1.Effect of transcutaneous electrical acupoint stimulation on postoperative pain in patients undergoing modified radical mastectomy for breast cancer.
Li YAN ; Bin SUN ; Meiyan ZHOU ; Yan ZHANG ; Fei GAO ; Qianwen ZHAO ; Liwei WANG
Chinese Acupuncture & Moxibustion 2025;45(2):162-166
OBJECTIVE:
To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain in patients undergoing modified radical mastectomy for breast cancer.
METHODS:
A total of 140 female patients scheduled for unilateral modified radical mastectomy for breast cancer undergoing general anesthesia were randomized into a TEAS group (70 cases) and a sham TEAS group (70 cases, 2 cases dropped out). Patients in both groups received TEAS or sham TEAS at bilateral Neiguan (PC6), Zusanli (ST36), and Danzhong (CV17), respectively, from 30 min before anesthesia induction until the end of surgery, and on 1st, 2nd, and 3rd days after surgery for 30 min a time, once a day. On 1st, 2nd, and 3rd days after surgery, the pain visual analogue scale (VAS) score was observed; on 3, 6, 12 months after surgery, the incidence rate of chronic pain was observed; before surgery, and on 1st, 3rd, and 7th days after surgery, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were detected; the number of analgesia pump press, rescue analgesia, and the occurrence of adverse reaction after surgery were recorded in the two groups.
RESULTS:
In the TEAS group, the VAS scores on 1st and 2nd days after surgery, and the incidence rates of chronic pain on 3 and 6 months after surgery were lower than those in the sham TEAS group (P<0.05). On 1st, 3rd, and 7th days after surgery, the serum levels of TNF-α, IL-6, and IL-10 were increased compared with those before surgery in both groups (P<0.05, P<0.01); the above indexes in the TEAS group were lower than those in the sham TEAS group (P<0.05). The number of analgesia pump press and the incidence rate of rescue analgesia after surgery in the TEAS group were lower than those in the sham TEAS group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions after surgery between the two groups (P>0.05).
CONCLUSION
TEAS can effectively improve both the postoperative acute pain and chronic pain in patients undergoing modified radical mastectomy for breast cancer, the mechanism may relate to inhibiting the inflammatory reaction.
Humans
;
Female
;
Acupuncture Points
;
Pain, Postoperative/blood*
;
Middle Aged
;
Breast Neoplasms/surgery*
;
Adult
;
Transcutaneous Electric Nerve Stimulation
;
Mastectomy, Modified Radical/adverse effects*
;
Interleukin-6/blood*
;
Tumor Necrosis Factor-alpha/blood*
;
Interleukin-10/blood*
;
Aged
2.Mechanism of 2,6-DMBQ attenuates airway inflammatory responses in asthmatic mice via the mTOR signaling pathway.
Juan LI ; Shu-Fang LI ; Xiao-Man XIONG ; Qiu-Yan YANG ; Xue-Li XIE ; Yan-Li ZHANG
Chinese Journal of Contemporary Pediatrics 2025;27(4):472-479
OBJECTIVES:
To investigate the therapeutic effects and mechanisms of 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) in a mouse model of asthma.
METHODS:
SPF-grade BALB/c mice were randomly divided into 7 groups (n=8 each group): normal control group, ovalbumin (OVA) group, dimethyl sulfoxide+corn oil group, budesonide (BUD) group, and low, medium, and high dose 2,6-DMBQ groups. An asthma mouse model was established by OVA induction, followed by corresponding drug interventions. Non-invasive lung function tests were performed to measure airway hyperresponsiveness, and enzyme-linked immunosorbent assay was used to determine levels of interleukin (IL)-17, IL-10, and serum immunoglobulin E in bronchoalveolar lavage fluid. A cell counter was employed to detect eosinophil counts in bronchoalveolar lavage fluid, while hematoxylin-eosin staining and periodic acid-Schiff staining were used to assess lung tissue pathological changes. Western blot was conducted to examine the expression of proteins related to the mammalian target of rapamycin pathway (p-AKT/AKT and p-p70S6K/p70S6K), and a fully automated biochemical analyzer was used to evaluate liver and kidney functions.
