1.Research progress of inducing ferroptosis of cancer stem cells against colorectal cancer
Li-Na GONG ; Meng-Ling YUAN ; Xue-Ying CHENG ; Chen-Yang XU ; Jun PAN ; Qiu-Tong CHEN ; Ling WANG ; Zi-Li ZHANG ; Mei GUO
Chinese Pharmacological Bulletin 2024;40(6):1030-1034
Cancer stem cell(CSC)are the"seed"cells in the occurrence,development,metastasis and recurrence of colorectal cancer.Targeted killing of CSC provides a new target for anti-colorectal cancer therapy.Ferroptosis is an iron-dependent cell death mode due to the abnormal accumulation of intracellular i-ron ions,which results in the massive reactive oxygen species(ROS)and lipid peroxides,leading to cell death.Studies have shown that cancer stem cells are more enriched in iron ions than non-CSC,which provides a new perspective for targeting ferropto-sis in cancer stem cells against colorectal cancer.This article re-views the research progress of inducing CSC ferroptosis in the treatment of colorectal cancer,such as targeted regulation of SLC7A11 expression in CSC,chelating iron in CSC lysosomes,targeting CSC phenotypic plasticity,reversing CSC iron homeo-stasis,and targeting CSC lipid droplet metabolism induce CSC ferroptosis,which provides new ideas for anti-tumor therapy.
2.Bibliometric analysis of current status of global and Chinese anesthesiology research in 2023
Yuxiang MENG ; Zijie LING ; Sumin YUAN ; Li ZHANG ; Zhibiao XU ; Yuyun LIU ; Hongyan LIU ; Qingfeng WANG ; Linlin ZHAO
Chinese Journal of Anesthesiology 2024;44(10):1239-1246
Objective:To analyze the current status of anesthesiology research in the world and China in 2023 and to identify the anesthesiology research hotspots using bibliometrics.Methods:The literature related to anesthesiology published in PubMed in 2023 was searched, and the country and author of the literature, as well as the key words of the literature were visually analyzed by using the software CiteSpace6.2. R4.Results:A total of 22 473 articles were included, the country with the largest number of publications was the United States, and China ranked second. The author with the highest number of publications in the field of anesthesiology in the worldwide in 2023 was Kaye Alan D from the United States. Chronic pain, general anesthesia and pain management were the research hotspots in the field of anesthesiology worldwide in 2023. The research hotspots in the field of anesthesiology in China focused on general anesthesia, oxidative stress and neuropathic pain.Conclusions:The United States is the leader in the research in the field of anesthesiology, with China following behind. The keywords of the literature in the field of anesthesiology between China and the world are roughly the same, reflecting the convergence of Chinese scientific research with global scientific research. Domestic anaesthesia practitioners can refer to or learn from the research hotspots of related countries and strengthen communication and cooperation between teams while conducting academic research.
3.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
4.Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB
Liu YANG ; Yu Shi WANG ; Ting Ting JIANG ; Wen DENG ; Min CHANG ; Ling Shu WU ; Hua Wei CAO ; Yao LU ; Ge SHEN ; Yu Ru LIU ; Jiao Yuan GAO ; Jiao Meng XU ; Ping Lei HU ; Lu ZHANG ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(3):303-314
Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.
5.Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury
Hua Wei CAO ; Ting Ting JIANG ; Ge SHEN ; Wen DENG ; Yu Shi WANG ; Yu Zi ZHANG ; Xin Xin LI ; Yao LU ; Lu ZHANG ; Yu Ru LIU ; Min CHANG ; Ling Shu WU ; Jiao Yuan GAO ; Xiao Hong HAO ; Xue Xiao CHEN ; Ping Lei HU ; Jiao Meng XU ; Wei YI ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(5):494-502
Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.
