1.Anmei Dan Regulates SIRT3/Nrf2 Signaling Pathway-mediated Mitochondrial Oxidative Stress to Improve Cognitive Function in Aged Sleep-deprived Mouse Model
Lichun WANG ; Jinxu MA ; Zi'ao WANG ; Ping WANG ; Guangjing XIE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):77-86
ObjectiveTo investigate the mechanism by which Anmei Dan (AMD) regulates recombinant sirtuin 3/nuclear factor erythroid 2-related factor 2(SIRT3/Nrf2) signaling to ameliorate mitochondrial oxidative stress and improve the cognitive function in aged sleep-deprived mice. MethodsSixty aged C57 mice were randomly assigned to a control group, a model group, a melatonin (1.3 mg·kg-1·d-1) group, and high-, medium-, and low-dose (26.26, 13.13, 6.565 g·kg-1·d-1, respectively) AMD groups, with ten mice per group. Continuous sleep deprivation was administered for 4 weeks via a custom-built sleep deprivation chamber. The cognitive function of mice was assessed via the Morris water maze test. Hematoxylin-eosin (HE) staining was performed to observe morphological alterations in pyramidal neurons. Biochemical assays were carried out to measure the hippocampal and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC). Transmission electron microscopy was adopted to examine mitochondrial pathological alterations in the hippocampus. Immunohistochemical assay was conducted to examine the expression of nuclear factor E2-related factor 2 (Nrf2), sirtuin 3 (SIRT3), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), and brain-derived neurotrophic factor (BDNF) in the mouse hippocampus. The protein levels of Nrf2, SIRT3, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in mouse hippocampal tissue were determined by Western blot. Immunofluorescence double labeling was employed to determine the protein levels of SIRT3/Nrf2 in mouse hippocampal tissue. ResultsCompared with the control group, the model group exhibited prolonged latency to navigate, increased total swimming distance, reduced number of platform crossings, and shortened time spent in the target quadrant (P<0.05, P<0.01), disorganized morphology and arrangement of hippocampal neurons, with increased damaged mitochondria, mitochondrial swelling, reduced cristae, and vacuolization, declined levels of SOD, GSH-Px, CAT, and T-AOC and elevated levels of MDA in the hippocampus and serum (P<0.01), and downregulated protein levels of SIRT3, Nrf2, PGC-1α, TFAM, BDNF, HO-1, and NQO1 (P<0.01). Compared with the model group, the melatonin group and AMD groups exhibited shortened spatial navigation latency, reduced total swimming distance, increased number of platform crossings, and prolonged activity time in the target quadrant (P<0.05, P<0.01), reduced neuronal damage and mitochondrial damage in the hippocampal tissue, declined level of MDA and elevated levels of SOD, GSH-Px, CAT, and T-AOC in the hippocampus and serum (P<0.05, P<0.01), and upregulated protein levels of SIRT3, Nrf2, PGC-1α, TFAM, BDNF, HO-1, and NQO1 in the hippocampus (P<0.05, P<0.01). ConclusionAMD may improve the learning and memory in aged sleep-deprived mice by mediating mitochondrial oxidative damage through the SIRT3/Nrf2 signaling pathway.
