1.Regulatory Pathways of Cell Apoptosis in Diabetic Kidney Disease and Intervention by Traditional Chinese Medicine: A Review
Yunjie YANG ; Mingqian JIANG ; Chen QIU ; Yaqing RUAN ; Senlin CHEN ; Wenxin HUANG ; Hangbin ZHENG ; Yi WEI ; Pengfei LI ; Xueqin LIN ; Jing WU ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):294-306
Diabetic kidney disease(DKD) is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise, DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease(ESRD), posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD, with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)/B-cell lymphoma-2(Bcl-2)/cysteinyl aspartate-specific proteinase(Caspase)-3, protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)/activating transcript factor 4(ATF4)/CCAAT enhancer-binding protein homologous protein(CHOP), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β), Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) and silent information regulator 1(SIRT1)/tumor suppressor protein 53(p53), thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine(TCM), leveraging its unique therapeutic advantages of multi-target, multi-component and multi-pathway approaches, has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile, traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation, detoxifying and dredging collaterals, tonifying kidney essence, and removing stasis and purging turbidity, thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this, this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms, while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components, compound formulations, and proprietary Chinese medicines on DKD through modulation of these pathways, with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.
2.LC-MS Analysis on Material Basis of Famous Classical Formula Xuefu Zhuyutang
Shujing ZHONG ; Zhaoyue LIU ; Mengge WANG ; Lan MIAO ; Changying REN ; Mingqian SUN ; Li LIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):188-196
ObjectiveTo systematically identify the chemical constituents of Xuefu Zhuyutang(XFZY) and quantitatively determine its main components, aiming to elucidate its pharmacodynamic material basis and provide a scientific foundation for improving its quality control standards. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed for qualitative analysis of XFZY, and the identification of compounds was accomplished by comparing their retention times, secondary MS fragment ion information, 52 reference standards and relevant databases, followed by attribution of their herbal sources. A total of 22 representative compounds were screened out, and UPLC-quadrupole-linear ion trap mass spectrometry(UPLC-Q-TRAP-MS/MS) was applied for quantitative analysis of the compounds in the formula. ResultsA total of 77 compounds were identified in XFZY, including 31 flavonoids mainly derived from Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, Persicae Semen, Carthami Flos, Bupleuri Radix, Paeoniae Radix Rubra and Achyranthis Bidentatae Radix, 24 terpenoids mainly derived from Platycodonis Radix, Glycyrrhizae Radix et Rhizoma, Paeoniae Radix Rubra and Rehmanniae Radix, 9 phenylpropanoids and their derivatives mainly derived from Chuanxiong Rhizoma, Angelicae Sinensis Radix and Rehmanniae Radix, 4 phenolic acids mainly derived from Chuanxiong Rhizoma, Angelicae Sinensis Radix and Paeoniae Radix Rubra, 3 saccharides mainly derived from Rehmanniae Radix and Achyranthis Bidentatae Radix, and 6 other compounds mainly derived from Persicae Semen, Rehmanniae Radix and Angelicae Sinensis Radix. The results of quantitative analysis showed that the contents of protocatechuic acid, hydroxypaeoniflorin, amygdalin, vanillic acid, paeoniflorin, liquiritin apioside, liquiritin, isoquercitrin, naringin, cosmosiin, hesperidin, neohesperidin, isoliquiritin, liquiritigenin, naringenin, benzoylpaeoniflorin, hesperetin, isoliquiritigenin, formononetin, glycyrrhizic acid, nobiletin and ligustilide in XFZY were determined to be 0.12, 1.57, 54.53, 0.29, 36.17, 4.29, 4.84, 0.09, 46.67, 0.04, 3.44, 31.95, 0.82, 0.10, 0.11, 0.43, 0.07, 0.03, 0.01, 8.24, 0.13, 1.81 mg·g-1. ConclusionThe qualitative method established in this study enables rapid and sensitive analysis of the chemical constituents in XFZY. Among the identified compounds, 52 are confirmed by reference standards, ensuring the accuracy of identification. The quantitative analysis of 22 key components provides a reliable experimental basis for the pharmacodynamic material basis research and quality control standard improvement of XFZY.