RESULTS:
Compared with the normal control group, the OVA group showed increased enhanced pause values, inflammation scores from hematoxylin-eosin staining, positive area from periodic acid-Schiff staining, percentage of eosinophils, IL-17/IL-10 ratio, serum immunoglobulin E levels, and relative expression levels of p-AKT/AKT and p-p70S6K/p70S6K (P<0.05). The BUD group and the medium and high dose 2,6-DMBQ groups exhibited decreased values for these indicators compared to the OVA group (P<0.05).
CONCLUSIONS
2,6-DMBQ can inhibit the mTOR pathway to alleviate airway inflammation in asthmatic mice, possibly by mitigating the imbalance between Th17 and regulatory T cells.
Animals
;
Asthma/pathology*
;
Mice, Inbred BALB C
;
Signal Transduction/drug effects*
;
Mice
;
TOR Serine-Threonine Kinases/physiology*
;
Female
;
Benzoquinones/pharmacology*
;
Immunoglobulin E/blood*
;
Interleukin-10/analysis*
;
Interleukin-17/analysis*
;
Bronchoalveolar Lavage Fluid
;
Lung/pathology*
3.Predictive Value of Peripheral Blood cfDNA Combined with IL-10 in Central Nervous System Infiltration of Diffuse Large B-Cell lymphoma.
Yuan ZHANG ; Li-Hua WANG ; Yan GUO ; Guo-Qing LYU ; Sun WU ; Jing-Hang ZHANG
Journal of Experimental Hematology 2025;33(4):1063-1068
OBJECTIVE:
To investigate the predictive value of circulating free DNA (cfDNA) combined with interleukin 10 (IL-10) in predicting central nervous system infiltration (CNSI) in diffuse large B-cell lymphoma (DLBCL).
METHODS:
The clinical data of 63 patients with DLBCL in our hospital from May 2021 to April 2023 were retrospectively analyzed. The 63 patients were divided into CNSI group (15 cases) and non-CNSI group (48 cases) base on whether CNSI occurred. The age, sex, Ann Arbor stage, ECOG score, IPI risk, CNS-IPI risk, number of extranodal sites involved, bone marrow involvement, hypertrophic disease, B symptoms, source cells, glucose quantification, Pandy test, cerebrospinal fluid (CSF) chlorine, CSF nucleated cell count, CSF protein, peripheral blood cfDNA, and IL-10 status were compared between the two groups. The correlation between cfDNA, IL-10 in peripheral blood and CSF protein was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of peripheral blood cfDNA and IL-10 on secondary CNSI in DLBCL patients. The last follow-up was on November 30, 2023. Kaplan-Meier method was used to calculate the time of secondary CNSI in the non-CNSI group.
RESULTS:
The IPI risk, CNS-IPI risk, number of extranodal sites involved, and CSF protein in the CNSI group were significantly higher than those in the non-CNSI group (all P <0.05). The levels of cfDNA and IL-10 in peripheral blood of CNSI group were significantly higher than those of non-CNSI group (both P <0.01). cfDNA and IL-10 in peripheral blood were both positively correlated with CSF protein (r =0.402 4, 0.315 1). ROC curve analysis showed that peripheral blood cfDNA and IL-10 had certain predictive value for CNSI, and the area under the curve (AUC) was 0.829 and 0.742, respectively. The AUC of the combined detection was 0.910, with a sensitivity of 80.00% and a specificity of 93.70%. The diagnostic efficacy was significantly higher than that of the two prediction values alone. The median follow-up time was 20 (6-31) months. Non-CNSI patients were grouped based on peripheral blood cfDNA combined with IL-10 positive or negative pairs. The time of secondary CNSI in positive group was significantly shorter than that in negative group (P <0.05).
