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1.
Acta Pharmaceutica Sinica ; (12): 200-210, 2022.
Article in Chinese | WPRIM | ID: wpr-913169

ABSTRACT

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3+CD4+ cells, CD3+CD8+ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

2.
Acta Pharmaceutica Sinica ; (12): 2327-2333, 2022.
Article in Chinese | WPRIM | ID: wpr-937048

ABSTRACT

Tumor vaccine is one of the most promising therapeutic strategies in tumor immunotherapy. It promotes the antigen presentation process by delivering tumor antigen and then activates the anti-tumor immune response. As a new class of vaccines, messenger RNA (mRNA) vaccines can activate the immune system to achieve the purpose of immunotherapy by delivering the mRNA sequence of a specific antigen into the body and expressing the corresponding antigen protein. Compared with traditional vaccines, mRNA vaccines have the advantages of a short production cycle, high effectiveness, and strong immunogenicity. In recent years, the application of mRNA vaccines in tumor immunotherapy has attracted widespread attention, but the instability and low delivery efficiency of mRNA limit its application. Nano delivery system can effectively solve the problem of mRNA vaccine delivery, greatly promote the research process and clinical application of mRNA tumor vaccines, and has become a hot spot in the research of mRNA vaccines. In this review, we introduced the mRNA tumor vaccines, focusing on the application of nano delivery system in mRNA tumor vaccines, in order to provide new ideas and new methods for the efficient delivery of mRNA tumor vaccines and tumor immunotherapy.

3.
Article in Chinese | WPRIM | ID: wpr-936349

ABSTRACT

OBJECTIVE@#To investigate the molecular mechanism by which miR-20a-5p regulates HOXB13 gene expression and inhibits lung cancer cell proliferation.@*METHODS@#The expression levels of HOXB13 mRNA and protein in lung cancer A549 cells transfected with HOXB13 overexpression plasmid or HOXB13 siRNA were detected with real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting. CCK-8 and EdU assays were used to examine the effect of modulation of HOXB13 expression on cell proliferation. We screened possible binding miRNAs of HOXB13 by bioinformatics analysis. In A549 cells transfected with miR-20a-5p mimic or miR-20a-5p inhibitor, the expression level of miR-20a-5p was detected by qRT-PCR and the protein expression of HOXB13 was determined with Western blotting. CCK-8 and EdU assays were used to assess the effect of miR-20a-5p overexpression on the proliferation of A549 cells. miR-20a-5p mimic and HOXB13 overexpression plasmids were co-transfected into A549 cells, and the changes in cell proliferation were evaluated with CCK-8 and EdU assays.@*RESULTS@#HOXB13 overexpression obviously promoted the proliferation of A549 cells (P < 0.05). miR-20a-5p was identified as the potential binding miRNA of HOXB13. Overexpression of miR-20a-5p in A549 cells significantly decreased the expression of HOXB13 protein (P < 0.05), while interference of miR-20a-5p obviously increased HOXB13 expression (P < 0.05). The results of cell proliferation experiment showed that miR-20a-5p and HOXB13 had opposite effects on cell proliferation, and the cells overexpressing both miR-20a-5p and HOXB13 showed a lower proliferation activity than the cells overexpressing HOXB13 but higher than the cells overexpressing miR-20a-5p alone (P < 0.05).@*CONCLUSION@#miR-20a-5p inhibits proliferation of lung cancer cells by down-regulating the expression of HOXB13.


