1.Bioactive metallic nanoparticles for synergistic cancer immunotherapy.
Lulu WANG ; Demin LIN ; Muqing LI ; Yu JIANG ; Yanfang YANG ; Hongliang WANG ; Hongqian CHU ; Jun YE ; Yuling LIU
Acta Pharmaceutica Sinica B 2025;15(4):1869-1911
Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.
2.A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers.
Jialing CHENG ; Zhiyang CHEN ; Demin LIN ; Yanfang YANG ; Yanjing BAI ; Lingshuang WANG ; Jie LI ; Yuchen WANG ; Hongliang WANG ; Youbai CHEN ; Jun YE ; Yuling LIU
Acta Pharmaceutica Sinica B 2025;15(7):3767-3787
An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.
3.Effects of different dialysis frequencies combined with furosemide on residual kidney function in end-stage renal disease
Jun LIU ; Quandong BU ; Huifang WANG ; Hang LIU ; Demin XIE ; Xuemei LIU
Chinese Journal of General Practitioners 2025;24(11):1387-1393
Objective:To investigate the protective effects of incremental hemodialysis (iHD) combined with furosemide on residual kidney function (RKF) in end-stage renal disease patients who initiate dialysis with preserved RKF.Methods:This was a randomized controlled trial. The patients diagnosed with end-stage renal disease who initiated hemodialysis at the Department of Nephrology, the Affiliated Hospital of Qingdao University from May 2021 to May 2023 were enrolled. The clinical data were collected and analyzed. The patients were randomly assigned to either iHD group (two 4-hour sessions per week or three 3-hour sessions per week, with oral furosemide 40-80 mg twice daily) or the standard HD group (three 4-hour sessions per week, with oral furosemide 40-80 mg twice daily). Differences in clinical characteristics and RKF were assessed between the two groups of patients at 3 months and 6 months, and the differences between the clinical characteristic and the baseline level at 6 months were analyzed, along with the incidence of adverse events.Results:A total of 87 patients met the inclusion and exclusion criteria, of whom 75 completed this study. The mean age was (53.45±12.57) years old, with 37 females (49.33%) and 38 males (50.67%). The patients were assigned to iHD group (39 cases) and standard HD group (36 cases). At 3 months of the trial, compared with standard HD group, the level of serum C-reactive protein was significantly decreased, and the level of eGFR was significantly increased in the iHD group. At 6 months of the trial, the levels of systolic blood pressure, serum β 2-microglobulin, average ultrafiltration volume and C-reactive protein were significantly decreased, and the levels of eGFR, 24-hour urine volume were significantly increased in the iHD group ( P<0.05). The difference in eGFR, urine volume and systolic blood pressure between the iHD group and the baseline level was significantly smaller than that between the standard HD group and the baseline level (all P<0.05). In contrast, the differences in C-reactive protein was significantly greater than that in standard HD group and the baseline level ( P<0.05). At the 3rd, 6th month of the trial, the 24-h urine volumes of iHD group and standard HD group were (955±219) ml/24 h vs. (847±143) ml/24 h, (914±151) ml/24 h vs. (827±124) ml/24 h, showing statistically significant differences ( t=2.510, P=0.014; t=2.729, P=0.008). Adverse events mainly included pulmonary infections (22 cases), fluid overload during the dialysis interval (or more than 5% of the ideal dry weight, 12 cases), heart failure (4R or 4NR grade, 7 cases), hyperkalemia (6 cases), and thrombosis or failure of vascular access (3 cases). The incidence of adverse events did not differ statistically between the two groups ( P>0.05). Conclusion:iHD combined with furosemide helps preserve RKF and maintain urine output within 6 months compared with standard HD in patients with end-stage renal disease.
