1.The core issue of the management of occupational health technical service institutions in China under new circumstances
Xiaodong SHI ; Shijie HU ; Han ZHAO ; Dongshan LIU
China Occupational Medicine 2025;52(1):82-88
Occupational health technical service (OHTS) is one of the core contents in the technical support system of occupational disease prevention and control, and efficient management of OHTS institutions is necessary for improving the service ability. At present, OHTS institutions in China face several issues, such as uneven distribution in terms of quantity, function, unclear area coverage and roles and overlapping responsibilities among different types of institutions, and insufficient service capabilities with inconsistent service levels in some institutions. With the implementation of the national reform like the “separating permits from business license” and “delegate power, streamline administration and optimize government services"”policies, the management mode and operational approach of OHTS institutions have been profoundly changed. In light of this, five key recommendations are proposed to improve the management of OHTS institutions and enhance their management effectiveness, ensuring the sustainable development of national OHTS services. Firstly, it is necessary to clarify the relationship between national and provincial administrative levels in managing OHTS institutions to ensure their healthy and orderly development. Secondly, multiple measurements are taken to strengthen OHTS institutional capacity building to address regional disparities in technical capabilities and service quality. Thirdly, both technical capabilities and service quality should be focused on strengthening the supervision and management of OHTS institutions, preventing the decline of key conditions such as staffing, laboratories, equipment, and quality management after obtaining qualifications. Fourthly, “dual randomized- inspections and one open” and “internet+supervision” methods are used as basic tools for managing OHTS institutions operating across multiple provincial regions and enforcing cross-regional law. Fifthly, professional integrity of radiological health service institutions should be restored to effectively apply their technical advantages in their specialized fields.
2.Dynamic changes of iron metabolism and the effectiveness of health education among apheresis donors in Guangzhou under the GLMM framework
Xiaowen CHEN ; Fanhai LI ; Bi ZHONG ; Guanghuan LIU ; Jinyan CHEN ; Hao WANG ; Shijie LI
Chinese Journal of Blood Transfusion 2025;38(6):817-823
Objective: To investigate the current status of iron metabolism among apheresis donors in Guangzhou and analyze the improvement effects of health education on iron deficiency in frequent apheresis donors. Methods: Using a generalized linear mixed model (GLMM), a 180-day follow-up was conducted on 261 eligible apheresis donors at the Guangzhou Blood Center from January to July 2024. Hemoglobin (Hb), serum ferritin (SF), unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), and transferrin saturation (TS) were selected as outcome variables. The effects of gender, age group, and number of donations within 180 days on these outcomes were analyzed and modeled. A general linear model (GLM) with repeated measures was applied to 55 donors who received health education interventions, comparing changes in Hb and iron metabolism-related indicators before and after follow-up and health education. Results: No significant difference in Hb levels was observed between first-time and regular apheresis donors, but SF levels were significantly higher in first-time donors (F=6.195, P<0.05). The GLMM revealed that female donors exhibited more significant reductions in Hb (T=-12.546) and SF (T=-5.829)(P<0.05 for both). Age group showed no interactive effects on Hb or SF changes. While number of donations within 180 days had no interactive effect on Hb, SF levels significantly decreased with increased number of donations (using ≥9 donations as the reference group; P<0.05 for all groups). After health education, Hb levels remained unchanged, but SF increased compared to pre-intervention levels (mean difference: -18.571, P<0.05), though a declining trend persisted compared to baseline (mean difference from baseline to post-intervention: 23.068,P<0.05). Conclusion: Female and number of donations are primary factors contributing to SF reduction in apheresis donors. Health education interventions promote SF recovery. Extending donation intervals and reinforcing iron deficiency-related health education may improve iron status in donors.
