001). The overall image quality score and diagnostic confidence score of DIBH-30s group were higher than those of FB-30s group and FB-8min group ( H values: 70.13, 24.22, χ2 values: 2.11-2.48, all P<0.001). The SUV and TBR of lesions in DIBH-30s group were higher than those of FB-8min group ( Z values: from -3.82 to -2.44, all P<0.05), while the MTV, contraposition offset and offset rate were lower than those of FB-8min group ( Z values: from -6.20 to -3.18, all P<0.001). Conclusions:DIBH-30s scanning with total-body PET/CT can make the focus alignment more accurate, which is suitable for short-time collection or low drug administration activity. It has a unique value in improving the poor focus alignment of chest and upper abdomen tumors.
7.Intraosseous and periosteal arteries of hallux phalanx: a 3D observational study
Zirun XIAO ; Jia CHEN ; Kuo WEI ; Zhenfeng LI ; Chaofeng XING ; Weiguang ZHANG
Chinese Journal of Microsurgery 2025;48(5):547-551
Objective:To explore the feasibility of obtaining three-dimensional (3D) models of intraosseous and periosteal arteries of hallux phalanx using micro-arteriography with micro-CT scan.Methods:From January 2022 to April 2025, the Department of Orthopaedic, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA conducted a study on 7 fresh-frozen specimens of distal lower limb (right lower limb) from an 85-year-old male, and both lower limbs from an 82-year-old male, a 78-year-old female and a 66-year-old male in the Department of Human Anatomy & Histology and Embryology, Peking University School of Basic Medical Sciences. Red lead oxide powder (Pb 3O 4) was ground and filtered through a 300 mesh, and then mixed with turpentine at ratios of 1 g ∶ 1.5 ml, 1 g ∶ 1.0 ml, and 1 g ∶ 0.5 ml to prepare lead-based contrast agent suspensions. After thawing the specimens at room temperature, the suspensions were injected via the popliteal artery in ascending order of concentration. After injections, the specimens were fixed in 10% methanal for 2 weeks. The proximal and distal phalanges of the hallux, with the surrounding periosteum preserved intact, were then harvested. The harvested specimens were scanned using micro-CT at an ultimate resolution of 12 μm. Subsequently, Mimics Medical software was used to reconstruct 3D models of the intraosseous and periosteal arteries within the phalanges. Results:Periosteal arteries in the proximal phalanx were primarily distributed near the joint region. A consistently large trunk artery entered from plantar side, supplying most of the diaphysis and head. There was a rich periosteal arterial network on both sides of the distal phalanx, which communicates with each other through the arterial arch in the bone groove. However, trunk intraosseous artery could be absent. Intraosseous arteries in the proximal ends of both the proximal and distal phalanges originated from periosteal arteries. These formed an interconnected arteriosomes and coursed parallel to the articular surfaces.Conclusion:The micro-arteriography acquired by micro-CT scan effectively visualizes intraosseous and periosteal arteries and enables the reconstruction and analysis of 3D models of the arteriosomes. The characteristics of arteriolar distribution provide a theoretical basis for osteotomy or internal fixation procedures involving a hallux phalanx.
8.Interpretation of"Standard for prevention and control of catheter-associated urinary tract infection"(WS/T862-2025)
Weiguang LI ; Jian SUN ; Hua XU ; Keke LIU ; Zhiyuan CHEN ; Gui ZHANG
Chinese Journal of Nosocomiology 2025;35(20):3041-3044
In order to effectively prevent and control the occurrence of catheter-associated urinary tract infection and ensure the safety of both patients and medical personnel,the National Health Commission of the People's Re-public of China officially released the recommended health industry standard"Standard for prevention and control of catheter-associated urinary tract infection"(WS/T862-2025)in Aug.2025.This paper provides an interpreta-tion of the standard,covering its drafting background,basis and content,to assist relevant medical personnel in healthcare institutions in enhancing their understanding and recognition of the standard,and to further promote its implementation and enforcement.
9.Study on the value of abnormal prothrombin in the diagnosis of HBV-related hepatocellular carcinoma
Jiaming ZHANG ; Suxian ZHAO ; Lingdi LIU ; Fang HAN ; Weiguang REN ; Xiaoqing WU ; Mengjiao SUN ; Jingjing SONG ; Yuemin NAN
Chinese Journal of Hepatology 2025;33(4):340-347
Objective:To establish and explore a novel model and its clinical application value based on abnormal des-gamma-carboxy prothrombin (DCP) for the early-stage diagnosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Methods:A total of 420 cases with chronic HBV infection with nodular liver lesions examined by imaging at the Third Hospital of Hebei Medical University from January 2021 to June 2024 were retrospectively selected. They were divided into the HBV-HCC group (182 cases) and the control group (238 cases) according to the current HCC diagnostic criteria. The basic information of patients, liver-related biochemical indicators, serum DCP, alpha-fetoprotein (AFP) levels, and the efficacy of combined detection in diagnosing early-stage HCC were collected and analyzed. A DSGAA model based on DCP (D) combined with gender (S), γ-glutamyl transferase (GGT, G), AFP (A) and age (A) as independent variables was constructed. The diagnostic performance of the novel model was compared with that of the traditional model through nomogram visualization output and calibration curve.Results:The age, sex, hemoglobin, albumin, alanine aminotransferase, alkaline phosphatase, and GGT levels were significantly higher in patients with HCC than those of the control group ( P<0.05). The positivity detection rate in patients with HBV-HCC was significantly higher in DCP than that of AFP (85.71% vs. 59.89%, P<0.05). The abnormal detection rate of DCP in patients with AFP-negative was 76.7%. The sensitivity for diagnosing HCC was significantly higher in DCP than AFP (73.63% vs. 64.29%, P<0.05), with specificity of 83.6% in all. The specificity for diagnosing early-stage HCC was 89.09%, surpassing that of AFP at 68.06% ( P<0.05). The area under the receiver operating characteristic curve (AUC) for the constructed DSGAA diagnostic model was 0.8841, with an optimal cutoff value of 0.377, a sensitivity of 80.22%, and a specificity of 86.13%. The AUC for diagnosing early-stage HCC was 0.8122, with a sensitivity of 66.18%, and a specificity of 86.13%, and the diagnostic efficacy was higher than other models ( P<0.05). Conclusion:DCP has superior diagnostic efficacy for HBV-related HCC, and the DSGAA model is expected to be used as a new method for screening and diagnosing early-stage HBV-related HCC.
10.Subordinate inclusion and indefinite reference of the concepts of TCM
Xiangyang ZHANG ; Fangce LIU ; Jiazhen LI ; Canran XIE ; Xiaofeng LIU ; Na CAO ; Weiguang WANG
International Journal of Traditional Chinese Medicine 2025;47(9):1202-1206
Concepts are the cornerstone of the development of disciplines. The concepts of TCM present that a superior concept contains more subordinate concepts. The superordinate concepts are often used to refer to different subordinate concepts, which can refer to both superior concepts themselves and non-specific subordinate concepts, that is, the characteristics of subordinate coverage and indefinite reference, which cause confusion in concept meaning, concept relationships, reasoning logic, and other problems. Nowadays, the TCM scholars pay little attention to this characteristic. Therefore, this article analyzed this characteristic, discussed its impact on the inheritance and development of TCM, and proposed that starting from the anchoring of concepts and entities to clarify the connotation of concepts, looking forward to provide new ideas for the definition of the concepts of TCM and the development of the discipline.

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