1.Effect of Faeces Bombycis Extract on Cajal Interstitial Cells in Diabetic Gastroparesis Rats Based on PI3K/Akt/mTOR Signaling Pathway
Huizhen ZHANG ; Hong ZHANG ; Wei LI ; Kai ZHAO ; Yudi QIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):66-73
ObjectiveTo explore the therapeutic mechanism of Faeces Bombycis on diabetic gastroparesis (DGP) rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/Akt/mTOR) signaling pathway. MethodDGP rat model was prepared by random selection of 15 out of 105 rats as blank group. The rats successfully constructed were randomly divided into model group, high-,medium- and low- dose groups (3.2, 1.6, 0.8 g·kg-1) and moxapride group (1.5 mg·kg-1), with 12 rats in each group, and were given gavage for 4 weeks. The gastric emptying rate and random blood glucose were measured. The morphological changes of gastric antrum were observed by hematoxylin-eosin (HE) staining, and the expression of the c-Kit gene was analyzed by immunohistochemistry. The apoptosis of Cajal interstitial cells was observed by in situ end labeling (TUNEL) staining, and the protein expressions of PI3K, phosphorylation(p)-PI3K, Akt, p-Akt, mTOR, and p-mTOR were detected by Western blot. ResultCompared with the blank group, the gastric emptying rate of the model group decreased significantly (P<0.01), and the glandular structure of the gastric antrum was destroyed. The expression of c-Kit decreased (P<0.01), and the apoptosis of Cajal interstitial cells (ICC) increased. Compared with the model group, the gastric emptying rate in the high, middle, and low-dose groups of Faeces Bombycis extract and mosapride group increased significantly (P<0.01). The glandular structure of the gastric antrum became closer, and the apoptosis of ICC decreased. The expression of c-Kit in the high dose group of Faeces Bombycis extract increased significantly. After Western blot testing, compared with the blank group, the protein expression of p-Akt/Akt, p-PI3K/PI3K, and p-mTOR/mTOR in the model group increased. Compared with the model group, the protein expression of p-Akt/Akt in the high dose group of Faeces Bombycis extract decreased (P<0.01), and the protein expression of p-PI3K/PI3K decreased in the middle and low dose groups of Faeces Bombycis extract and mosapride group decreased (P<0.05, P<0.01). The protein expression of p-mTOR/mTOR decreased in the low dose group of Faeces Bombycis extract (P<0.05). In terms of random blood glucose, compared with the blank group, the random blood glucose in the model group increased significantly (P<0.01), and compared with the model group, the random blood glucose in the high and middle dose groups of Faeces Bombycis extract decreased significantly (P<0.05). Compared with mosapride group, the protein expression of p-Akt/Akt decreased in the high dose group of Faeces Bombycis extract (P<0.05), and the protein expression of p-PI3K/PI3K increased in the high, middle, and low dose groups of Faeces Bombycis extract (P<0.05, P<0.01). ConclusionFaeces Bombycis extract can increase gastric emptying rate, reduce ICC apoptosis, and lower random blood glucose in DGP rats. The high dose group of Faeces Bombycis extract has a significant effect on inhibiting ICC apoptosis, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.
2. A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer
Qiu-Ping ZHANG ; Zhi-Ping CHENG ; Wei XUE ; Qiao-Feng LI ; Hong-Wei GUO ; Qiu-Ping ZHANG ; Jie-Jun FU ; Hong-Wei GUO
Chinese Pharmacological Bulletin 2024;40(1):146-154
Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.
3.Pathological Characteristics and Classification of Unstable Coronary Atheroscle-rotic Plaques
Yun-Hong XING ; Yang LI ; Wen-Zheng WANG ; Liang-Liang WANG ; Le-Le SUN ; Qiu-Xiang DU ; Jie CAO ; Guang-Long HE ; Jun-Hong SUN
Journal of Forensic Medicine 2024;40(1):59-63
Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.