Subject(s)
A549 Cells , Apoptosis , Cell Line, Tumor , Cell Proliferation , Homeodomain Proteins/genetics , Humans , Lung Neoplasms/genetics , MicroRNAs/genetics , Sincalide
4.
Journal of Preventive Medicine ; (12): 511-514, 2022.
Article in Chinese | WPRIM | ID: wpr-923707

ABSTRACT

Objective@#To analyze the trends in incidence of thyroid cancer in Fuling District, Chongqing Municipality from 2016 to 2020 and predict the incidence of thyroid cancer from 2021 to 2023, so as to provide insights into thyroid cancer control.@*Methods@#The data pertaining to incidence of thyroid cancer in Fuling District from 2016 to 2020 were collected through National Central Cancer Registry of China. The crude incidence rate ( CR ) of thyroid cancer, the standardized incidence rate of thyroid cancer by Chinese standard population ( ASR China ) and by world standard population ( ASR world ) were calculated. The trend in thyroid cancer incidence was analyzed using annual percent change ( APC ). The GM ( 1, 1 ) grey model was created to predict the crude incidence of thyroid cancer in Fuling District from 2021 to 2023, and the fitting effect and predictive accuracy of the model were evaluated using posterior error ratio ( C ), small probability error ( p ) and mean absolute percent error ( MAPE ).@*Result@#A total of 686 new cases of thyroid cancer were reported in Fuling District from 2016 to 2020, with CR of 11.84/105, ASR China of 11.93/105 and ASR world of 10.02/105. Among the 686 new cases of thyroid cancer, there were 165 male cases, with CR of 5.69/105, ASR China of 5.66/105 and ASR world of 4.81/105, and 521 female cases, with CR of 18.02/105, ASR China of 18.17/105 and ASR world of 15.24/105. The CR appeared a tendency towards a rise among the whole population and women in Fuling District from 2016 to 2021, with APC values of 38.40% ( t=3.369, P=0.043 ) and 38.68% ( t=4.035, P=0.027 ). The incidence of thyroid cancer peaked among patients at ages of 25 to 34 years and 50 to 54 years, with CR of 22.82/105 and 39.06/105, respectively. The GM ( 1, 1 ) grey model was qualified to fit the incidence of thyroid cancer among the whole population ( C=0.56, p=0.75 ) and women ( C=0.53, p=1.00 ). In addition, the CR of thyroid cancer was predicted to be 19.48/105, 22.51/105 and 26.03/105 ( MAPE=9.93% ) among the whole population, and 31.43/105, 37.37/105 and 44.46/105 ( MAPE=11.30% ) among women, respectively.@*Conclusions@#The incidence of thyroid cancer appeared a tendency towards a rise in Fuling District from 2016 to 2021, and is projected to increase among the whole population and women from 2021 to 2023. Women and the elderly are at high risk of thyroid cancer.

5.
Acta Pharmaceutica Sinica ; (12): 638-643, 2022.
Article in Chinese | WPRIM | ID: wpr-922879

ABSTRACT

A large number of cancer-associated fibroblasts (CAFs) in tumor tissues create a favorable environment for the development of tumor. CAFs inhibit immune cells activation and viability by cytokine secretion, and CAFs prohibit drugs and immune cells infiltration by producing extracellular matrix to weaken cancer treatment efficacy. Regulating CAFs or overcoming CAFs barriers are new strategies for cancer therapy. Hence, designing nano-carriers for regulating CAFs to suppress tumor progression or promoting drug delivery to tumor site by overcoming CAFs barriers has attracted much attention. Therefore, this manuscript reviewed the recent progresses of nano-carriers for CAFs-targeting cancer therapies, in order to provide a reference for clinical cancer treatment.

6.
Acta Pharmaceutica Sinica B ; (6): 2568-2577, 2022.
Article in English | WPRIM | ID: wpr-929388

ABSTRACT

Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.

