1.Clinical observation of sacituzumab tirumotecan combined with bevacizumab in the treatment of HER2-negative breast cancer with brain metastases
Yufeng YANG ; Xiuli YANG ; Peng CHENG ; Ling SHEN ; Qian YANG ; Yingbo SHAO
China Pharmacy 2026;37(16):2156-2160
OBJECTIVE To evaluate the efficacy and safety of sacituzumab tirumotecan combined with bevacizumab for the treatment of human epidermal growth factor receptor 2-negative (HER2-) breast cancer with brain metastases.METHODS Clinical data of 90 patients with HER2- breast cancer with brain metastases treated at the First Affiliated Hospital of Nanyang Medical College from December 2024 to November 2025 were retrospectively collected. According to the treatment regimens, the patients were divided into a control group ( n =55) and an experimental group ( n =35). Patients in the experimental group received sacituzumab tirumotecan combined with bevacizumab, whereas those in the control group received conventional systemic therapy, including albumin-bound paclitaxel-based regimens, capecitabine-based regimens, or gemcitabine/vinorelbine combined with platinum-based regimens. Short-term efficacy, progression-free survival (PFS), brain metastasis-related efficacy, adverse events, treatment discontinuation due to adverse events, and treatment-related deaths were compared between the two groups.RESULTS The objective response rate (ORR), disease control rate, median PFS, intracranial disease control rate, and proportion of patients with improvement in neurological symptoms in the experimental group were significantly higher than in the control group ( P <0.05). Stratified analysis showed that PFS of the experimental group was significantly longer than the control group among patients with Breast-Graded Prognostic Assessment scores ≥2.0 and <2.0 ( P <0.05). There were no statistically significant differences in the proportion of patients with glucocorticoid dose reduction/discontinuation, the incidence of adverse events of different grades, or the rate of treatment discontinuation due to adverse events between the two groups ( P >0.05). No treatment-related deaths occurred in either group.CONCLUSIONS Compared with conventional systemic therapy, sacituzumab tirumotecan combined with bevacizumab can improve the ORR and prolong PFS in patients with HER2- breast cancer with brain metastases, with an overall manageable safety profile.
2.Study on the correlation between blood glucose fluctuations and type 2 diabetic foot based on flash glucose monitoring technology
Xiuli FENG ; Zhichen ZHENG ; Tongyu ZHANG ; Li ZHOU ; Ning XU ; Renhao ZHAO ; Teng YANG ; Na WANG ; Guofeng WANG
The Journal of Practical Medicine 2025;41(4):569-574
Objective To investigate the correlation between glycemic variability metrics and the risk of diabetic foot(DF)in patients with type 2 diabetes mellitus(T2DM)utilizing flash glucose monitoring(FGM)tech-nology.Methods A retrospective analysis was conducted on 233 hospitalized patients with T2DM,with or without DF,who were treated in the Department of Endocrinology at Lianyungang First People's Hospital from January 2021 to May 2022 and monitored using FGM.Patients were categorized into a non-DF group(n=147)and a DF group(n=86)based on the presence of DF.The study compared general clinical characteristics,biochemical parameters,and glycemic variability metrics between the two groups and performed subgroup analyses.Binary logistic regression was employed to identify factors associated with the risk of DF,while receiver operating characteristic(ROC)curves were utilized to assess the predictive value of glycemic variability metrics for DF.Results Compared with the non-DF group,patients in the DF group exhibited significantly longer disease duration,higher body mass index(BMI),glycated hemoglobin(HbA1c),urinary albumin-to-creatinine ratio(UACR),alanine aminotransferase(ALT),serum uric acid(SUA),mean amplitude of glycemic excursions(MAGE),coefficient of variation(CV),mean of daily differences(MODD),and mean blood glucose(MBG),but lower fasting C-peptide(FCP),fasting insulin(FINS),high-density lipoprotein cholesterol(HDL-C),and time in range(TIR),with statistically signifi-cant differences(P<0.05).Subgroup analysis revealed that TIR was associated with the incidence of DF and diabetic retinopathy(DR).Binary logistic regression analysis identified HbA1c,MAGE,MODD,and MBG as risk factors for DF,while TIR was a protective factor(P<0.05).ROC curve analysis demonstrated that the area under the curve(AUC)for predicting DF using HbA1c,TIR,MAGE,MODD,MBG,and their combination were 0.646,0.850,0.868,0.764,0.619,and 0.967,respectively,indicating superior performance of the combined prediction model.Conclusions HbA1c,TIR,MAGE,MODD,and MBG are critical factors associated with the development of DF in patients with T2DM.Targeted early interventions aimed at optimizing these glycemic variability indicators may effectively reduce the incidence of DF.
