1.Effect and Mechanism of Liangyi Paste on Hepatic Lipid Deposition in Naturally Aged Mice with High-fat Diet via Cuproptosis/Oxidative Stress Pathway
Meiling ZHANG ; Yuanguang DONG ; Xiaofei SUN ; Jiaxin WANG ; Yu LIU ; Jingxuan ZHU ; Qun WANG ; Nan SONG ; Guoyuan SUI ; Lianqun JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):91-99
ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point, this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding, 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups (10 mice per group): The 12-month-old control group (12MCON), the 15-month-old control group (15MCON), and the 15-month-old group with a high-fat diet (15MHFD). The 12MCON and 15MCON groups were continuously fed a standard diet, while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups (10 mice per group): the 20-month-old control group (20MCON), the model group, and the low-, medium-, and high-dose Liangyi Paste groups (2.91 , 5.82 , 11.64 g·kg-1·d-1, respectively). The 20MCON group was continuously fed a standard diet, while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age, the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage, while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage (when the mice reached 20 months of age), tissue samples were collected. Hepatic TG levels were measured using assay kits; liver histology and lipid deposition were observed via hematoxylin-eosin (HE) and oil red O staining; reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA); Cu2+, superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured by colorimetry; mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction(Real-time PCR) and Wes automated protein expression system. ResultsCompared with 12MCON, the 15MCON group showed significantly increased hepatic TG, Cu2+, ROS, and MDA levels (P<0.01), decreased SOD (P<0.01), hepatocyte swelling, and disordered arrangement. The mRNA and protein levels of ferredoxin 1 (FDX1), dihydrolipoamide S-acetyltransferase (DLAT), heat shock protein 70 (HSP70), dihydrolipoamide dehydrogenase (DLD), pyruvate dehydrogenase E1 subunit-β (PDHB), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor γ (PPARγ) were significantly elevated (P<0.05, P<0.01). Compared with 15MCON group, the 15MHFD and 20MCON groups exhibited further increases in TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group, and no significant lipid deposition was observed in the 20MCON group. FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and protein levels were significantly increased (P<0.05, P<0.01). Compared with 20MCON group, the model group demonstrated markedly elevated TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), severe hepatic steatosis, and upregulated expression of FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and proteins (P<0.05, P<0.01). All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.
2.Correlation between the expression of serum miR-1298-5p,miR-625-5p and miR-155 and the degree of Helicobacter pylori infection in elderly gastric cancer patients
Chunli TANG ; Shujuan FAN ; Sheng TAO ; Jianning LIU ; Feng SU ; Caiyun YUAN ; Meiling ZHU ; Ruimei ZHONG ; JiaoJiao CAO ; Yun WANG
International Journal of Laboratory Medicine 2025;46(2):151-156
Objective To explore the correlation between the expression of serum microRNA(miR)-1298-5p,miR-625-5p,and miR-155 with the degree of Helicobacter pylori(Hp)infection in elderly gastric cancer patients.Methods From January 2021 to November 2023,120 elderly patients with gastric cancer admitted to the hospital from January 2021 to November 2023 were selected as the gastric cancer group,and 130 non-gas-tric cancer patients who underwent gastroscopy were selected as the control group.The expression levels of miR-1298-5p,miR-625-5p and miR-155 in serum were detected by fluorescence quantitative PCR(qPCR).Car-bon 13 urea breath test was used to detect the positive rate of Hp infection in two groups,and the degree of Hp infection in elderly patients with gastric cancer were evaluated.