2.Anmei Dan Regulates Hippocampal Inflammation via CX3CL1/CX3CR1 Signaling Pathway to Improve Learning and Memory in Aged Sleep-deprived Mice
Lichun WANG ; Zi'ao WANG ; Jinxu MA ; Yufeng CAI ; Huizhen LIU ; Ping WANG ; Guangjing XIE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):97-106
ObjectiveTo investigate the effects of Anmei Dan (AMD) on the expression of proteins in the C-X3-C motif chemokine ligand 1 (CX3CL1)/C-X3-C chemokine receptor 1 (CX3CR1) signaling pathway, hippocampal inflammation, and learning and memory in an aged sleep-deprived model. MethodsSixty aged C57 mice were randomly assigned into a control group, a model group, a melatonin group (1.3 mg·kg-1·d-1), and high-, medium-, and low-dose AMD groups (26.26, 13.13, 6.565 g·kg-1·d-1, respectively), with 10 mice per group. Continuous sleep deprivation was administered for 4 weeks through a custom-built sleep deprivation chamber. The cognitive function of mice was assessed via the Y-maze test. Histomorphological alterations in pyramidal cells of the hippocampal CA1 and DG regions were examined by hematoxylin-eosin (HE) and Nissl staining. Synaptic morphology in the hippocampus was visualized with Golgi staining. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampal tissue as well as the level of interleukin-10 (IL-10) in the prefrontal cortex. Real-time PCR was performed to detect markers of M1-type [cluster of differentiation (CD) 86 and inducible nitric oxide synthase (iNOS)] and M2-type [CD206 and arginase 1 (Arg1)] macrophages. Western blot was employed to quantify the protein levels of CX3CL1, CX3CR1, phosphorylated nuclear factor κB p65 subunit (p-NF-κB p65), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) in the hippocampus. Immunofluorescence double staining was performed to co-label CX3CR1 with ionized calcium-binding adapter molecule 1 (Iba-1) for observation of the co-localization of target proteins with microglia. ResultsCompared with the control group, the model group exhibited disrupted daily activity patterns with reduced spontaneous alternation rates (P<0.01), disorganized morphology and arrangement of hippocampal neurons, accompanied by reduced numbers of Nissl bodies and dendritic spines (P<0.01), upregulated protein levels of IL-6, IL-10, IL-1β, TNF-α, CX3CL1, CX3CR1, p-NF-κB p65, p-p38 MAPK, and Iba-1 and mRNA levels of CD86 and iNOS (P<0.01), and downregulated mRNA levels of CD206 and Arg1 (P<0.05,P<0.01). Compared with the model group, the melatonin group and medium- and high-dose AMD groups showed increased spontaneous alternation rates (P<0.01), improved neuronal morphology, number, and spine density in the hippocampal CA1 and DG regions (P<0.01), declined levels of IL-6, IL-10, IL-1β, and TNF-α (P<0.05, P<0.01), downregulated protein levels of CX3CL1, CX3CR1, p-NF-κB p65, p-p38 MAPK, and Iba-1 and mRNA levels of CD86 and iNOS, and upregulated mRNA levels of CD206 and Arg1 (P<0.01). ConclusionAMD may improve the learning and memory in aged sleep-deprived mice by mediating neuroinflammation through the CX3CL1/CX3CR1 signaling pathway.
3.Role of circCCDC138 in early malignant transformation of human lung epithelial cells induced by carbon black nanoparticles
Runfeng LI ; Lichun MA ; Shulin QIN ; Wen LIU
Journal of Environmental and Occupational Medicine 2025;42(4):475-481
Background With the large-scale production and application of carbon black nanoparticles (CBNPs), occupational and general exposure is obviously increasing. Related studies have shown that exposure to CBNPs can induce oxidative stress, inflammation, and DNA damage. Objective To establish a CBNPs-induced malignant transformation (C-BEAS-2B) model of human lung epithelial cells (BEAS-2B) and explore the role and mechanism of circCCDC138 in the malignant transformation process. Methods At 0, 10, 20, 40 and 80 μg·mL−1 CBNPs concentrations, cell viability was detected by CCK8 assay. BEAS-2B cells were exposed to 20 mg·mL−1 CBNPs for three months, and a malignant transformation model of BEAS-2B induced by CBNPs was constructed. The migration and invasion abilities of the cells were detected by cell scratch and Transwell assays. The expressions of circ-CCDC138 in BEAS-2B and C-BEAS-2B were detected by qRT-PCR, and its stability was verified by a digestive resistance test. A cell model with interference or overexpression of circCCDC138 was constructed, and the expression of circCCDC138 in the