3.Role of pulmonary phospholipids and their PLA2-derived metabo-lites lysophospholipids and fatty acids in the induction of acute lung injury in mice
Jianyu WANG ; Ruizhi LIN ; Xinran ZHAO ; Yajing WEI ; Lin WANG ; Xiuli ZHAO ; Jun YANG ; Yongan WANG
Chinese Journal of Pharmacology and Toxicology 2025;39(10):751-760
OBJECTIVE To investigate the acute lung injury effects of pulmonary phospholipids and their phospholipase A2(PLA2)decomposition products-lysophospholipids and fatty acids-on mice.METHODS Mice were randomly assigned to the following groups:① solvent control(PBS)and PLA2;② solvent control and glycerol phospholipid groups:1,2-dioleoyl-sn-glycero-3-phosphoserine(DOPS),1,2-dipalmitoyl-sn-glycero-3-phosphoserine(DPPS),1,2-dioleoyl-sn-glycero-3-phosphoethanol-amine(DOPE),1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine(DPPE),1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC),and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine(SOPC);③ solvent con-trol and fatty acid groups:palmitic acid(PA),oleic acid;④ solvent control and lysophospholipid groups:1-oleoyl-2-hydroxy-sn-glycero-3-phosphoserine(18∶1 LysoPS),1-stearoyl-sn-glycero-3-phosphoserine(18∶0 LysoPS),1-palmitoyl-sn-glycero-3-phosphoserine(16∶0 LysoPS),1-palmitoyl-sn-glycero-3-phos-phoethanolamine(16∶0 LysoPE),1-palmitoyl-sn-glycero-3-phosphocholine(16∶0 LysoPC);⑤ solvent control,PLA2,DPPC,PA,16∶0 LysoPC,16∶0 LysoPS,and 18∶1 LysoPS.Following anesthesia,mice were administered nebulized PBS in the solvent control group,2.1 ug·kg-1 PLA2 in PBS in the PLA2 group and 2.5 mg·kg-1 of the corresponding substance in PBS in other experimental groups.For group①,survival times were recorded and survival curves were plotted.At 1 h post-treatment,lung tissues from groups ①②③④ were collected,photographed to obtain white light images,and subjected to HE staining to assess histopathological changes and pathological scoring.At 2 h post-treatment,pulmonary blood flow in group ⑤ was assessed using laser speckle contrast imaging,arterial blood gas was analyzed with a blood gas analyzer,and lung function was evaluated using whole-body pleth-ysmography.At 6 hours post-treatment,blood cells from group ⑤ were analyzed using an automated hematology analyzer.RESULTS Compared with the solvent control group,severe pathological changes were observed in lung tissues of the PLA2 group,accompanied by extensive inflammatory infiltration and interstitial thickening,with all mice succumbing within 240 min.In mice treated with glyc-erol phospholipids,alveolar structures remained clear,alveolar walls were intact and continuous,and alveolar spaces were translucent,with only occasional minor inflammatory cell infiltration in the septa.No significant pathological alterations were detected in the fatty acid groups.Minor inflammatory cell infiltration was seen in the 16∶0 LysoPE and 16∶0 LysoPC groups.However,such pathological changes as patchy hemorrhage,alveolar interstitial edema,increased alveolar wall thickness,and elevated neutrophil counts were observed in the 18∶1 LysoPS,18∶0 LysoPS,and 16∶0 LysoPS groups.Pathological scores based on HE staining were significantly increased in the 16∶0 LysoPS and 18∶1 LysoPS groups com-pared with the solvent control.The percentage of the lung tissue injury area was also markedly higher in the 16∶0 LysoPS group.A significant decrease in the mean fluorescence intensity of blood