3.Mechanism of Xiezhuo Jiedu Formula in Treating Ulcerative Colitis Through Pyroptosis Regulation Based on Bioinformatics and Animal Experiments
Qiang CHUAI ; Wenjing ZHAI ; Shijie REN ; Xiaomeng LANG ; Xin KANG ; Wenli WEI ; Jingyuan LIU ; Jianping LIU ; Jie REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):105-113
ObjectiveThis study aims to explore the potential mechanism of the Xiezhuo Jiedu formula in regulating pyroptosis for the treatment of ulcerative colitis (UC) using bioinformatics and in vivo animal experiments. MethodsDifferentially expressed genes (DEGs) in colon tissues of UC patients were retrieved from the Gene Expression Omnibus (GEO) database. Pyroptosis-related genes were obtained from the GEO and GeneCards databases. The intersection of these datasets yielded pyroptosis-related DEGs (Pyro-DEGs). Pyro-DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using the Metascape database. A protein-protein interaction (PPI) network was constructed using the STRING database. Least absolute shrinkage and selection operator (LASSO) prediction model and receiver operating characteristic (ROC) analysis were conducted to identify core Pyro-DEGs with diagnostic and therapeutic potential. Immune infiltration analysis of the UC datasets was performed using the deconvolution method (CIBERSORT), along with correlation analysis with core Pyro-DEGs. Sixty male Sprague-Dawley (SD) rats were randomly divided into a control group, a model group, high-, medium-, and low-dose groups of Xiezhuo Jiedu formula (26.64, 13.32, 6.66 g·kg-1), and a mesalazine group (0.27 g·kg-1), with 10 rats in each group. UC was established by intrarectal administration of 3,5-trinitrobenzenesulfonic acid (TNBS) dissolved in ethanol. The control and model groups were given distilled water by gavage, while the treatment groups were administered the corresponding drugs for 7 consecutive days. Hematoxylin-eosin (HE) staining was used to observe the colon histopathology. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors such as interleukin-1β (IL-1β), IL-10, IL-18, and transforming growth factor-β (TGF-β). Immunohistochemistry (IHC) and Western blot were applied to detect the expression of Caspase-1, gap junction alpha-1 protein (GJA1), peroxisome proliferator-activated receptor gamma (PPARG), and S100 calcium-binding protein A8 (S100A8). Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to measure mRNA expression of Caspase-1, GJA1, PPARG, and S100A8. Western blot was performed to assess protein expression levels of Caspase-1, GJA1, PPARG, and S100A8. ResultsGEO datasets GSE87466 and GSE87473 yielded 64 Pyro-DEGs. KEGG analysis indicated that these genes were enriched in the NOD-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and hypoxia-inducible factor 1 (HIF-1) signaling pathway. Four core Pyro-DEGs (Caspase-1, GJA1, PPARG, and S100A8) were identified. Immune infiltration analysis showed that expression of these genes was positively correlated with mast cells, neutrophils, M0 macrophages, M1 macrophages, and dendritic cells. Animal experimental results indicated that compared with the control group, the model group had significantly increased levels of IL-1β and IL-18, significantly decreased levels of IL-10 and TGF-β. The model group showed enhanced Caspase-1, GJA1, and S100A8 staining, and significantly increased mRNA and protein expression of Caspase-1, GJA1, and S100A8 (P<0.01). In contrast, the expression of PPARG was reduced in the model group (P<0.01). After treatment, all dosage groups showed varying degrees of improvement (P<0.05, P<0.01), with the high-dose group showing the most significant improvement (P<0.01). ConclusionCaspase-1, GJA1, PPARG, and S100A8 are core Pyro-DEGs closely associated with the pathogenesis of UC. These genes may collaborate with immune cells such as mast cells, neutrophils, and M0 macrophages to mediate disease development. The Xiezhuo Jiedu formula may regulate the expression of core Pyro-DEGs through the NOD-like receptor, TNF, and HIF-1 core signaling pathways, thereby modulating immune homeostasis in UC rats and effectively alleviating UC.
