1.Exploring Mechanism of Hei Xiaoyaosan Regulating PI3K/Akt Pathway to Improve Learning and Memory Ability of Insomnia Rats with Liver Depression Syndrome Based on Transcriptomics
Jiamin LIU ; Yale WANG ; Hai HUANG ; Yue LI ; Xin FAN ; Pengpeng LIANG ; Shizhao ZHANG ; Mei YAN ; Guiyun LI ; Hongyan WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):114-125
ObjectiveBased on transcriptomics, to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group, model group, eszopiclone group (0.09 mg·kg-1), and low, medium, and high dose groups of Hei Xiaoyaosan (3.82, 7.65, 15.30 g·kg-1), with ten rats in each group. Except for the blank group, the other groups were induced insomnia rat model with liver depression by chronic restraint, tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine (PCPA). Each treatment group received intragastric administration according to the specified dosage, once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test, open field test, and Morris water maze test were used to test the sleep quality, depressive-like behavior, and learning and memory abilities of rats. Additionally, enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nitric oxide (NO) in hippocampus. Hematoxylin-eosin (HE) staining was performed to observe pathological changes of the hippocampal tissue, while terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group, as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the intersecting genes. Subsequently, the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was utilized to assess the mRNA expression levels of phosphatase and tensin homolog (PTEN), B-cell lymphoma-2 (Bcl-2)-like protein 11 (BCL2L11), and mitogen-activated protein kinase 1 (MAPK1) in hippocampus, and Western blot was employed to evaluate the protein expressions of PI3K, phosphorylation (p)-PI3K, Akt, p-Akt, Bcl-2, Bcl-2-associated X protein (Bax), and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group, the model group exhibited a reduction in body weight, an increase in sleep latency, and a decrease in sleep duration (P<0.01). Additionally, rats showed obvious depression-like behavior, and their learning and memory abilities decreased. Furthermore, the contents of 5-HT, GABA, NO, BDNF and GDNF in hippocampus decreased (P<0.01). Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus, characterized by irregular cell shapes, a reduced cell count, deeply stained and pyknotic nuclei, increased vacuolar degeneration, and an elevated apoptosis rate (P<0.01). Compared with the model group, the body weight of the high and medium dose groups of Hei Xiaoyaosan increased, the sleep latency shortened and the sleep time prolonged (P<0.05, P<0.01). Additionally, depression-like behavior and learning and memory abilities of rats were significantly improved, the levels of 5-HT, GABA, NO, BDNF and GDNF in the hippocampus increased (P<0.05, P<0.01). These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons (P<0.01). Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN, BCL2L11, and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group, the expression levels of PTEN, BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased (P<0.01), while the protein expression levels of p-PI3K, p-Akt and Bcl-2 were decreased (P<0.01), and the protein expression levels of PTEN, Bax and cleaved Caspase-3 were increased (P<0.01). Compared with the model group, the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN, BCL2L11 and MAPK1 mRNAs (P<0.01), up-regulate the expressions of p-PI3K, p-Akt and Bcl-2 proteins (P<0.01), and down-regulate the protein expressions of PTEN, Bax and cleaved Caspase-3 (P<0.05, P<0.01). ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN, BCL2L11 and MAPK1, and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.