3.Clinical Efficacy of Yishen Jiangtang Decoction Combined with Conventional Western Medicine Treatment for Diabetic Kidney Disease with Pattern of Qi-Yin Deficiency Combined with Dampness-heat and Blood Stasis
Yunjie YANG ; Yasheng DENG ; Kaiying HE ; Qi ZHANG ; Yongxin YU ; Yaqing RUAN ; Zhuang HAN ; Qiwei CHEN ; Yi WEI ; Qiu CHEN ; Jing WU ; Mingqian JIANG ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU ; Lixiang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):157-167
ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease (DKD) in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis, and to explore its mechanism of inhibiting the endoplasmic reticulum stress (ERS)-apoptosis axis and delaying renal fibrosis (RF). MethodsA single-center, randomized, parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine (TCM) pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group (conventional Western medicine treatment) and an experimental group (Yishen Jiangtang decoction combined with conventional Western medicine treatment), with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters: Blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum glucose-regulated protein 78 (GRP78), serum cysteinyl aspartate-specific protease-3 (Caspase-3), and serum and urinary transforming growth factor-β1 (TGF-β1) levels before and after treatment. TCM symptom scores, TCM syndrome efficacy, and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3, as well as serum and urinary levels of TGF-β1, with renal function, proteinuria, and glucose and lipid metabolism indicators in patients with DKD. In addition, safety indicators were also monitored. ResultsA total of 75 patients completed the study (38 in the control group and 37 in the experimental group). ① Baseline data: The two groups were comparable in terms of sex and age, with no statistically significant difference. ② Efficacy outcomes: Compared with baseline levels, both groups showed reductions in BUN, SCr, UACR, FBG, TG, TC, LDL-C, and TCM symptom scores (P<0.01) and increases in eGFR level (P<0.01). Moreover, the experimental group outperformed the control group in altering the indicators above (P<0.05). Regarding TCM syndrome efficacy, the total response rate in the experimental group was 83.78%, which was higher than that (57.89%) in the control group (P<0.05). Regarding overall clinical efficacy, the total response rate in the experimental group was 78.38%, which was higher than that (50.00%) in the control group (P<0.05). ③ Mechanism outcomes: Compared with baseline levels, both groups showed declined serum levels of GRP78, Caspase-3, and TGF-β1 and urinary level of TGF-β1 after treatment (P<0.01). Moreover, the experimental group showed greater declines than the control group (P<0.05). The serum levels of GRP78, Caspase-3,and TGF-β1 and the urinary level of TGF-β1 in DKD patients showed positive correlations with BUN, SCr, UACR, and FBG and negative correlations with eGFR (P<0.05). ④ Safety outcomes: Neither group showed drug-related adverse reactions, and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms, correct glucose and lipid metabolism disorders, and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.
4.Clinical Efficacy of Yishen Jiangtang Decoction Combined with Conventional Western Medicine Treatment for Diabetic Kidney Disease with Pattern of Qi-Yin Deficiency Combined with Dampness-heat and Blood Stasis
Yunjie YANG ; Yasheng DENG ; Kaiying HE ; Qi ZHANG ; Yongxin YU ; Yaqing RUAN ; Zhuang HAN ; Qiwei CHEN ; Yi WEI ; Qiu CHEN ; Jing WU ; Mingqian JIANG ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU ; Lixiang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):157-167
ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease (DKD) in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis, and to explore its mechanism of inhibiting the endoplasmic reticulum stress (ERS)-apoptosis axis and delaying renal fibrosis (RF). MethodsA single-center, randomized, parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine (TCM) pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group (conventional Western medicine treatment) and an experimental group (Yishen Jiangtang decoction combined with conventional Western medicine treatment), with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters: Blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum glucose-regulated protein 78 (GRP78), serum cysteinyl aspartate-specific protease-3 (Caspase-3), and serum and urinary transforming growth factor-β1 (TGF-β1) levels before and after treatment. TCM symptom scores, TCM syndrome efficacy, and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3, as well as serum and urinary levels of TGF-β1, with renal function, proteinuria, and glucose and lipid metabolism indicators in patients with DKD. In addition, safety indicators were also monitored. ResultsA total of 75 patients completed the study (38 in the control group and 37 in the experimental group). ① Baseline data: The two groups were comparable in terms of sex and age, with no statistically significant difference. ② Efficacy outcomes: Compared with baseline levels, both groups showed reductions in BUN, SCr, UACR, FBG, TG, TC, LDL-C, and TCM symptom scores (P<0.01) and increases in eGFR level (P<0.01). Moreover, the experimental group outperformed the control group in altering the indicators above (P<0.05). Regarding TCM syndrome efficacy, the total response rate in the experimental group was 83.78%, which was higher than that (57.89%) in the control group (P<0.05). Regarding overall clinical efficacy, the total response rate in the experimental group was 78.38%, which was higher than that (50.00%) in the control group (P<0.05). ③ Mechanism outcomes: Compared with baseline levels, both groups showed declined serum levels of GRP78, Caspase-3, and TGF-β1 and urinary level of TGF-β1 after treatment (P<0.01). Moreover, the experimental group showed greater declines than the control group (P<0.05). The serum levels of GRP78, Caspase-3,and TGF-β1 and the urinary level of TGF-β1 in DKD patients showed positive correlations with BUN, SCr, UACR, and FBG and negative correlations with eGFR (P<0.05). ④ Safety outcomes: Neither group showed drug-related adverse reactions, and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms, correct glucose and lipid metabolism disorders, and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.