4.Trends in age-, period- and cohort-specific incidence of hepatitis C in Chifeng City from 2008 to 2022
LI Wenjun ; LI Hui ; YANG Jingyuan ; YANG Hong ; GAO Ya ; GAO Baicheng ; LI Yao ; ZHANG Qiyue ; QIU Yafei
Journal of Preventive Medicine 2024;36(6):514-517,522
Objective:
To explore incidence trend of hepatitis C in Chifeng City, Inner Mongolia Autonomous Region from 2008 to 2022, so as to provide the basis for formulating prevention and control measures for hepatitis C.
Methods:
Data of reported hepatitis C cases in Chifeng City from 2008 to 2022 was collected through the Infectious Disease Information Reporting Management System. Trends in incidence of hepatitis C were analyzed using annual percent change (APC) and average annual percent change (AAPC). Impact of age, period and birth cohort on the risk of developing hepatitis C were analyzed by an age-period-cohort model.
Results:
The annual average reported incidence rate of hepatitis C in Chifeng City was 59.13/105 from 2008 to 2022. The incidence showed an upward trend from 2008 to 2018 (APC=9.405%, P<0.05) and a downward trend from 2018 to 2022 (APC=-17.475%, P<0.05), but the overall trend was not statistically significant (AAPC=0.937%, P>0.05). The age-period-cohort model analysis showed that the incidence risks of hepatitis C in the residents aged 0 to 4 years and 45 to 84 years were higher than those in the residents aged 40 to 44 years (the control group). The incidence risk of hepatitis C increased with age from 40 to 79 years. Compared with 2008-2012, the incidence risk of hepatitis C showed an increasing trend followed by a decline in 2008-2022. The incidence risk was higher in 2013-2017 and lower in 2018-2022 than in 2008-2012. The incidence risk of hepatitis C showed an increasing trend followed by a decreasing trend by using the birth cohort from 1968 to 1972 as the control. The birth cohort from 1953 to 1977 had a higher incidence risk of hepatitis C than other birth cohorts.
Conclusions
The overall incidence of hepatitis C in Chifeng City from 2008 to 2022 appeared a tendency towards a decline, and the incidence risk increased with age. Screening and health education for the elderly and high-risk birth cohorts should be strengthened.
5.Research status on bioactivity of Cecropin A and its derivatives
Jing-Ru CHAO ; Chun-Li SU ; Jin-Qiu MO ; Chun-Miao LI ; Xin LI ; Hong-Li LIAO
The Chinese Journal of Clinical Pharmacology 2024;40(19):2905-2908
In recent years,natural antimicrobial peptides have become an important direction in the development of novel antibiotics.Cecropin has the characteristics of wide antibacterial spectrum,good tolerance and low adverse drug reactions.As the first antimicrobial peptide discovered in the family of Cecropin,Cecropin A has many important biological activities.In this paper,the research on the antibacterial,antifungal,antiparasitic and antitumor activities of Cecropin A and its derivatives in recent years was reviewed,and its application prospect was prospected,in order to provide reference for further research and development of cecropin.
6.Effects of blockade of visceral adipose afferent nerve on cardiac function and neural remodeling in rats after myocardial infarction
Jiaxing HUANG ; Wuping TAN ; Qinfang QIU ; Haosong XI ; Rui LI ; Liping ZHOU ; Yueyi WANG ; Hong JIANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):192-196
Objective To investigate the effect of afferent blockade of visceral adipose tissue(VAT)on cardiac function and cardiac neural remodeling in rats after myocardial infarction(MI).Methods After 30 healthy SPF-grade male SD rats were subjected,12 of them were randomly divided into control group(n=6)and activation group(n=6).In the activation group,low-dose capsaicin(1 mmol/L)was used to activate VAT afferent nerves,while in the control group,an equal amount of normal saline was injected,and real-time blood pressure and heart rate were monitored for 30 min.The other 18 rats were randomly assigned into sham group(n=6),MI group(n=6),and high-dose capsaicin blockade group(n=6).The MI model was established by ligating the left anterior descending coronary artery.After MI modeling,the high-dose capsaicin blockade group was give 33 mmol/L capsaicin to block VAT afferent nerve,and the sham opera-tion group and MI group were injected with the same amount of normal saline.After 2 weeks,car-diac function was measured by echocardiography,infarct size was measured by TTC staining,heart rate variability was analyzed,and myocardial tyrosine hydroxylase(TH)was measured.The levels of myocardial superoxide dismutase(SOD)and malondialdehyde(MDA)were measured by biochemical methods.Results More significant changes in blood pressure and heart rate were observed in the activation group than the control group(P<0.01).The MI group had obviously larger infarct size,higher LVEDD and LVESD,and increased myocardial TH density and MDA level,but lower LVEF and myocardial SOD activity than the sham group(P<0.05).However,the infarct size,LVEDD(9.15±0.37 mm vs 10.1±0.85 mm),LVESD(6.33±0.40 mm vs 7.87±0.86 mm)were obviously decreased,while LVEF[(67.04±3.34)%vs(47.10±3.89)%]and myocar-dial FS[(33.26±2.50)%vs(20.81±2.14)%]activity were greatly increased in the high dose capsaicin group than the MI group(P<0.05).Conclusion Activation of VAT afferent nerve can increase blood pressure and heart rate;while its blockade can reduce the infarct size,protect cardiac function and inhibit cardiac nerve remodeling in MI rats,possibly by reducing oxidative stress.