CONCLUSION
cfDNA and IL-10 in peripheral blood of DLBCL patients with CNSI are significantly increased, and the combined detection of cfDNA and IL-10 has good predictive value for CNSI.
Humans
;
Interleukin-10/blood*
;
Lymphoma, Large B-Cell, Diffuse/blood*
;
Retrospective Studies
;
Female
;
Male
;
Cell-Free Nucleic Acids/blood*
;
Middle Aged
;
ROC Curve
;
Prognosis
;
Central Nervous System Neoplasms
;
Central Nervous System/pathology*
;
Adult
;
Predictive Value of Tests
4.Expression of CSF-1/CSF-1R in the Peripheral Blood of Children with Immune Thrombocytopenia and Its Clinical Significance.
Dan-Lu LI ; Hai-Chen SONG ; Yong-Feng CHENG ; Mei YAN
Journal of Experimental Hematology 2025;33(4):1131-1137
OBJECTIVE:
To investigate the expression of CSF-1 and CSF-1R in the peripheral blood of children with immune thrombocytopenia (ITP) and its clinical significance.
METHODS:
Forty-four children with ITP treated in our hospital from February 2023 to January 2024 were selected as the observation group, and 40 healthy children were selected as the control group during the same period, and relevant clinical data were collected. Peripheral blood mononuclear cells (PBMC) of children with ITP and healthy children were separated, and the plasma levels of M1 macrophage-associated cytokines (TNF-α, IL-6), M2 macrophage-associated cytokines (IL-10, TGF-β), and CSF-1 were detected by ELISA in the children of both groups. The mRNA levels of M1 macrophage surface markers (CD86, iNOS), M2 macrophage surface markers (CD206, Arg-1) and CSF-1R were detected by RT-PCR in PBMC of children in both groups. Western blot was used to detect the expression of CSF-1R protein in PBMC of the two groups of children. The correlation between platelet count and CSF-1R mRNA expression in PBMC, TNF-α, IL-6, IL-10, TGF-β and CSF-1 in plasma was analyzed.
RESULTS:
Compared with the control group, the levels of IL-10, TGF-β, CSF-1 and platelet count in plasma of children with ITP were significantly decreased (P < 0.01), and the levels of TNF-α and IL-6 were significantly increased (P < 0.01); the mRNA levels of the M1 macrophage surface markers (CD86, iNOS) in PBMC of children with ITP were significantly increased (P < 0.05), mRNA levels of M2 macrophage surface marker CD206 in PBMC of children with ITP were decreased compared with controls but the difference was not statistically significant ( P >0.05), mRNA levels of Arg-1 were decreased, the difference was statistically significant (P < 0.05). The mRNA and protein levels of CSF-1R in PBMC of ITP children were higher than that in controls. CSF-1R expression in PBMC of ITP was positively correlated with platelet count, IL-10, CSF-1 were positively correlated (r =0.822,0.481,0.405).
CONCLUSION
CSF-1 is significantly reduced in the plasma of ITP, and CSF-1R mRNA and protein expression is significantly elevated in PBMC of ITP, which are involved in the regulation of macrophage M1/M2 imbalance, and could serve as a potential therapeutic target for ITP.
Humans
;
Purpura, Thrombocytopenic, Idiopathic/blood*
;
Macrophage Colony-Stimulating Factor/metabolism*
;
Leukocytes, Mononuclear/metabolism*
;
Child
;
Interleukin-10/blood*
;
Macrophages/metabolism*
;
Tumor Necrosis Factor-alpha/blood*
;
Interleukin-6/blood*
;
Male
;
Female
;
Transforming Growth Factor beta/blood*
;
Receptor, Macrophage Colony-Stimulating Factor/metabolism*
;
Clinical Relevance
5.The Expression and Significance of PD-1, Th1, Th2, and Th17 Cytokines in Multiple Myeloma.