5.Analysis of Major Syndromes and Their Typical Related Symptoms and Signs in 135 Patients with Metabolic Syndrome:A Clinical Study Based on Syndrome Element Differentiation and Latent Class Analysis
Tong WANG ; Mingqian JIANG ; Lifen MI ; Shanyi SHEN ; Shujie XIA ; Candong LI
Journal of Traditional Chinese Medicine 2025;66(4):376-381
ObjectiveTo explore the typical syndromes and their characteristic of symptoms and signs with high diagnostic value in patients with metabolic syndrome (MS). MethodsTraditional Chinese medicine (TCM) diagnostic information was collected from 135 MS patients. Syndrome element differentiation and latent class analysis (LCA) were applied to identify the major TCM syndromes in MS patients. Symptoms were analyzed based on the differentiated syndromes, and a binary logistic regression model was constructed to determine symptoms and signs with high diagnostic value. ResultsA total of 135 MS patients were included, involving 163 symptoms and signs with a total frequency of 1749; twenty-three syndrome elements were extracted, 367 times frequency in total, among which 8 syndrome elements occurred ≥10 times with 323 frequencies (88.01% of the total). These included location-related elements such as kidney (48 times), spleen (14 times), and stomach (14 times), and nature-related elements such as phlegm (71 times), yin deficiency (64 times), dampness (57 times), heat (42 times), and qi deficiency (13 times). Based on LCA, the 135 patients were categorized into two groups distinguished by the syndrome elements of dampness and phlegm, forming the "phlegm-dampness syndrome" as the major syndrome type. Nine high-frequency symptoms and signs associated with the phlegm-dampness syndrome were identified,i.e. obesity (39 times), greasy coating (38 times), slippery pulse (33 times), white coating (31 times), preference for fatty and heavy foods (30 times), excessive urination (30 times), fatigue and lack of strength (29 times), wiry pulse (25 times), and dark red tongue (25 times). A binary logistic regression model was constructed combining these nine symptoms and signs with the LCA classification results, ultimately identifying obesity, greasy coating, fatigue and lack of strength, and white coating as independent factors associated with the phlegm-dampness syndrome in MS patients (P<0.05). ConclusionThe major TCM syndrome in MS patients is phlegm-dampness syndrome, and obesity, greasy coating, fatigue and lack of strength, and white coating are the typical symptoms and signs for diagnosing phlegm-dampness syndrome in MS patients.
6.Real world clinical data analysis of fuzuloparib for the treatment of ovarian epithelial cancer patients
Danhui WENG ; Jie JIANG ; Yingjie YANG ; Mingqian LU ; Jiaying BAI ; Ming LIU ; Xiaoling LI ; Jun TIAN ; Yutao GUAN ; Quan LI ; Liang CHEN ; Qiubo LYU ; Lixia MA ; Yali WANG ; Huicheng XU ; Hailong GUO ; Li SUN ; Ding MA ; Qinglei GAO
Chinese Journal of Obstetrics and Gynecology 2025;60(8):590-599
Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.
7.Real world clinical data analysis of fuzuloparib for the treatment of ovarian epithelial cancer patients
Danhui WENG ; Jie JIANG ; Yingjie YANG ; Mingqian LU ; Jiaying BAI ; Ming LIU ; Xiaoling LI ; Jun TIAN ; Yutao GUAN ; Quan LI ; Liang CHEN ; Qiubo LYU ; Lixia MA ; Yali WANG ; Huicheng XU ; Hailong GUO ; Li SUN ; Ding MA ; Qinglei GAO
Chinese Journal of Obstetrics and Gynecology 2025;60(8):590-599
Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.
