1.LIU Xing's experience in treatment of primary trigeminal neuralgia by the integration of acupuncture and medication.
Changchang ZHANG ; Luyao SHI ; Wanchun HU ; Tong LIU ; Dunlin FANG ; Chu LI ; Tianhui TAN ; Xuemei CAO ; Junjie ZHANG
Chinese Acupuncture & Moxibustion 2025;45(12):1795-1799
The paper introduces Professor LIU Xing's clinical experience and characteristics of integrative acupuncture and medication in treatment of primary trigeminal neuralgia (PTN). It is believed that the essential pathogenesis of PTN is pathogenic wind, and qi and blood obstruction results from invasion of pathogenic wind. Hence, dispelling wind is the key principle of treatment. Palpation is done at first in the neck, face and buccal mucosal region to detect the masses in treatment. Acupotomy is operated at the masses distributed at Shangguan (GB3), Xiaguan (ST7) and the white line of buccal mucosa, so as to release masses. Additionally, five-wind points (Fengfu [GV16], bilateral Fengchi [GB20], Yifeng [TE17], Bingfeng [SI12] and Fengmen [BL12]), three-nape points (bilateral Naokong [GB19], Tianzhu [BL10] and Jianjing [GB21]) and three-governor-vessel points (Baihui [GV20], Zhiyang [GV9] and Yintang [GV24+]) are selected to dispel wind and stop pain. Besides, herbal decoction (wu feng tang) and blood-letting at ear apex are administered in combination. The integration of acupuncture and medication obtains a holistic effect on PTN by dispelling wind pathogen, and promoting qi and blood circulation.
Humans
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Trigeminal Neuralgia/drug therapy*
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Acupuncture Therapy
;
Acupuncture Points
;
Female
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Male
;
Middle Aged
;
Drugs, Chinese Herbal/administration & dosage*
;
Combined Modality Therapy
;
Adult
;
Aged
2.Evaluating the impact of relative dose intensity on efficacy of trastuzumab deruxtecan for metastatic breast cancer in the real-world clinical setting.
Han Yi LEE ; Vivianne SHIH ; Jack Junjie CHAN ; Shun Zi LIONG ; Ryan Shea Ying Cong TAN ; Jun MA ; Bernard Ji Guang CHUA ; Joshua Zhi Chien TAN ; Chuan Yaw LEE ; Wei Ling TEO ; Su-Ming TAN ; Phyu NITAR ; Yoon Sim YAP ; Mabel WONG ; Rebecca DENT ; Fuh Yong WONG ; Tira J TAN
Annals of the Academy of Medicine, Singapore 2025;54(8):458-466
INTRODUCTION:
Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges.
METHOD:
Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes.
RESULTS:
Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities.
CONCLUSION
Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans
;
Female
;
Breast Neoplasms/mortality*
;
Middle Aged
;
Trastuzumab/adverse effects*
;
Aged
;
Adult
;
Singapore/epidemiology*
;
Antineoplastic Agents, Immunological/adverse effects*
;
Camptothecin/adverse effects*
;
Immunoconjugates/adverse effects*
;
Retrospective Studies
;
Progression-Free Survival
;
Receptor, ErbB-2/metabolism*
;
Neoplasm Metastasis
;
Dose-Response Relationship, Drug
;
Treatment Outcome
;
Registries
3.Design, synthesis and anticancer activity of superoxide anion-releasing beta-galactoside prodrugs
Jiaxuan LIU ; Xueyan YAO ; Yunying TAN ; Jing HU ; Junjie FU ; Jian YIN
Journal of China Pharmaceutical University 2025;56(3):295-304
Four novel β-galactoside prodrugs were designed and synthesized from anthraquinones HAQ-OH and AQ-OH in an attempt to use the prodrugs to selectively release superoxide anion (O2−) in cancer cells and to achieve selected anticancer activity by utilizing the Warburg effect and the elevated level of β-galactosidase in certain cancer cells. Cellular assays showed that the prodrugs Gal-HAQ and Gal-AQ selectively inhibited the proliferation and induced apoptosis of ovarian cancer OVCAR-3 cells overexpressing β-galactosidase. Using O2− fluorescent probe, it was found that in OVCAR-3 cells Gal-HAQ and Gal-AQ could time-dependently release O2−, which was essential for their anticancer activity. Furthermore, it was found that Gal-HAQ and Gal-AQ were effective senolytics toward senescent cells overexpressing β-galactosidase without affecting the viability of corresponding non-senescent cells, further confirming the β-galactosidase-dependent cytotoxicity of the prodrugs. In conclusion, Gal-HAQ and Gal-AQ, which release O2− in response to β-galactosidase, are expected to serve as candidate prodrugs targeting cancer cells.