cells was detected by quantitative reverse transcription-PCR. The cell cycle and apoptosis were determined by flow cytometry. Western blot was used to analyze the expression of p53 protein. Results The CBNPs used in the experiment were spherical particles with a chain-like structure. In the 20 μg·mL−1 CBNPs group, the reduction in the viability of BEAS-2B cells was relatively small (10%). Compared with the control cells, the 20 μg·mL−1 CBNPs group showed more obvious cell migration and invasion at 24 h and 48 h, indicating that the exposure to CBNPs induced early malignant transformation of BEAS-2B cells (P<0.01). The circCCDC138 expression in C-BEAS-2B was upregulated in a time-dependent manner after exposure to CBNPs. Compared with the C-BEAS-2B cells, the C-BEAS-2B cells over-expressing circCCDC138 exhibited arrested S phase progression (36.9%) and apoptosis resistance (P<0.01), along with down regulation of p53 protein expression in the cells (P<0.01), while the C-BEAS-2B cells interfering with circCCDC138 showed the opposite results (P<0.01). Conclusion BEAS-2B cells exposed to CBNPs (20 μg·mL−1) have significantly enhanced migration and invasion abilities, showing early malignant transformation characteristics. In addition, circCCDC138 is highly expressed in C-BEAS-2B cells with RNase R digestive resistance and increases in a time-dependent manner with CBNPs exposure. More importantly, circCCDC138 may promote the induction of malignant transformation of cells by inhibiting p53 protein expression.
4.The influence of fortified whey protein enteral nutrition preparations on the nutritional status and disease benefit perception of patients with advanced non-small cell lung cancer undergoing chemotherapy
Chunqin TIAN ; Lichun CUI ; Ling MA
Journal of Chinese Physician 2025;27(5):667-672
Objective:To evaluate the effects of fortified whey protein enteral nutrition preparations on the nutritional status and disease benefit perception of patients with advanced non-small cell lung cancer (NSCLC) during chemotherapy.Methods:A total of 96 patients with advanced non-small cell lung cancer admitted to the Chang′an Hospital from June 2020 to June 2023 were included and divided into two groups according to the random number table method. The control group ( n=48) received standard chemotherapy and conventional nutritional support, while the observation group ( n=48) was treated with whey protein and enteral nutrition preparations in addition to the control group. During the treatment period, the nutritional sign indicators of the patients [body mass index (BMI), triceps skinfold thickness (TSF), Patient-Generated Subjective Global Assessment (PG-SGA) score], serum indicators [albumin (ALB), prealbumin (PAB), hemoglobin (Hb)], and immune function (CD3 + , CD4 + , CD8 + , CD4 + /CD8 + ) patient quality of life scores [Karnofsky Performance Status (KPS), Zubrod Performance Status (ZPS), Quality of Life Score (QOL)], Specific Disease Benefit Scale (BFS) score and chemotherapy response were monitored. Results:After chemotherapy, the levels of ALB, PAB and Hb in the observation group were significantly higher than those in the control group (all P<0.05), BMI and TSF were significantly higher than those in the control group, PG-SGA score was significantly lower than that in the control group ( P<0.05), and CD3 + , CD4 + and CD4 + /CD8 + were significantly higher than those in the control group (all P<0.05). CD8 + was lower than that of the control group ( P<0.05); The KPS and QOL of patients in the observation group were significantly higher than those in the control group, and the ZPS was significantly lower than that in the control group. The differences were statistically significant (all P<0.05). The scores of acceptance, healthy behavior and personal growth dimensions of the BFS score in the observation group were significantly higher than those in the control group (all P<0.05). During the intervention period, the incidence of gastrointestinal reactions and thrombocytopenia in the observation group was significantly lower than that in the control group (all P<0.05). Conclusions:The fortified whey protein enteral nutrition preparations have a significant improvement effect on the nutritional status and disease benefit perception of patients with advanced NSCLC during chemotherapy, and may help improve the overall condition and chemotherapy tolerance of patients.