2.circFOXK2 Regulates Proliferation,Migration and Invasion of Lung Cancer Cells by Targeting miR-409-3p
Fang ZHOU ; Meng WANG ; Shizhao CHENG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2024;53(1):13-18
Objective To investigate the effect of circFOXK2 on the proliferation,migration and invasion of lung cancer cells and its possible mechanism.Methods The cancer tissues and adjacent tissues of 45 patients with lung cancer were collect-ed,and the expression of circFOXK2 and miR-409-3p in the tissues were detected by qRT-PCR.Lung cancer cell A549 and H1299 was cultured in vitro,and the dual-luciferase reporter assay was used to verify the regulatory relationship between circ-FOXK2 and miR-409-3p.The CCK-8,clone formation and Transwell assays were used to detect cell proliferation,migration and invasion.Western blot was used to detect the protein expression of E-cadherin and N-cadherin in cells.Results The expression of circFOXK2 was significantly higher(P<0.05),but the expression of miR-409-3p was significantly lower(P<0.05)in lung cancer tissues.circFOXK2 could target miR-409-3p and negatively regulate its expression in lung cancer cells.The proliferation,migration and invasion were reduced in circFOXK2(all P<0.05),N-cadherin level was decreased(P<0.05),but E-cadherin level was increased(P<0.05)in circFOXK2 knockdown or miR-409-3p overexpressed A549 and H1299 cells.The inhibitory effects of circFOXK2 knockdown on the proliferation,migration and invasion of lung cancer cells could be reversed by miR-409-3p inhibitor.Conclusion The circFOXK2 was upregulated in lung cancer,which promoted the proliferation,migration and inva-sion of lung cancer cells by targeting miR-409-3p.
3.Evaluation index system of health literacy for seaman
Fang YU ; Wei FU ; Lin XU ; Shizhao MA ; Nana WANG
Journal of Navy Medicine 2024;45(6):577-581
Objective To establish the evaluation index system of seaman health literacy.Methods Two rounds of questionnaire consultation was conducted by Delphi method among 17 experts,and the indexes were modified according to expert opinions,so as to establish seaman health literacy.Results The response rates of the 2 rounds of questionnaires were 94.4%and 100%,the expert authority coefficients were 0.821 and 0.844,and the Kendall's coefficient of concordance were 0.398 and 0.411,respectively.After the 2 rounds of consultation,the importance score of indexes at all levels was 4.00-4.94,and the coefficient of variation was 0.05-0.21.Finally,the evaluation system of seaman health literacy was constructed,including 4 first-level indicators,20 second-level indicators and 27 items.Conclusion The evaluation system of seaman health literacy constructed in this study is reliable,scientific and practical.It can provide a basis for the decision-making to regulate seaman health literacy.
4.Current status of health literacy and its influencing factors in seamen
Wei FU ; Fang YU ; Shizhao MA ; Lin XU ; Nana WANG
Journal of Navy Medicine 2024;45(6):582-585
Objective To investigate the current status and influencing factors of health literacy in seamen.Methods The random cluster sampling method was adopted to select 302 naval officers and soldiers,and a questionnaire survey was conducted to investigate their health literacy.Results The proportion of respondents with health literacy was 55.1%.The level of health literacy ranked from high to low as follows:basic health concept(72.1%),basic health behaviors(54.0%),basic health knowledge(41.3%),and basic health skills(33.4%).Multivariate logistic regression analysis showed that education background,the length of time to board,smoking and sleep late were influencing factors for health literacy in seamen(P<0.05).Conclusion The overall health literacy level is unbalanced in seamen,especially in health knowledge and health skills,which need to be strengthened.It is essential to carry out targeted health education,correct unhealthy lifestyles and constantly improve the level of health literacy of seamen.
5.Understanding and prevention of D-dimer elevation in coronavirus disease 2019 in traditional Chinese medicine
Qianfei WANG ; Chenxi WANG ; Jianqiang MEI ; Lili HE ; Jia LI ; Shizhao LIU ; Fenqiao CHEN
Chinese Critical Care Medicine 2020;32(5):622-624
2019 Novel coronavirus (2019-nCoV) infection caused a pandemic in the world. From the reported cases in the literatures, the level of D-dimer in patients with coronavirus disease 2019 (COVID-19) is positively correlated with the severity of illness, which needs the attention of clinical workers. According to Western medicine, the increase of D-dimer is related to the hyperactivity of fibrinolytic system and the shortening of prothrombin time (PT), resulting in excessive production and degradation of plasma fibrin and hypercoagulable state of blood, while traditional Chinese medicine (TCM) believes that the above syndromes belong to the pathogenesis of "blood stasis" according to TCM theories. Over the years, TCM has a significant effect on promoting blood circulation, removing blood stasis and improving microcirculation. This article reviews the mechanism, clinical significance, understanding of TCM and common methods of promoting blood circulation and removing blood stasis caused by 2019-nCoV, in order to provide ideas for the prevention and treatment of impaired blood coagulation in patients with COVID-19.