7.Simultaneous content determination of ten constituents in Tianma Toufengling Capsules by QAMS
Xu-Sheng GUO ; Xue-Wei QIU ; Li LI ; Ai-Ying WU ; An-Zhen CHEN ; Hong-Bing LIU ; Jing-Guang LU
Chinese Traditional Patent Medicine 2024;46(2):359-364
AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.
8.Aphasia in Right Hemiparesis and Pain in Left Waist:A Deceiving Case in Vascular Ehlers-Danlos Syndrome
Yining FU ; Jingmin ZHOU ; Feng LI ; Shangzhi HUANG ; Yining WANG ; Xia HONG ; Ke LYU ; Yaping LIU ; Ling LENG ; Wenjie ZHENG ; Zhengqing QIU ; Yicheng ZHU ; Yuehong ZHENG ; Yuexin CHEN
JOURNAL OF RARE DISEASES 2024;3(2):224-231
The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.
9.Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis
Zonglong LI ; Jialu CHEN ; Yue TANG ; Delong QIN ; Chen CHEN ; Yinghe QIU ; Hong WU ; Yu HE ; Xianhai MAO ; Wenlong ZHAI ; Jingdong LI ; Xiao LIANG ; Chuandong SUN ; Kai MA ; Zhimin GENG ; Zhaohui TANG ; Zhiwei QUAN
Chinese Journal of Surgery 2024;62(7):685-696
Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
10.Clinical phenotype and genetic analysis of a rare case with 6p duplication and terminal deletion syndrome
Yanhong YU ; Jian LU ; Hong LI ; Yingying GAO ; Xia YE ; Xuzhuo ZHANG ; Jingtian LU ; Juan QIU
Chinese Journal of Medical Genetics 2024;41(9):1117-1123
Objective:To explore the genetic basis for a child with developmental delay and intellectual deficit (DD/ID).Methods:A child who was admitted to the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City on June 3, 2023 due to DD/ID, craniofacial malformations, and recurrent infections of upper respiratory tract was selected as the study subject. G-banded chromosomal karyotyping was carried out for the child and her parents. Low-depth genome-wide copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) were used to screen for genome-wide copy number variation (CNV), and fluorescence in situ hybridization (FISH) was used to verify the origin of candidate CNV. This study was approved by the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City(Ethics No. 2023052504). Results:The child, an 8-year-old girl, had featured unexplained growth and intellectual development delay, multiple craniofacial malformations, and recurrent infections of the upper respiratory tract. She was found to have a karyotype of 46, XX, der(6)add(6)(q23), while both of her parents were normal. Both CNV-seq and CMA showed that the child has harbored a 21.38 Mb interstitial duplication at 6p25.3p22.3 and a 0.78 Mb terminal deletion at 6p25. FISH verified that both the duplication and deletion had occurred de novo. Conclusion:The abnormal phenotype of the child may be attributed to the 6p duplication and terminal deletion.


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