7.
Article in Chinese | WPRIM | ID: wpr-942334

ABSTRACT

ObjectiveTo compare the effects of different drying methods on volatile components of Pseudostellariae Radix. MethodThe samples were dried by different methods, including air drying, sun drying, hot air drying (40, 60, 80 ℃) and vacuum freeze drying. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to compare the changes of volatile components in the samples after different treatments. The samples were incubated at 80 ℃ and 500 r·min-1 for 15 min, the injection temperature was 85 ℃, the injection volume was 200 μL, the flow rate of carrier gas was from 2 mL to 150 mL during 20 min, and the temperature of IMS detector was 60 ℃. SE-54 capillary column (0.32 mm×30 m, 0.25 μm) was used, the column temperature was 60 ℃, and the analysis time was 35 min. The differential spectra of volatile components were constructed and analyzed by principal component analysis (PCA). ResultA total of 37 volatile components were identified from dried Pseudostellariae Radix. The number of compounds in descending order was ketones, aldehydes and alcohols. There were some differences in the volatile components in samples dried by different methods. And the volatile components in samples with sun drying, air drying and hot air drying at 40 ℃ were similar, compared with other drying methods, vacuum freeze drying and hot air drying at 80 ℃ had great effects on the volatile components of Pseudostellariae Radix, and the compounds in the samples with vacuum freeze drying were the least. ConclusionIn this study, GC-IMS for the detection and analysis of volatile components in Pseudostellariae Radix is established, which has the characteristics of high efficiency, nondestructive inspection and simple sample processing. This method can be used for the distinction of Pseudostellariae Radix dried by different methods. And hot air drying at 40 ℃ can effectively retain the volatile components of Pseudostellariae Radix, and achieve similar flavor to samples with sun drying and air drying.

8.
Acta Pharmaceutica Sinica ; (12): 2662-2670, 2022.
Article in Chinese | WPRIM | ID: wpr-941525

ABSTRACT

Glioblastoma (GBM) is the most common primary brain tumor, which is prone to recurrence and metastasis with poor prognosis. In recent years, immunotherapy has prolonged the survival of patients with GBM, providing a new option for the treatment of GBM. Target selection is very important for immunotherapy. Epidermal growth factor receptor variant III (EGFRvIII) is highly expressed on the surface of GBM cells in some patients, and EGFRvIII was not expressed in normal tissues. EGFRvIII are pivotal for the occurrence and progression of GBM, various targeted therapy including immunotherapy is promising to improve the efficacy of GBM. Currently, there are various approaches to target EGFRvIII, including humanized monoclonal antibodies, adoptive cell therapies and therapeutic vaccines. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM.

9.
Article in Chinese | WPRIM | ID: wpr-940809

ABSTRACT

ObjectiveTo explore the distribution mechanism of network modules in the combined treatment of liver cancer with Jiuwei Zhengxiao granules (JWZX) based on the analysis framework of module pharmacology. MethodThe cell experiment and the animal experiment were carried out to investigate the in vitro anti-liver cancer efficacy of JWZX of different concentrations and the effect on the survival time of H22 ascites tumor mice. By virtue of the analysis strategy of modular pharmacology,the distribution characteristics of nine Chinese drugs in the liver cancer disease network modules were investigated based on the constructed liver cancer disease network and module division by MCODE. In this study,the average degree (AD) of the nodes in the modules was used as an index to screen the main modules of the disease,and the intervention of the sovereign drugs,minister drugs,and assistant drugs on the main modules was explored. Finally,the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the drug-acted modules by Metascape. ResultAs revealed by the cell experiment,JWZX could significantly inhibit the proliferation of H22 cells. The animal experiment demonstrated that the medium- and high-dose JWZX could significantly prolong the survival time of mice with H22 ascites tumor (P<0.05,P<0.01). The distribution of targets of JWZX in the liver cancer disease network modules showed that JWZX interfered with tumor necrosis factor (TNF),epidermal growth factor receptor (EGFR),vascular endothelial growth factor A (VEGFA),transcription factor (JUN),tumor protein p53 (TP53),and other 26 targets and 8 modules. The sovereign drug Ginkgo Semen mainly intervened in modules 3 and 8,and the minister drugs such as Centipeda Herba jointly intervened in modules 1,3,5,8,10,and 12. Centipeda Herba and Phyllanthi Fructus intervened in module 7 and module 19 individually. Artemisiae Annuae Herba and other assistant drugs jointly intervened in modules 3,5,10,and 12. KEGG pathway enrichment analysis found that 135 pathways were enriched in 8 modules,and the pathway functions involved 12 categories including cancer,signal transduction,immune system,endocrine system,and amino acid metabolism. The functions of the four major modules involved cancer,signal transduction,and immune system. According to the results of literature verification,the key links of JWZX on the liver cancer disease network and the core mechanism were presumedly related to the inhibition of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and hypoxia-inducible factor-1 (HIF-1) signaling pathways,reduction of the immunosuppressive effect in the tumor microenvironment,and improvement of the anti-tumor immune response. ConclusionJWZX possesses pharmacological activity against liver cancer,and the therapeutic efficacy was achieved through the multiple targets,multiple modules,and multiple functions of drugs alone or in combination to intervene in the disease. The present study reduced the complexity of drug-disease target network analysis with module analysis strategy and explored the network module distribution mechanism of JWZX in the treatment of liver cancer,which provides a new idea for interpreting the complex mechanism of prescription compatibility.

