1.Effect and mechanism of transplantation of human umbilical cord mesenchymal stem cells with overexpression of the Numb gene in treatment of cholestatic liver fibrosis
Shihao ZHANG ; Changqing ZHAO ; Mingyan YANG ; Feifei XING ; Wei LIU ; Gaofeng CHEN ; Jiamei CHEN ; Ping LIU ; Yongping MU
Journal of Clinical Hepatology 2026;42(1):80-89
ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell (hUC-MSC) with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis (CLF). MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC (hUC-MSCNumb-OE), and hUC-MSC transfected with empty vector (hUC-MSCOE-EV) was used as negative control. Bile duct ligation (BDL) was performed to establish a rat model of CLF, and then the rats were randomly divided into BDL group, hUC-MSC group, hUC-MSCOE-EV group, and hUC-MSCNumb-OE group, while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL, and samples were collected at the end of week 4. Related indicators were measured, including serum biochemistry, liver histopathology, the content of hydroxyproline (Hyp) in the liver, hepatic stellate cell activation, ductular reaction, liver regeneration, and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group, the hUC-MSC group and the hUC-MSCOE-EV group had significant reductions in the levels of serum biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, total bile acid, total bilirubin, and direct bilirubin), liver fibrosis markers (the content of Hyp and the expression levels of alpha-smooth muscle actin, tumor necrosis factor-α, and transforming growth factor-beta 1), and ductular reaction markers (the expression levels of CK7 and CK19) (all P <0.05), and compared with the hUC-MSCOE-EV group, the hUC-MSCNumb-OE group had significantly greater improvements in the above indicators (all P <0.05). In addition, compared with the hUC-MSCOE-EV group, the hUC-MSCNumb-OE group had significant improvements in the expression levels of liver regeneration-related markers (albumin and hepatocyte nuclear factor 4α) and the molecules associated with the Numb-p53 signaling axis (Numb, pNumb, Mdm2, and p53) (all P <0.05). ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF, possibly by activating the Numb-PTBL-p53-HNF4α axis, promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.
2.Emerging breakthroughs and future prospects of Claudin18.2 in targeted therapy and immuno-therapy for gastric cancer
Jiayu JIANG ; Zhen FANG ; Kexin ZHENG ; Baoshan CAI ; Yulong ZHAO ; Zhaodong LIU ; Changqing JING ; Leping LI ; Liang SHANG
Chinese Journal of Digestive Surgery 2025;24(3):343-349
Gastric cancer, a highly malignant tumor, has seen a persistent rise in global incidence in recent years. Claudin 18.2, a protein with highly specific expression in gastric cancer, has emerged as a prominent research target in therapeutic development. The overexpression of Claudin 18.2 in gastric cancer cells and its abnormal surface exposure provide novel opportunities for targeted and immunotherapeutic interventions. Therapeutic approaches targeting Claudin 18.2 have shown promising initial results in clinical trials, primarily including monoclonal antibodies and chimeric antigen receptor T-cell therapies. The authors systematically summarize the biological characteristics, mechanism of action, clinical research progress, and future treatment prospects and challenges of Claudin 18.2.
