1.Mechanism of phlegm-stasis co-treatment for myocardial protection in rats with diabetes mellitus by regulating JNK signaling pathway
Yueqi WANG ; Quangen CHU ; Jun CHU ; Jin YU ; Feixiang LI ; Baolu LUO ; Jing CHEN
International Journal of Traditional Chinese Medicine 2023;45(5):574-580
Objective:To observe the intervention mechanism of phlegm-stasis co-treatment for the JNK signaling pathway in the myocardium of diabetes rats.Methods:Totally 50 male SD rats of SPF grade were selected. Diabetes model was established by single intraperitoneal injection of 55 mg/kg streptozotocin (STZ) solution. After continued feeding for 3 weeks, the rats were divided into normal group, model group, alachloramine group, blood stasis removing group, phlegm removing group and phlegm-blood stasis co-treatment group according to random number table method, with 6 rats in each group. Xiaoxianxiong Decoction (4.05 g/kg), Xuefu Zhuyu Decoction (7.02 g/kg), Didang Xianxiong Decoction (8.10 g/kg) were administered to the stomach respectively in the phlegm removing group, the blood stasis removing group and the phlegm-blood stasis co-treatment group. Alachloramine (3 mg/kg) was administered to the stomach by gavage in the alachloramine group. After 8 weeks, HE staining was used to observe the morphological changes of myocardial tissue in diabetic rats. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium in rats. The expression of JNK1 protein was determined by immunohistochemistry. JNK1 mRNA, IRS1 mRNA and NLRP3 expression levels were detected by Real-time PCR. Western blot was used to detect the protein expressions of IRS-1, p-Akt and NLRP3.Results:The myocardial cells in the model group were disorganized, with hypertrophy, blurred texture, inflammatory infiltration of interstitium, increased collagen fibers, and focal necrosis. All treatment groups could improve fibrosis, inflammatory infiltration and reduce myocardial collagen deposition in different degrees. Compared with the model group, the mRNA and protein expressions of JNK1 and NLRP3 bodies decreased ( P<0.01), the IRS-1 mRNA and protein increased ( P<0.01), and p-Akt protein expression increased ( P<0.01). Conclusions:The phlegm and stasis co-treatment can effectively improve the cardiomyopathy of diabetes rats, and the effect is better than the phlegm-resolving method or the stasis resolving method alone. The mechanism may be related to the inhibition of JNK signaling pathway activation, reduce the expressions of JNK1 and NLRP3, and increase the IRS-1 and Akt.
2.Evaluation on the rationality of "Sandwich principle teaching mode" for internal medicine
Tao JIN ; Yixiao HE ; Yueqi ZHENG ; Zhijian GU ; Huiying WANG ; Xiaolong WANG
Chinese Journal of Medical Education Research 2020;19(5):530-534
Objective:To evaluate the rationality of the "Sandwich Principle teaching mode" adopted in our teaching of internal medicine and verify the necessity of its "Intergroup intersecting discussion".Methods:33 students majoring in traditional Chinese medicine were divided into control group (taught by standard process of sandwich principle) and experiment group (taught by simplified process of sandwich principle). The Dundee Ready Education Environment Measure (DREEM) was used to evaluate students' feelings toward the two teaching modes.Results:The total score of DREEM in the control group was higher than that in the experiment group, with statistically significant difference; the total score in the academic perception subscale in the control group was higher than that in the experiment group, among which the scores of "I have faith in passing the exam this year" and other 2 items were better than that in the experiment group, with statistically significant difference ( P<0.05); there were no statistical difference in the total scores of other perception subscales between the two groups( P>0.05), but the scores of the 9 items including "the atmosphere is very harmonious in the clinical teaching process" in the control group were significantly better than those in the experiment group, with statistically significant difference( P<0.05). Conclusion:The teaching mode of Sandwich Principle can create a positive and effective learning environment for supporting students. "Intergroup intersecting discussion" can encourage students to actively participate in the teaching process, and help increase their academic confidence and sense of achievement in learning. It is also helpful to build a harmonious teacher-student relationship and create a relaxing and pleasant learning environment so that students can gain a better learning experience. Therefore, "Intergroup intersecting discussion" is indispensable in medical teaching.
3.Th2 cells infiltrating high-grade serous ovarian cancer: a feature that may account for the poor prognosis
Hao SU ; Yueqi JIN ; Changyu TAO ; Hua YANG ; Ence YANG ; Wei-Guang ZHANG ; Fengzhi FENG
Journal of Gynecologic Oncology 2023;34(4):e48-
Objective:
We aimed to investigate the differences of transcriptome profile between 2 groups of high-grade serous ovarian cancer (HGSOC) patients with distinct outcomes and identify potential biomarkers for recurrence.
Methods:
RNA sequencing was performed in 2 groups of HGSOC patients with similar demographic characteristics but exhibiting distinct progression-free survival (PFS). Transcriptome data of poor response (PR; PFS ≤6 months) and good response (GR; PFS ≥12 months) group were compared. We employed xCell to evaluate the abundance of 63 cells in tumor microenvironment. The predictive value of recurrence-related tumor infiltration cells was validated in cohort data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) dataset. The weighted correlation network analysis was performed to identify the genes related to cell infiltration.
Results:
PR patients exhibited a distinct tumor infiltration immune cells-related transcriptional profile compared to GR patients, such as lower signatures of leukocyte differentiation, activation and chemotaxis. The fraction of T-helper 2 (Th2) cells infiltration was significantly higher in PR group than in GR group. High infiltration of Th2 was significantly associated with unfavorable prognosis in the GEO cohort (area under the curve=0.84 at 6 months recurrence) and TCGA cohort (p=0.008). Genes enriched to extracellular matrix organization and integrin binding were relevant to Th2 infiltration.
Conclusion
Patients with HGSOC having shorter PFS exhibited a distinct gene signature that related to tumor-infiltrating immune cells. The level of Th2 infiltration could facilitate patient recurrence risk stratification and may be a promising biomarker for prognosis prediction and immune-related treatment.
4.Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels.
Bo ZHUANG ; Ting CHEN ; Yueqi HUANG ; Zhimei XIAO ; Yiguang JIN
Acta Pharmaceutica Sinica B 2022;12(3):1447-1459
Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π‒π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.
5.Mechanisms and therapeutic drugs of high-altitude lung diseases
Yueqi HUANG ; Jinglu HU ; Qi LI ; Miao LI ; Fei XIE ; Lina DU ; Yiguang JIN
Journal of Pharmaceutical Practice 2022;40(4):289-295
The heavily harsh plateau environment including low pressure, hypoxia, cold, dryness and strong ultraviolet radiation, seriously threatens the physical and mental health of those who quickly enter the plateau area. Lungs are the sensitive organs for high altitude injury. High-altitude lung diseases include the acute high-altitude lung disease (i.e., high-altitude pulmonary edema), the chronic high-altitude lung disease (i.e., high-altitude pulmonary artery hypertension) and the high-altitude de-adapted reaction. This review summarizes the pathogenic mechanisms and the main therapeutic drugs of high-altitude lung diseases based on the recent research. Moreover, the related formulations and administration routes are also reviewed here. It will provide support and counsel for the diagnosis and treatment of high-altitude lung diseases.
6.Inhaled curcumin mesoporous polydopamine nanoparticles against radiation pneumonitis.
Ting CHEN ; Bo ZHUANG ; Yueqi HUANG ; Yan LIU ; Bochuan YUAN ; Wanmei WANG ; Tianyu YUAN ; Lina DU ; Yiguang JIN
Acta Pharmaceutica Sinica B 2022;12(5):2522-2532
Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.