1.Traditional Chinese Medicine Regulation of MAPK Pathway for Treatment of Obesity: A Review
Lei CAO ; Mingjun LIU ; Chunwei WU ; Hailong CHEN ; Ruolin WANG ; Yang BAO ; Ze HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):254-262
With a global rise in morbidity rates, obesity has become a pressing public health issue. With increased adipocyte number and volume as the main characteristics, obesity is also manifested by metabolic disorders to varying degrees. At the same time, obesity is a risk factor for diabetes, hypertension, stroke, cancer, and cardiovascular diseases, imposing burdens on society and families. Influenced by lifestyle, environment, behavior, and genetics, obesity is caused by the interaction of many factors, and its pathological process is complex, involving inflammation, autophagy, and intestinal dysbiosis. The mitogen-activated protein kinase (MAPK) cascade reaction, a pivotal signaling pathway, plays a crucial role in cellular processes such as proliferation, differentiation, apoptosis, and stress responses. Both Chinese and international studies indicate that the MAPK signaling pathway can effectively regulate obesity through various pathways, including the modulation of adipocyte differentiation and apoptosis, appetite control, and inflammation improvement. Moreover, traditional Chinese medicine (TCM) has demonstrated significant efficacy in preventing and treating obesity, leveraging advantages such as multiple targets, diverse components, and minimal adverse effects. Research indicates that the MAPK signaling pathway is a primary focus of TCM regulation in this context, although a systematic review in this field is currently lacking. Therefore, this paper, by reviewing the latest Chinese and international research, provided a concise overview of the basic structure of the MAPK pathway, with a specific emphasis on recent progress in TCM interventions targeting the MAPK pathway for obesity treatment. The results indicate that regulating adipose tissue formation, differentiation, and thermogenesis, reducing inflammation and oxidative stress levels, and improving insulin sensitivity and metabolic disorders seem to be the main ways for TCM to regulate the MAPK pathway to prevent and treat obesity. However, it is necessary to find more research methods and explore potential mechanisms underlying TCM formulations based on the MAPK pathway for obesity prevention and treatment.
2.Modified Danggui Beimu Kushen Pills Inhibit Tumor Growth and Regulates T Cell Subsets in H22 Hepatocellular Carcinoma-bearing Mice
Xiaojie MA ; Ben LIU ; Lei WANG ; Hailong LI ; Yaling LI ; Changtian LI ; Yali SHE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):87-96
ObjectiveTo explore the effects of modified Danggui Beimu Kushen pills on tumor growth and T-cell subsets in H22 hepatocellular carcinoma-bearing mice and to provide an experimental basis for the treatment of hepatocellular carcinoma with modified Danggui Beimu Kushen pills combined with immune checkpoint antibodies. MethodA H22 hepatocellular carcinoma-bearing mouse model was established. The modeled mice were randomized into model, cisplatin, low- (4 g·kg-1·d-1), medium- (8 g·kg-1·d-1), and high-dose (16 g·kg-1·d-1) modified Danggui Beimu Kushen pills groups. After continuous administration for 14 days, the mice were sacrificed on day 15. The tumor volume was measured on days 0, 4, 8, 12, 15 of drug administration. Tumors were weighed and thymus index and spleen index were calculated. Spleen lymphocytes were co-cultured with H22 hepatoma cells, and the tumor cell-killing rate was detected by the cell counting kit-8 (CCK-8). Real-time polymerase chain reaction was carried to determine the mRNA levels of programmed cell death protein-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) in spleen and tumor tissues. The number of CD4+ and CD8+ T cells and the expression of PD-1 and LAG-3 were detected by immunohistochemistry (IHC). ResultOn day 8 of drug administration, tumor volumes in all treatment groups decreased compared with that in the model group. On day 15, both tumor volume and tumor weight were significantly lower in the treatment groups than in the model group (P<0.01), with the cisplatin group showing the most pronounced reduction. Compared with the model and cisplatin groups, medium- and high-dose modified Danggui Beimu Kushen pills increased the thymus index (P<0.01). Compared with the model group, all treatment groups showed increased spleen index (P<0.05, P<0.01), with the cisplatin group showing the most significant increase. Compared with the model and cisplatin groups, all the groups of modified Danggui Beimu Kushen pills demonstrated increased number of CD4+ and CD8+ T cells and tumor cell-killing rate in the spleen and tumor tissues (P<0.01) and down-regulated mRNA and protein levels of LAG-3 (P<0.05, P<0.01). The high-dose group of modified Danggui Beimu Kushen pills had lower mRNA level of PD-1 in the tumor tissue than the model and cisplatin groups (P<0.01). ConclusionModified Danggui Beimu Kushen pills may promote the proliferation and tumor microenvironment infiltration of CD4+ and CD8+ T cells in H22 tumor-bearing mice by down-regulating LAG-3 expression, thereby improving T-cell immune activity and inhibiting tumor growth. This study provides an experimental basis for the combination of modified Danggui Beimu Kushen pills and immune checkpoint antibodies in the treatment of hepatocellular carcinoma.
