1.Mechanism of Yueju Wan in Treatment of Functional Dyspepsia Based on Regulation of 5-HT Signaling Pathway
Haoran SHEN ; Yaru GU ; Muqing ZHANG ; Zhikuo DONG ; Xingxing GAO ; Dantong LI ; Ying GU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):20-28
ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine (5-HT) signaling pathway in rats with functional dyspepsia (FD) and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley (SD) rats were randomly divided into a normal group, model group, mosapride group (1.575 mg·kg-1), and Yueju Wan low-, medium-, and high-dose groups (0.735, 1.47, and 2.94 g·kg-1, respectively). The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling, rats were administered the corresponding drugs by gavage for 28 days. After treatment, gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT, tryptophan hydroxylase (TPH), and substance P (SP) were detected by enzyme-linked immunosorbent assay (ELISA), and acetylcholine (ACh) levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin (HE) staining. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor (5-HT4R), SP, and acetylcholinesterase (AChE) in colon tissue, as well as 5-hydroxytryptamine 3 receptor (5-HT3R), SP, and AChE in hypothalamic tissue. Immunohistochemistry (IHC) was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased (P<0.01). Serum levels of 5-HT, SP, ACh, and TPH were significantly reduced (P<0.01). Histopathological examination revealed irregular arrangement of glands in the gastric antrum, slight mucosal atrophy, and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R, SP, and AChE in colon tissue, as well as 5-HT3R, SP, and AChE in hypothalamic tissue, were significantly decreased (P<0.01), and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced (P<0.01). Compared with the model group, all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate (P<0.01). The glands in the gastric antrum were more regularly arranged, with no inflammatory cell infiltration observed. Serum levels of 5-HT, SP, ACh, and TPH were significantly increased (P<0.01). The mRNA and protein expression levels of 5-HT4R, SP, and AChE in colon tissue and 5-HT3R, SP, and AChE in hypothalamic tissue were significantly upregulated (P<0.05, P<0.01), and 5-HT protein expression in both the colon and hypothalamus was significantly increased (P<0.01). ConclusionYueju Wan has preventive and therapeutic effects on FD, and its mechanism may be related to regulation of the 5-HT signaling pathway, promotion of brain-gut peptide secretion, and enhancement of gastric motility.
2.KRAS mutant colon cancer-targeted induction of ferroptosis via photocatalytic activation of BiVO4-embedded silica nano with cascadic downregulation of GPX4/xCT axis.
Yixin JIANG ; Ratchapol JENJOB ; Dahee RYU ; Zheyu SHEN ; Su-Geun YANG
Acta Pharmaceutica Sinica B 2025;15(9):4932-4944
Kirsten rat sarcoma virus (KRAS) is a common oncogene in human cancers. Approximately 40% of the patients diagnosed with colorectal cancer (CRC) have KRAS mutations that exhibit strong resistance to targeted molecular therapy and EGFR antibody treatment. In this study, we present photocatalytic silica nanoparticles (A6-FS/BiVO4 DMSNs) for targeted therapy of KRAS mutant CRC with the induction of cascadic ferroptosis events. Dendritic mesoporous silica nanoparticles (DMSNs) were impregnated with photocatalytic BiVO4, loaded with ferroptotic agents (benzoyl ferrocene: B and sorafenib: S), and encoded with CD44-targeting A6 peptides. For the targeting design, we observed CD44 overexpression in KRAS mutant CRC cells using CPTAC data analysis. Upon laser irradiation, A6-FS/BiVO4 DMSNs generate electron-hole pairs (e-/h+), which produce hydroxyl radical (OH·) and superoxide anions (O2 · -). Laser irradiation simultaneously initiates the dissociation of iron (Fe2+) from benzoyl ferrocene and the release of sorafenib. This cascade induces ferroptosis in KRAS mutant CRC cells, especially under conditional inhibition of redox-regulating proteins (cystine/glutamate antiporter and glutathione peroxidase 4), and significantly inhibits tumor growth in a KRAS mutant CRC xenograft animal model.