5.The influence of fortified whey protein enteral nutrition preparations on the nutritional status and disease benefit perception of patients with advanced non-small cell lung cancer undergoing chemotherapy
Chunqin TIAN ; Lichun CUI ; Ling MA
Journal of Chinese Physician 2025;27(5):667-672
Objective:To evaluate the effects of fortified whey protein enteral nutrition preparations on the nutritional status and disease benefit perception of patients with advanced non-small cell lung cancer (NSCLC) during chemotherapy.Methods:A total of 96 patients with advanced non-small cell lung cancer admitted to the Chang′an Hospital from June 2020 to June 2023 were included and divided into two groups according to the random number table method. The control group ( n=48) received standard chemotherapy and conventional nutritional support, while the observation group ( n=48) was treated with whey protein and enteral nutrition preparations in addition to the control group. During the treatment period, the nutritional sign indicators of the patients [body mass index (BMI), triceps skinfold thickness (TSF), Patient-Generated Subjective Global Assessment (PG-SGA) score], serum indicators [albumin (ALB), prealbumin (PAB), hemoglobin (Hb)], and immune function (CD3 + , CD4 + , CD8 + , CD4 + /CD8 + ) patient quality of life scores [Karnofsky Performance Status (KPS), Zubrod Performance Status (ZPS), Quality of Life Score (QOL)], Specific Disease Benefit Scale (BFS) score and chemotherapy response were monitored. Results:After chemotherapy, the levels of ALB, PAB and Hb in the observation group were significantly higher than those in the control group (all P<0.05), BMI and TSF were significantly higher than those in the control group, PG-SGA score was significantly lower than that in the control group ( P<0.05), and CD3 + , CD4 + and CD4 + /CD8 + were significantly higher than those in the control group (all P<0.05). CD8 + was lower than that of the control group ( P<0.05); The KPS and QOL of patients in the observation group were significantly higher than those in the control group, and the ZPS was significantly lower than that in the control group. The differences were statistically significant (all P<0.05). The scores of acceptance, healthy behavior and personal growth dimensions of the BFS score in the observation group were significantly higher than those in the control group (all P<0.05). During the intervention period, the incidence of gastrointestinal reactions and thrombocytopenia in the observation group was significantly lower than that in the control group (all P<0.05). Conclusions:The fortified whey protein enteral nutrition preparations have a significant improvement effect on the nutritional status and disease benefit perception of patients with advanced NSCLC during chemotherapy, and may help improve the overall condition and chemotherapy tolerance of patients.
6.Effect of laparoscopic radical resection based on membrane anatomy vs traditional laparoscopic procedure for the treatment of right colonic cancer
Huiyuan JIANG ; Qian ZHAO ; Sheng GAO ; Lichun WANG ; Jian MA ; Shuai JIAO ; Bo JIANG
Chinese Journal of General Surgery 2024;39(8):577-583
Objective:To compare the clinical efficacy of laparoscopic right colon cancer radical resection(CME+D3,60 cases) based on membrane anatomy and traditional laparoscopic right colon cancer radical resection(CME/D3, 120 cases).Methods:A retrospective cohort study was used to collect the consecutively admitted cases undergoing laparoscopic radical right colon cancer resection at the Department of Colorectal Surgery, Shanxi Hospital from Jan 2018 to Jun 2020.The postoperative data , postoperative complications, follow-up outcomes were compared between the two groups.Results:Compared with the CME/D3 group, that the based on membrane anatomy(CME+D3) group had a decreased intraoperative blood loss [(79.3±16.7) ml vs. (103.6±20.8) ml, t=-3.894, P<0.001],and more lymph node harvest [(27.0±5.1) vs. (25.1±6.2), t=2.138, P=0.034]; The sectional grading of surgical specimens was also better than that in the traditional operation group(χ 2=4.146, P=0.042); while the operation time was slightly longer than that of the traditional operation group [(161.1±18.4) minutes vs.(142.6±19.5) minutes, t=-6.166, P<0.001]. There was no significant difference in the length of specimen resection, postoperative exhaust time, hospital stay, incidence of postoperative complications, proportion of unplanned reoperation within 30 days, re-admission within 30 days, and mortality within 30 days ( all P>0.05). The median follow-up time was 36.7 (5.3-48.7) months, and there was no significant difference in overall survival rates between the two groups ( P>0.05); The difference in disease-free survival rates between the two groups is significant(χ 2=4.246, P=0.039). Conclusions:Compared with the traditional laparoscopic right colon cancer radical surgery (CME/D3),laparoscopic radical resection of right colon cancer (CME+D3) based on membrane anatomy reduces intraoperative bleeding, improves the number of lymph node dissection and specimen quality, and has higher 1-year and 3-year disease-free survival rate .