3.Analysis of the effectiveness of radioiodine therapy for papillary thyroid cancer at intermediate and high risk of recurrence
Yu WANG ; Hailong TAN ; Shi CHANG
Chinese Journal of Endocrine Surgery 2024;18(1):40-44
Objective:To analyze the effectiveness of radioactive iodine (RAI) treatment for papillary thyroid cancer (PTC) with an intermediate and high risk of recurrence.Methods:The clinical data of 709 cases of PTC, comprising 226 men and 483 women, who underwent surgical treatment for thyroid cancer at Xiangya Hospital of Central South University from Oct. 2010 to Jan. 2020 were retrospectively analyzed. According to whether RAI treatment was performed after initial surgery or not, they were divided into a RAI group (253 cases with intermediate risk and 209 cases with high risk) and a non-RAI group (147 cases with intermediate risk and 100 cases with high risk), and the relationship between RAI treatment and clinicopathological characteristics such as sex, age, and tumor size for intermediate- and high-risk PTC was analyzed by χ2 test or Fisher’s exact test and Logistic regression analysis. The Kaplan-Meier method was used to calculate the recurrence-free survival rate. Results:The treatment rate of intermediate-risk PTC RAI was 63.25% (253/400) and that of high-risk PTC RAI was 67.64% (209/309). Univariate analysis of intermediate-risk PTC showed that age, bilateral tumors, lymph node metastasis stage, number of lymph node metastases, and intermediate-risk PTC RAI treatment were closely related (all P values <0.05). Multi-factor regression analysis of intermediate-risk PTC showed that age ≥ 55 ( OR=0.282, P=0.005), lymph node metastasis stage N1b ( OR=19.245, P<0.001), and the number of lymph node metastases ≤ 5 ( OR=0.322, P<0.001) were independent predictors of RAI treatment for intermediate-risk PTC (all P values < 0.05). The recurrence-free survival curve for intermediate-risk PTC showed a lower recurrence-free survival rate in the RAI group than in the non-RAI group, but the difference was borderline significant ( P=0.049). Univariate analysis of high-risk PTC showed that age, multifocal tumors, bilateral tumors, lymph node metastasis stage, number of lymph node metastases and high-risk PTC RAI treatment were strongly associated (all P values <0.05). Multifactorial regression analysis for high-risk PTC showed that age ≥ 55 ( OR=0.382, P=0.020), bilateral tumors ( OR=2.173, P=0.030), lymph node metastasis stage N1b ( OR=11.215, P<0.001), and the number of lymph node metastases ≤5 ( OR=0.389, P=0.004) were independent predictors of RAI treatment for high-risk PTC patients (all P values <0.05). The recurrence-free survival curve for high-risk PTC showed a lower recurrence-free survival rate in the RAI group than in the non-RAI group, however, the difference was not statistically significant ( P=0.07) . Conclusions:No significant benefit was observed with RAI treatment for intermediate- and high-risk PTC and rigorous screening of eligible patients is recommended.