4.Effects of different dialysis frequencies combined with furosemide on residual kidney function in end-stage renal disease
Jun LIU ; Quandong BU ; Huifang WANG ; Hang LIU ; Demin XIE ; Xuemei LIU
Chinese Journal of General Practitioners 2025;24(11):1387-1393
Objective:To investigate the protective effects of incremental hemodialysis (iHD) combined with furosemide on residual kidney function (RKF) in end-stage renal disease patients who initiate dialysis with preserved RKF.Methods:This was a randomized controlled trial. The patients diagnosed with end-stage renal disease who initiated hemodialysis at the Department of Nephrology, the Affiliated Hospital of Qingdao University from May 2021 to May 2023 were enrolled. The clinical data were collected and analyzed. The patients were randomly assigned to either iHD group (two 4-hour sessions per week or three 3-hour sessions per week, with oral furosemide 40-80 mg twice daily) or the standard HD group (three 4-hour sessions per week, with oral furosemide 40-80 mg twice daily). Differences in clinical characteristics and RKF were assessed between the two groups of patients at 3 months and 6 months, and the differences between the clinical characteristic and the baseline level at 6 months were analyzed, along with the incidence of adverse events.Results:A total of 87 patients met the inclusion and exclusion criteria, of whom 75 completed this study. The mean age was (53.45±12.57) years old, with 37 females (49.33%) and 38 males (50.67%). The patients were assigned to iHD group (39 cases) and standard HD group (36 cases). At 3 months of the trial, compared with standard HD group, the level of serum C-reactive protein was significantly decreased, and the level of eGFR was significantly increased in the iHD group. At 6 months of the trial, the levels of systolic blood pressure, serum β 2-microglobulin, average ultrafiltration volume and C-reactive protein were significantly decreased, and the levels of eGFR, 24-hour urine volume were significantly increased in the iHD group ( P<0.05). The difference in eGFR, urine volume and systolic blood pressure between the iHD group and the baseline level was significantly smaller than that between the standard HD group and the baseline level (all P<0.05). In contrast, the differences in C-reactive protein was significantly greater than that in standard HD group and the baseline level ( P<0.05). At the 3rd, 6th month of the trial, the 24-h urine volumes of iHD group and standard HD group were (955±219) ml/24 h vs. (847±143) ml/24 h, (914±151) ml/24 h vs. (827±124) ml/24 h, showing statistically significant differences ( t=2.510, P=0.014; t=2.729, P=0.008). Adverse events mainly included pulmonary infections (22 cases), fluid overload during the dialysis interval (or more than 5% of the ideal dry weight, 12 cases), heart failure (4R or 4NR grade, 7 cases), hyperkalemia (6 cases), and thrombosis or failure of vascular access (3 cases). The incidence of adverse events did not differ statistically between the two groups ( P>0.05). Conclusion:iHD combined with furosemide helps preserve RKF and maintain urine output within 6 months compared with standard HD in patients with end-stage renal disease.
5.miRNA-126 reverses cisplatin resistance in lung cancer A549/DDP cells by inhibiting autophagy
Xiali TANG ; Jun CHEN ; Demin JIAO ; Xiang LIU
Chinese Journal of Pathophysiology 2024;40(8):1378-1383
AIM:Autophagy levels in lung cancer cisplatin-resistant A549/DDP cells and cisplatin-sensitive A549 cells were compared.The effects of microRNA-126(miRNA-126)on autophagy in lung cancer cisplatin-resistant cells were assessed,and the role of miRNA-126 in lung cancer cisplatin-resistant cells was discussed.METHODS:An MTT assay was used to detect the half maximal inhibitory concentration of cisplatin.The miRNA-126 expression was de-tected by RT-qPCR.Autophagolysosomes were observed under a fluorescence microscope using acridine orange staining.Protein levels of autophagy-associated molecule microtubule-associated protein 1 light chain 3(LC3)in lung cancer cells were determined by Western blot.RESULTS:Autophagy was significantly elevated in A549/DDP cells compared with A549 cells(P<0.01).The expression level of miRNA-126 was significantly elevated in A549/DDP cells after transfection with miRNA-126(P<0.01).miRNA-126 reversed cisplatin resistance of A549/DDP cells,and the level of intracellular acid dye follicular bright red fluorescence in the A549/DDP cells was significantly reduced after transfection with miRNA-126(P<0.01).The LC3-Ⅱ protein level in A549/DDP cells was significantly reduced after transfection with miRNA-126(P<0.01),and inhibition of cell autophagy by 3-methyladenine(3-MA)enhanced cisplatin sensitivity of A549/DDP cells(P<0.01).Compared with 3-MA+NC group,miRNA-126 combined with 3-MA further increased cisplatin sensitivity of A549/DDP cells(P<0.01).CONCLUSION:miRNA-126 reverses the cisplatin resistance in lung cancer A549/DDP cells by inhibiting autophagy.