Di LIU ; Qian CHEN ; Ling LI ; Hua-Xin JIANG
Journal of Experimental Hematology 2025;33(5):1366-1373
OBJECTIVE:
To explore the expression and clinical significance of programmed death receptor 1 (PD-1), Th1, Th2, and Th17 cytokines in multiple myeloma (MM).
METHODS:
A total of 76 MM patients treated in the Tengzhou Central People's Hospital from May 2021 to May 2023 were collected as MM group, and 48 healthy individuals who underwent physical examination during the same period were included as control group. The expression of PD-1 on the surface of CD4+ and CD8+ T cells and the levels of serum Th1 cytokines [interleukin (IL) -2, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α)], Th2 cytokines (IL-4, IL-6, IL-10) and Th17 cytokines (IL-17) were detected in the two groups. Spearman correlation was used to examine the relationship between PD-1, Th1, Th2 and Th17 cytokines and clinical stage and immune typing of MM patients. Multivariate logistic regression analysis was used to analyze the related factors affecting the efficacy of chemotherapy in MM patients, and the factors were tested for multicollinearity. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of PD-1, Th1, Th2 and Th17 cytokines in chemotherapy efficacy of MM patients.
RESULTS:
The levels of CD4+T PD-1, CD8+T PD-1, IL-4, IL-6, IL-10, and IL-17 in the MM group were higher than those in the control group, while the levels of IL-2, IFN-γ, and TNF-α were lower (all P <0.001). The levels of CD4+T PD-1, CD8+T PD-1, IL-4, IL-6, IL-10, and IL-17 in R-ISS stage III patients were higher than those in stage II and I patients, and the levels in stage II patients were higher than those in stage I patients (all P <0.05). The IL-2 level in R-ISS stage III patients was lower than that in stage II and I patients, and IL-2 level in R-ISS stage II patients was lower than that in stage I patients (all P <0.05). The levels of CD4+T PD-1, CD8+T PD-1, IL-4, IL-6, IL-10, and IL-17 in IgG patients were higher than those in IgA, light chain, and non secretory patients, while the level of IL-2 was lower (all P <0.05). Correlation analysis showed that CD4+T PD-1, CD8+T PD-1, IL-4, IL-6, IL-10, and IL-17 were positively correlated with R-ISS staging in MM patients (r =0.623, 0.635, 0.728, 0.330, 0.742, 0.412), and negatively correlated with immune classification (r =-0.664, -0.756, -0.642, -0.479, -0.613, -0.323). IL-2 was negatively correlated with R-ISS staging in MM patients (r =-0.280), and positively correlated with immune classification (r =0.483). The levels of CD4+T PD-1, CD8+T PD-1, IL-4, IL-6, IL-10, and IL-17 in the non-remission group were higher than those in the remission group, while the level of IL-2 was lower (all P <0.001). Multivariate logistic regression analysis showed that the increased CD4+T PD-1, CD8+T PD-1, IL-4, IL-6, IL-10 and IL-17 were risk factors for the efficacy of chemotherapy in MM patients (OR >1, P <0.05), while the increased IL-2 was a protective factor (OR < 1, P <0.05). The results of multicollinearity test showed that the tolerance of the seven factors included was between 0.714-0.885, and the variance inflation factor was between 1.130-1.400. There was no multicollinearity. The ROC curve analysis results showed that the area under the curve for the combined prediction of chemotherapy efficacy in MM patients by the above 7 factors was 0.942, with specificity of 0.741 and sensitivity of 0.909.
CONCLUSION
The expression levels of PD-1 on the surface of CD4+ and CD8+ T cells and serum Th2 and Th17 cytokines in MM patients are high, while Th1 cytokines are low. PD-1, Th1, Th2, and Th17 cytokines are related to clinical stage and immune classification of MM patients. The combined detection of these indicators can help predict the chemotherapy efficacy of MM patients.
