1. 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.
2. Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice
Lei YUAN ; Zhi-Wei YANG ; Wei WAN ; Hui YANG ; Zheng-Hai LIU ; Jie HE
Acta Anatomica Sinica 2024;55(1):25-31
Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/ 6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.
3.Application of droplet digital PCR in etiological diagnosis of severe acute pancreatitis patients with suspected bloodstream infection
Xin-Yu WANG ; Gang LI ; Wen-Jian MAO ; Jie YANG ; Jing-Zhu ZHANG ; Lu KE ; Wei-Qin LI ; Zhi-Hui TONG
Chinese Journal of Infection Control 2024;23(1):9-15
Objective To explore the value of droplet digital polymerase chain reaction(ddPCR)in the etiological diagnosis of severe acute pancreatitis(SAP)patients with suspected bloodstream infection(BSI).Methods SAP patients admitted to the department of critical care medicine in a hospital July to September 2022 were enrolled.When BSI was suspected,venous blood was collected for both ddPCR detection and blood culture(BC)with antimi-crobial susceptibility testing(AST)simultaneously.The time required for two detection methods was recorded,and the detection results of ddPCR and BC were compared.The etiological diagnostic efficacy of ddPCR was calculated,and the correlation between the value of pathogen load detected by ddPCR and the level of infection parameters was explored.Results A total of 22 patients were included in the analysis,and 52 venous blood specimens were collec-ted for detection.BC revealed 17 positive specimens(32.7%)and 29 pathogenic strains,while ddPCR showed 41 positive specimens(78.8%)and 73 pathogenic strains.Detection time required for ddPCR was significantly lower than that of BC([0.16±0.03]days vs[5.92±1.20]days,P<0.001).Within the detection range of ddPCR and taking BC results as the gold standard,the sensitivity and specificity of ddPCR were 80.0%and 28.6%,respective-ly.With the combined assessment of BSI based on non-blood specimen microbial evidence within a week,the sensi-tivity and specificity of ddPCR detection increased to 91.9%and 76.9%,respectively.ddPCR detected resistance genes of blaKPC,blaNDM/IMP,VanA/VanM,and mecA from 19,9,6,and 5 specimens,respectively.Correlation analysis showed a positive correlation between pathogen load and levels of C-reactive protein as well as procalcitonin(r=0.347,0.414,P<0.05).Conclusion As a supplementary detection method for BC in BSI diagnosis,ddPCR has the advantages of higher sensitivity and shorter detection time,and is worthy of further exploration in clinical application.
4.Analysis of factors influencing lymph node metastasis and prognosis of Siewert Ⅱ/Ⅲ esophagogastric junction adenocarcinoma
Wei MI ; Yidong HUANG ; Zhi ZHENG ; Xiaoye LIU ; Jie YIN ; Jun ZHANG
International Journal of Surgery 2024;51(5):307-314
Objective:To explore the factors influencing lymph node metastasis and prognosis in patients with Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG).Methods:A retrospective analysis was conducted on clinical data of 239 patients with Siewert Type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction who underwent surgical treatment at Beijing Friendship Hospital, Capital Medical University, from July 2013 to December 2022. Among them, there were 204 males and 35 females. The patients′ ages ranged from 27 to 83 years, with a mean age of 63.1 years. Statistical analysis was performed using SPSS 26.0 software, with categorical data presented as n(%) and compared using χ2 tests, corrected χ2 tests, or Fisher′s exact tests. Ordinal data were expressed as frequencies and percentages and compared using rank-sum tests. Multivariate analysis was conducted using Logistic regression, and survival analysis was performed using the Cox regression model. Follow-up was conducted every 6 months, with the last follow-up conducted in November 2023. Results:Multivariate analysis identified infiltration depth ( OR=0.038, 95% CI: 0.011-0.139, P<0.001), tumor deposit ( OR=0.101, 95% CI: 0.011-0.904, P=0.040) and intravascular cancer embolus ( OR=0.234, 95% CI: 0.108-0.507, P<0.001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert Ⅲ AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert Ⅱ. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert Ⅱ AEG, with rates of 5.45% and 3.64%, respectively. A three-year survival analysis underscored LNM as a significant prognostic factor ( P=0.001). Conclusions:Siewert Ⅱ AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert Ⅲ AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No.5 and No.6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.
5.Rapid screening the chemical components in Jiawei Dingzhi pills using precursor ion selection UHPLC-Q-TOF-MS/MS
Zu-ying WEI ; Cong FANG ; Kui CHEN ; Hao-lan YANG ; Jie LIU ; Zhi-xin JIA ; Yue-ting LI ; Hong-bin XIAO
Acta Pharmaceutica Sinica 2024;59(8):2350-2364
A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.
6.Identification and quality evaluation of germplasm resources of commercial Acanthopanax senticosus based on DNA barcodes and HPLC
Shan-hu LIU ; Zhi-fei ZHANG ; Yu-ying HUANG ; Zi-qi LIU ; Wen-qin CHEN ; La-ha AMU ; Xin WANG ; Yue SHI ; Xiao-qin ZHANG ; Gao-jie HE ; Ke-lu AN ; Xiao-hui WANG ; Sheng-li WEI
Acta Pharmaceutica Sinica 2024;59(7):2171-2178
italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial
7.Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology
Jin Zi ZHAO ; Ping Xiao CHEN ; Wei Shao HUA ; Yu Feng LI ; Meng ZHAO ; Hao Chen XING ; Jie WANG ; Yu Feng TIAN ; Qing Rui ZHANG ; Na Xiao LYU ; Qiang Zhi HAN ; Xin Yu WANG ; Yi Hong LI ; Xin Xin SHEN ; Jun Xue MA ; Qing Yan TIE
Biomedical and Environmental Sciences 2024;37(4):387-398
Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.