4.Extracellular vesicles carrying non-coding RNA regulate the activation of osteoclasts
Jianhong LIU ; Shijie LIAO ; Boxiang LI ; Shengping TANG ; Zhendi WEI ; Xiaofei DING
Chinese Journal of Tissue Engineering Research 2024;28(7):1076-1082
BACKGROUND:It has been demonstrated that osteoclast activation plays an important role in skeletal system-related diseases.The mechanism of regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA has not been fully elucidated. OBJECTIVE:To review and summarize relevant literature in and outside China,and to review the regulation of osteoclast activation by different non-coding RNAs in extracellular vesicles in different diseases,so as to provide a certain direction for subsequent research. METHODS:"Non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclasts,extracellular vesicles,exosome,microparticle,apoptotic bodies"were used as search terms to search the databases of CNKI,WanFang,and VIP."Extracellular vesicles,exosome,microparticle,apoptotic bodies,non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclast"were used as search terms to search PubMed.Finally,71 articles were included. RESULTS AND CONCLUSION:(1)The activation of osteoclasts is affected by many factors,among which the specific mechanism of non-coding RNA regulating osteoclast activation is not clear.(2)Extracellular vesicles can be secreted by osteoblasts,bone marrow mesenchymal stem cells,tumor cells and other cells.As a carrier of intercellular communication,extracellular vesicles can carry non-coding RNA to regulate osteoclast activation.(3)In the current studies on the regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA,most of the diseases are osteoporosis,followed by tumor bone metastasis,and most types of non-coding RNA are miRNA.(4)There are relatively few studies on the regulation of extracellular vesicles carrying lncRNA and circRNA and snoRNA on osteoclast activation,and the regulatory mechanism is mainly ceRNA mechanism.(5)In conclusion,an in-depth study of the regulatory mechanism of extracellular vesicles carrying non-coding RNA on osteoclast activation is helpful to find key targets for the treatment of skeletal system-related diseases.
5.Predictive value of lipoproteins on progression to chronic critical illness in intensive care unit patients
Shijie HUANG ; Xiancheng CHEN ; Ming CHEN ; Yanyu HAN ; Jianfeng DUAN ; Jiali LIU ; Zhanghua ZHU ; Wenkui YU
Chinese Critical Care Medicine 2024;36(1):78-81
Objective:To explore the predictive value of lipoproteins on the progression of critically ill patients to chronic critical illness (CCI).Methods:A retrospective cohort study was conducted to analyze clinical data of patients admitted to the intensive care unit (ICU) of Nanjing Drum Tower Hospital from January 1, 2020, to December 31, 2022. The levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apolipoproteins (ApoA-Ⅰ, ApoB) at 1, 3, 7, 14 and 21 days after admission to ICU were collected. The progression to CCI was recorded. CCI was defined as the length of ICU stay ≥14 days with sustained organ dysfunction [sequential organ failure assessment (SOFA) score ≥2]. Differences in lipoprotein levels between the patients with and without CCI were compared. Multivariate Logistic regression was used to analyze risk factors for critically ill patients progressing to CCI. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of lipoproteins on critically ill patients progressing to CCI.Results:A total of 200 patients were enrolled in the final analysis. 137 patients (68.5%) progressed to CCI, and 63 patients (31.5%) did not. The lipoprotein indicators in the CCI group showed a decrease after the acute phase, while the lipoprotein indicators in the non-CCI group showed an increase. The levels of HDL, LDL, ApoA-Ⅰ, and ApoB at various time points in the CCI group were significantly lower than those in the non-CCI group. HDL at 7 days in the CCI group was significantly lower than that in the non-CCI group [mmol/L: 0.44 (0.31, 0.61) vs. 0.67 (0.49, 0.75), P < 0.01]. Multivariate Logistic regression analysis showed that 7-day HDL was an independent risk factor for critically ill patients progressing to CCI [odds ratio ( OR) = 0.033, 95% confidence interval (95% CI) was 0.004-0.282, P = 0.002]. ROC curve analysis showed that the area under the ROC curve (AUC) of 7-day HDL for predicting critically ill patients progressing to CCI was 0.702, with a 95% CI of 0.625-0.779, P < 0.001. When the optimal cut-off value was 0.59 mmol/L, the sensitivity was 69.8%, and the specificity was 72.4%. Conclusions:The low level of lipoproteins is closely related to the progression of critically ill patients, and 7-day HDL has a certain predictive value for critically ill patients progressing to CCI. Continuously observation of the change trend of lipoprotein level is helpful to judge the progression of CCI in critically ill patients.