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum miR-1298-5p,miR-625-5p,and miR-155 expression levels for Hp infection in elderly gastric cancer patients.Pearson method was applied to analyze the correlation between serum miR-1298-5p,miR-625-5p,miR-155 expression and positive rate of Hp infection in elderly gas-tric cancer patients.Results Compared with the control group,the expression levels of miR-1298-5p and miR-625-5p in serum of gastric cancer group decreased(P<0.05),while the positive rate of Hp infection and the expression level of serum miR-155 increased(P<0.05).The expression levels of serum miR-1298-5p and miR-625-5p in elderly gastric cancer patients with Hp grade Ⅰ,Ⅱ,and Ⅲ infection were lower than those without Hp infection,while the expression level of miR-155 was higher(P<0.05).Patients with poor differ-entiation,lymph node metastasis,and TNM stage Ⅲ-Ⅳ had lower expressions of serum miR-1298-5p and miR-625-5p(P<0.05),and higher expression of miR-155(P<0.05)than those with moderate-high differen-tiation,no lymph node metastasis,and TNM stage Ⅰ-Ⅱ.The expression levels of serum miR-1298-5p and miR-625-5p were negatively correlated with the positive rate of Hp infection in elderly patients with gastric cancer(r=-0.443,-0.386,both P<0.001),and the expression levels of serum miR-155 were positively correlated with the positive rate of Hp infection(r=0.525,P<0.001).The area under the curve(AUC)of serum miR-1298-5p,miR-625-5p and miR-155 combined diagnosis of Hp infection in elderly gastric cancer pa-tients was higher than that of single diagnosis(P<0.05).Conclusion The expression levels of miR-1298-5p and miR-625-5p in serum of elderly gastric cancer patients with Hp infection decrease,while the expression level of miR-155 increases.These three factors are related to the degree of Hp infection and have good diag-nostic value for the occurrence of Hp infection.
3.Protective effects of Zhibai Dihuang Pills on neurons in mice with D-galactose cognitive dysfunction
Meiling JIN ; Ziyue ZHU ; Xue CHEN ; Qing LIU ; Tongtong CHEN ; Xia LEI ; Ning ZHANG
International Journal of Traditional Chinese Medicine 2025;47(1):44-50
Objective:To investigate the effects of Zhibai Dihuang Pills on neurons of cognitive dysfunction in D-galactose (D-gal) model mice.Methods:Totally 60 male mice were divided into four groups using a random number table method: control group, model group, donepezil group, and Zhibai Dihuang Pills group, with 15 mice in each group. Except for the control group, the other groups were subcutaneously injected with D-galactose solution at a dosage of 125 mg/kg once a day for 8 weeks to prepare the aging model. Mice in the donepezil group were intragastrically administered donepezil solution at a dosage of 0.65 mg/kg, and those in the Zhibai Dihuang Pills group were intragastrically administered Zhibai Dihuang Pills solution at a dosage of 1.56 g/kg. The control group was intragastrically administered an equal volume of physiological saline once a day for 8 weeks. The object recognition test and Morris Water Maze were used to assess object recognition memory and spatial learning memory abilities of mice in each group, respectively. Hematoxylin-Eosin (HE) staining and Nissl staining were employed to observe the morphology of neurons in the hippocampal region; Golgi staining was used to observe neuronal dendritic spines; Western Blot was used to detect the protein expression levels of PI3K, p-Akt/Akt, glycogen synthase kinase 3β (GSK3β), postsynaptic density protein-95 (PSD-95), and synaptophysin (SYP) in the hippocampus region; RT-qPCR was performed to detect mRNA expression of PI3K, Akt and GSK3β in the hippocampus region.Results:Compared with the model group, the recognition index in both the donepezil group and the Zhibai Dihuang Pills group increased ( P<0.05), the escape latency was shortened ( P<0.05), the platform crossings times and the target quadrant dwell time increased ( P<0.05), the number of nerve cells in the hippocampal region increased, arranged closely, the number of Nissl bodies increased, the morphology returned to normal, and the density of dendritic spines increased; the protein expressions of PI3K, PSD-95, and SYP in the hippocampal region and the ratio of p-Akt/Akt increased ( P<0.01), the mRNA level of PI3K increased ( P<0.01 or P<0.05), and the protein and mRNA levels of GSK3β decreased ( P<0.01 or P<0.05). Conclusion:Zhibai Dihuang Pills can improve the learning and memory ability and rescue neuronal damage in D-gal model mice, and the mechanism may be related to the activation of PI3K/Akt pathway and the restoration of synaptic connections.