4.Visual Analysis of Current Situation,Hotspot and Trend of Traditional Chinese Medicine in Treating Carotid Atherosclerosis Based on CiteSpace and VOSviewer
Yihuan CHEN ; Di ZHANG ; Yuwen XIA ; Junjie JIANG ; Cheng LYU ; Qingqiao SONG ; Yong TAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(2):498-507
Objective To explore the current situation,hot spots and trends of clinical research on the treatment of carotid atherosclerosis(CAS)with traditional Chinese medicine.Methods Search CNKI,Wanfang,VIP,Web of Science core collection database related literature,using Python 3.9.6 cleaning data,using CiteSpace and VOSviewer for visual analysis of authors,institutions,keywords,etc.Results 910 Chinese literatures and 5 English literatures were included.The most published authors were Wang Changyin and Yin Chunping,and the institution was Handan Hospital of Traditional Chinese Medicine,Hebei Province.The cooperation between institutions was independent and regional.Research focus on:phlegm stasis interjunction,dyslipidemia,inflammatory factors,vascular endothelial function,nerve function defect,Banxia Baizhu Tianma decoction,coronary heart disease and so on;The treatment of CAS from"interjunction of phlegm and blood stasis"will continue to become a research hotspot in this field.Conclusion The clinical research of traditional Chinese medicine in the treatment of CAS should be closely combined with the observation of curative effect and the revelation of mechanism,and the law of traditional Chinese medicine in the treatment of CAS should be explored.In the future,the treatment of CAS should focus on the treatment of"phlegm and blood stasis",and the pathogenesis principle of"phlegm and blood stasis",the efficacy and mechanism of resolving phlegm and removing blood stasis in the treatment of CAS should be systematically and deeply explored.
5.Comparison of the Phoenix scoring system and commonly used pediatric sepsis scores in predicting mortality risk in pediatric patients with severe sepsis under traditional standards
Haonan WANG ; Yinglang HE ; Rui TAN ; Han LI ; Xian LI ; Nan HOU ; Chen JI ; Zhe LI ; Yue WANG ; Shuangshuang PENG ; Le JING ; Liye GU ; Junjie ZHAO ; Hongjun MIAO
Chinese Journal of Burns 2025;41(3):222-231
Objective:To explore the differences between the Phoenix sepsis scoring system including Phoenix sepsis score (PSS) and Phoenix-8 organ dysfunction score (hereinafter referred to as Phoenix-8) and the commonly used pediatric sepsis scores in evaluating clinical characteristics and prognostic analysis of pediatric patients with severe sepsis diagnosed under traditional standards, namely the diagnostic criteria from the 2005 International Pediatric Sepsis Consensus Conference.Methods:This study was a retrospective observational study. From December 2020 to March 2023, 202 pediatric patients with severe sepsis meeting the inclusion criteria were admitted to the Children's Hospital of Nanjing Medical University. Based on the sepsis diagnostic criteria outlined in the International Consensus Criteria for Pediatric Sepsis and Septic Shock (2024), the pediatric patients were categorized into a sepsis group and a non-sepsis group. Sepsis group was further subdivided into a death subgroup and a survival subgroup based on the outcomes. The age, hospitalization costs, disease outcome indicators (e.g., mortality rate and incidence of septic shock), major organ (e.g., heart, liver, lungs, and kidneys) damage and their correlations, as well as PSS, Phoenix-8 and commonly used pediatric sepsis scores (e.g., pediatric sequential organ failure assessment (pSOFA), pediatric risk of mortality score Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 score (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), and pediatric early warning score (PEWS)) were collected and compared. Receiver operating characteristic (ROC) curve and precision-recall curve were plotted to evaluate the predictive ability of PSS, Phoenix-8, and commonly used pediatric sepsis scores for mortality risk in pediatric patients with severe sepsis under traditional standards. Predictive performance was quantified using the area under the ROC curve (AUROC). Univariate logistic regression analysis was employed to quantify the odds ratios of PSS and Phoenix-8 for predicting mortality risk. Patients with severe sepsis under traditional standards were further stratified into subgroups based on complications and comorbidities, including central nervous system (CNS) diseases, multiple infections, cardiovascular system diseases, shock, and malignancies. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of PSS and Phoenix-8, and the DeLong test was used to compare whether there were statistically significant differences in the AUROC of PSS and Phoenix-8 for predicting mortality risk among different subgroups of pediatric patients. Results:Compared with those in non-sepsis group, pediatric patients in sepsis group were significantly older ( Z=-2.92, P<0.05) with higher incidences of septic shock and mortality, hospitalization costs, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, PSS, and Phoenix-8 (with χ2 values of 21.28 and 13.64, respectively, Z values of -1.99, -5.33, -5.10, -8.55, -6.91, -10.98, and -9.93, respectively, P<0.05), and lower PCIS ( Z=-3.34, P<0.05). Compared with those in survival subgroup, hospitalization costs, PSS, Phoenix-8, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, and P-MODS of pediatric patients in death subgroup was significantly higher (with Z values of -2.50, -3.50, -2.47, -5.11, -3.84, -2.94, -3.61, and -3.04, respectively, P<0.05). Compared with those in survival subgroup, the incidences of lung damage and liver damage of pediatric patients in death subgroup were also significantly higher (with χ2 values of 6.20 and 10.94, respectively, P<0.05), and 64.7% (97/150) of patients exhibited two or more concurrent organ damage. For predicting mortality risk in pediatric patients with severe sepsis under traditional standards, the AUROC values for PRISM Ⅲ, PCIS, PEWS, pSOFA, PELOD-2, P-MODS, PSS, and Phoenix-8 were approximately 0.70, with optimal cutoff values of 17.5, 91.0, 5.5, 4.5, 2.5, 4.5, 3.5, and 4.5, respectively; PELOD-2 demonstrated the highest sensitivity (0.83); while PRISM Ⅲ, PSS, and Phoenix-8 showed high specificity (>0.80). Univariate logistic regression analysis showed that for every 1-point increase in the PSS within 24 hours of pediatric intensive care unit admission, the relative risk of mortality increased by 63.7% (with odds ratio of 1.64, 95% confidence interval of 1.34-1.99, P<0.05). Similarly, for every 1-point increase in the Phoenix-8, the relative risk of mortality increased by 37.5% (with odds ratio of 1.38, 95% confidence interval of 1.18-1.60, P<0.05). The AUROC values (around 0.80) of PSS and Phoenix-8 for predicting mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases were relatively high. In contrast, the AUROC values (0.60-0.80) for predicting mortality risk in pediatric patients with severe sepsis combined with shock or malignant tumors were moderate. All models passed the Hosmer-Lemeshow goodness-of-fit test ( P>0.05). The DeLong test indicated no statistically significant differences in predictive ability between PSS and Phoenix-8 across subgroups of pediatric patients ( P>0.05). Conclusions:PSS and Phoenix-8 exhibited higher specificity than most of the commonly used pediatric sepsis scores in predicting mortality risk under traditional standards. Both scores performed much better in predicting the mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases.
6.Evaluation of the therapeutic effect and analysis of the causes of complications of allogeneic decellularized dermal matrix grafts in the treatment of gingival recession using tunneling method
Junjie ZHAO ; Yanfen LI ; Jianping XIAO ; Cheng XU ; Baochun TAN
Journal of Practical Stomatology 2025;41(5):656-661
Objective:To evaluate the efficacy and analyze the causes of complications of allogeneic decellularized dermal matrix grafts in the treatment of gingival recession using tunneling technology.Methods:Sixty patients with single or multiple gingival re-cession were randomly divided into an allogeneic decellularized matrix(ADM)group and a connective tissue(SCTG)group.Tunne-ling technique(TUN)were used in both groups to cover the root surface,and the gingival margin position,gingival margin morpholo-gy,and mucogingival junction position of the affected teeth at 1 week,3 weeks,3 months,and 6 months after surgery were observed.Check and record the gingival recession depth(RD)and mean root coverage(MRC)at the implant site before and 6 months after surgery.Record patient satisfaction at 3 weeks and 6 months after surgery.Results:Compared with the traditional SCTG group,the MRC of the ADM group was significantly lower before surgery and 6 months after surgery(P<0.05).The satisfaction level of the ADM group was higher 3 weeks after surgery,with a significant difference compared to the SCTG group(P<0.05).But 6 months after surgery,the satisfaction levels of the two groups tended to be consistent,with no significant difference.After TUN+ADM surgery,there was 1 case of abscess infection lesion,and another 3 cases showed local tissue necrosis at the gingival margin one week after surgery.After 3 months of treatment,the gingival color of these 4 patients was pink and tough texture,without swelling and bleeding.Conclusion:Although ADM is slightly inferior to SCTG in the treatment of gingival recession,it may be related to poor postoperative tissue healing complications.However,as long as it is handled properly,long-term follow-up observations have shown that gingival tissue can still achieve complete healing.TUN+ADM is a highly effective treatment for gingival recession and is suitable for further clinical application.