10.
Article in Chinese | WPRIM | ID: wpr-940693

ABSTRACT

ObjectiveTo explore the intervention effect of Erxian decoction on intestinal microflora after ovariectomy in rats by 16S rRNA gene sequencing. MethodThirty-two female healthy SD rats were randomly divided into a Sham operation (Sham) group, a model (OVX) group, an estrogen (E) group, and an Erxian decoction (EXD) group, with 8 rats in each group. The rats in the E group and the EXD group received 1.8×10-4 g·kg-1 estradiol valerate solution and 9 g·kg-1 Erxian decoction, respectively, and those in the Sham group and the OVX group received an equal volume of distilled water once a day for 16 weeks. After 16 weeks, the levels of serum estrogen and blood lipid were detected. The fecal DNA was extracted, followed by 16S rRNA gene sequencing and analysis. ResultCompared with the Sham group, the OVX group showed reduced serum estrogen level (P<0.01) and increased serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P<0.05). Compared with the OVX group, the E group and the EXD group showed increased serum estrogen level (P<0.01) and reduced TC and LDL-C (P<0.05). Alpha diversity showed that there was no significant change in intestinal microflora diversity after ovariectomy. Beta diversity showed that there were significant differences in the structure of intestinal microflora in the four groups. The intervention of Erxian decoction could improve the changes in intestinal microflora after ovariectomy. LEfSe was used to analyze the differential flora in the four groups. The results showed that the Sham group and the OVX group had 3 differential bacterial phyla and 18 differential bacterial genera, the OVX group and the E group had 1 differential bacterial phylum and 12 differential bacterial genera, and the OVX group and the EXD group had 3 differential bacterial phyla and 5 differential bacterial genera. Estrogen intervention could reverse the change trend of Ruminococcus 1, Anaerovibrio, and Turicibacter in the OVX group. Erxian decoction intervention could reverse the change trend of Bacteroidetes, Firmicutes, Prevotella 9, Ruminococcaceae UCG-014, Ruminococcus 1, and Fusicatenibacter in the OVX group. ConclusionThe structure and function of intestinal microflora in ovariectomized rats changed obviously, and Erxian decoction could ameliorate the change.

