1.Effect of Anmeidan on Cognitive Function and Metabolic Profiling in Insomnia Model Rats Based on Untargeted Metabolomics
Feizhou LI ; Bo XU ; Zijing YE ; Lianyu LI ; Andong ZHANG ; Ping WANG ; Linlin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):54-64
ObjectiveTo elucidate the potential mechanisms by which the classic prescription Anmeidan alleviates cognitive impairment in insomnia model rats through metabolic profiling. MethodsA total of 60 SD rats were randomly divided into six groups: blank group, model group, low-, medium-, and high-dose Anmeidan groups, and the Suvorexant group, with 10 rats in each group. Except for the blank group, the insomnia model was established in all other groups via intraperitoneal injection of para-chlorophenylalanine. The Suvorexant group was administered Suvorexant solution (30 mg·kg-1·d-1) by gavage, while the low-, medium-, and high-dose Anmeidan groups received Anmeidan decoction (4.55, 9.09, 18.18 g·kg-1·d-1) by gavage. The blank group received an equivalent volume of normal saline. The open field test was used to assess spatial exploration and anxiety/depressive-like behaviors in rats. Serum levels of epidermal growth factor (EGF), brain-derived neurotrophic factor (BDNF), and vasoactive intestinal peptide (VIP) were measured using enzyme-linked immunosorbent assay (ELISA). Untargeted metabolomics was employed to identify differential metabolites in rat serum, and systematic biological methods were applied to analyze the potential targets and pathways of Anmeidan. ResultsCompared to the blank group, the model group exhibited significant reductions in total distance traveled, average speed, number of entries into the central area, time spent in the central area, and frequency of upright events (P<0.01), along with significant decreases in VIP, EGF, and BDNF levels (P<0.05,P<0.01). A total of 100 differential metabolites were identified between the model and blank groups. Compared to the model group, the low-, medium-, and high-dose Anmeidan groups showed significant increases in total distance traveled, average speed, number of entries into the central area, time spent in the central area, and frequency of upright events (P<0.05,P<0.01), as well as a significant increase in VIP levels (P<0.05,P<0.01). Anmeidan significantly reversed abnormal changes in 67 metabolites compared to the model group. A combined analysis identified 134 potential targets of Anmeidan, with network topology analysis suggesting that Caspase-3, B-cell lymphoma 2 (Bcl-2), nuclear transcription factor-κB (NF-κB), interleukin-1β (IL-1β), interleukin-2 (IL-2), matrix metalloproteinase-9 (MMP-9), and Toll-like receptor 4 (TLR4), among others, may serve as key targets of Anmeidan. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed major enriched pathways, including the cyclic adenosine monophosphate (cAMP) signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, and IL-17 signaling pathway. ConclusionThis study demonstrates that Anmeidan can recalibrate abnormal metabolic profiles in insomnia model rats to mitigate cognitive impairment, with its mechanisms of action potentially involving the regulation of immune-inflammatory responses, energy metabolism, and apoptosis-related pathways.
2.Effect of knockdown IGSF10 on proliferation,migration and invasion capacity of lung adenocarcinoma cells
Lianyu Cheng ; Beibei Ma ; Yu Huang ; Yanli Li ; Zhongwei Zhang ; Guangbin Ye ; Bo Ling
Acta Universitatis Medicinalis Anhui 2024;59(1):45-51
Objective :
To investigate the effects of immunoglobulin gene superfamily 10 (IGSF10) on prolifera- tion,migration and invasion of lung adenocarcinoma cells.
Methods :
ioinformatics was applied to study the ex- pression levels of IGSF10 in tumor tissues and normal tissues. Western blot and quantitative real-time PCR ( qPCR) were used to detect the expression level of IGSF10 in lung adenocarcinoma cell lines and normal lung epi- thelial cells.Knockdown of IGSF10,the effect of knockdown of IGSF10 on proliferation,migration and invasion of lung adenocarcinoma A549 cells was examined using cell counting kit-8 ( CCK-8) ,Transwell migration and inva- sion assay,scratch assay and plate cloning assay.The effects of knockdown of IGSF10 on the expression of invasion and migration-related genes in A549 cells were examined by Western blot and qPCR assays.
Results :
IGSF10 ex- pression in lung adenocarcinoma tissues was lower than that in normal tissues (P <0. 05) .IGSF10 expression in lung adenocarcinoma cell lines was lower than that in lung epithelial cells (P<0. 05) .Knockdown of IGSF10 pro- moted the ability of lung adenocarcinoma A549 cells to proliferate ,proliferation ,migration and invasion ( P < 0. 05) .Knockdown of IGSF10 promoted the expression of regulatory epithelial-mesenchymal transition marker Neu- ral-cadherin (N-cadherin) and key transcription factors Snail family transcriptional repressor 1 (Snail) and Snail family transcriptional repressor 2 (Slug) (P<0. 05) and inhibited the expression of Epithelial-cadherin (E-cad- herin) (P<0. 05) .