8.Cystitis myofibroblastoma combined with urachal cyst: a case report
Jiahao SU ; Mingqian YANG ; Chaolong LIANG ; Jian WANG
Clinical Medicine of China 2024;40(3):216-219
Inflammatory myofibroblastoma is a rare soft tissue tumor that is most common in the lungs and less common in the bladder. Inflammatory myofibroblastoma is a borderline tumor with a probability of malignant transformation, and surgical resection is the preferred treatment. Umbilical duct cysts belong to benign lesions and can be treated conservatively for asymptomatic patients. Surgical resection is preferred for those with concurrent infections. Due to the lack of specificity in clinical and imaging manifestations of cystitis myofibroblastoma, it is prone to misdiagnosis and over treatment. Currently, the diagnosis mainly relies on postoperative pathological results.
9.Rapamycin restores CD4 + T cell subsets imbalance in Graves′ ophthalmopathy mice model
Meng ZHANG ; Ling WANG ; Xi DING ; Mingqian HE ; Ziyi CHEN ; Xiaoyan WU ; Liping WU ; Bingyin SHI ; Yue WANG
Chinese Journal of Endocrinology and Metabolism 2023;39(11):964-973
Objective:To study the effect of rapamycin on the disorder of CD4 + T cell subsets in Graves′ ophthalmopathy(GO) mice, as well as the ophthalmopathy and hyperthyroidism phenotype, providing new possibilities for the treatment of GO. Methods:6-8 weeks old female Balb/c mice were injected intramuscularly with adenovirus expressing the A-subunit of TSHR(A-sub-Ad) 9 times. Rapamycin was given by embedding in the feed(14 ppm). The animals were euthanized 4 weeks after the final injection to obtain blood, spleen cells, thyroid glands, and orbital tissue. TT 4, thyrotropin receptor antibody(TRAb), thyroid, and orbital pathologic changes were detected, and the CD4 + T cell subgroup was evaluated by flow cytometry and immunohistochemistry. Results:After final immunization, the mice showed characteristics of GO: increased retrobulbar fibrosis and retrobulbar adipogenesis that indicated ophthalmopathy, increased autoantibodies, and serum total thyroxin that indicated hyperthyroidism. After the intervention of rapamycin, retrobulbar fibrosis and retrobulbar adipogenesis were significantly improved, and the incidence of ophthalmopathy was reduced from 80%-90% to 20%. Moreover, the increase of total thyroxin was reduced from 80% to 20%, and the metabolic condition and thyroid pathology were also improved. Flow cytometry of the spleen, immunohistochemistry of the thyroid and orbital tissue revealed that GO mice exhibited Th1 dominance in Th1/Th2 balance and reduction of Treg cells. After the intervention of rapamycin, flow cytometry showed that the ratio of Th1 and Th17 cells decreased and the ratio of Th2 and Treg cells increased. Immunohistochemistry of thyroid and orbital tissues also confirmed improvement of Th1/Th2 cell imbalance and Treg cell reduction.Conclusion:GO mouse model showed a significant imbalance of CD4 + T cell subsets, and rapamycin could not only regulate the disorder of CD4 + T cell subsets in GO mice, but also effectively improve the phenotype of ophthalmopathy and hyperthyroidism. Therefore, the imbalance of CD4 + T cell subsets is one of the etiological intervention targets of GO, and rapamycin is a potential intervention mode of GO, which can be further explored by randomized clinical studies in the future.
10.Research progress of PD-1/PD-L1 inhibitors in the treatment of advanced bladder cancer
Jiahao SU ; Mingqian YANG ; Chaolong LIANG ; Jian WANG
Clinical Medicine of China 2023;39(5):394-400
Bladder cancer is one of the most common malignant tumors of the urinary system, among which urothelial carcinoma is the main one. The traditional treatment methods are mainly surgical resection and chemotherapy, but the treatment effect of advanced patients is not good, and the prognosis is poor. In recent years, with the development of immune checkpoint inhibitors, there are many treatment options that are more effective than traditional therapies. Programmed cell death protein 1 (PD-1)and programmed cell death ligand 1(PD-L1)inhibitors stop the negative regulation of the immune system by blocking the binding of PD-1 and PD-L1, thereby enhancing the anti-tumor activity of the body's immune system. This article mainly reviews the efficacy and safety of PD-1/PD-L1 inhibitors commonly used in the clinical treatment of locally advanced or metastatic urinary tract carcinoma of the bladder.

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