11.
Article in Chinese | WPRIM | ID: wpr-940512

ABSTRACT

ObjectiveTo explore the effect of Qishengwan on ileal flora during its treatment of Alzheimer's disease (AD) under the guidance of the theory of "interior-exterior relationship between heart and small intestine". MethodThe AD model was established by bilateral intraventricular injection of β-amyloid 1-42 (Aβ1-42). The rats were then randomly divided into the blank group, sham-operated group, model group, low-, medium-, and high-dose (5.6, 11.2,22.4 g·kg-1·d-1) Qishengwan groups, and donepezil (0.46 mg·kg-1·d-1) group. After medication for 28 successive days, the spatial memory ability of rats was observed in water maze test, and the levels of Aβ1-42, nuclear transcription factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the hippocampus were analyzed by enzyme-linked immunosorbent assay (ELISA). Additionally, the contents of the ileum were collected and subjected to 16SrRNA-sequencing analysis for figuring out the changes in ileal flora. ResultCompared with the blank group and sham-operated group, the model group exhibited significantly reduced stay time in the target quadrant and number of target quadrant and platform crossings (P<0.05, P<0.01) and elevated Aβ1-42 content in the hippocampus (P<0.01) and central inflammatory factors NF-κB, TNF-α, and IL-6 (P<0.05, P<0.01). Compared with the model group, Qishengwan at each dose significantly alleviated the impaired spatial memory function (P<0.05, P<0.01), improved the deposition of Aβ1-42 in the hippocampus of rats (P<0.05, P<0.01), and reduced the expression of central nervous system inflammatory factors (P<0.05, P<0.01), thus exerting a good therapeutic effect on AD rats. The 16SrRNA-sequencing analysis results showed that the structure of the ileal flora in the model group was significantly separated from those in the blank group and sham-operated group. The abundance of Lachnospiraceae NK4A136 group was significantly increased (P<0.01), while that of Escherichia-Shigella was reduced (P<0.05, P<0.01). Qishengwan at each dose significantly changed the ileal flora structure and regulated the relative abundance of Lachnospiraceae NK4A136 group, Escherichia-Shigella, and Ruminococcaceae. ConclusionQishengwan has a positive therapeutic effect on AD. It can significantly enhance the memory and cognitive abilities in AD rats, which may be related to its regulation of the structure of rat ileal flora and the relative abundance of Lachnospiraceae NK4A136 group, Escherichia-Shigella, and Ruminococcaceae, the attenuation of the central neuroinflammatory response, and the reduction of central Aβ1-42 deposition.

12.
Article in English | WPRIM | ID: wpr-939849

ABSTRACT

Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3'-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.


Subject(s)
Adipose Tissue/metabolism , Animals , Cell Differentiation/genetics , Cells, Cultured , Histone Deacetylases/metabolism , Humans , Mice , MicroRNAs/metabolism , Osteogenesis/genetics , RNA, Circular/metabolism , Repressor Proteins/metabolism , Signal Transduction , Stem Cells/metabolism
13.
Article in Chinese | WPRIM | ID: wpr-939696

ABSTRACT

OBJECTIVE@#To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP).@*METHODS@#Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed.@*RESULTS@#The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment.@*CONCLUSION@#RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.


Subject(s)
Adult , Aged , Female , Glucocorticoids/therapeutic use , Humans , Male , Middle Aged , Platelet Count , Platelet Transfusion , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Recombinant Proteins/therapeutic use , Thrombopoietin/therapeutic use , Young Adult
14.
Article in Chinese | WPRIM | ID: wpr-939662

ABSTRACT

OBJECTIVES@#To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC.@*METHODS@#A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model.@*RESULTS@#The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P<0.05). The ROC curve of the development set had an area under the curve (AUC) of 0.833 (95%CI: 0.715-0.952), and the ROC curve of the validation set had an AUC of 0.826 (95%CI: 0.797-0.862), suggesting that the nomogram model had a good discriminatory ability. The calibration curve analysis and the Hosmer-Lemeshow goodness-of-fit test showed good accuracy and consistency between the predicted value of the model and the actual value.@*CONCLUSIONS@#Neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding are independent risk factors for NEC in very preterm infant. The nomogram model based on the multivariate logistic regression analysis provides a quantitative, simple, and intuitive tool for early assessment of the development of NEC in very preterm infants in clinical practice.


Subject(s)
Asphyxia/complications , Child , Enterocolitis, Necrotizing/etiology , Female , Fetal Growth Retardation , Humans , Hypoalbuminemia , Infant , Infant, Newborn , Infant, Newborn, Diseases , Infant, Premature , Infant, Premature, Diseases/etiology , Nomograms , Sepsis/complications
15.
Acta Physiologica Sinica ; (6): 479-488, 2022.
Article in Chinese | WPRIM | ID: wpr-939582

ABSTRACT

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.