flow was observed in the 16∶0 LysoPS group.Arterial partial pressure of oxygen(pO2)was significantly reduced in the PLA2 group,while arterial partial pressure of carbon dioxide(pCO2)was markedly elevated in the 16∶0 LysoPS and 18∶1 LysoPS groups.Lung function tests revealed that the 16∶0 LysoPS group exhibited significant increases in expiratory time,end-expiratory pressure,and enhanced pause,in contrast to significant decreases in tidal volume,expired volume,and minute volume.The 18∶1 LysoPS group also exhibited a significant decline in minute volume.No significant changes in inflammatory cell concentrations were detected in blood,with the exception of neutrophils in the 16∶0 LysoPS group,which showed a significant but physiologically normal increase.CONCLUSION Pulmonary phospholipids and their PLA2-derived fatty acid metabolites do not induce severe lung injury in mice while the lyso-phospholipid metabolites,particularly lysophosphatidylserine,are found to cause significant lung injury.
4.The Study of Preoperative Routine Multichannel Urodynamic Testing for Un-complicated Stress Urinary Incontinence
Aixin WANG ; Xiuli SUN ; Xin YANG
Journal of Practical Obstetrics and Gynecology 2025;41(8):649-653
Objective:To investigate the effectiveness of multi-channel urodynamic testing(MUT)in preopera-tive evaluation of stress urinary incontinence(SUI),and its impact on postoperative complications and treatment efficacy.Methods:The clinical data of 120 patients were collected.They were hospitalized for SUI and received surgical treatment in the gynecology department of Peking University People's Hospital from May 2020 to June 2022.Among them,60 cases(no-MUT group)were evaluated only by the six-step preoperative evaluation of un-complicated SUI recommended by the American College of Obstetrics and Gynecology without routine MUT,and another 60 cases(MUT gruop)underwent routine MUT and clinical evaluation.Both groups of patients underwent tension-free vaginal tape(TVT-E).The differences in general conditions,intraoperative conditions,postoperative complications,and subjective and objective cure rates between the two groups were compared.Pelvic floor dis-tress inventory-20(PFDI-20)and incontinence quality of life(l-QOL)were used to evaluate the quality of life,and patient-initiated sexual questiornaire-12(PISQ-12)was used to evaluate patients' quality of sex life.Results:①The positive rate of urodynamic SUI diagnosis was 53.3%(32/60)in MUT group.②The subjective cure rates of both groups were 96.7%;the objective cure rate was 98.3%and 96.7%respectively.No significant difference was observed in the postoperative subjective and objective cure rate of patients between two groups(P>0.05).③After the removal of the urinary catheter,the rate of voiding dysfunction was 5.0%in the no-MUT group and 8.3%in the MUT group.The rate of sling release was 1.7%and 3.3%respectively.The rate of newly developed overactive bladder(OAB)was 1.7%and 3.3%,respectively,with no statistically significant differences(P>0.05).④No significant difference was observed in the postoperative complications,sexual activity,and quality of life scores between the two groups(P>0.05).Conclusions:Patients with uncomplicated SUI assessed by the six step preoperative evaluation method can skip routine MUT without increasing surgical complications,and the treatment effect is comparable to that of routine MUT.