4.Effects of tumor location on the prognosis of upper tract urothelial carcinoma and development and validation of a prognostic nomogram
Zewei WANG ; Hailong LI ; Gang LI ; Zhimin GAO ; Rumin WEN
Journal of Modern Urology 2024;29(2):146-153
【Objective】 To investigate the prognostic value of tumor location in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU), and to develop and validate a nomogram model for predicting the overall survival (OS). 【Methods】 UTUC patients undergoing RUN at our hospital during Jan.2010 and Dec.2022 were retrospectively collected, 70% of whom were included in the training group and 30% in the validation group.According to the tumor location, patients were divided into renal pelvis tumor (RPT) group and ureteral tumor (UT) group.The differences in clinicopathological features and prognosis were analyzed.Based on multivariate Cox results, a nomogram model for predicting OS was developed and validated. 【Results】 A total of 366 patients (196 RPT and 170 UT) were included in this study.There were statistically significantly differences in urine cytology (P=0.001), hydronephrosis (P<0.001), history of bladder tumor (P=0.021), pathological T stage (P<0.001) and histological structure (P=0.037) between the two groups.Multivariate Cox results showed that patients with UT had a worse prognosis (HR=2.00, 95%CI: 1.22-3.27, P=0.006).Factors of the nomogram for predicting OS included age, tumor location, lymphovascular invasion and pathological T stage.The model showed good discrimination and calibration, and performed well in internal verification. 【Conclusion】 Compared with RPT, UT has a worse prognosis and the fat around the tumor should be surgically removed more thoroughly to avoid micro-residual.We successfully coustructed a nomogram model that can be used to predict the OS of UTUC patients after RNU surgery.
5.Mechanism research progress of traditional Chinese medicine intervening in lung cancer by regulating p53 signaling pathway
Qian MA ; Ya LI ; Yizhao MA ; Kai CHEN ; Yuanyuan WANG ; Hailong ZHANG
China Pharmacy 2024;35(11):1403-1407
Lung cancer, the most common malignant tumor, is characterized by a complex pathogenesis and high malignancy, and poses a significant threat to the health and lives of affected individuals. p53 signaling pathway plays a crucial role in the progression of lung cancer and is considered one of the potential targets for targeted therapy. In recent years, multiple studies have indicated that traditional Chinese medicine (TCM) can exert anticancer effects by modulating the p53 signaling pathway. Based on this, this article systematically summarizes the current status and progress of research on TCM intervening in lung cancer by regulating p53 signaling pathway. It was found that TCM formula and preparations, such as Qingjin desheng tablet, Tiaoqi xiaoji decoction, Bufei tongluo jiedu formula, Jianpi bushen formula and Yiqi fuzheng jiedu formula, can promote autophagy and apoptosis of lung cancer cells, inhibit the growth and metastasis of lung cancer cells and strengthen the immune function of the body by activating p53 signaling pathway, thereby inhibiting lung cancer. TCM monomers, such as pseudoginsenoside-Rh2, saikosaponin D, polyphyllin Ⅶ, dendrobiine, sophoridine, gambogic acid, triptolide and triptolide succinate monoester YJ-4, can accelerate cell apoptosis, inhibit the proliferation of lung cancer cells and regulate cell cycle by activating p53 signaling pathway, thereby inhibiting lung cancer.
6.Mechanism research progress of traditional Chinese medicine intervening in lung cancer by regulating p53 signaling pathway
Qian MA ; Ya LI ; Yizhao MA ; Kai CHEN ; Yuanyuan WANG ; Hailong ZHANG
China Pharmacy 2024;35(11):1403-1407
Lung cancer, the most common malignant tumor, is characterized by a complex pathogenesis and high malignancy, and poses a significant threat to the health and lives of affected individuals. p53 signaling pathway plays a crucial role in the progression of lung cancer and is considered one of the potential targets for targeted therapy. In recent years, multiple studies have indicated that traditional Chinese medicine (TCM) can exert anticancer effects by modulating the p53 signaling pathway. Based on this, this article systematically summarizes the current status and progress of research on TCM intervening in lung cancer by regulating p53 signaling pathway. It was found that TCM formula and preparations, such as Qingjin desheng tablet, Tiaoqi xiaoji decoction, Bufei tongluo jiedu formula, Jianpi bushen formula and Yiqi fuzheng jiedu formula, can promote autophagy and apoptosis of lung cancer cells, inhibit the growth and metastasis of lung cancer cells and strengthen the immune function of the body by activating p53 signaling pathway, thereby inhibiting lung cancer. TCM monomers, such as pseudoginsenoside-Rh2, saikosaponin D, polyphyllin Ⅶ, dendrobiine, sophoridine, gambogic acid, triptolide and triptolide succinate monoester YJ-4, can accelerate cell apoptosis, inhibit the proliferation of lung cancer cells and regulate cell cycle by activating p53 signaling pathway, thereby inhibiting lung cancer.