6.Spatiotemporal distribution of newly diagnosed echinococcosis patients in Qinghai Province from 2016 to 2022
Xinlu CUI ; Xiao MA ; Na LIU ; Jia LIU ; Wen LEI ; Shusheng WU ; Xianglan QIN ; Chunhua GONG ; Xiaojin MO ; Shijie YANG ; Ting ZHANG ; Li CAO
Chinese Journal of Schistosomiasis Control 2024;36(5):474-480
Objective To investigate the spatiotemporal distribution characteristics and potential influencing factors of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, so as to provide insights into the formulation of the echinococcosis control strategy in Qinghai Province. Methods The number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases, number of registered dogs and number of stray dogs were captured from the annual reports of echinococcosis control program in Qinghai Province from 2016 to 2022, and the detection of newly diagnosed echinococcosis cases was calculated. The number of populations, precipitation, temperature, wind speed, sunshine hours, average altitude, number of year-end cattle stock, number of year-end sheep stock, gross domestic product (GDP) per capita, and number of village health centers in each county (district) of Qinghai Province were captured from the Qinghai Provincial Statistical Yearbook, and county-level electronic maps in Qinghai Province were downloaded from the National Platform for Common Geospatial Information Services. The software ArcGIS 10.8 was used to map the distribution of newly diagnosed echinococcosis cases in Qinghai Province, and the spatial autocorrelation analysis of newly diagnosed echinococcosis cases was performed. In addition, the spacetime scan analyses of number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases and geographical coordinates in Qinghai Province were performed with the software SaTScan 10.1.2, and the spatial stratified heterogeneity of the detection of newly diagnosed echinococcosis cases was investigated with the software GeoDetector. Results A total of 6 569 426 residents were screened for echinococcosis in Qinghai Province from 2016 to 2022, and 5 924 newly diagnosed echinococcosis cases were found. The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline over years from 2016 to 2022 (χ2 = 11.107, P < 0.01), with the highest detection in Guoluo Tibetan Autonomous Prefecture in 2017 (82.12/105). There were spatial clusters in the detection of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2018 (Moran’s I = 0.34 to 0.65, all Z values > 1.96, all P values < 0.05), and the distribution of newly diagnosed echinococcosis cases appeared random distribution from 2019 to 2022 (Moran’s I = −0.09 to 0.04, all Z values < 1.96, all P values > 0.05). Local spatial autocorrelation analysis showed high-high clusters and low-low clusters in the detection of new diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, and space-time scan analysis showed that the first most likely cluster areas of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022 were mainly distributed in Yushu Tibetan Autonomous Prefecture and Guoluo Tibetan Autonomous Prefecture. GeoDetector-based analysis of the driving factors for the spatial stratified heterogeneity of detection of newly diagnosed echinococcosis cases in Qinghai Province showed that average altitude, number of village health centers, number of cattle and sheep stock, GDP per capita, annual average sunshine hours, and annual average temperature had a strong explanatory power for the spatial distribution of newly diagnosed echinococcosis cases, with q values of 0.630, 0.610, 0.600, 0.590, 0.588, 0.537 and 0.526, respectively. Conclusions The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline in Qinghai Province over years from 2016 to 2022, showing spatial clustering. Targeted control measures are required in cluster areas of newly diagnosed echinococcosis cases for further control of the disease.