7.Study on metabolites derived from Zhideke granules in rats in vivo
Jie LIANG ; Piaoxue ZHENG ; Huihua CHEN ; Chunyan HUANG ; Yanli LIANG ; Chunlian LU ; Jingjing XIE ; Yuming MA ; Jiawen PENG ; Lichun ZHAO ; Rilan CHEN
China Pharmacy 2024;35(2):172-178
OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group (Zhideke granules, 9.45 g/kg); they were given ultrapure water or relevant medicine, twice a day, every 6-8 h, for 3 consecutive days. Serum, urine and feces samples of rats were collected, and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules; their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules, 16 prototype components (i.g. irisflorentin, baicalin, chlorogenic acid) and 11 metabolites (i.g. hydration products of kaempferol or luteolin, methylation products of chlorogenic acid, and hydroxylation products of baicalin) were identified in serum, urine and feces of rats. Among them, 8 prototype components and 4 metabolites were identified in serum samples; 10 prototype components and 7 metabolites were identified in urine samples; 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin, irisflorentin,chlorogenic acid, and the main metabolic pathways included methylation, hydroxylation, glucuronidation.
8.Comprehensive evaluation of the quality of Amomum tsao -ko based on entropy weight TOPSIS method
Jiaxu HAO ; Yuanzeng LI ; Xiao FAN ; Lichun ZHA ; Yunshu MA
China Pharmacy 2022;33(17):2087-2092
OBJECTIVE To evaluate the quality of Amomum tsao -ko from different origins and harvesting periods comprehensively. METHODS The contents of total volatile oil in A. tsao -ko were determined by volatile oil measurement method A stated in 2020 edition of Chinese Pharmacopoeia (part Ⅳ);the contents of total flavonoids and total polyphenols in A. tsao -ko were determined by aluminum nitrate-sodium nitrite colorimetry and folin-ciocalteu method. The contents of α-pinene,β-pinene, 1,8-cineole,α-terpineol,geraniol and trans-nerolidol in the volatile oil of A. tsao -ko were determined by gas chromatography ;the contents of protocatechuate and vanillic acid in A. tsao -ko were determined by ulta high performance liquid chromatography. The above 11 indicators were selected ,and entropy weight TOPSIS method was used to comprehensively evaluate the quality of 16 batches of A. tsao -ko. RESULTS The contents of total volatile oil ,total flavonoids ,total polyphenols ,α-pinene,β-pinene, 1,8-cineole,α-terpineol,geraniol,trans-nerolidol,protocatechuate and vanillic acid in 16 batches of A. tsao -ko were 15.833 3- 28.000 0 μL/g,29.100 5-78.199 6 mg/g,6.789 8-35.797 7 mg/g,0.088 7-0.401 3 mg/g,0.106 3-0.408 0 mg/g,3.709 6-8.533 1 mg/g,0.259 8-0.599 6 mg/g,0.314 8-1.324 1 mg/g,0.272 3-0.576 4 mg/g,9.301 2-19.818 5 μg/g,8.180 9-27.666 3 μg/g, respectively. Entropy weight TOPSIS results showed that the top three of relative closeness rankings were A. tsao -ko produced by Yunnan Baoshan in July ,Yunnan Honghe in October ,Yunnan Wenshan in September ;the last three of relative closeness rankings were A. tsao -ko produced by Yunnan Dehong in September ,Yunnan Dehong in November ,Yunnan Dehong in December. CONCLUSIONS A. tsao -ko produced by Yunnan Baoshan in July ,Yunnan Honghe in October and Yunnan Wenshan in September present better quality.