Humans
;
Programmed Cell Death 1 Receptor/metabolism*
;
Multiple Myeloma/blood*
;
Cytokines/metabolism*
;
Th17 Cells/metabolism*
;
Th1 Cells/metabolism*
;
Th2 Cells/metabolism*
;
Female
;
Male
;
Interleukin-10
;
Interferon-gamma
;
Middle Aged
;
Interleukin-17
;
Interleukin-2
;
Interleukin-4
;
Tumor Necrosis Factor-alpha
;
Interleukin-6
;
Aged
6.Clinical characteristics and prognosis analysis of 108 cases of recurrent nasopharyngeal carcinoma from a single center.
Qing WANG ; Fusheng LIN ; Ran ZHANG ; Lin GAO ; Xingqian ZHAO ; Jie YANG ; Xiaojiang LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(8):743-748
Objective:Retrospective analysis of the correlation between clinicopathologic features and related indexes and prognosis in patients with recurrent nasopharyngeal carcinoma. Methods:One hundred and eight nasopharyngeal cancer(NPC) patients with post-treatment recurrence in Yunnan Cancer Hospital from January 2013 to January 2018 were collected, and the survival time was estimated by Kaplan-Meier method, and clinicopathological characteristics were analyzed by log-rank test; risk factors and prognosis were analyzed by Cox proportional risk model for single-factor and multifactorial analysis. A P-value <0.05 was considered statistically significant. Results:The median survival of all patients was 54 months, with a 3-year survival rate of 80.2% and a 5-year survival rate of 39.8%. The 5-year overall survival rate was 50.2% for patients >46 years old and 27.9% for patients ≤46 years old(P<0.05), a statistically significant difference. Univariate analysis showed that overall survival was associated with age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, γ-interferon, α-tumor necrosis factor, IL-10, and IL-4(P<0.05). Multifactorial analysis revealed that age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, and interleukin 10 were independent influences on the prognosis of recurrent nasopharyngeal carcinoma(P<0.05). Conclusion:Differences in chemotherapy regimens affect the prognosis of recurrent nasopharyngeal carcinoma. Elevated plasma D-dimer, glycan antigen 125, and interleukin 10 levels affect the overall survival of recurrent nasopharyngeal carcinoma, which may be a valid independent prognostic factor, and are expected to provide new biomarkers for nasopharyngeal carcinoma in the clinic.
Humans
;
Prognosis
;
Nasopharyngeal Neoplasms/mortality*
;
Nasopharyngeal Carcinoma
;
Retrospective Studies
;
Neoplasm Recurrence, Local
;
Male
;
Middle Aged
;
Female
;
Survival Rate
;
Adult
;
Risk Factors
;
Interleukin-10/blood*
;
Aged
;
Proportional Hazards Models
7.Schistosoma japonicum cystatin has protective effects against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Wenjuan DUO ; Yixiang WANG ; Jiaxing WANG ; Xinlong XU ; Linxian LI ; Dongchen YANG ; Qili SHEN ; Lichun YANG ; Xiaojing LIU ; Qiwang JING ; Liang CHU ; Xiaodi YANG
Journal of Southern Medical University 2025;45(1):110-117
OBJECTIVES:
To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis.
METHODS:
Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3+CD4+CD25+Foxp3+ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival.
RESULTS:
The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment.
CONCLUSIONS
rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals
;
Mice
;
Sepsis/drug therapy*
;
Male
;
Schistosoma japonicum/chemistry*
;
Mice, Inbred C57BL
;
Cystatins/therapeutic use*
;
Interleukin-10/metabolism*
;
Interleukin-6/blood*
;
Tumor Necrosis Factor-alpha/blood*
;
Disease Models, Animal
;
Transforming Growth Factor beta/metabolism*
8.Molecular mechanism of Xixian Pills for improving rheumatoid arthritis in rats: a proteomic analysis.
Yahui LI ; Xin YANG ; Xueming YAO ; Cong HUANG
Journal of Southern Medical University 2025;45(11):2330-2339
OBJECTIVES:
To analyze the molecular mechanism of Xixian Pills for treatment of rheumatoid arthritis (RA).