7.Effects of Paeoniflorin on Cardiac Dysfunction and Myocardial Cell Injury Induced by Cisplatin in Rats Based on ERK/p38 MAPK Signaling Pathway
Shijie ZHANG ; Ruiqi TIAN ; Yinchuan DING ; Qi WU ; Yiran WANG ; Lei LIU ; Hong SUN ; Min XUE
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1476-1483
OBJECTIVE
To investigate the protective effect of paeoniflorin(PF) on cardiac dysfunction and myocardial cell injury induced by cisplatin(CDDP) in rats.
METHODS
SD male rats were randomly divided into control group, CPPD group, and CDDP PF+low-dose, high-dose group. PowerLab multifunctional recorder was used to detect the related indexes of cardiac function: the changes of left ventricular peak pressure(LVSP), left ventricular end-diastolic pressure(LVEDP) and left ventricular pressure change rate(±dp/dt). Serum levels of inflammatory factors TNF-α, IL-1β and IL-6 were measured in each group. Myocardial tissue was stained to observe the changes of tissue structure. H9c2 cardiomyocytes were divided into control group, CDDP group, PF group and CDDP+PF group. The activity of H9c2 cardiomyocytes was measured by CCK-8. The apoptosis of cardiomyocytes in each group was detected by flow cytometry. The expressions of MAPK signaling pathway related proteins p38, ERK, JNK and their phosphorylated proteins and apoptosis-related proteins Bax, Bcl-2, Casp3, Cl-casp3 were detected in cardiomyocytes by Western blotting.
RESULTS
Compared with the control group, LVSP and ±dp/dt decreased, LVEDP increased in rats of CDDP group(P<0.01). Compared with CDDP group, both CDDP+low-dose and high-dose PF pretreatment increased LVSP and ±dp/dt value(P<0.05 or P<0.01), decreased LVEDP(P<0.01), and could decrease the serum inflammatory factor TNF-α, IL-1β and IL-6(P<0.01). Cell level results showed that compared with control group, in CDDP group, the cell activity decreased, the apoptosis-related protein Bax, Cl-casp3 increased(P<0.01), expression of anti-apoptotic protein Bcl-2 decreased(P<0.01), and the expression of p38 and ERK phosphorylation also increased(P<0.01). Compared with CDDP group, PF could restore cell activit, down-regulate apoptosis-related protein Bax, Cl-casp3(P<0.05 or P<0.01), and increase anti-apoptotic protein Bcl-2 expression(P<0.01), inhibit MAPK pathway p38 and ERK phosphorylation expression(P<0.01).
CONCLUSION
PF can restore cardiac dysfunction and myocardial cell injury induced by cisplatin in rats, which may be related to inhibiting inflammation and apoptosis by regulating ERK/p38 MAPK signal expression.