Conclusion
Knockdown of IGSF10 may promote proliferation,migration and invasion of lung adenocarcinoma cells through activation of Snail,Slug / E-cadherin signaling axis,and this result may provide a po- tential new target for clinical diagnosis and treatment of lung adenocarcinoma.
3.Effect of goal-directed fluid therapy on postoperative acute kidney injury in elderly patients undergoing long-time abdominal surgery
Yaoyao QIN ; Lan ZHENG ; Dingxin ZHANG ; Penghui ZHANG ; Lianyu LI ; Jiaqi ZHANG ; Weiwei ZHANG
Chinese Journal of Anesthesiology 2024;44(2):155-159
Objective:To evaluate the effect of goal-directed fluid therapy (GDFT) on postoperative acute kidney injury (AKI) in elderly patients undergoing long-time abdominal surgery.Methods:The medical records from elderly patients of both sexes, aged ≥ 65 yr, with a duration of operation ≥ 8 h and American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective first abdominal surgery for gastrointestinal tumors at the Shanxi Provincial People′s Hospital from October 1, 2016 to June 30, 2022, were collected from the electronic medical record database. Patients were divided into conventional fluid therapy group (group C) and GDFT group (group G) according to whether GDFT was employed during operation. In group C, blood pressure was maintained ≥90/60 mmHg or mean arterial pressure≥65 mmHg, and urine output more than 30 ml/h. In group G, the stroke volume variation was maintained ≤13%, and cardiac index ≥2.5 L·min -1·m -2. The patient general characteristics, requirement for fluid, urine output, blood loss, requirement for vasoactive agents and abdominal hyperthermic perfusion, and operation time were recorded during operation. The development of AKI within 72 h after operation and development of other complications (pneumonia, anastomotic leakage, surgical site infection, septic shock, arrhythmia) after operation were recorded. The length of hospital stay and 30-day mortality after operation were recorded. Results:A total of 125 patients were included in this study, with 41 patients in group C and 84 patients in group G. Postoperative AKI occurred in 19 patients, with an incidence of 15.2%. Compared with group C, the requirement for colloid, total volume of fluid infused and urine volume were significantly decreased during operation, the requirement for vasoactive agents was increased during operation ( P<0.05), the risk of postoperative AKI was reduced ( OR=0.23, P<0.05), and no significant change was found in the incidence of other postoperative complications, 30-day mortality, and length of hospital stay in group G ( P>0.05). Conclusions:GDFT can reduce the risk of AKI in the elderly patients undergoing long-time abdominal surgery.
4.Relationship between serum procalcitonin level and severity and prognosis in patients with traumatic brain injury in plateau areas
Lianyu ZHANG ; Fabin ZHANG ; Huanying BAI ; Huibin YUN ; Zhao ZHENG ; Shuncai LIU ; Shenghua A ; Zhongshan SHI ; Yuhai HU
Chinese Critical Care Medicine 2024;36(1):56-61
Objective:To analyze the changes rule of serum procalcitonin (PCT) levels in patients with traumatic brain injury in plateau areas, and to evaluate its value in assessing the severity and prognosis of the patients.Methods:A prospective cohort study was conducted. The patients with traumatic brain injury admitted to the critical care medicine departments of Xining Third People's Hospital (at an altitude of 2 260 metres) and Golmud City People's Hospital (at an altitude of 2 780 metres) from May 2018 to September 2022 were enrolled. According to the Glasgow coma scale (GCS) score at admission, the patients were divided into mild injury group (GCS score 13-15), severe injury group (GCS score 9-12), and critical injury group (GCS score 3-8). All patients received active treatment. Chemiluminescence immunoassay was used to measure the serum PCT levels of patients on the 1st, 3rd, 5th, and 7th day of admission. The Kendall tau-b correlation method was used to analyze the correlation between serum PCT levels at different time points and the severity of the disease. The patients were followed up until October 30, 2022. The prognosis of the patients was collected. The baseline data of patients with different prognosis were compared. The Cox regression method was used to analyze the relationship between baseline data, serum PCT levels at different time points and prognosis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of serum PCT levels at different time points for death during follow-up.Results:Finally, a total of 120 patients with traumatic brain injury were enrolled, including 52 cases in the mild injury group, 40 cases in the severe injury group, and 28 cases in the critical injury group. The serum PCT levels of patients in the mild injury group showed a continuous downward trend with the