6.Clinical Dominant Diseases in Traditional Chinese Medicine: A Series of Youth Salon Seminars for Clinical Dominant Diseases Held by China Association of Chinese Medicine
Zhanfeng YAN ; Lingbo KONG ; Jingshang WANG ; Baoli LIU ; Yuan XU ; Yingke LIU ; Ping WANG ; Cang ZHANG ; Weijing LIU ; Dawei ZOU ; Guowang YANG ; Demin LI ; Jiang CHEN ; Mei MO ; Yong ZHU ; Bin WANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):202-208
The discussion and research on the clinical dominant diseases of traditional Chinese medicine (TCM) have attracted increasing attention. Through approaches including modern technology, evidence-based medical methods, and multi-disciplinary treatment, we should construct a sound TCM inheritance and innovation system, establish a collaborative innovation mechanism, and integrate major research projects, striving to make breakthroughs in TCM theory, methodology, standards, and regulation system, promoting the scientific and technological progress of TCM, and thereby improving its curative effect. The China Association of Chinese Medicine (CACM) carried out a series of youth salon seminars for clinical dominant diseases in TCM, discussing and sorting out the advantages of the dominant diseases in clinical diagnosis and treatment of TCM and integrated traditional Chinese and western medicine in specific diseases or fields. Authoritative experts in the industry were invited to give comment and guidance to form a report. Centering on clinical research of dominant diseases, thematic research was carried out in the aspects of practice, human experience-based evidence, and transformation path. Through the systematic study of the dominant diseases, the advantages of TCM in different stages of disease treatment were excavated to constantly improve the prevention and treatment ability of TCM and carry forward the advancement of TCM theory and practice. At the same time, the communication and understanding between traditional Chinese and western medicine were improved, laying the foundation for the further formation of industry guidelines or consensus and comprehensive promotion. These seminars are expected to provide references for the development of policy planning, clinical diagnosis and treatment, health economy, and social services in TCM and lay the foundation for the formation of a new modern diagnosis and treatment system with Chinese characteristics.
7.Influence of prior percutaneous coronary intervention on outcome of coronary artery bypass grafting: A multi-center clinical study
Hongwei JIANG ; Hang ZHANG ; Wen CHEN ; Fangjing ZHENG ; Yongfeng SHAO ; Yongxiang QIAN ; Guoxiang WANG ; Mingqiu LI ; Qingsheng YOU ; Zhiyong LIU ; Yong WANG ; Zhenya SHEN ; Wei LI ; Demin LI ; Su HUANG ; Chongjun ZHONG ; Rui WANG ; Xin CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(11):1436-1441
Objective To investigate the influence of prior percutaneous coronary intervention (PCI) on the outcome of coronary artery bypass grafting (CABG). Methods Clinical data of 5 216 patients from Jiangsu Province CABG registry who underwent primary isolated CABG from 2016 to 2019 were retrospectively analyzed. Patients were divided into a PCI group (n=673) and a non-PCI group (n=4 543) according to whether they had received PCI treatment. The PCI group included 491 males and 182 females, aged 62.6±8.2 years, and the non-PCI group included 3 335 males and 1 208 females, aged 63.7±8.7 years. Multivariable logistic regression and propensity score matching (PSM) were used to compare 30-day mortality, incidence of major complications and 1-year follow-up outcomes between the two groups. Results Both in original cohort and matched cohort, there was no statistical difference in the 30-day mortality [14 (2.1%) vs. 77 (1.7%), P=0.579; 14 (2.1%) vs. 11 (1.6%), P=0.686], or the incidence of major complications (myocardial infarction, stroke, mechanical ventilation≥24 h, dialysis for new-onset renal failure, deep sternal wound infection and atrial fibrillation) (all P>0.05). The rate of reoperation for bleeding in the PCI group was higher than that in the non-PCI group [19 (2.8%) vs. 67 (1.5%), P=0.016; 19 (2.8%) vs. 7 (1.0%), P=0.029]. Both in original cohort and matched cohort, there was no statistical difference in 1-year survival rate between the two groups [613 (93.1%) vs. 4 225 (94.6%), P=0.119; 613 (93.1%) vs. 630 (95.2%), P=0.124], while the re-admission rate in the PCI group was significantly higher than that in the non-PCI group [32 (4.9%) vs. 113 (2.5%), P=0.001; 32 (4.9%) vs. 17 (2.6%), P=0.040]. Conclusion This study shows that a history of PCI treatment does not significantly increase the perioperative mortality and major complications of CABG, but increases the rate of cardiogenic re-admission 1 year postoperatively.
8.Macrophages in Ischemic Heart Failure: Yesterday, Today, and Tomorrow
Demin LIU ; Wenjun YAN ; Jinwen HUANG ; Jianli ZHAO ; Houston KILBY ; Christopher Theodore A. ; Bernard LOPEZ ; Ling TAO ; Xinliang MA ; Guoqiang GU ; Yajing WANG
Cardiology Discovery 2021;01(2):128-134
With continually improving reperfusion strategies and patient care, the overall mortality of acute myocardial infarction (AMI) has been significantly reduced during the past two decades. However, this success is a double-edged sword, as many patients surviving an AMI will progress towards ischemic heart failure (HF) over time. The pathologic causes of ischemic HF are undoubtedly multifactorial. However, the inflammatory response is considered one of the most important causes of pathological remodeling because it spans the whole process of HF development. The macrophage-mediated inflammatory response was once considered a purely harmful factor leading to pathological remodeling and HF. However, growing evidence demonstrates that multiple subgroups of macrophage exist and contribute differently to ischemic HF development. Understanding macrophage populations and how they contribute to post-MI remodeling and consequent ischemic HF is, therefore, critical to understanding and treating the disease. This review focuses on different macrophage populations that regulate post-MI cardiac injury and how immunoregulation therapy may benefit patients with ischemic HF.