7.The role and mechanism of palmitoleic acid in the pyroptosis of cardiomyocytes after hypoxia/reoxygenation-induced injury
Yunquan LI ; Zonggang DUAN ; Hailong BAO ; Qingteng WANG ; Hongxin AN ; Luanda XIAHOU ; Xu WANG ; Mengting JIANG ; Haiyan ZHOU ; Zhenhua LUO ; Wei LI
Acta Universitatis Medicinalis Anhui 2024;59(6):1006-1012
Objective To investigate the effect of palmitoleic acid(POA)on pyroptosis of cardiomyocytes after hy-poxia/reoxygenation-induced injury in the human myocardium.Methods The experiment comprised a control group(Control,normal culture),a hypoxia/reoxygenation group(HR),a palmitoleic acid-treated group(HR+POA),and an anhydrous ethanol control group(HR+ET).Cardiomyocytes viability was assessed using CCK-8 assay,and the level of pyroptosis of cardiomyocytes was measured through the double staining with Hoechst33342/PI and LDH assay.ELISA was employed to detect the release of inflammatory factors IL-1 β and IL-18 in the cell culture supernatant.qRT-PCR and Western blot were utilized to determine the relative expression levels of mRNA and protein of pyroptosis-related genes,namely NLRP3,ASC,Caspase-1,GSDMD,IL-1 β and IL-18,respective-ly.Results CCK-8 assay showed that the survival of hypoxic/reoxygenated cardiomyocytes increased with the ad-dition of POA at concentrations ranging from 25 to 100 μmol/L,as compared to the HR group;a hypoxia/reoxy-genation model of cardiomyocyte was established.The expression of protein and mRNA increased in NLRP3,ASC,Cleaved caspase-1,GSDMD-N,IL-Iβ and IL-18 vs the control group(P<0.05),the positive percentage of Ho-echst33342/PI staining in cardiomyocytes increased significantly(P<0.05),the release of LDH,IL-Iβ,and IL-18 increased(P<0.05).After intervention with 100 μmol/L POA,the protein and mRNA expression levels of NLRP3,ASC,Cleaved caspase-1,GSDMD-N,IL-Iβ,and IL-18 were significantly reduced in the HR+POA group vs HR+ET group(P<0.05).The positive percentage of Hoechst33342/PI staining in cardiomyocytes de-creased significantly,and the levels of LDH,IL-Iβ and IL-18 significantly decreased(P<0.05).Conclusion Palmitoleic acid may alleviate hypoxia/reoxygenation-induced injury of cardiomyocytes by inhibiting pyroptosis and inflammatory response after hypoxia/reoxygenation in human myocardium.
8.Establishing and validating a nomogram model for predicting the prognosis of bladder cancer patients based on the score of systemic inflammatory markers before radical cystectomy combined with pathological T stage
Gang LI ; Hailong LI ; Zewei WANG ; Zhimin GAO ; Rumin WEN
Journal of Modern Urology 2024;29(6):533-539
Objective To evaluate the value of systemic inflammatory markers(SIM)in the prognosis of patients with bladder cancer undergoing radical cystectomy.Methods Clinical data of 233 patients with bladder cancer who underwent radical cystectomy in the Affiliated Hospital of Xuzhou Medical University during Dec.2011 and Nov.2020 were retrospectively collected,the SIM score was calculated and patients were grouped.Progression-free survival(PFS)was assessed with Kaplan-Meier analysis,and differences between groups were compared with log-rank test.Factors affecting PFS were analyzed with Cox proportional risk model.The patients were randomly divided into a training set(n=164)and a verification set(n=69)according to 7:3 ratio,and a nomogram model was established and verified.Results Cox regression analysis showed that SIM score and pathological T staging were independent predictors of PFS(P<0.05).A predictive model was established based on SIM score and pathological T staging.The area under the receiver operating characteristic(AUC)curve for predicting 1-year,3-year,and 5-year PFS were 0.939,0.943,and 0.943,respectively.After the model was applied to evaluate the validation set,the performance was still stable.Conclusion The prediction model based on SIM score and clinicopathological T staging can accurately predict the survival of patients with bladder cancer after radical cystectomy,and can be used to guide individualized treatment of patients.
