1.Alleviating ulcerative colitis with Baitouweng decoction through Nrf2/HO-1 pathway activation and HMGB1 downregulation
Wei-na ZHU ; Chun-hua MA ; Jie RUAN ; Fu-qiong ZHOU ; Ya-jie ZHANG ; Hong-yan LONG
Chinese Pharmacological Bulletin 2025;41(1):186-192
Aim To explore the antioxidative effect of the Chinese medicine Baitouweng(BTW)on treating ulcerative colitis(UC).Methods Sixty male mice were randomly divided into six groups:control,dextran sulfate sodium(DSS)(3 g·105 L-1),BTW(20,10,and 5 g·kg-1),and 5-aminosalicylic acid(5-ASA)(800 mg·kg-1).UC model was constructed by 3%DSS for seven days,and the UC model was given by ga-vage once daily from the 5 th day of modeling for seven days.Results BTW effectively reduced the symptoms and histopathological scores of UC mice.Additionally,it downregulated the inflammatory factors,interleukin(IL)-6 and IL-1 β,the immunoglobulins vascular cell adhesion molecule 1 and intercellular adhesion mole-cule 1,and metalloprotease matrix metallopeptidase 9.Moreover,it downregulated high mobility group box 1 protein.Furthermore,it inhibited the nuclear factor er-ythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Conclusions BTW improves the general condition,inflammatory indexes and oxidative stress level,and its mechanism may be related to inhib-iting the level of HMGB1 to regulate the Nrf-2/HO-1 signaling pathway and rescue intestinal barrier-related protein expression.
2.Predictive value of intratumor and peritumoral edema radiomics combined with autoencoder algorithm for HER-2 status in breast cancer
Zhao-lei LU ; Yuan XU ; Chao MA ; Ya-wei LIU ; Wang CHEN ; Guan SUN
Chinese Medical Equipment Journal 2025;46(9):9-15
Objective To explore the predictive value of intratumor and peritumoral edema radiomics combined with the autoencoder algorithm for human epidermal growth factor receptor(HER-2)status in breast cancer to provide a new idea for preoperative noninvasive prediction of HER-2 status.Methods Totally 145 breast cancer patients from Yancheng Hospital Affiliated to Nanjing University Medical College(Center 1)and 52 ones from Jianhu Hospital Affiliated to Nantong University(Center 2)had their clinical and imaging data collected retrospectively,who were divided into a HER-2 positive group including 87 ones from Center 1 and 30 ones from Center 2 and a HER-2 negative group including 58 ones from Center 1 and 22 ones from Center 2.From December 2018 to October 2024 there were 78 patients with peritumoral edema from Center 1 randomly enrolled into a training set(55 patients)and a validation set(23 patients)in a ratio of 7∶3,and from November 2024 to March 2025 another 26 ones placed into a time validation set.The 52 patients with peritumoral edema from Center 2 were included into an external test set.Firstly,the Mazda software was used to delineate the regions of interest for the largest tumor layer and the peritumoral edema area.Secondly,multivariate analysis of variance(ANOVA),Kruskal-Wallis test,recursive feature elimination(RFE)and Relief algorithm were respectively employed to screen the radiomics features;finally,combined with ten-fold cross validation,the receiver operating characteristic curve was drawn,and the diagnostic efficacy of the models respectively constructed with radiomics parameters and ten types of machine learning algorithms,including auto encoder,support vector machine,linear discriminant analysis,random forest,Logistic regression,Logistic regression via Lasso,adaptive boosting,Gaussian process,native Bayes and decision tree,was evaluated for the HER-2 status in breast cancer.Results The model established by the auto encoder algorithm combined with three feature parameters including intratumor MaxNorm and Variance and peritumoral edema SumAverg behaved the best.The average AUC values of the training and validation sets were 0.808 and 0.735 resepctively,and the AUC values of the time validation and external test sets were 0.746 and 0.732 respectively.Conclusion The model developed with intratumor and peritumoral edema radiomics combined with the auto encoder algorithm can be used for preoperative noninvasive prediction of HER-2 status of breast cancer,which provides references for the preparation of individualized treatment scheme of breast cancer patients.[Chinese Medical Equipment Journal,2025,46(9):9-15]
3.Predictive value of intratumor and peritumoral edema radiomics combined with autoencoder algorithm for HER-2 status in breast cancer
Zhao-lei LU ; Yuan XU ; Chao MA ; Ya-wei LIU ; Wang CHEN ; Guan SUN
Chinese Medical Equipment Journal 2025;46(9):9-15