7.Evaluation of the therapeutic effect and analysis of the causes of complications of allogeneic decellularized dermal matrix grafts in the treatment of gingival recession using tunneling method
Junjie ZHAO ; Yanfen LI ; Jianping XIAO ; Cheng XU ; Baochun TAN
Journal of Practical Stomatology 2025;41(5):656-661
Objective:To evaluate the efficacy and analyze the causes of complications of allogeneic decellularized dermal matrix grafts in the treatment of gingival recession using tunneling technology.Methods:Sixty patients with single or multiple gingival re-cession were randomly divided into an allogeneic decellularized matrix(ADM)group and a connective tissue(SCTG)group.Tunne-ling technique(TUN)were used in both groups to cover the root surface,and the gingival margin position,gingival margin morpholo-gy,and mucogingival junction position of the affected teeth at 1 week,3 weeks,3 months,and 6 months after surgery were observed.Check and record the gingival recession depth(RD)and mean root coverage(MRC)at the implant site before and 6 months after surgery.Record patient satisfaction at 3 weeks and 6 months after surgery.Results:Compared with the traditional SCTG group,the MRC of the ADM group was significantly lower before surgery and 6 months after surgery(P<0.05).The satisfaction level of the ADM group was higher 3 weeks after surgery,with a significant difference compared to the SCTG group(P<0.05).But 6 months after surgery,the satisfaction levels of the two groups tended to be consistent,with no significant difference.After TUN+ADM surgery,there was 1 case of abscess infection lesion,and another 3 cases showed local tissue necrosis at the gingival margin one week after surgery.After 3 months of treatment,the gingival color of these 4 patients was pink and tough texture,without swelling and bleeding.Conclusion:Although ADM is slightly inferior to SCTG in the treatment of gingival recession,it may be related to poor postoperative tissue healing complications.However,as long as it is handled properly,long-term follow-up observations have shown that gingival tissue can still achieve complete healing.TUN+ADM is a highly effective treatment for gingival recession and is suitable for further clinical application.
8.Visual Analysis of Current Situation,Hotspot and Trend of Traditional Chinese Medicine in Treating Carotid Atherosclerosis Based on CiteSpace and VOSviewer
Yihuan CHEN ; Di ZHANG ; Yuwen XIA ; Junjie JIANG ; Cheng LYU ; Qingqiao SONG ; Yong TAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(2):498-507
Objective To explore the current situation,hot spots and trends of clinical research on the treatment of carotid atherosclerosis(CAS)with traditional Chinese medicine.Methods Search CNKI,Wanfang,VIP,Web of Science core collection database related literature,using Python 3.9.6 cleaning data,using CiteSpace and VOSviewer for visual analysis of authors,institutions,keywords,etc.Results 910 Chinese literatures and 5 English literatures were included.The most published authors were Wang Changyin and Yin Chunping,and the institution was Handan Hospital of Traditional Chinese Medicine,Hebei Province.The cooperation between institutions was independent and regional.Research focus on:phlegm stasis interjunction,dyslipidemia,inflammatory factors,vascular endothelial function,nerve function defect,Banxia Baizhu Tianma decoction,coronary heart disease and so on;The treatment of CAS from"interjunction of phlegm and blood stasis"will continue to become a research hotspot in this field.Conclusion The clinical research of traditional Chinese medicine in the treatment of CAS should be closely combined with the observation of curative effect and the revelation of mechanism,and the law of traditional Chinese medicine in the treatment of CAS should be explored.In the future,the treatment of CAS should focus on the treatment of"phlegm and blood stasis",and the pathogenesis principle of"phlegm and blood stasis",the efficacy and mechanism of resolving phlegm and removing blood stasis in the treatment of CAS should be systematically and deeply explored.