6.Preparation of Polyethylenimine Modified Nickel Ferrite-Graphene Oxide Material and Its Application in Enrichment of Phosphopeptides
Kai-Na ZHANG ; Yuan LIU ; Xiang-Feng WANG ; Hai-Ling LIU ; Meng-Xia XIE
Chinese Journal of Analytical Chemistry 2024;52(5):664-673
The NiFe2O4-graphene oxide nanocomposite modified with polyethylenimine(GO@PEI-NiFe2O4)was prepared to purify and enrich phosphopeptides from biosamples.The Ni2+and Fe3+ions on its surface could coordinate with phosphate groups and then selectively adsorb phosphopeptides.PEI was conducive to the above combination due to its high hydrophilicity.The material showed good magnetic response properties and could be rapidly separated from samples with the aid of magnet.With tryptic digest of β-casein as sample,the enrichment property of the material to phosphopeptides was studied,which was compared with the results of GO@NiFe2O4,revealing the adsorption mechanism of GO@PEI-NiFe2O4.The static and dynamic binding properties of GO@PEI-NiFe2O4 were investigated using pTyr as a representative phosphopeptide,and the adsorption capacity was 36.2 μg/mg.The results showed that the material could remove the interference of nonphosphopeptides and effectively enrich phosphopeptides in complex matrix.After enrichment by GO@PEI-NiFe2O4,1535 phosphopeptides were identified from the tryptic digest of rat liver by mass spectrum and the enrichment effect of GO@PEI-NiFe2O4 greatly outperformed commercial Fe3+-IMAC kits.This work provided an efficient material for the enrichment of phosphopeptides,showing potential applications in phosphoproteomics research.
7.A novel PAX9 variant in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants
Zhanyun JIN ; Junjia GUO ; Yunyun YUAN ; Lingqiang MENG ; Hui LI ; Ya ZHAO ; Jiabao REN ; Yongping MA ; Zun-Sheng XIAO ; Hong ZHANG ; Ling YANG ; Chenyun DOU ; Xiaoxue WANG ; Jinmei WANG ; Wenjing SHEN
West China Journal of Stomatology 2024;42(5):581-592
Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.
8.The characteristics and correlations of vaginal flora in women with cervical lesions.
Ming Xuan ZHANG ; Jia Hao WANG ; Le ZHANG ; Jia Xin YAN ; Cai Hong WU ; Rui Xin PEI ; Yuan Jing LYU ; Li SONG ; Meng CUI ; Ling DING ; Zhi Lian WANG ; Jin Tao WANG
Chinese Journal of Oncology 2023;45(3):253-258
Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.
Female
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Humans
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Vagina/microbiology*
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Uterine Cervical Neoplasms/genetics*
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Uterine Cervical Dysplasia
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Cervix Uteri
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Lactobacillus/genetics*
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Papillomavirus Infections
9.Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China.
Xin Cheng CAO ; Si Yuan JIANG ; Shu Juan LI ; Jun Yan HAN ; Qi ZHOU ; Meng Meng LI ; Rui Miao BAI ; Shi Wen XIA ; Zu Ming YANG ; Jian Fang GE ; Bao Quan ZHANG ; Chuan Zhong YANG ; Jing YUAN ; Dan Dan PAN ; Jing Yun SHI ; Xue Feng HU ; Zhen Lang LIN ; Yang WANG ; Li Chun ZENG ; Yan Ping ZHU ; Qiu Fang WEI ; Yan GUO ; Ling CHEN ; Cui Qing LIU ; Shan Yu JIANG ; Xiao Ying LI ; Hui Qing SUN ; Yu Jie QI ; Ming Yan HEI ; Yun CAO
Chinese Journal of Pediatrics 2023;61(1):29-35
Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant
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Infant, Newborn
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Humans
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Birth Weight
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Intensive Care Units, Neonatal
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Retrospective Studies
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Tertiary Care Centers
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Infant, Extremely Low Birth Weight
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Gestational Age
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Infant, Extremely Premature
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Sepsis/epidemiology*
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Retinopathy of Prematurity/epidemiology*
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Bronchopulmonary Dysplasia/epidemiology*
10.Quality evaluation of Cnidii Fructus in commodity grade based on theory of "quality evaluation through morphological identification".
Hui-Fang HU ; Shao-Yang XI ; Hou-Kang CAO ; Yan-Xiu GUO ; Yuan-Meng WANG ; Ling-Hui GE ; Xiao-Hui MA ; Zhi-Lai ZHAN ; Ling JIN
China Journal of Chinese Materia Medica 2023;48(4):900-907
From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.
Fruit
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Phenotype
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Principal Component Analysis
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Social Group

Result Analysis
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