3.Study on the association between different feeding methods during the first six months after birth and physical growth of children aged 3 to 5 years based on the Taicang and Wuqiang mother-child cohort study in China
Yifan DUAN ; Zhenyu YANG ; Ye BI ; Changqing LIU ; Yongli ZHAO ; Xuyang GU ; Jingtao DUAN ; Hua ZHAO ; Jianqiang LAI
Chinese Journal of Preventive Medicine 2025;59(1):30-38
Objective:To explore the association between different feeding methods during the first six months after birth and the physical growth of children aged 3 to 5 years.Methods:Data were from the "Taicang and Wuqiang mother-child cohort study"(TAWS) in China. Children were enrolled at birth between November 2016 and September 2020 and followed up at 1, 2, 3, 6, 8, 12, 18, and 24 months, as well as at ages 3 to 5 years. Based on feeding methods within six months of age, children were categorized into an "exclusive breastfeeding group" and a "formula-feeding group". Birth-related information and feeding practices between 8 and 24 months were collected, alongside dietary habits, physical activity, and illness during preschool years. Height and weight of preschool children were measured to calculate height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), body mass index-for-age Z-score (BAZ), and the rates of stunting, underweight, wasting, overweight, and obesity. After adjusting for demographic factors, birth-related information, feeding practices between 8 to 24 months, preschool dietary habits, physical activity, and health status, multiple linear regression and logistic regression were adopted to analyze the influence of feeding methods within six months of age on the physical growth of children aged 3 to 5 years.Results:A total of 1 233 children were included, comprising 629 boys and 604 girls. The number of children aged 3, 4, and 5 years was 436, 406, and 391, respectively. About 754 children were categorized into the exclusive breastfeeding group and 479 into the formula-feeding group. Children who were introduced to formula milk within six months of age had higher HAZ (0.09±0.99), WAZ (0.24±1.07) and BAZ (0.26±1.11) scores at ages 3 to 5 compared to the exclusive breastfeeding group [HAZ, WAZ, and BAZ were (-0.04±0.92), (0.06±1.02) and (0.11±1.08), respectively]. After adjusting for confounding factors, multiple linear regression analysis showed that the β (95% CI) values for HAZ, WAZ and BAZ in the formula-feeding group were 0.16 (0.06-0.25), 0.17 (0.06-0.29) and 0.15 (0.02-0.27), respectively, compared to the exclusive breastfeeding group. After adjusting for confounding factors, the results of the multivariate logistic regression model indicated that there were no statistically significant differences in the risks of stunting, underweight, wasting, overweight, and obesity during the preschool years between the exclusive breastfeeding group and the formula-feeding group, with OR (95% CI) values of 1.04 (0.41-2.62), 0.99 (0.27-3.57), 1.63 (0.53-4.95), 1.08 (0.66-1.74), and 1.58 (0.70-3.60), respectively. Conclusion:Exclusive breastfeeding within six months of age does not increase the risk of undernutrition (including stunting, underweight or wasting) during preschool years. However, the introduction of formula feeding within six months of age significantly increases the physical growth level of the preschool stage.
4.Predictive value of serum CTSB and NOX4 levels for the prognosis of sepsis related acute kidney injury patients
Naixi JI ; Yunyun CUI ; Wenhao LIU ; Shangzhen LI ; Xiankui WANG ; Changqing YAO
International Journal of Laboratory Medicine 2025;46(18):2207-2211,2218
Objective To investigate prognostic value of serum levels of cathepsin B(CTSB)and NADPH oxidase 4(NOX4)in patients with sepsis associated acute kidney injury(S-AKI).Methods A total of 306 pa-tients with sepsis treated to the hospital from June 2023 to June 2024 were selected,including 192 patients with S-AKI(S-AKI group)and 114 patients without S-AKI(non-S-AKI group).According to the prognosis of S-AKI patients,they were divided into poor prognosis group(n=127)and non-poor prognosis group(n=65).The differences of CTSB and NOX4 in different groups were compared.Pearson analysis was conducted to analyze the correlation between CTSB,NOX4 and clinical indicators.The influencing factors of poor prognosis in S-AKI patients was analyzed according to multivariate Logistic regression.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTSB and NOX4 on the poor prognosis of S-AKI pa-tients.Results Th e serum levels of CTSB,NOX4 and serum creatinine(SCr)in S-AKI group were signifi-cantly higher than those in non-S-AKI group(P<0.05),while the mean arterial pressure and oxygenation in-dex were lower than those in non-S-AKI group(P<0.05).Serum levels of CTSB and NOX4 in patients with sepsis were positively correlated with SCr(P<0.05).Compared to non-poor prognosis group,the age,SCr,CTSB and NOX4 of patients in the poor prognosis group were higher,while the mean arterial pressure and ox-ygenation index were lower(P<0.05).The increased mean arterial pressure and oxygenation index were pro-tective factors for poor prognosis in S-AKI patients(P<0.05),and the increased age,SCr,CTSB and NOX4 levels were risk factors for poor prognosis in S-AKI patients(P<0.05).ROC curve showed that the area un-der the curve(AUC)of CTSB combined with NOX4 was significantly higher than AUC of single detection of CTSB and NOX4(Z=4.066,P<0.001,Z=3.801,P<0.001).Conclusion The serum levels of CTSB and NOX4 in S-AKI patients are elevated,and can indirectly reflect kidney function.CTSB combined with NOX4 can significantly improve the prediction efficiency of poor prognosis in S-AKI patients,which has potential ap-plication value for clinical treatment and nursing.