6.Dosimetric comparison between CT-guided free-hand intracavity/interstitial adaptive brachytherapy and conventional point-A brachytherapy in the treatment of cervical cancer
Yanhong WANG ; Weijun YE ; Shizhao ZHAN ; Yi OUYANG ; Xinping CAO
Chinese Journal of Radiation Oncology 2020;29(10):882-887
Objective:To analyze the dosimetric differences between CT-guided free-hand intracavity/interstitial brachytherapy[image-guided adaptive brachytherapy (IGABT)] and conventional point-A plan (CP) in the treatment of cervical cancer.Methods:Twenty-six cervical cancer patients who received four cycles of IGABT in Sun Yat-sen University Cancer Center were enrolled in this study. Two sets of CT images were obtained before and after applicator adjustment to aid in the design of CP and IGABT plans. The high-risk clinical target volume (HRCTV), point A, and organs at risk (bladder, rectum, and sigmoid colon) were defined on CT images. CP and IGABT plans were designed on CT images. Parameter differences between CP and IGABT plans were analyzed with paired t-test and Wilcoxon test. Results:According to the coverage index (CI) of CP, plans were divided into two groups: in group A (CI≥0.90), 20 CP and corresponding IGABT plans were included, and 84 CP and corresponding IGABT plans in group B (CI<0.90). The mean volume of HRCTV and mean tumor diameter in group A were significantly smaller than those in group B (46.7 cm 3vs. 62.1 cm 3, P<0.001 and 3.1 cm vs. 4.4 cm, P<0.001). Compared with CP, IGABT significantly improved the value of D 90% in all plans and group B, whereas lowered the bladder dose. IGABT also reduced the dose of sigmoid colon in group A. IGABT significantly improved conformal index and dose homogeneity index. Conclusions:IGABT can significantly improve the target coverage, conformal index and dose homogeneity index, protect organs at risk. Compared with CP, IGABT has advantages in the treatment of patients with bulky tumor.
7.Systemic Therapy for Low-grade Pulmonary Neuroendocrine Tumor.
Zheng WANG ; Shizhao CHENG ; Fang ZHOU ; Xingpeng HAN ; Xike LU ; Daqiang SUN ; Xun ZHANG
Chinese Journal of Lung Cancer 2019;22(1):34-39
The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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Disease-Free Survival
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Drug Therapy
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methods
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Humans
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Lung
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drug effects
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radiation effects
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surgery
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Lung Neoplasms
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pathology
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surgery
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therapy
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Neoplasm Grading
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Neuroendocrine Tumors
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pathology
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surgery
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therapy
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Outcome Assessment (Health Care)
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Radiotherapy
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methods
8. Antiseptic effect of compound lysostaphin disinfectant and its preventive effect on infection of artificial dermis after graft on full-thickness skin defect wound in rats
Jian JIN ; Hao ZHOU ; Zhenci CUI ; Li WANG ; Pengfei LUO ; Shizhao JI ; Xiaoyan HU ; Bing MA ; Guangyi WANG ; Shihui ZHU ; Zhaofan XIA
Chinese Journal of Burns 2018;34(4):225-232
Objective:
To study the antiseptic effect of compound lysostaphin disinfectant and its preventive effect on infection of artificial dermis after graft on full-thickness skin defect wound in rats.