4.Key Genes in Phenylpropanoid Biosynthesis Pathway of Lonicera macranthoides Based on Transcriptome and Metabolome Conjoint Analysis
Jiawei HE ; Jingyu ZHANG ; Juan ZENG ; Jiayuan ZHU ; Simin ZHOU ; Meiling QU ; Ribao ZHOU ; Xiangdan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):167-175
ObjectiveBased on the conjoint analysis of transcriptome and metabolome, the key genes in the phenylpropanoid biosynthesis pathway of Lonicera macranthoides were explored, which provided a basis for further exploring the synthesis and regulation mechanism of phenylpropanoid compounds in "Xianglei" L. macranthoides. MethodsThe stem, leaves, and three flowering flowers of "Xianglei" L. macranthoides were selected as experimental materials to construct transcriptome and metabolome. The transcriptome and metabolomics were conjointly analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and weighted correlation network analysis (WGCNA), and the key genes in the phenylpropanoid biosynthesis pathway of L. macranthoides were explored. ResultsIn this study, 77 differential phenylpropanoids and 315 differential genes were found. Through the joint analysis of transcription and metabolism, nine key differential metabolites and four key genes related to them were finally discovered. Among them, cinnamic acid, 5-O-caffeoylshikimic acid,sinapyl alcohol, and chlorogenic acid were higher in flowers, and the content of the iconic effective component, namely chlorogenic acid,decreased sharply during the withering period. Caffeic acid,ferulic acid, 5-hydroxyconiferaldehyde,p-coumaryl alcohol, and syringin were higher in leaves. These four key genes belong to the cinnamic alcohol dehydrogenase (CAD) family, 4-coumaric acid: Coenzyme A (4CL) family, hydroxycinnamyl transferase (HCT) family, and L-phenylalanine ammonlyase (PAL) family genes. ConclusionAmong the four key genes excavated from L. macranthoides, TRINITY_DN42767_c0_g6 is related to the synthesis of p-coumaryl alcohol and sinapyl alcohol. TRINITY_DN43525_c4_g1 uses caffeic acid,ferulic acid,and cinnamic acid as substrates to catalyze the next reaction. TRINITY_DN47958_c3_g4 correlates with the synthesis of 3-p-coumaroyl quinic acid and caffeoyl-CoA, and TRINITY_DN52595_c1_g2 correlates with cinnamic acid synthesis. These findings provide a basis for further exploring the synthesis and regulation mechanism of phenylpropanoids in "Xianglei" L. macranthoides.
5.Osteomodulin modulates the inflammatory responses via the interleukin-1 receptor 1/nuclear factor-κB signaling pathway in dental pulpitis.
Yueyi YANG ; Xuchen HU ; Meiling JING ; Xiaohan ZHU ; Xiaoyu LIU ; Wenduo TAN ; Zhanyi CHEN ; Chenguang NIU ; Zhengwei HUANG
International Journal of Oral Science 2025;17(1):41-41
Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism*
;
NF-kappa B/metabolism*
;
Animals
;
Signal Transduction
;
Humans
;
Mice
;
Mice, Knockout
;
Dental Pulp/metabolism*
;
Disease Models, Animal
;
Lipopolysaccharides
6.Efficacy of acupuncture at Huiyin combined with Qingdu Lotion in the treatment of high-risk human pap-illomavirus(HPV)persistent infection
Tingting DU ; Jing XIAO ; Jingyan ZHU ; Xiaofeng CHEN ; Lingjuan HU ; Liner CAI ; Meiling YAO ; Hong TANG
The Journal of Practical Medicine 2025;41(16):2528-2532
Objective To retrospectively assess the clinical efficacy of acupuncture at the Huiyin point combined with Qingdu wash solution in the treatment of high-risk HPV infection.Methods A total of 264 patients who were initially diagnosed with high-risk HPV infection at the University City Gynecology Department of Guang-dong Provincial Hospital of Traditional Chinese Medicine between January 2022 and June 2024 were enrolled in the study.These patients were divided into two groups based on predefined inclusion and exclusion criteria.The ob-servation group included 134 patients who received acupuncture at the Huiyin acupoint combined with Qingdu wash solution,while the control group consisted of 130 patients who did not receive any intervention.The treatment pe-riod lasted for three months,during which the short-term clinical efficacy and safety profile were evaluated.Results The HR-HPV clearance rates in the observation group at 3 months and 6 months were 61.9%and 65.7%,respectively,which were significantly higher than those in the control group(16.9%and 21.5%),and the differences between the two groups were statistically significant(P<0.001).Following a three-month treatment regimen,the rate of HR-HPV positive-to-negative conversion in the observation group was significantly higher than that in the control group,with a statistically significant intergroup difference(P<0.001).The improvement in tra-ditional Chinese medicine(TCM)-related symptoms was also significantly better in the observation group compared to the control group(P<0.05).During the follow-up period,no cases of recurrence were observed in the observa-tion group,whereas the recurrence rate in the control group was 1.5%.Furthermore,no adverse reactions were re-ported in the observation group throughout the treatment period.Conclusion Acupuncture at the Huiyin point,when combined with Qingdu wash solution,can enhance the therapeutic outcomes of high-risk HPV infection and demonstrates a favorable safety profile.