5.Study on the association between different feeding methods during the first six months after birth and physical growth of children aged 3 to 5 years based on the Taicang and Wuqiang mother-child cohort study in China
Yifan DUAN ; Zhenyu YANG ; Ye BI ; Changqing LIU ; Yongli ZHAO ; Xuyang GU ; Jingtao DUAN ; Hua ZHAO ; Jianqiang LAI
Chinese Journal of Preventive Medicine 2025;59(1):30-38
Objective:To explore the association between different feeding methods during the first six months after birth and the physical growth of children aged 3 to 5 years.Methods:Data were from the "Taicang and Wuqiang mother-child cohort study"(TAWS) in China. Children were enrolled at birth between November 2016 and September 2020 and followed up at 1, 2, 3, 6, 8, 12, 18, and 24 months, as well as at ages 3 to 5 years. Based on feeding methods within six months of age, children were categorized into an "exclusive breastfeeding group" and a "formula-feeding group". Birth-related information and feeding practices between 8 and 24 months were collected, alongside dietary habits, physical activity, and illness during preschool years. Height and weight of preschool children were measured to calculate height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), body mass index-for-age Z-score (BAZ), and the rates of stunting, underweight, wasting, overweight, and obesity. After adjusting for demographic factors, birth-related information, feeding practices between 8 to 24 months, preschool dietary habits, physical activity, and health status, multiple linear regression and logistic regression were adopted to analyze the influence of feeding methods within six months of age on the physical growth of children aged 3 to 5 years.Results:A total of 1 233 children were included, comprising 629 boys and 604 girls. The number of children aged 3, 4, and 5 years was 436, 406, and 391, respectively. About 754 children were categorized into the exclusive breastfeeding group and 479 into the formula-feeding group. Children who were introduced to formula milk within six months of age had higher HAZ (0.09±0.99), WAZ (0.24±1.07) and BAZ (0.26±1.11) scores at ages 3 to 5 compared to the exclusive breastfeeding group [HAZ, WAZ, and BAZ were (-0.04±0.92), (0.06±1.02) and (0.11±1.08), respectively]. After adjusting for confounding factors, multiple linear regression analysis showed that the β (95% CI) values for HAZ, WAZ and BAZ in the formula-feeding group were 0.16 (0.06-0.25), 0.17 (0.06-0.29) and 0.15 (0.02-0.27), respectively, compared to the exclusive breastfeeding group. After adjusting for confounding factors, the results of the multivariate logistic regression model indicated that there were no statistically significant differences in the risks of stunting, underweight, wasting, overweight, and obesity during the preschool years between the exclusive breastfeeding group and the formula-feeding group, with OR (95% CI) values of 1.04 (0.41-2.62), 0.99 (0.27-3.57), 1.63 (0.53-4.95), 1.08 (0.66-1.74), and 1.58 (0.70-3.60), respectively. Conclusion:Exclusive breastfeeding within six months of age does not increase the risk of undernutrition (including stunting, underweight or wasting) during preschool years. However, the introduction of formula feeding within six months of age significantly increases the physical growth level of the preschool stage.