prolongation of admission time. The serum PCT levels in the severe injury and critical injury groups reached their peak at 3 days after admission, and were significantly higher than those in the mild injury group (μg/L: 3.53±0.68, 4.47±0.63 vs. 0.40±0.14, both P < 0.05), gradually decreasing thereafter, but still significantly higher than the mild injured group at 7 days. Kendall tau-b correlation analysis showed that there was a significant positive correlation between serum PCT levels on days 1, 3, 5, and 7 of admission and the severity of disease ( r value was 0.801, 0.808, 0.766, 0.528, respectively, all P < 0.01). As of October 30, 2022, 92 out of 120 patients with traumatic brain injury survived and 28 died, with a mortality of 23.33%. Compared with the survival group, the GCS score, serum interleukin-6 (IL-6) levels, white blood cell count (WBC) in peripheral blood, and PCT levels in cerebrospinal fluid at admission in the death group were significantly increased [GCS score: 5.20±0.82 vs. 4.35±0.93, IL-6 (ng/L): 1.63±0.45 vs. 0.95±0.27, blood WBC (×10 9/L): 14.31±2.03 vs. 11.95±1.98, PCT in cerebrospinal fluid (μg/L): 11.30±1.21 vs. 3.02±0.68, all P < 0.01]. The serum PCT levels of patients in the survival group showed a continuous downward trend with prolonged admission time. The serum PCT level in the death group peaked at 3 days after admission and was significantly higher than that in the survival group (μg/L: 4.11±0.62 vs. 0.52±0.13, P < 0.01), gradually decreasing thereafter, but still significantly higher than the survival group at 7 days. Cox regression analysis showed that serum IL-6 levels [hazard ratio ( HR) = 17.347, 95% confidence interval (95% CI) was 5.874-51.232], WBC in peripheral blood ( HR = 1.383, 95% CI was 1.125-1.700), PCT levels in cerebrospinal fluid ( HR = 1.952, 95% CI was 1.535-2.482) at admission and serum PCT levels on admission days 1, 3, 5, and 7 [ HR (95% CI) was 6.776 (1.844-24.906), 1.840 (1.069-3.165), 3.447 (1.284-9.254), and 6.666 (1.214-36.618), respectively] were independent risk factors for death during follow-up in patients with traumatic brain injury (all P < 0.05). ROC curve analysis showed that the AUC of serum PCT levels on days 1, 3, 5, and 7 for predicting death during follow-up in patients with traumatic brain injury was all > 0.8 [AUC (95% CI) was 0.898 (0.821-0.975), 0.800 (0.701-0.899), 0.899 (0.828-0.970), 0.865 (0.773-0.958), respectively], indicating ideal predictive value. The optimal cut-off value for serum PCT level at 3 days of admission was 1.88 μg/L, with the sensitivity of 78.6% and specificity of 88.0% for predicting death during follow-up. Conclusions:Abnormal expression of serum PCT levels in patients with traumatic brain injury on the 3rd day of admission was found. The serum PCT levels greater than 3 μg/L may be related to severe illness. The serum PCT levels greater than 1.88 μg/L can predict the poor prognosis of patients. Dynamic observation of changes in serum PCT levels has good evaluation value for the severity and prognosis of patients with traumatic brain injury in plateau areas.
5.Visualization Analysis on Research Literature about TCM for the Treatment of Attention Deficit Hyperactivity Disorder
Kangjian LI ; Jinghua YANG ; Xinqiang NI ; Lianyu WANG ; Xiyan DENG ; Wenting ZHONG ; Qi ZHOU ; Zhang WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):67-74
Objective To analyze the research status,hotspots and trends of TCM in the treatment of attention deficit hyperactivity disorder(ADHD).Methods The literature on the treatment of ADHD by TCM were was retrieved from CNKI,VIP,Wanfang Data,and CBM from the establishment of the databases to 7th,Sep.2023.NoteExpress 3.9 was used to manage and remove weight;Excel 2019 was used to draw a line trend chart for the number of published literature.CiteSpace 6.1R.6 software was used to perform co-occurrence and clustering analysis on authors,institutions and keywords,and a visual graph was drawn.Results A total of 1215 articles were included after screening.800 authors were involved,forming research teams with Han Xinmin,Wang Junhong,Ma Rong and Li Yirui as the cores respectively;Nanjing University of Chinese Medicine,Guangzhou University of Chinese Medicine,Beijing University of Chinese Medicine and so on published more papers.High-frequency keywords included clinical efficacy,acupuncture and moxibustion treatment,clinical experience,Chinese materia medica and so on;research frontiers included clinical efficacy,acupuncture and moxibustion treatment,clinical experience,data mining and attention.Conclusion The main research on the treatment of ADHD by TCM includes clinical efficacy,clinical experience,animal experiments and data mining,and relatively stable research teams have been formed,but there is less cooperation between teams and institutions.