Objective To explore the predictive value of intratumor and peritumoral edema radiomics combined with the autoencoder algorithm for human epidermal growth factor receptor(HER-2)status in breast cancer to provide a new idea for preoperative noninvasive prediction of HER-2 status.Methods Totally 145 breast cancer patients from Yancheng Hospital Affiliated to Nanjing University Medical College(Center 1)and 52 ones from Jianhu Hospital Affiliated to Nantong University(Center 2)had their clinical and imaging data collected retrospectively,who were divided into a HER-2 positive group including 87 ones from Center 1 and 30 ones from Center 2 and a HER-2 negative group including 58 ones from Center 1 and 22 ones from Center 2.From December 2018 to October 2024 there were 78 patients with peritumoral edema from Center 1 randomly enrolled into a training set(55 patients)and a validation set(23 patients)in a ratio of 7∶3,and from November 2024 to March 2025 another 26 ones placed into a time validation set.The 52 patients with peritumoral edema from Center 2 were included into an external test set.Firstly,the Mazda software was used to delineate the regions of interest for the largest tumor layer and the peritumoral edema area.Secondly,multivariate analysis of variance(ANOVA),Kruskal-Wallis test,recursive feature elimination(RFE)and Relief algorithm were respectively employed to screen the radiomics features;finally,combined with ten-fold cross validation,the receiver operating characteristic curve was drawn,and the diagnostic efficacy of the models respectively constructed with radiomics parameters and ten types of machine learning algorithms,including auto encoder,support vector machine,linear discriminant analysis,random forest,Logistic regression,Logistic regression via Lasso,adaptive boosting,Gaussian process,native Bayes and decision tree,was evaluated for the HER-2 status in breast cancer.Results The model established by the auto encoder algorithm combined with three feature parameters including intratumor MaxNorm and Variance and peritumoral edema SumAverg behaved the best.The average AUC values of the training and validation sets were 0.808 and 0.735 resepctively,and the AUC values of the time validation and external test sets were 0.746 and 0.732 respectively.Conclusion The model developed with intratumor and peritumoral edema radiomics combined with the auto encoder algorithm can be used for preoperative noninvasive prediction of HER-2 status of breast cancer,which provides references for the preparation of individualized treatment scheme of breast cancer patients.[Chinese Medical Equipment Journal,2025,46(9):9-15]
4.Ligustilide improves demyelination of dMCAO mouse model by inhibiting inflammation through AIM2/caspase-1 signaling pathway
Ya-jie LIANG ; Jian LIU ; Ying CHEN ; Zi-wei ZHANG ; Meng PU ; Yi-bin TANG ; Hai-fei ZHANG ; Guo-bin SONG ; Cun-gen MA ; Qing WANG
Chinese Pharmacological Bulletin 2025;41(5):851-860
Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P<0.05),the expression of IBA1 in CX decreased(P<0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P<0.01).The results of ELISA showed that the levels ofTNF-α(P<0.01),IL-6(P<0.01),IL-1β(P<0.05)and IL-17A(P<0.01)significantly decreased,while the ex-pression of BDNF increased(P<0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P<0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.
5.Alleviating ulcerative colitis with Baitouweng decoction through Nrf2/HO-1 pathway activation and HMGB1 downregulation
Wei-na ZHU ; Chun-hua MA ; Jie RUAN ; Fu-qiong ZHOU ; Ya-jie ZHANG ; Hong-yan LONG
Chinese Pharmacological Bulletin 2025;41(1):186-192
Aim To explore the antioxidative effect of the Chinese medicine Baitouweng(BTW)on treating ulcerative colitis(UC).Methods Sixty male mice were randomly divided into six groups:control,dextran sulfate sodium(DSS)(3 g·105 L-1),BTW(20,10,and 5 g·kg-1),and 5-aminosalicylic acid(5-ASA)(800 mg·kg-1).UC model was constructed by 3%DSS for seven days,and the UC model was given by ga-vage once daily from the 5 th day of modeling for seven days.Results BTW effectively reduced the symptoms and histopathological scores of UC mice.Additionally,it downregulated the inflammatory factors,interleukin(IL)-6 and IL-1 β,the immunoglobulins vascular cell adhesion molecule 1 and intercellular adhesion mole-cule 1,and metalloprotease matrix metallopeptidase 9.Moreover,it downregulated high mobility group box 1 protein.Furthermore,it inhibited the nuclear factor er-ythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Conclusions BTW improves the general condition,inflammatory indexes and oxidative stress level,and its mechanism may be related to inhib-iting the level of HMGB1 to regulate the Nrf-2/HO-1 signaling pathway and rescue intestinal barrier-related protein expression.
6.Metabolome and transcriptome association study reveals biosynthesis of specialized benzylisoquinoline alkaloids in Phellodendron amurense.
Tingxia LIU ; Wanran ZHANG ; Sijia WANG ; Ya TIAN ; Yifan WANG ; Ranran GAO ; Shilin CHEN ; Wei SUN ; Wei MA ; Zhichao XU
Chinese Herbal Medicines 2025;17(1):178-188
OBJECTIVE:
Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens.
METHODS:
The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity.