7.Effects of electroacupuncture on cognitive impairment and mitophagy mediated by KIF5A/Miro1 pathway in Parkinson's disease mice.
Mengzhu LI ; Jiafan CHEN ; Mengxuan CHEN ; Haiyan LI ; Zhenyi ZHANG ; Da GAO ; Weicong ZENG ; Lijun ZHAO ; Meiling ZHU
Chinese Acupuncture & Moxibustion 2025;45(8):1111-1119
OBJECTIVE:
To explore the improvement effect of electroacupuncture (EA) based on Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) on cognitive impairment in mice with Parkinson's disease (PD), and to explore its regulatory mechanisms on the kinesin family member 5A (KIF5A)/mitochondrial Rho GTPase 1 (Miro1) pathway and mitophagy in prefrontal cortical neurons.
METHODS:
A total of 70 male C57BL/6J mice of clean grade were randomly divided into a normal group (12 mice), a sham operation group (12 mice), and a model pre-screening group (46 mice). Unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle was adopted to establish the PD model in the model pre-screening group. Twenty-four mice after successful modeling were randomly selected and divided into a model group and an EA group, 12 mice in each one. In the EA group, acupuncture was applied at "Shuigou" (GV26) and bilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6), ipsilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6) were connected to EA respectively, with disperse-dense wave, 5 Hz/20 Hz in frequency, 0.5 mA in current intensity, 20 min a time, 6 times a week for 30 days. Cognitive function was assessed by Y-maze and Morris water maze tests; morphology of prefrontal cortex was observed by H.E. staining; reactive oxygen species (ROS) level in prefrontal cortex was detected by fluorescence probe method; mitochondrial morphology and autophagosome ultrastructure were observed by transmission electron microscopy; the mRNA expression of tyrosine hydroxylase (TH) was detected by quantitative real-time PCR; the protein expression of TH, KIF5A, Miro1, p62, Parkin and PTEN induced kinase 1 (PINK1) was detected by Western blot.
RESULTS:
Compared with the sham operation group, both the model group and the EA group exhibited increased rotation number of per minute (P<0.001). Compared with the sham operation group, in the model group, the novel arm exploration time of Y-maze test was shortened (P<0.001), the escape latency of Morris water maze test was prolonged (P<0.05) and the platform crossing number of Morris water maze test was reduced (P<0.01); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was increased (P<0.001), and mitochondrial autophagosomes could be observed; in the prefrontal cortex, the relative expression of ROS was increased (P<0.001), the protein and mRNA expression of TH was decreased (P<0.001), the protein expression of Miro1, PINK1, Parkin was increased (P<0.001, P<0.01), the protein expression of KIF5A and p62 was decreased (P<0.001). Compared with the model group, in the EA group, the novel arm exploration time of Y-maze test was prolonged (P<0.01), the escape latency of Morris water maze test was shortened (P<0.05) and the platform crossing number of Morris water maze test was increased (P<0.05); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was decreased (P<0.001), and the number of mitochondrial autophagosomes reduced and the mitochondrial morphology was improved; in the prefrontal cortex, the relative expression of ROS was decreased (P<0.01), the protein and mRNA expression of TH was increased (P<0.001, P<0.01), the protein expression of Miro1, PINK1, Parkin was decreased (P<0.001, P<0.01, P<0.05), the protein expression of KIF5A and p62 was increased (P<0.01, P<0.05).