9.Comparison of the Phoenix scoring system and commonly used pediatric sepsis scores in predicting mortality risk in pediatric patients with severe sepsis under traditional standards
Haonan WANG ; Yinglang HE ; Rui TAN ; Han LI ; Xian LI ; Nan HOU ; Chen JI ; Zhe LI ; Yue WANG ; Shuangshuang PENG ; Le JING ; Liye GU ; Junjie ZHAO ; Hongjun MIAO
Chinese Journal of Burns 2025;41(3):222-231
Objective:To explore the differences between the Phoenix sepsis scoring system including Phoenix sepsis score (PSS) and Phoenix-8 organ dysfunction score (hereinafter referred to as Phoenix-8) and the commonly used pediatric sepsis scores in evaluating clinical characteristics and prognostic analysis of pediatric patients with severe sepsis diagnosed under traditional standards, namely the diagnostic criteria from the 2005 International Pediatric Sepsis Consensus Conference.Methods:This study was a retrospective observational study. From December 2020 to March 2023, 202 pediatric patients with severe sepsis meeting the inclusion criteria were admitted to the Children's Hospital of Nanjing Medical University. Based on the sepsis diagnostic criteria outlined in the International Consensus Criteria for Pediatric Sepsis and Septic Shock (2024), the pediatric patients were categorized into a sepsis group and a non-sepsis group. Sepsis group was further subdivided into a death subgroup and a survival subgroup based on the outcomes. The age, hospitalization costs, disease outcome indicators (e.g., mortality rate and incidence of septic shock), major organ (e.g., heart, liver, lungs, and kidneys) damage and their correlations, as well as PSS, Phoenix-8 and commonly used pediatric sepsis scores (e.g., pediatric sequential organ failure assessment (pSOFA), pediatric risk of mortality score Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 score (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), and pediatric early warning score (PEWS)) were collected and compared. Receiver operating characteristic (ROC) curve and precision-recall curve were plotted to evaluate the predictive ability of PSS, Phoenix-8, and commonly used pediatric sepsis scores for mortality risk in pediatric patients with severe sepsis under traditional standards. Predictive performance was quantified using the area under the ROC curve (AUROC). Univariate logistic regression analysis was employed to quantify the odds ratios of PSS and Phoenix-8 for predicting mortality risk. Patients with severe sepsis under traditional standards were further stratified into subgroups based on complications and comorbidities, including central nervous system (CNS) diseases, multiple infections, cardiovascular system diseases, shock, and malignancies. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of PSS and Phoenix-8, and the DeLong test was used to compare whether there were statistically significant differences in the AUROC of PSS and Phoenix-8 for predicting mortality risk among different subgroups of pediatric patients. Results:Compared with those in non-sepsis group, pediatric patients in sepsis group were significantly older ( Z=-2.92, P<0.05) with higher incidences of septic shock and mortality, hospitalization costs, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, PSS, and Phoenix-8 (with χ2 values of 21.28 and 13.64, respectively, Z values of -1.99, -5.33, -5.10, -8.55, -6.91, -10.98, and -9.93, respectively, P<0.05), and lower PCIS ( Z=-3.34, P<0.05). Compared with those in survival subgroup, hospitalization costs, PSS, Phoenix-8, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, and P-MODS of pediatric patients in death subgroup was significantly higher (with Z values of -2.50, -3.50, -2.47, -5.11, -3.84, -2.94, -3.61, and -3.04, respectively, P<0.05). Compared with those in survival subgroup, the incidences of lung damage and liver damage of pediatric patients in death subgroup were also significantly higher (with χ2 values of 6.20 and 10.94, respectively, P<0.05), and 64.7% (97/150) of patients exhibited two or more concurrent organ damage. For predicting mortality risk in pediatric patients with severe sepsis under traditional standards, the AUROC values for PRISM Ⅲ, PCIS, PEWS, pSOFA, PELOD-2, P-MODS, PSS, and Phoenix-8 were approximately 0.70, with optimal cutoff values of 17.5, 91.0, 5.5, 4.5, 2.5, 4.5, 3.5, and 4.5, respectively; PELOD-2 demonstrated the highest sensitivity (0.83); while PRISM Ⅲ, PSS, and Phoenix-8 showed high specificity (>0.80). Univariate logistic regression analysis showed that for every 1-point increase in the PSS within 24 hours of pediatric intensive care unit admission, the relative risk of mortality increased by 63.7% (with odds ratio of 1.64, 95% confidence interval of 1.34-1.99, P<0.05). Similarly, for every 1-point increase in the Phoenix-8, the relative risk of mortality increased by 37.5% (with odds ratio of 1.38, 95% confidence interval of 1.18-1.60, P<0.05). The AUROC values (around 0.80) of PSS and Phoenix-8 for predicting mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases were relatively high. In contrast, the AUROC values (0.60-0.80) for predicting mortality risk in pediatric patients with severe sepsis combined with shock or malignant tumors were moderate. All models passed the Hosmer-Lemeshow goodness-of-fit test ( P>0.05). The DeLong test indicated no statistically significant differences in predictive ability between PSS and Phoenix-8 across subgroups of pediatric patients ( P>0.05). Conclusions:PSS and Phoenix-8 exhibited higher specificity than most of the commonly used pediatric sepsis scores in predicting mortality risk under traditional standards. Both scores performed much better in predicting the mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases.