METHODS:
Forty-eight rats were randomized into 6 groups (n=8), including a normal control group, a collagen-induced arthritis (CIA) model group, 3 Xixian Pills treatment (200, 400 and 800 mg/kg) groups, and a Tripterygium glycosides tablet (TGT) treatment group. In the latter 4 groups, the rats were treated with daily gavage of Xixian Pills or TGT 2 weeks after CIA modeling for 3 consecutive weeks. The differentially expressed proteins in high-dose Xixian Pills group and the model group compared with the normal control group were screened based on the tandem mass spectrometry tag (TMT) technology, and the core targets and signaling pathways were analyzed. The immune cell infiltration and gene expression data were analyzed using ggplot2 and tidyverse packages, and the correlation coefficients between the core targets and the immune cells were calculated.
RESULTS:
The CIA rats showed significantly increased serum levels of TNF-α and IL-6 and lowered serum IL-10 level. Treatments with high- and medium-dose Xixian Pills and TGT all significantly reduced serum TNF‑α and IL-6 and increased IL-10 levels in CIA rats. Proteomic analysis identified 160 differential proteins between the model group and high-dose Xixian Pills group, and the core targets included CCL5, STAT1, GZMB and IL7R. The areas under the ROC curve of CCL5 and STAT1 were both greater than 0.9. Immunohistochemical and immunofluorescence staining revealed increased levels of CCL5 and STAT1 in the ankle joints of CIA rats, which were significantly decreased after treatment with Xixian Pills.
CONCLUSIONS
Treatment with Xixian Pills offers protection of the joints in CIA rats possibly by inhibiting joint inflammation via regulating protein expressions of CCL5 and STAT1.
Animals
;
Drugs, Chinese Herbal/pharmacology*
;
Rats
;
Arthritis, Rheumatoid/metabolism*
;
Proteomics
;
Tripterygium/chemistry*
;
Arthritis, Experimental/metabolism*
;
Tumor Necrosis Factor-alpha/blood*
;
Interleukin-10/blood*
;
Interleukin-6/blood*
;
Male
;
Rats, Sprague-Dawley
;
Signal Transduction
9.Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia.
Shi-Xiang ZHAO ; Yuan-Yuan GE ; Zeng-Zheng LI ; Hai-Ping HE ; Cheng-Min SHEN ; Ke-Qian SHI ; Tong-Hua YANG ; Yun-Yun DU
Journal of Experimental Hematology 2023;31(5):1315-1321
OBJECTIVE:
To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL).
METHODS:
Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits.
RESULTS:
It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated.
CONCLUSION
Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.
Humans
;
Leukemia, Promyelocytic, Acute/diagnosis*
;
Cytokines/metabolism*
;
Interleukin-10
;
Interleukin-17/metabolism*
;
Interleukin-6/metabolism*
;
Interleukin-5/metabolism*
;
Blood Coagulation Disorders
;
Ferritins
;
Tretinoin
10.Tetrahydropalmatine alleviated diabetic neuropathic pain by inhibiting activation of microglia via p38 MAPK signaling pathway.
Lian-Zhi CHENG ; Jia-Mei ZHOU ; Jun-Long MA ; Fan-Jing WANG ; Kai CHENG ; Qian CHEN ; Hui-Lun YUAN ; Ai-Juan JIANG
China Journal of Chinese Materia Medica 2022;47(9):2533-2540
Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.
Animals
;
Berberine Alkaloids
;
Blood Glucose/metabolism*
;
Diabetes Mellitus
;
Diabetic Neuropathies/genetics*
;
Interleukin-10
;
Interleukin-6/metabolism*
;
Lipopolysaccharides/pharmacology*
;
Microglia
;
Neuralgia/metabolism*
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction
;
Spinal Cord/metabolism*
;
Streptozocin/therapeutic use*
;
Tumor Necrosis Factor-alpha/metabolism*
;
p38 Mitogen-Activated Protein Kinases/metabolism*

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