9.Macrophages in Ischemic Heart Failure: Yesterday, Today, and Tomorrow
Demin LIU ; Wenjun YAN ; Jinwen HUANG ; Jianli ZHAO ; Houston KILBY ; Christopher Theodore A. ; Bernard LOPEZ ; Ling TAO ; Xinliang MA ; Guoqiang GU ; Yajing WANG
Cardiology Discovery 2021;01(2):128-134
With continually improving reperfusion strategies and patient care, the overall mortality of acute myocardial infarction (AMI) has been significantly reduced during the past two decades. However, this success is a double-edged sword, as many patients surviving an AMI will progress towards ischemic heart failure (HF) over time. The pathologic causes of ischemic HF are undoubtedly multifactorial. However, the inflammatory response is considered one of the most important causes of pathological remodeling because it spans the whole process of HF development. The macrophage-mediated inflammatory response was once considered a purely harmful factor leading to pathological remodeling and HF. However, growing evidence demonstrates that multiple subgroups of macrophage exist and contribute differently to ischemic HF development. Understanding macrophage populations and how they contribute to post-MI remodeling and consequent ischemic HF is, therefore, critical to understanding and treating the disease. This review focuses on different macrophage populations that regulate post-MI cardiac injury and how immunoregulation therapy may benefit patients with ischemic HF.
10.Jiangsu Province Coronary Artery Bypass Grafting Registry study: a report of 4 661 patients in 13 centers
Rui WANG ; Yongfeng SHAO ; Yongxiang QIAN ; Guoxiang WANG ; Mingqiu LI ; Qingsheng YOU ; Zhiyong LIU ; Yong WANG ; Zhenya SHEN ; Wei LI ; Demin LI ; Su HUANG ; Chongjun ZHONG ; Xin CHEN
Chinese Journal of Surgery 2020;58(5):350-355
Objective:To examine the overall status of the Jiangsu Province Coronary Artery Bypass Grafting Registry database.Methods:The patients date of Jiangsu Province Coronary Artery Bypass Grafting Registry database from October 2017 to December 2019 was collected retrospectively.Risk factors, history, cardiac function (New York Heart Association class), extent of coronary artery lesion, European system for cardiac operative risk evaluation Ⅱ (EuroSCORE Ⅱ), cardiopulmonary bypss, arterial grafts, the numbers and flow of grafts and postoperative major adverse cardiac and cerebrovascular event(MACCE) information were analyzed. The clinical data of patients underwent on-pump CABG(ONCABG) or off-pump CABG (OPCAB) were compared by t test or χ 2 test. Results:Up till December 2019, the database enrolled 7 138 patients, in which 4 661 patients receiving primary isolated CABG. There were 3 486 males and 1 175 females with the age of (64.6±8.1) years (range:31 to 87 years). There were coronary left main disease in 960 patients, triple vessel disease in 3 934 patients, both left main and triple vessel disease in 837 patients, ejection fraction >50% in 3 841 patients, cardiac function class Ⅲ to Ⅳ in 1 664 patients. EuroSCORE Ⅱ was (2.3±0.7)% (range: 0.5% to 35.8%). There were 2 731 patients (58.59%) underwent ONCABG and 1 930 patients (41.41%) underwent OPCAB. There were 4 144 patients (88.91%) for whom the left internal thoracic artery was harvested. Seven centers (2 centers routinely) used left radial artery, 5 centers (3 centers routinely) used the transit time flow meter. The graft was 3.4±0.7 (range:1 to 7), the aortic crossclamp time was (65.0±20.4) minutes (range: 21 to 196 minutes), the cardiopulmonary bypass time was (90.0±24.2) minutes (range: 33 to 227 minutes). In-hospital death ocurred in 84 patients(1.80%), while re-operation in 93 patients (2.00%), myocardial infarction in 71 patients (1.52%), cerebral infarction in 33 patients (0.71%) and dialysis in 56 patients (1.20%). There were 2 936 patients prescribed with secondary prevention drugs(62.99%).Comparing with OPCAB group, ONCABG group had younger age, more female, more diabetes mellitus, more history of myocardial infarction and percutaneous transluminal coronary angioplasty, poorer cardiac function and coronary lesions, higher EuroSCORE Ⅱ, preoperatively (all P<0.05), and was associated with higher MACCE (135/2 731 vs. 71/1 930, χ 2=4.280, P=0.039), and of more grafts, transfusion and intra-aortic balloon counterpulsation application (all P<0.05). Conclusions:Jiangsu Province Coronary Artery Bypass Grafting Registry database is generally in good operation, and some parameters still need to be improved. Comparing with OPCAB group, ONCABG has more severe preoperative general conditions, while the outcomes is acceptable.

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