1.Predictive value of multimodal nomogram on the risk of metastasis and recurrence in patients with stage Ⅱ colorectal cancer without adjuvant treatment
Yi WEI ; Chunhui RAO ; Huize LIU ; Wen CHEN
The Journal of Practical Medicine 2025;41(23):3723-3729
Objective To develop a multimodal nomogram for predicting the risk of postoperative metastasis and recurrence in patients with stage Ⅱ colorectal cancer(CRC)who do not receive adjuvant therapy.Methods A total of 424 patients with stage Ⅱ CRC who underwent radical resection without adjuvant therapy at our institution between January 2016 and December 2021 were retrospectively enrolled.Clinicopathological characteristics[including T stage,carcinoembryonic antigen(CEA)levels,and tumor differentiation],inflammatory markers(preoperative neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio),radiomic features(MRI texture entropy),and molecular biomarkers(KRAS mutation status)were collected.Radiologically confirmed metastasis or recurrence was defined as the primary endpoint.Univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors and construct a predictive nomogram.The model's discriminatory performance was assessed using receiver operating characteristic(ROC)curve analysis.Internal validation was conducted via bootstrapping,and model calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit test.Decision curve analysis was applied to assess the clinical utility of the nomogram,and risk stratification was subsequently performed.Results Among the patients,104(24.53%)developed metastasis or recurrence within three years after surgery.Multivariate analysis revealed the following independent risk factors(all P<0.05):CEA>5 μg/L,moderate to poor differentiation,presence of lymphovascular invasion,perineural invasion,elevated neutrophil-to-lymphocyte ratio(NLR),increased radiomic entropy,and KRAS mutation.The nomogram demonstrated strong predictive accuracy(AUC=0.870,95%CI:0.850~0.930),and the calibration curve indicated excellent agreement between predicted and observed outcomes.Following risk stratification,the recurrence rate was only 6.1%in the low-risk group,compared to 74.2%in the high-risk group(P<0.05).Conclusions This study develops a clinical-inflammatory-radiomic integrated prediction model specifically for stage Ⅱ colorectal cancer patients who do not receive adjuvant therapy.The model effectively identifies the risk of postoperative metastasis and recurrence,enabling the establishment of a risk stratification system to guide subsequent treatment decisions.
2.Study on mechanism of Vaccarin improving EMT in renal fibrosis model mice through regulating STAT3
Meng-jiao CUI ; Qi-ming XU ; Yu CAO ; Ye-nan FAN ; Yi-qing YANG ; Guang-bo GE ; Wen-rui LIU ; Jian-rao LU ; Jing HU
Chinese Pharmacological Bulletin 2025;41(4):745-752
Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.
3.Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis.
Meng-Jie ZHU ; Yi-Jie SONG ; Pei-Li RAO ; Wen-Yi GU ; Yu XU ; Hong-Xi XU
Journal of Integrative Medicine 2025;23(3):297-308
OBJECTIVE:
Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis.
METHODS:
An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels.
RESULTS:
PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability.
CONCLUSION
PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure. Please cite this article as: Zhu MJ, Song YJ, Rao PL, Gu WY, Xu Y, Xu HX. Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis. J Integr Med. 2025; 2025; 23(3): 297-308.