Methods:
(1) Each one standard strain of
9.Effects of obesity on dose-response curve of rocuronium in female patients
Shizhao WANG ; Lining HUANG ; Rongtian KANG
The Journal of Clinical Anesthesiology 2017;33(1):33-36
Objective To observe the effects of obesity on dose-response curve of rocuronium in female patients and calculate ED9 5 of rocuronium.Methods Eighty female patients,aged 18-45 years, falling into ASA grade Ⅰ or Ⅱ,schedualed for elective surgery under general anesthesia,undergoing surgery less than 1.5 h,were included in the study.The patients with body mass index of 20-25 kg/m2 as group N were randomized to divided group N1,group N2,group N3 and group N4.Anoth-er 40 patients with body mass index of 30-35 kg/m2 as group B were randomized to divided group B1, group B2,group B3 and group B4.When the first twitch height of TOF (T1)was 100%,groups N1-N4 and groups B1-B4 patients were injected rocuronium 0.075,0.1,0.1 5,0.3 mg/kg respectively. The first dose of rocuronium in each group,T1 maximum inhibition degree and onset time were re-corded.The relationship between probit-transformed depression of T1 and the logarithm dose of rocu-ronium was analyzed by linear regression.ED50 and ED9 5 of rocuronium in obese and normal body weight patients were calculated.Results Dose-response curve equation of each group were Y1 =3.464X1 -2.23 and Y2 = 3.843X2 - 2.750 respectively(P < 0.05 ).The ED50 and ED9 5 (95% CI)of rocuronium were 0.122 (0.092-0.1 65 )mg/kg and 0.324 (0.242-0.433 )mg/kg in group N,and were 0.103 (0.078-0.133)mg/kg and 0.25 1 (0.1 93-0.326)mg/kg in group B.Conclusion Obesity significantly affects the dose-response curve of young women and can enhance the sensitivity of them to the rocuronium.The ED9 5 of obese patients is 0.25 1 mg/kg.
10.Functional electrical stimulation and weight loss treadmill synchronous training after botulinum toxin injection can relieve foot-drop and strephenopodia among stroke survivors
Huajun CHENG ; Lianghua LIAO ; Shangjie CHEN ; Rui JIAO ; Dan WANG ; Wenfang GAO ; Shizhao HUANG
Chinese Journal of Physical Medicine and Rehabilitation 2016;38(9):674-678
Objective To explore the effect of functional electrical stimulation combined with treadmill training and botulinum toxin type A injection on foot-drop and strephenopodia among stroke survivors.Methods Sixty-seven stroke survivors with foot-drop and strephenopodia were randomly divided into an electrical stimulation group (n=23),a conventional treatment group (n =22) and a combined treatment group (n =22).All 3 groups received a 400 U injection of BTX-A and electrical stimulation.After 24 hours,the patients in the conventional treatment group received conventional treatment including a brain protection agent,limb function exercises,gait training,balance training and training in the activities of daily living.The patients in the combined treatment group received that conventional treatment,plus functional electrical stimulation and weight loss training on a treadmill.The patients in the electrical stimulation group received functional electrical stimulation treatment supplementing the conventional treatment.Therapeutic effects were evaluated before and after six weeks of treatment using integral electromyography (iEMS) of the anterior tibial muscle and the lateral head of the gastrocnemius muscle,the co-contraction ratio (CR) during ankle dorsiflexion,the modified Ashworth Scale (MAS),the Berg balance scale (BBS),a functional walking score (FAC),and the active range of motion (AROM) of the ankle in dorsiflexion and eversion.Results After the treatment,significant improvement was observed in all three groups in the average iEMS value of the anterior tibial muscle and the lateral head of the gastrocnemius muscle,the CR in ankle dorsiflexion,and in their MAS,BBS,FAC and AROM results.There was no significant difference among the three groups after treatment in their average iEMS values at the lateral head of the gastrocnemius.The average values of the other indicators were,however,significantly better in the combined treatment group than in the other 2 groups.Conclusion Functional electrical stimulation combined with treadmill training and botulinum toxin type A injection can significantly improve foot-drop,strephenopodia and the walking function of stroke survivors.This combined treatment deserves popularization and application in clinical practice.

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