5.HFA-ICOS score in predicting cancer therapy-related cardiac dysfunction among breast cancer and lymphoma patients
Chang SHAN ; Mingyue JU ; Mei YANG ; Yanli ZHANG ; Xinxin ZHANG ; Xuefu CHEN ; Jia LI ; Fengqi FANG ; Xiuli SUN ; Yunlong XIA ; Ying LIU
Chinese Journal of Cardiology 2025;53(8):882-890
Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.
6.Cytopathological analysis of 522 cases of neoplastic serous effusion
Xiuli GUO ; Lixia WANG ; Jing YANG ; Jing LU
Cancer Research and Clinic 2025;37(3):218-222
Objective:To explore the morphological characteristics of tumor cells and the key diagnostic points of immunocytochemistry in neoplastic serous effusions.Methods:A retrospective case series study was conducted. A total of 522 samples which were ultimately diagnosed as neoplastic serous effusions by immunocytochemistry were collected in Shanxi Province Cancer Hospital from January 2019 to December 2023. The microscopic morphological characteristics of tumor cells in the samples were analyzed, and the diagnostic points of immunocytochemistry and the differential diagnostic points between rare tumors and adenocarcinoma were summarized.Results:Among the 522 samples of neoplastic serous effusion, there were 305 cases of pleural effusion, 178 cases of abdominal effusion, and 39 cases of pericardial effusion. Immunocytochemical diagnosis revealed 380 cases of adenocarcinoma [198 cases (52.1%) of pleural effusion, 155 cases (40.8%) of peritoneal effusion, and 27 cases (7.1%) of pericardial effusion], 55 cases of small cell carcinoma [47 cases (85.5%) of pleural effusion, 1 case (1.8%) of peritoneal effusion, and 7 cases (12.7%) of pericardial effusion], 23 cases of squamous cell carcinoma [18 cases (78.3%) of pleural effusion, 4 cases (17.4%) of peritoneal effusion, and 1 case (4.3%) of pericardial effusion], 5 cases of large cell neuroendocrine carcinoma (4 cases of pleural effusion and 1 case of pericardial effusion), and 31 cases of lymphoma [21 cases (67.7%) of pleural effusion, 7 cases (22.6%) of peritoneal effusion, and 3 cases (9.7%) of pericardial effusion], 20 cases of malignant mesothelioma [17 cases (85.0%) of pleural effusion and 3 cases (15.0%) of peritoneal effusion], 6 cases of ovarian borderline tumors (all of which were peritoneal effusions), and 2 cases of yolk sac tumors (both of which were peritoneal effusions). Under the microscope, the morphological characteristics of tumor cells in squamous cell carcinoma, large cell neuroendocrine carcinoma, lymphoma, malignant mesothelioma, ovarian borderline tumor, and yolk sac tumor were similar to those of adenocarcinoma cells, making them prone to misdiagnosis as adenocarcinoma. Immunocytochemical examination was necessary for the clear diagnosis.Conclusions:Adenocarcinoma accounts for the vast majority of neoplastic serous effusions, while the cell morphologies of other rare tumors overlap with adenocarcinoma. Careful observation and combination with clinical data and immunocytochemical examination results of patients are necessary for making the correct diagnosis.
7.HFA-ICOS score in predicting cancer therapy-related cardiac dysfunction among breast cancer and lymphoma patients
Chang SHAN ; Mingyue JU ; Mei YANG ; Yanli ZHANG ; Xinxin ZHANG ; Xuefu CHEN ; Jia LI ; Fengqi FANG ; Xiuli SUN ; Yunlong XIA ; Ying LIU
Chinese Journal of Cardiology 2025;53(8):882-890
Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.