RESULTS:
The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine.
CONCLUSION
Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.
7.Occupational Hazard Factors and the Trajectory of Fasting Blood Glucose Changes in Chinese Male Steelworkers Based on Environmental Risk Scores: A Prospective Cohort Study.
Ming Xia ZOU ; Wei DU ; Qin KANG ; Yu Hao XIA ; Nuo Yun ZHANG ; Liu FENG ; Fei Yue LI ; Tian Cheng MA ; Ya Jing BAO ; Hong Min FAN
Biomedical and Environmental Sciences 2025;38(6):666-677
OBJECTIVE:
We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers.
METHODS:
The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories.
RESULTS:
FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45).
CONCLUSION
An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans
;
Male
;
Adult
;
Blood Glucose/analysis*
;
China
;
Prospective Studies
;
Occupational Exposure/adverse effects*
;
Risk Factors
;
Middle Aged
;
Steel
;
Fasting/blood*
;
Metal Workers
;
East Asian People
8.Validity and Cost-Consequence Analysis of the Brief Version of the Montreal Cognitive Assessment for Discriminating Cognitive Impairment in a Community-Based Middle-Aged and Elderly Population.
Ting PANG ; Ya-Ping ZHANG ; Ren-Wei CHEN ; Ai-Ju MA ; Xiao-Yi YU ; Yi-Wen HUANG ; Yi-Chun LU ; Xin XU
Acta Academiae Medicinae Sinicae 2025;47(3):382-389
Objective To evaluate the reliability and validity and perform cost-consequence analysis of the brief version of the Montreal cognitive assessment(MoCA)for identifying cognitive impairment in a community-based population ≥50 years of age.Methods The internal consistency and retest reliability of the brief version of the MoCA were analyzed,and the area under the curve(AUC),sensitivity,and specificity were determined to discriminate mild cognitive impairment(MCI)and dementia with the clinical dementia rating(CDR)as the diagnostic criterion.The consistency between the brief version and the full version was analyzed by the Kappa test and the Bland-Altman method,and the number of individuals entering the diagnostic assessment and the overall assessment time were estimated and compared between the two versions.Results A total of 303 individuals were included in this study,of whom 192,94,and 17 had normal cognitive function,MCI,and dementia,respectively.The Cronbach's α and re-test coefficients of the brief version of MoCA were 0.754 and 0.711(P<0.001),respectively.The brief version showed the AUC,sensitivity,and specificity of 0.889,74.5%,and 93.8% for identifying MCI,and 0.994,100%,and 93.8% for identifying dementia,respectively.When the brief version of MoCA was used to identify 94 patients with MCI in 303 individuals,107 individuals required additional diagnostic assessment,with an overall assessment time of 142.4 h,which represented decreases of 21.3% and 32.7%,respectively,compared with those of the full version.When the brief version of MoCA was used to identify 17 patients with dementia in 303 individuals,35 individuals required additional diagnostic assessment,with an overall assessment time of 70.4 h,a decrease of 29.5% in the time cost compared with the full version.Conclusions The brief version of MoCA can identify cognitively impaired individuals in a community-based middle-aged and elderly population,with diagnostic validity comparable to that of the full version but less time cost and fewer individuals needing additional diagnostic assessment to detect true-positive cases.It could be expanded for use in the community-based primary screening setting.
Humans
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Aged
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Middle Aged
;
Cognitive Dysfunction/diagnosis*
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Male
;
Female
;
Mental Status and Dementia Tests
;
Reproducibility of Results
;
Dementia/diagnosis*
;
Sensitivity and Specificity
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Aged, 80 and over
;
Cost-Benefit Analysis
9.Construction of Saccharomyces cerevisiae cell factory for efficient biosynthesis of ferruginol.
Mei-Ling JIANG ; Zhen-Jiang TIAN ; Hao TANG ; Xin-Qi SONG ; Jian WANG ; Ying MA ; Ping SU ; Guo-Wei JIA ; Ya-Ting HU ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2025;50(4):1031-1042
Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics*
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Diterpenes/metabolism*
;
Metabolic Engineering
;
Fermentation
;
Abietanes
10.Evidence evaluation of 12 commonly-used Chinese patent medicines in treatment of osteoporosis based on Eff-iEC and GRADE.
Guang-Cheng WEI ; Zhi-Long ZHANG ; Xin-Wen ZHANG ; Ye LUO ; Jin-Jie SHI ; Rui MA ; Jie-Yang DU ; Ke ZHU ; Jiu-Cheng PENG ; Yu-Long YA ; Wei CAO
China Journal of Chinese Materia Medica 2025;50(15):4372-4385
This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use*
;
Osteoporosis/drug therapy*
;
Humans
;
Nonprescription Drugs/therapeutic use*
;
Evidence-Based Medicine
;
Medicine, Chinese Traditional

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