9.Application of 68Ga-PSMA PET/CT in the precision treatment of prostate cancer
Peng WU ; Jianhua JIAO ; Chunjuan TIAN ; Shuaijun MA ; Lichun WEI ; Jing ZHANG ; Jing REN ; Daliang LIU ; Fuli WANG ; Weijun QIN
Chinese Journal of Urology 2021;42(Z1):63-66
We retrospectively analyzed the clinical characteristic of one patient with metastatic prostate cancer and the relative literatures were reviewed. A 40-year-old man was admitted and diagnosed as prostate cancer on March 20, 2018(T 4N 1M 1a) with prostate-specific antigen (PSA) at 47.99 ng/ml. The first 68Ga-PSMA PET/CT showed multiple nodular lesions in the bilateral peripheral bands of the prostate, multiple nodular lesions in the right apex, abnormal uptake of nuclides in multiple lymph nodes in the abdominal aortic wandering zone, the abdominal aortic bifurcation zone, and the bilateral iliac artery wandering zone at the level of the lumbar 2-5 vertebral body, and metastasis was considered. The patient was treated with six cycles of drug castration combined with antiandrogenic treatment and pre-operative system chemotherapy(docetaxel). Six months later, the PSA decreased to 0.225ng/ml. Robot-assisted laparoscopic prostatectomy and expanded pelvic lymph node dissection was performed. Postoperative total androgen blocking therapy was maintained, and PSA slowly increased. Ten months after operation, salvage radiotherapy for enlarged lymph nodes was performed in pelvic extension field, prostate tumor bed area and pelvic cavity. PSA remained stable for 7 months postradiotherapy, and then increased. The patient developed castration-resistant prostate cancer and was treated with triptorelin combined with abiraterone. PSA was decreased, and local radiotherapy was performed for new lymph node metastases in the neck. 68Ga-PSMA PET/CT could provide a decision-making basis for accurate clinical staging, therapeutic effect evaluation and distant metastatic lesions location with guiding value for the formulation of individualized treatment plans.
10.Analysis of visceral metastasis hormone sensitive prostate cancer: a case report and literature review
Peng WU ; Weijun QIN ; Yu LI ; Shuaijun MA ; Lichun WEI ; Jing ZHANG ; Jing REN ; Daliang LIU ; Fuli WANG ; Chunjuan TIAN
Chinese Journal of Urology 2021;42(Z1):67-71
Hormone-sensitive prostate cancer with visceral metastasis is a difficulty in clinical diagnosis and treatment. We treated a patient with hormone-sensitive prostate cancer with visceral metastasis and managed it under the multi-disciplinary treatment model (MDT). A 55-year-old man presented to the hospital complaining of increased prostate-specific antigen (PSA) found in the physical examination for 2 days. At admission, the PSA was 389.2ng/ml, and 68Ga-PSMA PET/CT showed metastatic malignant lesions of the prostate, with lymph node metastasis, lumbar vertebral metastases and liver tubercles. Transrectal prostate puncture biopsy: prostate adenocarcinoma, Gleason score of 4+ 5=9. The patient has no history of androgen deprivation therapy (ADT) and diagnosed as metastatic hormone-sensitive prostate cancer (mHSPC). Then the patient received total androgen blockade therapy (CAB regimen). After MDT discussion, metastatic prostate cancer was diagnosed based on the liver histopathology of percutaneous biopsy. After the second MDT discussion, the regimen was changed to abirone plus ADT. After 6 months, the blood PSA was controlled at a level between 0.003 to 0.006 ng/ml, and the testosterone was less than 2.5ng/dl. Re-examination of 68Ga-PSMA PET/CT showed that lower signal of radionuclide in all lesions, especially no more abnormal uptake lesions were identified in the liver.

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