6. Expressions and prognostic significance of PTEN and PD-1 protein in patients with classical Hodgkin’s lymphoma
Bing XIA ; Dongwei WU ; Tengteng WANG ; Shanqi GUO ; Yi WANG ; Hongliang YANG ; Wen XU ; Chen TIAN ; Lianyu ZHANG ; Baochun SUN ; Yizhuo ZHANG
Chinese Journal of Hematology 2018;39(10):839-844
Objective:
To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin’s lymphoma (CHL) to further determine their clinical role and prognostic significance.
Methods:
The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed.
Results:
This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL.
Conclusions
This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.
7. Role of Magnetic Resonance Imaging in distinguishing the origin of adenocarcinoma at the junction of the lower uterine segment and endocervix
Jie ZHANG ; Yichen WANG ; Xiaoduo YU ; Yuan TIAN ; Xiaolu LI ; Lianyu ZHANG ; Jin ZHANG ; Xinming ZHAO ; Yan CHEN
Chinese Journal of Oncology 2018;40(12):912-916
Objective:
To evaluate Magnetic Resonance Imaging (MRI) at 3.0T in differential diagnosis of the origin of adenocarcinoma at the junction of the lower uterine segment and endocervix.
Methods:
71 patients with adenocarcinoma at the junction of the lower uterine segment and endocervix were retrospectively collected. Pelvic MR examinations, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences, were performed within 2 weeks before surgery. MR images were analyzed and measured by two radiologists, including the location of the tumor center, the enhancement pattern, the anterior and posterior diameters, the left and right diameters, the upper and lower diameters, and the apparent diffusion coefficient (ADC) of the tumor. Immunohistochemical method was used as gold standard in distinguishing cervical adenocarcinoma and uterine adenocarcinoma.
Results:
The upper and lower diameters of uterine adenocarcinoma were [(5.80±2.31) cm], significantly larger than those of cervical adenocarcinoma [(4.16±2.17) cm,
8.Mechanism of thymoquinone mediates NSCLC cytotoxicity by phosphorylation of p38MAPK pathway
Zisheng CHEN ; Xiaowen LIAO ; Yifei ZHANG ; Jinghua XIAO ; Yun CHEN ; Qingxia LIU ; Peng WANG ; Pengbiao CHE ; Lianyu ZHU ; Dongbo TIAN
Journal of Clinical Medicine in Practice 2018;22(11):6-9,14
Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P > 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.
9.Mechanism of thymoquinone mediates NSCLC cytotoxicity by phosphorylation of p38MAPK pathway
Zisheng CHEN ; Xiaowen LIAO ; Yifei ZHANG ; Jinghua XIAO ; Yun CHEN ; Qingxia LIU ; Peng WANG ; Pengbiao CHE ; Lianyu ZHU ; Dongbo TIAN
Journal of Clinical Medicine in Practice 2018;22(11):6-9,14
Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P > 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.
10.A correlated study between-L-alpha glucosidase and intrauterine growth and glucose and lipid metabolism in fetus below the gestational age
Wenbin DONG ; Xiaopin LEI ; Lingpin ZHANG ; Lianyu ZHANG ; Na HE
The Journal of Practical Medicine 2017;33(10):1605-1607
Objective To investigate the change of serum alpha-L-fucosidase(AFU)and its correlation with the blood glucose and lipid level in small for gestational age(SGA)fetuses. Methods 125 SGA fetuses and 128 fetuses in appropriate for gestational age(AGA)with wet lung were treated in our hospital and were investigated as case control study. The serum of AFU ,blood glucose and lipid were measured and compared within 24 hours after birth in these 2 groups. Results Comparing with the AGA infants ,the SGA babies had lower level of serum AFU,high density lipoprotein,apolipoprotein A and apolipoprotein B(P<0.05). The correlation analysis showed that the serum AFU level has positive correlation with blood glucose,total cholesterol,high density lipoprotein, low density lipoproteinand apolipoprotein A(P < 0.05),while it has negative correlation with serum triglycerides in SGA(P<0.05). Conclusions The SGA infants have lower level of serum AFU and lipid metabolic disorders after birth,and its serum AFU level has correlation with its blood glucose and lipid level.


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