Animals
;
Non-alcoholic Fatty Liver Disease/drug therapy*
;
Male
;
Dysbiosis/drug therapy*
;
Mice, Inbred C57BL
;
Gastrointestinal Microbiome/drug effects*
;
Polysaccharides/therapeutic use*
;
Prunella/chemistry*
;
Mice
;
Liver/metabolism*
;
Plant Extracts/therapeutic use*
;
Disease Models, Animal
;
Diet, High-Fat
4.Characteristics of ocular biometric parameters and distribution of corneal astigmatism before cataract surgery in cataract patients with high myopia
Yehui TAN ; Yi SHAO ; Zhonggang PEI ; Tao ZHANG ; Jie RAO ; Mengying PENG ; Chun LIU ; Lijuan ZHANG
International Eye Science 2025;25(12):1919-1925
AIM:To evaluate the characteristics of ocular biometric parameters and the distribution of corneal astigmatism(CA)in patients with high myopia before cataract surgery.METHODS:A prospective cross-sectional study was conducted, and 695 cataract patients(695 eyes)with high myopia [defined as an axial length(AL)≥26.00 mm] scheduled to undergo cataract surgery at our hospital from January 2022 to December 2024 were consecutively enrolled, another 695 cataract patients(695 eyes)with normal ALs(22.00 mm ≤AL≤25.00 mm)who underwent cataract surgery at our hospital during the same period were included in the control group. For patients with both eyes eligible, the right eye was used for analysis. Before cataract surgery, IOL Master 700 was used to measure the ocular biometric parameters of both eyes for each patient in the two groups. The medical records and ocular biometric data in the two groups were recorded and collected.RESULTS:There were no statistically significant differences between the two groups in genger, age, corneal diameter, and central corneal thickness(all P>0.05). In the high myopia group, the mean AL was 29.20±2.61 mm, and 252 eyes(34.1%)had AL ≥30.00 mm(extremely high myopia). The mean anterior chamber depth(ACD), lens thickness, vitreous chamber depth(VCD), CA, AL/corneal radius of curvature and VCD/AL in the high myopia group were 3.45±0.40, 4.41±0.47, 21.34±2.60 mm, 1.18±0.78 D, 3.79±0.38, and 0.73±0.03, respectively, which were all greater than those in the control group(all P<0.01). In the high myopia group, 350 eyes(50.4%)had CA ≥1.00 D, 192 eyes(27.6%)had CA ≥1.50 D, and 94 eyes(13.5%)had CA ≥2.00 D, which were all higher than those in the control group(32.8%, 15.1%, and 6.6%, respectively; all P<0.001). In the high myopia group, 87 eyes(12.5%)had flat corneas, 424 eyes(61.0%)had moderate CA, and 40 eyes(5.8%)had high CA. These proportions were all higher than those in the control group(6.0%, 46.9%, and 2.9%, respectively; all P<0.001). In the high myopia group, ACD and ACD/AL were negatively correlated with AL(r=-0.162 and -0.661, respectively; all P<0.001), while both ACD and ACD/AL in the control group were positively correlated with AL(r=0.338 and 0.105, respectively; both P<0.01). In the high myopia group, CA increased with age when the patient's age was ≥50 years(r=0.197, P<0.001), which was consistent with the control group.CONCLUSION: The standardized ocular biometric data of cataract patients with high myopia before cataract surgery are helpful for ophthalmologists to accurately calculate the intraocular lens(IOLs)power and select the appropriate IOL type. The majority of high myopia patients need simultaneous correction of CA during cataract surgery.
5.Research progress on pentacyclic triterpenoids in medicinal Ilex species and their pharmacological activities.
Yu-Ling LIU ; Yi-Ran WU ; Bao-Lin WANG ; Xiao-Wei SU ; Qiu-Juan CHEN ; Yi RAO ; Shi-Lin YANG ; Li-Ni HUO ; Hong-Wei GAO
China Journal of Chinese Materia Medica 2025;50(12):3252-3266
Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry*
;
Plants, Medicinal/chemistry*
;
Pentacyclic Triterpenes/pharmacology*
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/pharmacology*
;
Humans
;
Animals
7.Study on mechanism of Vaccarin improving EMT in renal fibrosis model mice through regulating STAT3
Meng-jiao CUI ; Qi-ming XU ; Yu CAO ; Ye-nan FAN ; Yi-qing YANG ; Guang-bo GE ; Wen-rui LIU ; Jian-rao LU ; Jing HU
Chinese Pharmacological Bulletin 2025;41(4):745-752
Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.
8.Predictive value of multimodal nomogram on the risk of metastasis and recurrence in patients with stage Ⅱ colorectal cancer without adjuvant treatment
Yi WEI ; Chunhui RAO ; Huize LIU ; Wen CHEN
The Journal of Practical Medicine 2025;41(23):3723-3729
Objective To develop a multimodal nomogram for predicting the risk of postoperative metastasis and recurrence in patients with stage Ⅱ colorectal cancer(CRC)who do not receive adjuvant therapy.Methods A total of 424 patients with stage Ⅱ CRC who underwent radical resection without adjuvant therapy at our institution between January 2016 and December 2021 were retrospectively enrolled.Clinicopathological characteristics[including T stage,carcinoembryonic antigen(CEA)levels,and tumor differentiation],inflammatory markers(preoperative neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio),radiomic features(MRI texture entropy),and molecular biomarkers(KRAS mutation status)were collected.Radiologically confirmed metastasis or recurrence was defined as the primary endpoint.Univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors and construct a predictive nomogram.The model's discriminatory performance was assessed using receiver operating characteristic(ROC)curve analysis.Internal validation was conducted via bootstrapping,and model calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit test.Decision curve analysis was applied to assess the clinical utility of the nomogram,and risk stratification was subsequently performed.Results Among the patients,104(24.53%)developed metastasis or recurrence within three years after surgery.Multivariate analysis revealed the following independent risk factors(all P<0.05):CEA>5 μg/L,moderate to poor differentiation,presence of lymphovascular invasion,perineural invasion,elevated neutrophil-to-lymphocyte ratio(NLR),increased radiomic entropy,and KRAS mutation.The nomogram demonstrated strong predictive accuracy(AUC=0.870,95%CI:0.850~0.930),and the calibration curve indicated excellent agreement between predicted and observed outcomes.Following risk stratification,the recurrence rate was only 6.1%in the low-risk group,compared to 74.2%in the high-risk group(P<0.05).Conclusions This study develops a clinical-inflammatory-radiomic integrated prediction model specifically for stage Ⅱ colorectal cancer patients who do not receive adjuvant therapy.The model effectively identifies the risk of postoperative metastasis and recurrence,enabling the establishment of a risk stratification system to guide subsequent treatment decisions.