8.Protective Effect of Dihydromyricetin Against Exercise-Induced Muscle Damage and Its Mechanism
Wu YING ; Wang DA-WEI ; Li JUN ; Xu XIAN-JIE ; Gao ZHI-DAN ; Li HONG-YAN ; Zhang YONG ; Liu PENG
Chinese Medical Sciences Journal 2024;39(1):46-53,中插5
Objective lo investigate the protective effect of dihydromyricetin(DHM)against exercise-induced muscle damage(EIMD)in mice and its potential mechanism. Methods Adult male C57BL/6J mice were randomly divided into control group(CG),exercise group(EG),and exercise+100 mg/kg weightd DHM(DHM)group.The intervention lasted for four weeks,during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day.The day after the training,a 90-min treadmill exercise(slope:0 and speed:18 m/min)was conducted in both EG and DHM groups.Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise,followed by the measurement of serum creatine kinase(CK)and lactate dehydrogenase(LDH)activities,total superoxide dismutase(T-SOD)activity,malondialdehyde(MDA),and skeletal muscle mitochondrial enzyme complex Ⅰ and Ⅱ activities.Histological changes in the skeletal muscle were observed by transmission electron microscopy,and the protein expressions of mitochondrial function-related pathways were detected by Western blotting. Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG.The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention.Western blotting demonstrated that the expressions of sirtuin type 3(SIRT3),estrogen-related receptor alpha,and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention. Conclusion DHM can relieve EIMD in mice,possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.
9.Comparison of the posterior hemipelvectomy of the greater trochanter approach with the standard Kocher-Langen-beck approach in the treatment of posterior acetabulum wall fractures
Jin ZHANG ; Jian-Jun SHEN ; Xiang HAI ; Chuan-Yuan LIU ; Wen-Jie ZHOU ; Zhi-Wei CHEN
China Journal of Orthopaedics and Traumatology 2024;37(8):786-792
Objective To compare the clinical efficacy of the posterior hemipelvectomy of the greater trochanter approach with the standard Kocher-Langenbeck(K-L)approach in the treatment of posterior acetabulum wall fractures and to explore a more optimal approach for the treatment of posterior acetabulum wall fractures.Methods Total of 26 patients with posterior ac-etabulum wall fractures were retrospectively analysed and divided into two groups:the posterior hemipelvectomy of the greater trochanter group(test group)and the standard K-L approach group(control group).In the test group,there were 24 patients including 16 males and 8 females with an average age of(42.00±4.52)years old,the time of injury to surgery was(6.75±1.15)d.In the control group,there were 23 patients including 16 males and 7 females with an average age of(41.00±5.82)years old,the time of injury to surgery was(7.09±1.20)days.The total hospital stay,length of incision,operation time,intraoperative bleeding,postoperative drainage,discharge,fracture reduction quality(Matta criteria),hip abduction muscle strength,hip func-tion(Merle d'Aubigne-Postel score),postoperative complications and the incidence of ectopic ossification were compared.Results All cases were followed up for 6 months.There was no significant difference in incision length,intraoperative bleeding and postoperative drainage between two groups(P>0.05).However,the operation time of the test group was shorter than that of the control group(P<0.05).There was no statistically significant difference in fracture reduction and hip function between two groups(P>0.05).The hip abduction muscle strength of test group was better than that of control group(P<0.05).In addition,there was no significant difference in the incidence of postoperative complications and heterotopic ossification between two groups(P>0.05).Conclusion Compared with the standard K-L approach,the posterior hemipelvectomy of the greater trochanter approach can shorten the operative time,has better recovery of the postoperative hip abduction muscle strength,ex-poses the view of the fracture involving the more comminuted posterior acetabulum wall or the fracture of the roof of the socket,improved the rate of fracture anatomical repositioning,provides a new idea for the clinical treatment of posterior acetabulum wall fractures,and allows patients to perform functional exercises at an early stage.
10.Human resource efficiency and spatial distribution characterization of district-level center for disease control and prevention in city N of Jiangsu Province
Yang LI ; Yu-Meng WEI ; Yu-Qi YANG ; Wen-Jie XU ; Ming-Yao GU ; Zi-Fa HUANG ; Zhi-Hao ZHANG ; Fang WU
Chinese Journal of Health Policy 2024;17(10):52-58
Objective:To analyze the efficiency of human resource allocation and its spatial distribution characteristics of district-level Center for Disease Control and Prevention(CDC)in city N of Jiangsu Province in 2020,in order to provide a strong decision-making reference for optimizing and strengthening the CDC talent team.Methods:The efficiency of human resources of district-level CDC of City N in2020 was measured using the Super-Efficiency SBM model,and the spatial association pattern was analyzed using the natural break point classification method and Moran's index,with the visualization presented through LISA maps.Results:The overall level of human resource efficiency in district-level CDC of City N is relatively high.However,spatially,there are significant differences among the regions,showing a trend of high efficiency in the central areas and low efficiency at the ends.Moran's index and LISA maps indicate a negative spatial correlation in efficiency,with a low-high(L-H)cluster centered on Area L and a high-low(H-L)cluster centered on Area J.The high-high(H-H)cluster pattern has not yet formed,exhibiting a characteristic of interspersed high and low efficiency.Conclusions:There are regional differences in the human resource efficiency of the Disease Control Center in City N,and the spatial cluster pattern needs to be optimized.It is recommended to focus on efficiency improvement in Areas P and L,formulate appropriate policies,and promote coordinated regional development.

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