9.Effect of Electricity Targeting TGF-β 1/smads Signaling in Oligoasthenthymic Rats
Chunxue MENG ; Fei WANG ; Wenjing SUN ; Nan YANG ; Hailong ZHAO ; Shengfu ZHANG ; Huisheng MA ; Bin GUO
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):797-805
[Objective]To explore the effects of electricity on sperm quality,sex hormone levels,and related proteins in TGF-β 1/smads signaling in testicular tissue.[Methods]Forty male SD rats were randomly divided into blank group,model group,electroacupuncture group,and positive drug group.Adenine gavage method was used to establish the model,in the electroacupuncture group,rats received electroacupuncture treatment at the acupoints Zhongji,Guanyuan,Zusanli,and Sanyinjiao once daily for 30 minutes;in the positive drug group,rats were administered L-carnitine oral solution via gavage at a dosage of 10 mL/kg,both intervention groups underwent continuous treatment for 28 days.After treatment,the changes of sperm number,sperm motility rate,follicle-stimulating hormone(FSH),luteizing hormone(LH)and serum sex hormone testosterone(T)were detected by HE staining,and the expression of TGF-β-1/smads signaling pathway in testicular tissue was examined by Western Blot.[Results]Compared to the blank group,the model group showed a significant decrease in sperm count and sperm motility rate(P<0.05),both the electroacupuncture group and the positive drug group exhibited significant increases compared to the model group(P<0.05).Compared to the blank group,the model group had a significant decrease in serum testosterone(T)levels(P<0.05),and significant increases in serum FSH and LH levels(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant increases in serum T levels(P<0.05),and significant decreases in serum FSH and LH levels(P<0.05).The HE staining results showed typical pathological features of AR in the testicular tissue of model group rats,with varying degrees of improvement observed in electroacupuncture and positive drug group rats.Western Blot analysis revealed that in the model group,the protein levels of TGF-β,p-smad2,and p-smad3 in the TGF-β1/smads pathway in testicular tissue were significantly increased(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant decreases in the protein levels of TGF-β,p-smad2,and p-smad3(P<0.05).[Conclusion]Acupuncture can improve the sperm number and sperm motility rate,regulate sex hormone level and improve the spermatogenic environment,and affect the spermatogenesis process via TGF-β 1/smads signaling pathway.
10.Comparison of Single or Double Titanium Mesh Cage for Anterior Reconstruction After Total En Bloc Spondylectomy for Thoracic and Lumbar Spinal Tumors
Ao LENG ; Qi WANG ; Jiacheng LI ; Yu LONG ; Song SHI ; Lingzhi MENG ; Mingming GUO ; Hailong YU ; Liangbi XIANG
Neurospine 2024;21(2):656-664
Objective:
To compare the clinical efficacy of anterior column reconstruction using single or double titanium mesh cage (TMC) after total en bloc spondylectomy (TES) of thoracic and lumbar spinal tumors.
Methods:
A retrospective cohort study was performed involving 39 patients with thoracic or lumbar spinal tumors. All patients underwent TES, followed by anterior reconstruction and screw-rod instrumentation via a posterior-only procedure. Twenty-two patients in group A were treated with a single TMC to reconstruct the anterior column, whereas 17 patients in group B were reconstructed with double TMCs.
Results:
The overall follow-up is 20.5 ± 4.6 months. There is no significant difference between the 2 groups regarding age, sex, body mass index, tumor location, operative time, and intraoperative blood loss. The time for TMC placement was significantly shortened in the double TMCs group (5.2 ± 1.3 minutes vs. 15.6 ± 3.3 minutes, p = 0.004). Additionally, postoperative neural complications were significantly reduced with double TMCs (5/22 vs. 0/17, p = 0.046). The kyphotic Cobb angle and mean intervertebral height were significantly corrected in both groups (p ≤ 0.001), without obvious loss of correction at the last follow-up in either group. The bone fusion rates for single TMC and double TMCs were 77.3% and 76.5%, respectively.
Conclusion
Using 2 smaller TMCs instead of a single large one eases the placement of TMC by shortening the time and avoiding nerve impingement. Anterior column reconstruction with double TMC is a clinically feasible, and safe alternative following TES for thoracic and lumbar tumors.


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