8.Mechanism of Xiezhuo Jiedu Recipe in Preventing Colorectal Adenoma in Mice Through miRNA-34a-5p/PI3K/Akt Signalling Pathway
Sujie JIA ; Chaodi SUN ; Yifan ZHANG ; Xiaomeng LANG ; Jianping LIU ; Xin KANG ; Shijie REN ; Jingyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):156-165
ObjectiveKey microRNAs (miRNAs) of colorectal adenoma (CRA) were identified and analyzed by bioinformatics methods, and differentially expressed genes (DEGs) were screened to construct regulatory relationships. The mechanism of Xiezhuo Jiedu recipe in preventing CRA was speculated and verified by animal experiments. MethodThe miRNAs dataset GSE50194 was obtained from the Gene Expression Omnibus (GEO) database of intestinal mucosal tissue of CRA patients, and the differentially expressed miRNAs were screened by GEO2R and Excel. TargetScan, miRTarbase, and miRDB databases were used to predict the target genes of the differentially expressed miRNAs, and an intersection was obtained. Key DEGs were screened through the STRING database and Cytoscape software, and the TRRUST database was used to predict downstream binding transcription factors (TFs). The mRNA intersection was enriched by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) in the Metascape database. DIANA TOOLS were applied to perform KEGG enrichment analysis of key miRNAs, and the key signaling pathways were selected for animal experiments. In animal experiments, the CRA mice model was established by using sodium glycan sulfate (DSS) drinking combined with intraperitoneal injection of azomethane oxide (AOM), and Xiezhuo Jiedu recipe and aspirin were given by intragastric administration at the same time. The experiment lasted for nine weeks. The pathological changes in intestinal tissue were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-34a-5p in adenoma tissue. Protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phosphoryl-PI3K (p-PI3K), phosphoryl-Akt (p-Akt), and B cell lymphoma (Bcl)-2 were detected by Western blot. The expression of Cyclin D1 (CCND1) was detected by immunohistochemistry (IHC). In situ terminal transferase labeling (TUNEL) was used to detect apoptosis of adenoma tissue cells. ResultThe GEO database screened the GSE50194 dataset, and miR-34a-5p was selected as the research object from CRA and normal tissue. A total of 93 DEGs were selected. Among them, GO and KEGG enrichment analyses were closely related to biological processes such as transcriptional regulatory complex, RNA polymerase Ⅱ transcriptional regulatory complex, enzyme-linked receptor protein signaling pathway, and DNA-binding transcriptional activator activity, cancer pathway, PI3K/Akt pathway, etc. miR-34a-5p is mainly enriched in PI3K/Akt, cell cycle, and colorectal cancer pathways. Five key DEGs were screened out through the Matescape database, among which Bcl-2 and CCND1 were the key DEGs of miR-34a-5p. Further screening of the TFs of key DEGs revealed that E2F transcription factor 1 (E2F1) and tumor protein P53 (TP53) were the main TFs of Bcl-2 and CCND1. Animal experiments showed that Xiezhuo Jiedu recipe could effectively up-regulate mRNA level of miR-34a-5p, down-regulate the expression of PI3K, Akt, Bcl-2, p-PI3K, and p-Akt proteins in the intestinal tissue of CRA mice, down-regulate the positive expression rate of CCND1, and increase the apoptosis rate of intestinal epithelial cells. ConclusionIt is speculated that Xiezhuo Jiedu recipe may inhibit the abnormal proliferation and promote the apoptosis of intestinal epithelial cells in CRA mice by regulating the miR-34a-5p/PI3K/Akt signaling pathway, thus playing a role in the prevention of CRA.
9.Anti-tumor effects of phytosphingosine on leukemia cells by inducing cell apoptosis
Guancui YANG ; Jinyi LIU ; Peijie JIANG ; Yuxi XU ; Xiaolong TIAN ; Xiaoqi WANG ; Rui WANG ; Shijie YANG ; Qingxiao SONG ; Jin WEI ; Xi ZHANG
Journal of Army Medical University 2024;46(4):359-368
Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P<0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P<0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P<0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.
10.Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog
Jingyu ZHOU ; Haixia WU ; Jingnan QUAN ; Yanna YANG ; Shijie ZHONG ; Yi CHENG ; Meng LI ; Zengming WANG ; Nan LIU ; Aiping ZHENG ; Hui ZHANG
China Pharmacy 2024;35(10):1174-1178
OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride; the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model, the morphological changes of maxillary mucosa were investigated, and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride; cmax was (814.58±418.80) ng/mL, AUC0-∞ was (203.75± 92.76) ng·h/mL, and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride, it was observed that the cilia of bullfrog were arranged neatly, the edges were clear, the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was (178.17±13.30) min for the first time, and after the cilia moved again, the ciliary movement time measured again was (24.50±9.19)min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action, high bioavailability, and low ciliary toxicity.


Result Analysis
Print
Save
E-mail