CONCLUSION
Xingnao Kaiqiao electroacupuncture effectively alleviates cognitive impairment and damage of neuronal function in PD mice, its mechanism may be related to the regulation of KIF5A/Miro1 pathway, hence reducing the mitophagy in prefrontal cortical neurons.
Animals
;
Electroacupuncture
;
Male
;
Mice
;
Parkinson Disease/physiopathology*
;
Cognitive Dysfunction/psychology*
;
Kinesins/genetics*
;
Humans
;
Mitophagy
;
Mice, Inbred C57BL
;
rho GTP-Binding Proteins/genetics*
;
Mitochondria/genetics*
;
Prefrontal Cortex/metabolism*
8.Efficacy of acupuncture at Huiyin combined with Qingdu Lotion in the treatment of high-risk human pap-illomavirus(HPV)persistent infection
Tingting DU ; Jing XIAO ; Jingyan ZHU ; Xiaofeng CHEN ; Lingjuan HU ; Liner CAI ; Meiling YAO ; Hong TANG
The Journal of Practical Medicine 2025;41(16):2528-2532
Objective To retrospectively assess the clinical efficacy of acupuncture at the Huiyin point combined with Qingdu wash solution in the treatment of high-risk HPV infection.Methods A total of 264 patients who were initially diagnosed with high-risk HPV infection at the University City Gynecology Department of Guang-dong Provincial Hospital of Traditional Chinese Medicine between January 2022 and June 2024 were enrolled in the study.These patients were divided into two groups based on predefined inclusion and exclusion criteria.The ob-servation group included 134 patients who received acupuncture at the Huiyin acupoint combined with Qingdu wash solution,while the control group consisted of 130 patients who did not receive any intervention.The treatment pe-riod lasted for three months,during which the short-term clinical efficacy and safety profile were evaluated.Results The HR-HPV clearance rates in the observation group at 3 months and 6 months were 61.9%and 65.7%,respectively,which were significantly higher than those in the control group(16.9%and 21.5%),and the differences between the two groups were statistically significant(P<0.001).Following a three-month treatment regimen,the rate of HR-HPV positive-to-negative conversion in the observation group was significantly higher than that in the control group,with a statistically significant intergroup difference(P<0.001).The improvement in tra-ditional Chinese medicine(TCM)-related symptoms was also significantly better in the observation group compared to the control group(P<0.05).During the follow-up period,no cases of recurrence were observed in the observa-tion group,whereas the recurrence rate in the control group was 1.5%.Furthermore,no adverse reactions were re-ported in the observation group throughout the treatment period.Conclusion Acupuncture at the Huiyin point,when combined with Qingdu wash solution,can enhance the therapeutic outcomes of high-risk HPV infection and demonstrates a favorable safety profile.
9.LBP3 promotes production of SCFAs to inhibit PMN-MDSC function and exert anti-tumor effects
Yanping CAI ; Meiling ZHANG ; Xuting XIE ; Junjie LIANG ; Ying ZHU ; Xiangliang DENG ; Yunliang CHEN ; Xia LUO ; Lian ZHOU ; Qing WANG
Chinese Journal of Immunology 2025;41(7):1543-1551
Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.