10.Investigating Mechanism of Fritillariae Cirrhosae Bulbus Against Pulmonary Fibrosis Based on Spatial Metabolomics
Shanbo QIN ; Peng TAN ; Lu HAO ; Junjie XIE ; Junzhi LIN ; Lei ZHANG ; Junning ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):150-159
ObjectiveBased on spatial metabolomics technology combined with pharmacological indexes, to analyze the mechanism of Fritillariae Cirrhosae Bulbus(FCB) powder in improving bleomycin-induced pulmonary fibrosis in rats. MethodSixty SD rats were randomly divided into five groups, including the blank group, the model group, and high, medium, low dosage groups of FCB. Except for the blank group, rats in all other groups were injected with bleomycin by tracheal injection to establish a pulmonary fibrosis model. Postoperatively, the high, medium and low dosage groups of FCB were administered aqueous solutions of FCB powder at doses of 0.36, 0.18, 0.09 g·kg-1, respectively, continuously for 28 d. The blank and model groups were given an equal volume of distilled water by gavage. After the last administration, lung tissues and blood samples were collected, the pathological conditions of rat lung tissues were comprehensively evaluated by hematoxylin-eosin(HE) and Masson staining, and aerodynamic assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI) was used for MSI of rat lung tissues from different experimental groups. Spatial metabolomics analysis was conducted on the fibrotic areas of lung tissues in the model group and the high dosage group of FCB based on HE staining images. Differential metabolites between groups were screened by orthogonal partial least squares-discriminant analysis(OPLS-DA), with variable importance in the projection(VIP) values>1, t-test P<0.05, and fold change analysis. Metabolic pathway analysis of the identified differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG). Protein expression levels of nuclear transcription factor-κB p65(NF-κB p65) and heme oxygenase-1(HO-1) in rat lung tissues were detected by Western blot. Biochemical assessments of superoxide dismutase(SOD), malondialdehyde(MDA) and glutathione(GSH) levels in rat lung tissues were conducted. Serum levels of interleukin(IL)-1β, IL-6, nuclear factor erythroid 2 related factor 2(Nrf2), and tumor necrosis factor-α(TNF-α) were measured by enzyme linked immunosorbent assay(ELISA), and some of the screened signaling pathways with strong correlation were verified. ResultThe results of MSI experiment showed that after 28 d of the administration of FCB powder to rats with pulmonary fibrosis, the content of L-arginine in the fibrotic regions of lung tissues was significantly different from that of rats in the model group, and the content of phosphatidylcholine was lower than that in the fibrotic region of lung tissues of rats in the model group. Western blot results confirmed that, in comparison to the model group, oral administration of FCB powder for 28 d could inhibit the elevated expression of NF-κB p65 protein in the lung tissues of rats with pulmonary fibrosis. Furthermore, high dose of FCB powder was able to significantly inhibit the expression of HO-1 after oral administration (P<0.05). The cytokine detection results indicated that the concentrations of IL-1β, IL-6 and TNF-α in the serum of rats from the high, medium, low dosage groups of FCB were reduced by comparing with the model group, and the high dose of Chuanbeimu powder administered by gavage could significantly inhibit the trend of decreased SOD, GSH, Nrf2 contents and increased MDA content induced by bleomycin. ConclusionOral administration of FCB powder has the potential to partially ameliorate bleomycin-induced pulmonary fibrosis in rats, and its mechanism may be related to the regulation of pathways associated with inflammation(NF-κB p65) and oxidative stress(Nrf2/HO-1).

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