3.Analysis on research trends and hotspots of TCM papers in high impact factor journals from 2014 to 2024
Yalei ZHANG ; Yuejing CHEN ; Yile LU ; Yixin SHI ; Zhenmin LI ; Qiuwen FAN ; Yunhui SHEN ; Xinyang SONG ; Lili XU
International Journal of Traditional Chinese Medicine 2025;47(11):1595-1601
Objective:To understand trends and hotspots of TCM research papers published in journals with high IF basing on a bibliometric analysis.Methods:TCM research papers published between January 1, 2014 and December 31, 2024 from 80 journals with IF higher than 16.0 were retrieved from medical, life sciences and comprehensive journals in Journal Citation Reports of 2024. CiteSpace 6.3.R1 and Excel 2021 were used to analyze and visualize annual publication volume, research fields, features of clinical study, institutes, funds and keywords.Results:A total of 51 papers were included, showing an increasing trend in annual publication volume; the main research areas were pharmacology, acupuncture&moxibustion and internal medicine. Multi-center randomized controlled trials were the main clinical studies; China Academy of Chinese Medical Sciences was the leading institute in terms of publication volume; 84 funds were involved, including National Natural Science Foundation of China. Keywords that appeared most frequently were TCM, efficacy, double blind, electroacupuncture, stimulation and management.Conclusion:The number and quality of TCM research papers are improved simultaneously; future research needs to deepen international cooperation, and pay attention to the integration of TCM diagnosis and treatment characteristics and modern scientific research methods.
4.Correlations of Mas-related G protein-coupled receptor X2 and interleukin in patients with chronic spontaneous urticaria
Yiqi ZHU ; Yixin SHAO ; Duoqin WANG ; Yanyun SHEN ; Taiyu JIN ; Lisi PENG ; Hui TANG ; Zijing XIAO
Chinese Journal of Clinical Medicine 2024;31(6):875-882
Objective To explore the correlations between serum Mas-related G protein-coupled receptor X2 (MRGPRX2), interleukin (IL)-4, IL-5, IL-6, IL-13, IL-23 and IL-33 levels and chronic spontaneous urticaria (CSU). Methods The clinical characteristics and laboratory data from 55 patients with CSU and 21 healthy controls at Huashan Hospital, Fudan University from February 2021 to September 2023 were collected. The disease activity and severity of CSU patients were assessed. Serum level of MRGPRX2 was tested using enzyme-linked immunosorbent assay (ELISA), and levels of IL-4, IL-5, IL-6, IL-13, IL-23, and IL-33 were measured using Luminex multiplex assay in all subjects. Spearman correlation analysis was used to evaluate the correlations between biomarkers and other parameters in CSU patients, and logistic regression analysis was performed to identify factors influencing CSU. Results CSU patients exhibited significantly higher serum levels of MRGPRX2 (2.41[0, 11.51] ng/mL vs 0[0, 2.86] ng/mL, P=0.015) and IL-23 (0.09[0.04, 0.56] pg/mL vs 0.05[0.03, 0.08] pg/mL, P=0.033) than healthy controls. There was no difference in levels of other cytokines between the two groups. There was no difference in levels of MRGPRX2 and cytokines between severe and non-severe CSU patients. Correlation analysis showed that serum MRGPRX2 levels in CSU patients were positively correlated with IL-4 (r=0.345, P=0.010) and IL-6 (r=0.395, P=0.003) levels. Logistic regression analysis indicated that MRGPRX2≥0.055 ng/mL and IL-23≥0.135 pg/mL were independent risk factors for CSU (P<0.05). Conclusions Serum levels of MRGPRX2 and IL-23 in CSU patients are elevated, which may be involved in the pathogenesis of CSU.
5.Optical coherence tomography angiography manifestations of different degrees of nonproliferative diabetic retinopathy
Menghuan DAI ; Dongli LI ; Yixin CUI ; Lu SHEN ; Qirui LI ; Lingna RAO ; Shurong GUO ; Ling YUAN
International Eye Science 2024;24(2):307-311
AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P<0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P<0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.