10.Predictive value of serum sEC and COX-2 levels for postoperative recurrence and metastasis of breast cancer
Zhaohui ZHU ; Xu QIAN ; Meiling XUE ; Aijun SUN ; Weimin SUN
Chinese Journal of Endocrine Surgery 2025;19(5):671-677
Objective:To explore the value of serum soluble E-cadherin (sEC) and cyclooxygenase-2 (COX-2) levels in predicting postoperative recurrence and metastasis of breast cancer.Methods:198 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) From Mar. 2023 to Mar. 2025 were selected and followed up for 3 years. The recurrence and metastasis were counted. Patients with recurrence and metastasis were included in the poor prognosis group, and patients without recurrence and metastasis were included in the good prognosis group. The general data, preoperative serum sEC and COX-2 levels were compared between the two groups. The influencing factors of recurrence and metastasis of breast cancer after operation were analyzed. The dose-response relationship and predictive value of serum sEC and COX-2 levels with recurrence and metastasis were analyzed. Logistic regression equation (LR) model 1 was constructed according to conventional influencing factors, and LR model 2 was constructed according to conventional influencing factors combined with serum sEC and COX-2. The predictive efficacy and accuracy of the two models were analyzed by receiver operating characteristic curve (ROC) and calibration curve. According to the ratio of 7∶3, another 85 female breast cancer patients who underwent surgical treatment in Huai’an Hospital Affiliated to Xuzhou Medical University (Huai’an Second People’s Hospital) from May. 2023 to May. 2025 were selected for external validation (validation set) .Results:Among 198 breast cancer patients who underwent postoperative follow-up for 3 years, 3 cases were lost to follow-up, and the recurrence and metastasis rate among the 195 patients who completed the 3-year postoperative follow-up was 26.15% (51/195). In the good prognosis group, the proportion of TNM stage III was 20.14%, the proportion of lymph node metastasis was 11.81%, the preoperative serum carbohydrate antigen 153 (CA153) level was (54.19±10.84) U/mL, the carbohydrate antigen 125 (CA125) level was (46.03±10.27) U/mL, the sEC level was (1987.65±191.37) ng/mL, and the COX-2 level was (17.85±5.21) ng/mL. In the poor prognosis group, the proportion of TNM stage III was 45.10%, the proportion of lymph node metastasis was 35.29%, the preoperative serum CA153 level was (65.87±12.23) U/mL, the CA125 level was (57.76±11.51) U/mL, the sEC level was (2 295.37±261.48) ng/mL, and the COX-2 level was (10.42±3.16) ng/mL. Compared with the good prognosis group, they were increased ( t/χ 2=12.00, 14.11, 6.39, 6.79, 8.92, 12.00, P<0.05). Multivariate Logistic regression analysis showed that TNM stage III ( OR=2.078, 95%CI =1.569-2.751, P<0.05), lymph node metastasis ( OR=2.435, 95 %CI=1.843-3.216, P<0.05), serum CA153 ( OR= 1.180,95 %CI=1.026-1.357, P<0.05), CA125 ( OR=1.206,95 %CI=1.033-1.408, P<0.05), sEC ( OR=1.011,95 %CI= 1.007-1.015, P<0.05), COX-2 ( OR=1.378,95 %CI=1.128-1.683, P<0.05) were independent risk factors for postoperative recurrence and metastasis of breast cancer. Restricted cubic spline (RCS) analysis showed that serum sEC and COX-2 levels were positively correlated with the risk of recurrence and metastasis of breast cancer ( P<0.05). ROC analysis showed that serum sEC (AUC=0.762,95 %CI=0.696-0.820, P<0.05) and COX-2 (AUC=0.757,95 %CI=0.691-0.815, P<0.05) could be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. The AUC of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was 0.862 (95 %CI=0.805-0.907, P<0.05). The AUC of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 0.965 (95 %CI= 0.891-0.983, P<0.05), which was significantly larger than that of LR model 1 ( Z=2.015, P<0.05). The calibration curve analysis showed that the calibration degree of LR model 1 in predicting postoperative recurrence and metastasis of breast cancer was good, and the prediction results were in good agreement with the actual observation results. The calibration degree of LR model 2 was high, and the prediction results were in good agreement with the actual observation results. The results of external validation showed that the sensitivity of LR model 2 in predicting postoperative recurrence and metastasis of breast cancer was 82.61%, the specificity was 93.55%, the accuracy was 90.59%, and the Kappa value was 0.762 (95 %CI: 0.549-0.974) . Conclusions:Preoperative serum sEC and COX-2 levels are independent risk factors for postoperative recurrence and metastasis of breast cancer. They can be used as biological indicators to predict postoperative recurrence and metastasis of breast cancer. Combined with conventional indicators, they can significantly improve the predictive efficacy.

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