1.Lactoferrin improved radioactive lung damage by regulating HMGB1/TLR4 inflammation
Yuzhong CHEN ; Lin ZHAO ; Jia GU ; Yafang DU ; Yunhong LI ; Guangxin DUAN ; Liqiang QIN ; Jiaying XU
Chinese Journal of Radiological Medicine and Protection 2021;41(3):161-165
Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.
2.Study on the Effect of Polygonatum Sibiricum Red.on Immune Dysfunction of Middle-aged Rats with Kidney Essence Defi-ciency
Jingjing YU ; Yuzhong DU ; Jie SU
Journal of Zhejiang Chinese Medical University 2024;48(8):895-904
[Objective]To study the regulatory effect of Polygonatum sibiricum Red.on immune dysfunction in middle-aged rats with kidney essence deficiency caused by sexual overstrain.[Methods]To simulate the immune dysfunction caused by kidney essence deficiency due to sexual overstrain in middle-aged men,middle-aged rats with kidney essence deficiency model caused by sexual overstrain were prepared by"middle-aged male rats+male and female with the same cage".The spleen coefficient of rats was measured during the experiment;the morphological changes of spleen were observed by hematoxylin-eosin(HE)staining;the proportion of neutrophils and lymphocytes in bone marrow was measured,and the number and proportion of lymphocytes in peripheral blood and the proportion of neutrophils were measured;splenic lymphocyte proliferation assay was used to detect splenic lymphocyte proliferation;the proportion of T lymphocyte subsets in spleen tissue was determined by flow cytometry;terminal deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)was used to observe the apoptosis of spleen cells;Western blot was used to detect the protein expression of phospho-phosphatidylinositol 3-kinase(p-PI3K),phospho-protein kinase B(p-AKT),B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X(Bax)in spleen tissue.[Results]The results showed that Polygonatum sibiricum Red.could reduce the proportion of neutrophils in bone marrow and peripheral blood of middle-aged rats with kidney essence deficiency caused by sexual overstrain;increase the proportion of lymphocyte in bone marrow;increase the number and proportion of peripheral blood lymphocytes;reduce the ratio of T lymphocytes(CD4+/CD8+)in spleen;improve the proliferation of T lymphocyte in spleen;reduce cell apoptosis in spleen tissue;increased spleen tissue proliferation related protein p-PI3K and p-AKT expression.[Conclusion]Polygonatum sibiricum Red.can improve the immune dysfunction caused by kidney essence deficiency due to sexual overstrain in middle-aged rats by affecting the proportion of T lymphocytes and their subpopulations,and its mechanism may be related to regulating the spleen tissue proliferation related protein expression of PI3K/AKT.
3.Clinical Study on Huoxue Bitong Plaster Treating Lumbar Osteoarthritis with Blood Stasis and Cold-dampness Blocking Collaterals Syndrome
Ayong HUANG ; Guoqiang LI ; Lianbo CAO ; Haiyan YANG ; Sitao DU ; Yuxin YANG ; Qingsheng WU ; Yongsheng LIANG ; Yuzhong SUN
Chinese Journal of Information on Traditional Chinese Medicine 2015;(6):28-31
Objective To observe the clinical efficacy of Huoxue Bitong Plaster on lumbar osteoarthritis with blood stasis and cold-dampness blocking collaterals syndrome. Methods Totally 120 patients were randomly divided into treatment group (60 cases) and control group (60 cases). Huoxue Bitong Plaster was applied externally in the treatment group, while Goupigao Plaster was used externally in the control group, once a day, for two weeks. The clinical efficacy was evaluated by observing TCM symptom scores, VAS, Oswestry dability index (ODI), and onset time in both groups before and after treatment. Results The total effective rate was 86.67%(52/60) in treatment group, and 85.00% (51/60) in the control group, with no statistical significance (P>0.05). TCM symptom scores of both groups decreased after treatment (P<0.05). For the effect of relieving back pain and morning stiffness, the treatment group was superior to control group (P<0.05). For the effect of relieving waist heaviness, the control group was better than the treatment group (P<0.05). Besides, VAS and ODI of the treatment group were lower than the control group after treatment (P<0.05). The onset time of lightening back pain, morning stiffness in the treatment group was quicker than control group (P<0.05). For waist heaviness, the onset time in control group was quicker than treatment group (P<0.05). Conclusion Huoxue Bitong Plaster has good efficacy for lumbar osteoarthritis with blood stasis and cold-dampness blocking collaterals syndrome.
4.Peripheral Blood Inflammation Indicators as Predictive Indicators in Immunotherapy of Advanced Non-small Cell Lung Cancer.
Jingwei XIA ; Yuzhong CHEN ; Shaodi WEN ; Xiaoyue DU ; Bo SHEN
Chinese Journal of Lung Cancer 2021;24(9):632-645
BACKGROUND:
Lung cancer is the leading cause of cancer-related death, of which non-small cell lung cancer (NSCLC) is the most common type. Immune checkpoint inhibitors (ICIs) have now become one of the main treatments for advanced NSCLC. This paper retrospectively investigated the effect of peripheral blood inflammatory indexes on the efficacy of immunotherapy and survival of patients with advanced non-small cell lung cancer, in order to find strategies to guide immunotherapy in NSCLC.
METHODS:
Patients with advanced non-small cell lung cancer who were hospitalized in The Affiliated Cancer Hospital of Nanjing Medical University from October 2018 to August 2019 were selected to receive anti-PD-1 (pembrolizumab, sintilimab or toripalimab) monotherapy or combination regimens. And were followed up until 10 December 2020, and the efficacy was evaluated according to RECIST1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were followed up for survival analysis. A clinical prediction model was constructed to analyze the predictive value of neutrophil-to-lymphocyte ratio (NLR) based on NLR data at three different time points: before treatment, 6 weeks after treatment and 12 weeks after treatment (0w, 6w and 12w), and the accuracy of the model was verified.
RESULTS:
173 patients were finally included, all of whom received the above treatment regimen, were followed up for a median of 19.7 months. The objective response rate (ORR) was 27.7% (48/173), the disease control rate (DCR) was 89.6% (155/173), the median PFS was 8.3 months (7.491-9.109) and the median OS was 15.5 months (14.087-16.913). The chi-square test and logistic multi-factor analysis showed that NLR6w was associated with ORR and NLR12w was associated with ORR and DCR. Further Cox regression analysis showed that NLR6w and NLR12w affected PFS and NLR0w, NLR6w and NLR12w were associated with OS.
CONCLUSIONS
In patients with advanced non-small cell lung cancer, NLR values at different time points are valid predictors of response to immunotherapy, and NLR <3 is often associated with a good prognosis.
Aged
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Antibodies, Monoclonal, Humanized/therapeutic use*
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Antineoplastic Agents, Immunological/therapeutic use*
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Biomarkers/blood*
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Carcinoma, Non-Small-Cell Lung/pathology*
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Female
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Humans
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Immunotherapy/methods*
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Inflammation/blood*
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Leukocyte Count
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Lung Neoplasms/pathology*
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Lymphocytes
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Male
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Middle Aged
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Neutrophils
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Predictive Value of Tests
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Prognosis
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Retrospective Studies
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Survival Analysis
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Treatment Outcome