6.Study on the characteristics of lymphocyte-specfic protein-tyrosine kinase methylation in the peripheral blood circulation of patients with rheumatoid arthritis
Lingxia XU ; Cen CHANG ; Ping JIANG ; Kai WEI ; Jia′nan ZHAO ; Yixin ZHENG ; Yu SHAN ; Yiming SHI ; Hua Ye JIN ; Yi SHEN ; Shicheng GUO ; Dongyi HE ; Jia LIU
Chinese Journal of Rheumatology 2024;28(3):155-161
Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.
7.Predictive value of serum SOCS3 and TXNIP levels for the prognosis of patients with hepatocellular carcinoma treated with TACE
Journal of International Oncology 2024;51(4):217-222
Objective:To investigate the prognostic value of serum suppressor of cytokine signaling 3 (SOCS3) and thioredoxin-interacting protein (TXNIP) levels in transcatheter arterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC) .Methods:A total of 107 HCC patients who underwent TACE treatment in Wuhan Hanyang Hospital from December 2019 to July 2021 were selected as the observation objects. According to the situation after TACE treatment, the patients were divided into poor prognosis group ( n=47) and good prognosis group ( n=60). Serum SOCS3 and TXNIP levels were detected by enzyme-linked immunosorbent assay, the prognostic factors were analyzed by logistic regression. The predictive value of serum SOCS3 and TXNIP levels before treatment for TACE treatment prognosis in patients with HCC was analyzed by receiver operator characteristic (ROC) curve. Results:There were no statistically significant differences between good prognosis group and poor prognosis group in age ( χ2=0.56, P=0.453), gender ( χ2=0.06, P=0.800), tumor size ( χ2=1.46, P=0.227), Child-Pugh grade ( χ2=0.26, P=0.608), tumor number ( χ2=0.77, P=0.382), cirrhosis ( χ2=0.03, P=0.860), TACE times ( χ2=0.16, P=0.691), alpha-fetoprotein level before treatment ( χ2=0.79, P=0.374), and hepatitis B surface antigen ( χ2=0.58, P=0.446). The proportion of TNM stage Ⅲ patients in the poor prognosis group (57.45%, 27/47) was higher than that in the good prognosis group (25.00%, 15/60), with a statistically significant difference ( χ2=11.64, P=0.001). The serum levels of SOCS3 and TXNIP in the good prognosis group before treatment were (114.34±20.39) and (45.64±6.41) pg/ml, respectively, while those in the poor prognosis group were (82.83±15.97) and (34.82±6.36) pg/ml, respectively, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=8.71, P<0.001; t=8.70, P<0.001). After treatment, the serum SOCS3 and TXNIP levels in the good prognosis group were (139.65±24.32) and (64.75±7.58) pg/ml, respectively, while those in the poor prognosis group were (92.41±16.15) and (41.74±7.23) pg/ml, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=11.48, P<0.001; t=15.90, P<0.001). Serum SOCS3 and TXNIP levels in both groups were significantly higher after treatment than before (all P<0.05). Multivariate analysis showed that TNM stage ( OR=2.53, 95% CI: 1.27-5.02, P=0.008) was an independent risk factor for prognosis in HCC patients after TACE treatment, SOCS3 ( OR=0.65, 95% CI: 0.44-0.96, P=0.031) and TXNIP ( OR=0.57, 95% CI: 0.36-0.89, P=0.014) were independent protective factors for prognosis in HCC patients after TACE treatment. ROC curve analysis showed that the sensitivity and specificity of the combined detection of serum SOCS3 and TXNIP before treatment in predicting prognosis of TACE treatment in HCC patients were 81% and 92%, respectively, the area under the curve was 0.92 (95% CI: 0.85-0.96) . Conclusion:The low levels of serum SOCS3 and TXNIP before TACE treatment in HCC patients may indicate poor prognosis after TACE treatment. The combined detection of the two has certain predictive value for judging the prognosis of HCC patients after TACE treatment.