6.Role of intestinal macrophages in food antigen-induced abdominal pain in mice with visceral hypersensitivity
Li LIU ; Zhipeng ZHAO ; Xiaohui SHEN ; Yuwei WANG ; Changqing YANG
Chinese Journal of Internal Medicine 2025;64(8):745-752
Objective:To examine the role of intestinal macrophages and the mechanism by which they produce reactive oxygen species (ROS) in abdominal pain induced by food antigens in mice with visceral hypersensitivity.Methods:Mouse models of visceral hypersensitivity were established by subjecting animals to acute cold restraint stress (ACRS) or acetic acid enema (AAE). Visceral sensitivity was evaluated using food antigen ovalbumin (OVA)-induced responses and rectal reflex measurements following ROS scavenging. The activity of intestinal macrophages was assessed using flow cytometry. In vitro enzyme immunoassays and in vivo imaging techniques were employed to quantify ROS levels. Furthermore, the influence of OVA on ROS levels following intestinal macrophage depletion was investigated. Cell culture experiments were conducted to investigate the effects of OVA on intestinal macrophage function and ROS production.Results:The two visceral hypersensitivity mouse models exhibited a significantly lower pain threshold compared to the control group. OVA-induced visceral hypersensitivity mice demonstrated enhanced visceral motor responses (VMRs), with an increase in abdominal ROS levels (ACRS vs. control: 62.00±7.68 vs. 19.80±2.39, P<0.001; AAE vs. control: 461.80±17.25 vs. 19.80±2.39, P<0.001). When ROS were cleared from the abdominal cavity of mice, VMRs were restored to normal levels (AAE vs. AAE+ROS: 83.50±8.72 vs. 71.66±2.67, P=0.010). In this mouse model, intestinal macrophages could be classified into CD45 Med and CD45 High subtypes based on the level of CD45 expression. In the AAE group, the expression of CD45 Med macrophages in the intestinal tract decreased (AAE vs. control: 0.121±0.026 vs. 0.194±0.021, P=0.007), whereas the expression of CD45 High macrophages increased (AAE vs. control: 0.249±0.087 vs. 0.018±0.003, P=0.027). Compared with the control group, the expression of CD11b in both types of macrophages increased significantly (CD45 Med vs. control: 39 547.00±4 422.59 vs. 4 055.67±506.05, P<0.05; CD45 High vs. control: 18 960.00±1 197.84 vs. 3 147.50±286.38, P=0.008), while the expression of F4/80 decreased (CD45 Med vs. control: 6 141.67±750.06 vs. 10 544.33±974.92, P=0.008; CD45 High vs. control: 1 291.50±119.50 vs. 4 007.50±327.39, P<0.001). These findings suggest that the activity of intestinal macrophages in visceral hypersensitivity mice is altered following OVA induction. By injecting different populations of macrophages into the peritoneal cavity of mice, it was found that compared to the AAE group, the injection of CD45 High macrophages significantly increased the VMR in mice (AAE vs. AAE CD45 High: 83.50±8.72 vs. 114.38±7.15, P<0.001), and aggravated the severity of diarrhea significantly. In vitro experiments revealed that food antigens could directly induce ROS production in macrophages. Compared with the control group, both the ACRS and AAE groups of mice exhibited significant diarrhea symptoms. In contrast, the severity of diarrhea in the Macrophages exhaust+ACRS and Macrophages exhaust+AAE groups was substantially reduced, with a significantly shortened recovery period. Additionally, compared with the AAE group, the degree of diarrhea in the AAE+ROSS group was alleviated. Conclusions:Food antigens may act on intestinal macrophages, inducing abdominal pain and diarrhea in visceral hypersensitive mice via the ROS pathway. CD45 High macrophages may play a pivotal role in this process.