8.The Study of Preoperative Routine Multichannel Urodynamic Testing for Un-complicated Stress Urinary Incontinence
Aixin WANG ; Xiuli SUN ; Xin YANG
Journal of Practical Obstetrics and Gynecology 2025;41(8):649-653
Objective:To investigate the effectiveness of multi-channel urodynamic testing(MUT)in preopera-tive evaluation of stress urinary incontinence(SUI),and its impact on postoperative complications and treatment efficacy.Methods:The clinical data of 120 patients were collected.They were hospitalized for SUI and received surgical treatment in the gynecology department of Peking University People's Hospital from May 2020 to June 2022.Among them,60 cases(no-MUT group)were evaluated only by the six-step preoperative evaluation of un-complicated SUI recommended by the American College of Obstetrics and Gynecology without routine MUT,and another 60 cases(MUT gruop)underwent routine MUT and clinical evaluation.Both groups of patients underwent tension-free vaginal tape(TVT-E).The differences in general conditions,intraoperative conditions,postoperative complications,and subjective and objective cure rates between the two groups were compared.Pelvic floor dis-tress inventory-20(PFDI-20)and incontinence quality of life(l-QOL)were used to evaluate the quality of life,and patient-initiated sexual questiornaire-12(PISQ-12)was used to evaluate patients' quality of sex life.Results:①The positive rate of urodynamic SUI diagnosis was 53.3%(32/60)in MUT group.②The subjective cure rates of both groups were 96.7%;the objective cure rate was 98.3%and 96.7%respectively.No significant difference was observed in the postoperative subjective and objective cure rate of patients between two groups(P>0.05).③After the removal of the urinary catheter,the rate of voiding dysfunction was 5.0%in the no-MUT group and 8.3%in the MUT group.The rate of sling release was 1.7%and 3.3%respectively.The rate of newly developed overactive bladder(OAB)was 1.7%and 3.3%,respectively,with no statistically significant differences(P>0.05).④No significant difference was observed in the postoperative complications,sexual activity,and quality of life scores between the two groups(P>0.05).Conclusions:Patients with uncomplicated SUI assessed by the six step preoperative evaluation method can skip routine MUT without increasing surgical complications,and the treatment effect is comparable to that of routine MUT.
9.Synergistic cytotoxic effect of chrysin and venetoclax on AML cells and its mechanism
Yan WANG ; Peixiong ZHU ; Pengyue YANG ; Xiuli WU ; Yangqiu LI ; Xi-bao YU ; Ling XU
Chinese Journal of Pathophysiology 2025;41(7):1300-1307
AIM:This study aims to investigate the synergistic cytotoxic effects of chrysin and venetoclax on acute myeloid leukemia(AML)cells and to elucidate the underlying mechanisms.METHODS:Human AML cell lines MV411 and MOLM13 were cultured in vitro and treated with chrysin in combination with venetoclax.Cell viability was as-sessed using the CCK8 assay,while flow cytometry was employed to measure cell cycle distribution and apoptosis rates.Western blot was used to detect the expression of apoptosis-related proteins and protein kinase B(PKB/Akt)/nuclear factor-κB(NF-κB)signaling pathway-related proteins.RESULTS:The results from the CCK8 assay and flow cytometry demon-strated that treatment with 16 and 32 μmol/L chrysin significantly inhibited the viability of AML cells and increased the proportion of cells in G1 phase,as well as the apoptosis rate.Notably,the cells in combination treatment group exhibited a marked reduction in proliferation and an elevated apoptosis rate compared with either chrysin or venetoclax group alone.Western blot analysis indicated that increasing concentrations of chrysin led to an elevation in cleaved poly(ADP-ribose)polymerase(PARP)level,alongside a down-regulation of proteins associated with the Akt/NF-κB signaling pathway.Fur-thermore,the combination treatment significantly up-regulated cleaved PARP level and down-regulated Akt/NF-κB path-way-related proteins compared with the treatment with chrysin or venetoclax alone.CONCLUSION:Chrysin and veneto-clax synergistically inhibit the proliferation of AML cells and promote apoptosis by modulating the Akt/NF-κB signaling pathway.
10.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.

Result Analysis
Print
Save
E-mail