8.Optimization of β-cyclodextrin Inclusion Process of Cinnamomi Ramulus Formula Granules Volatile Constituents Based on Standard Relation and Information Entropy Method
Yaxi CHEN ; Zhuoyuan LI ; Lin TAO ; Nana CHEN ; Yixin KE ; Wen SHEN ; Wei XIE ; Wen ZHANG ; Junsong LI
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):582-588
OBJECTIVE To optimize β-cyclodextrin(β-CD)inclusion process of Cinnamomi Ramulus Formula Granules vola-tile constituents by orthogonal test,based on standard relation and information entropy method.METHODS On the basis of single factor experiments,the ratio of β-CD to aromatic aqueous solution,the inclusion temperature,and the inclusion time were selected as the investigating factors;the inclusion rate,drug loading,and standard relation of cinnamic aldehyde in inclusion complex were used as the evaluation index.The information entropy method was used to determine the weight coefficient of each index,then the comprehen-sive score was calculated,the inclusion process conditions were optimized by orthogonal experiment.The inclusion complex was charac-terized by thin layer chromatography,ultraviolet absorption spectroscopy,Fourier infrared spectroscopy,and X-ray diffraction.RE-SULTS The best inclusion process was that the ratio of β-CD to aromatic aqueous solution was 3∶100(g·mL-1),the inclusion temperature was 50℃,and the inclusion time was 1 h.The average inclusion rate of the obtained inclusion compound was 80.84%,the drug loading was 8.63%,and the standard relation was 0.91.The results of thin-layer chromatography,ultraviolet,infrared spec-troscopy and other characterization experiments showed that the volatile components in the aromatic aqueous solution successfully en-tered the β-CD cavity,and the inclusion complex was successfully prepared.CONCLUSION The optimum inclusion process is sta-ble and feasible,which can provide references for the preparation process of Cinnamomi Ramulus Formula Granules.
9.Long-Term Survival Trend of Gynecological Cancer:A Systematic Review of Population-Based Cancer Registration Data
Zhou XIAOHUI ; Yang DANNI ; Zou YIXIN ; Tang DANDAN ; Chen JUN ; Li ZHUOYING ; Shen QIUMING ; Xu QUN ; Xiang YONGBING
Biomedical and Environmental Sciences 2024;37(8):897-921
Gynecological cancer significantly affect the health of women.This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers.We searched PubMed,Embase,Web of Science,SinoMed,and SEER for survival analyses of cancer registration data of cervical,endometrial,and ovarian cancers published between 1980 and 2022.Globally,the highest 5-year observed survival rate for cervical cancer was 76.5%in Anshan,Liaoning,China(2008-2017).The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland(1995-1999,82.5%)and Singapore(1988-1992,62.0%).The 5-year relative survival rate of cervical cancer patients was higher in Haining,Zhejiang,China(2011-2014,85.8%).Korea ranked first at 89.0%and 64.5%for endometrial and ovarian cancers,respectively.Survival rates have improved for cervical,endometrial,and ovarian cancers.Patients aged≥75 years and those with advanced-stage disease had the worst 5-year survival rates.Survival rates were better for squamous cell carcinoma in cervical cancer,for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer,and for germ cell and sex-cord stromal tumors in ovarian cancer.Over the past four decades,the survival rates of gynecological cancers have increased globally,with notable increases in cervical and endometrial cancers.Survival rates are higher in developed countries,with a slow-growing trend.Future studies should focus on improving survival,especially in ovarian cancer patients.
10.Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8.
Ying HU ; Shuxian WANG ; Lan WU ; Kai YANG ; Fan YANG ; Junfa YANG ; Shuang HU ; Yan YAO ; Xun XIA ; Yixin LIU ; Li PENG ; Jihong WAN ; Chuanpu SHEN ; Tao XU
Chinese Journal of Natural Medicines (English Ed.) 2023;21(9):670-681
Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

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