9.Study on Quality Markers of Saorilao Qingfei Zhike Capsules Based on UPLC-QTOF-MS and Network Pharmacology Technology
Zhaozuo ZOU ; Tongqiang SHANGGUAN ; Huajie YANG ; Yingying LUO ; Shang LYU ; Shuangling YANG ; Xueyan LI ; Yuying LUO ; Yi RAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):103-114
Objective Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and network pharmacology technology combined with pharmacodynamic experiments were used to analyze the quality markers(Q-markers)in Saorilao Qingfei Zhike Capsules.Methods Using UPLC-Q-TOF-MS technology,the chemical components in different polar extracts of Saorilao Qingfei Zhike Capsules was analyzed.Potential pharmacological components were screened by using antitussive and expectorant models.The"components-targets-diseases"network was constructed and potential Q-markers were screened by network pharmacology technology.Then we conducted pharmacodynamic validation to confirm the Q-markers,which have antitussive and expectorant effects in Saorilao Qingfei Zhike Capsules.Results A total of 120 compounds were obtained from the Saorilao Qingfei Zhike Capsules through qualitative analysis.Among the extracts of different polarity,44 compounds were derived from petroleum ether extract,85 compounds were derived from ethyl acetate extract,79 compounds were derived from n-butanol extract,and 71 compounds were derived from water extract.The results of pharmacological experiments showed that among extracts of different polarity,petroleum ether extract had the best antitussive effect,while n-butanol extract had the best expectorant effect.Three core components for eliminating phlegm and relieving cough were screened through network pharmacology techniques:farcalinol,farcalinediol,and rubimaillin.Pharmacodynamic studies verified that all core components mentioned above have certain antitussive and expectorant effects.Conclusion Based on the above research,farcalinol,farcalindiol,and rubimaillin can be used as Q-markers for the antitussive and expectorant effects of Saorilao Qingfei Zhike Capsules.This paper provides reference for the quality standard of Saorilao Qingfei Zhike Capsules.
10.Exploration on the Clinical Application of Ephedrae Herba in Stimulating Yang Qi
Yi-Shan ZHOU ; Xian-Yong LIAO ; Ke-Lang RAO ; Ying PI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):234-239
Based on the literature review and the analysis of specific cases of postpartum frequent micturition,pediatric enuresis,elderly uremia complicated with bradyarrhythmia in clinic,the clinical application of the action of Ephedrae Herba in stimulating yang qi is discussed.Ephedrae Herba has the meridian tropism of the lung and bladder meridians,and is pungent,warm and dispersing,which is the most important medicine for the treatment of external contraction.Ephedrae Herba has the actions of inducing diaphoresis,calming asthma and inducing diuresis,and is widely used for the treatment of external contraction,coughing and asthma,and edema.For the patients with deficiency of both kidney yin and kidney yang without obvious bias of yin-yang consumption which result from the postpartum impairment of qi and blood,deficient innate endowment,and gradually exhaustion of essence in the kidney in the elderly or during chronic illness,a small dosage of Ephedrae Herba can stimulate yang qi during the treatment of warming kidney yang,which is helpful for promoting the drug arriving at the back shu-points of the internal organs distributed along the bladder meridian and enhancing the recovery of zang-fu organ function.Ephedrae Herba is strong in inducing diaphoresis with an intense action.When Ephedrae Herba is used to stimulate yang,the dosage of 3~9 g is appropriate,and medicines for warming yang are needs to be used together.The course of treatment with Ephedrae Herba should be avoided to be too long,in order to prevent the vital energy from the damage by its large cumulative dose.

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