7.Effect of unilateral or bilateral transcranial direct current stimulation on post-stroke dysphagia
Fei GAO ; Lixu LIU ; Xueyan HU ; Xiaoli WU ; Lingyu YANG ; Yuqi YANG ; Changqing YE ; Xiaoxia DU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):993-999
Objective To investigate the effect of unilateral or bilateral transcranial direct current stimulation(tDCS)on post-stroke dysphagia.Methods From February,2023 to March,2025,27 stroke patients with dysphagia and nasal feeding in Beijing Bo'ai Hos-pital were randomly divided into healthy side stimulation group,bilateral stimulation group and sham stimulation group,with nine cases in each group.All the groups received conventional swallowing training and tDCS,while the healthy side stimulation group stimulated on the healthy side of oropharyngeal cortex;and the bilateral stimu-lation group alternatively stimulated bilateral oropharyngeal cortex,with one hour interval between bilateral stim-ulation;the sham stimulation group stimulated the healthy side of oropharyngeal cortex for 30 seconds and then stop.The course lasted two weeks.The scores of Standard Swallowing Function Assessment Scale(SSA),Modi-fied Mann Assessment of Swallowing Ability(MMASA)and Rosenbek Penetration-Aspiration Scale(PAS)were compared before and after treatment.Results The intra-group effect(F=16.185,P<0.01)was significant in the scores of SSA,the intra-group effect(F=28.650,P<0.01)and interaction effect(F=3.453,P<0.01)were significant in the scores of MMASA,and there was no significant difference in the inter-group effect,intra-group effect and interaction effect in the scores of PAS(P>0.05).Post hoc test showed that there was no significant difference in the scores of SSA,MMASA and PAS among three groups(P>0.05).There was significant difference in the score difference of MMASA be-fore and after treatment among three groups(F=4.698,P<0.05).Post hoc test showed that the score difference of MMAS was more in the healthy side stimulation group than in the bilateral stimulation group and the sham stimulation group(P<0.05),with no significant difference between the bilateral stimulation group and the sham stimulation group(P>0.05).Conclusion tDCS can partly improve post-stroke dysphagia.The healthy side anode stimulation is superior to the alter-nating bilateral hemisphere anode stimulation.
8.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
9.Expert consensus on the prevention and treatment of radiochemotherapy-induced oral mucositis.
Juan XIA ; Xiaoan TAO ; Qinchao HU ; Wei LUO ; Xiuzhen TONG ; Gang ZHOU ; Hongmei ZHOU ; Hong HUA ; Guoyao TANG ; Tong WU ; Qianming CHEN ; Yuan FAN ; Xiaobing GUAN ; Hongwei LIU ; Chaosu HU ; Yongmei ZHOU ; Xuemin SHEN ; Lan WU ; Xin ZENG ; Qing LIU ; Renchuan TAO ; Yuan HE ; Yang CAI ; Wenmei WANG ; Ying ZHANG ; Yingfang WU ; Minhai NIE ; Xin JIN ; Xiufeng WEI ; Yongzhan NIE ; Changqing YUAN ; Bin CHENG
International Journal of Oral Science 2025;17(1):54-54
Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans
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Chemoradiotherapy/adverse effects*
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Consensus
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Risk Factors
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Stomatitis/etiology*
10.Analysis of Differences in Secondary Metabolites Between Dendrobium nobile Bionic Wild Cultivated on Epiphytic Stones and Trees Based on Widely Targeted Metabolomics
Yifan SHI ; Changqing ZHOU ; Jiaojiao WANG ; Lin CHEN ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):218-224
ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees, so as to elucidate the scientific connotation of "only those that grow on stones has superior quality", and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry(UPLC-QTRAP-MS/MS)-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis(PCA), hierarchical cluster analysis(HCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection(VIP) value≥1 and log2fold change(FC)≥1 or ≤-1, and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes, dominated by flavonoids(292), phenolic acids(284), and alkaloids(189). Through OPLS-DA screening, 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile, epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids, phenolic acids, alkaloids, lignans and coumarins, while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids, and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis, flavonoid biosynthesis, tyrosine metabolism, and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids, flavonoids, and alkaloids in D. nobile, indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis, and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.

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