Subject(s)
Aging/pathology , Cellular Senescence , Humans , Lung/pathology , Lung Diseases/pathology , Respiration Disorders/pathology , Telomere , Telomere Shortening
16.
Chinese Journal of Pediatrics ; (12): 435-441, 2022.
Article in Chinese | WPRIM | ID: wpr-935716

ABSTRACT

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Child , China/epidemiology , Cryptorchidism/genetics , Disorders of Sex Development/genetics , Female , Genital Diseases, Male , Genotype , Humans , Hypospadias/genetics , Male , Membrane Proteins/genetics , Penis/abnormalities , Phenotype , Retrospective Studies , Steroid 21-Hydroxylase/genetics
17.
Chinese Journal of Epidemiology ; (12): 548-553, 2022.
Article in Chinese | WPRIM | ID: wpr-935425

ABSTRACT

Objective: To analyze the incidence of leptospirosis in Fujian province from 2015 to 2020 and provide the scientific evidences for the risk assessment, prevention and control of leptospirosis. Methods: The incidence data of leptospirosis in Fujian during 2015-2020 were collected from China Information System for Disease Control and Prevention for a descriptive analysis, and software ArcGIS 10.3.1 was used for spatial autocorrelation analysis, and rats were captured in 17 surveillance areas during the same period, and the rat organs were collected for pathogen culture, the level of Leptospira antibody was detected in serum samples of rats, healthy population and the serum samples of patients sent by the hospitals. The infection status of Leptospira in human and rats were analyzed. Results: The incidence of leptospirosis in Fujian showed a downward trend from 2015 to 2020. A total of 176 cases of leptospirosis were reported. There were obvious seasonality and bimodal distribution. The majority of cases were farmers, accounting for 49.43% (87/176). Most cases were aged 30-69 years (85.80%, 151/176). The male to female ratio of the cases was 3.51∶1 (137∶39). Spatial autocorrelation analysis showed that leptospirosis had high or low clustering areas. From 2015 to 2020, the average capture rate of rats in 17 surveillance areas was 6.96% (1 519/21 838), Rattus losea, Rattus flavipectus and Niviventer fulvescens were the main species. The average positive rate of Leptospira antibody in rats was 28.64% (252/880). Java and Autumnalis were the predominant serogroups, accounting for 56.75% (143/252) and 17.46% (44/252), respectively. The average positive rate of Leptospira antibody in healthy population was 16.13% (254/1 575), and Autumnalis and Australis were the predominant serogroups, accounting for 71.65% (182/254). The confirmation rate of leptospirosis in patient serum samples sent by the hospitals was 2.23% (188/8 431), Autumnalis (56.38%, 106/188) and Hebdomadis (19.68%, 37/188) were the major serogroups. Conclusions: The incidence of leptospirosis in Fujian showed a downward trend from 2015 to 2020, there were obvious area clustering and seasonality. The high clustering areas were mainly distributed in northern, western and central Fujian. Java and Autumnalis were the predominant serogroups in rats. The infection rate in healthy population decreased year by year. Autumnalis and Hebdomadis were the main serogroups in population in Fujian.


Subject(s)
Animals , Antibodies, Bacterial , Female , Humans , Incidence , Leptospira , Leptospirosis/epidemiology , Male , Rats , Serogroup
18.
Article in Chinese | WPRIM | ID: wpr-935351

ABSTRACT

Objective: To examine the associations between metabolic syndrome (MS) and the risks for impaired activities of daily living (ADL) in the middle-aged and elderly population in China and provide basis for improving healthy life expectancy. Methods: Prospective cohort study design was used in this study. Based the data of China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018 and the baseline data in 2011, the follow up for ADL outcomes was conducted in 2013, 2015 and 2018 respectively, and the participants recruited in 2013 and 2015 were new baseline populations. The participants with impaired ADL in three baseline populations were excluded. Cox proportional hazard model was used to estimate the effect of different components and number of MS components on the risk for ADL impairment in the middle-aged and elderly population in China. Results: In 59 795 person-years of follow-up, a total of 1 011 cases of ADL impairments were recorded. The incidence density of ADL impairment was 16.91 per 1 000 person-year; The findings of Cox regression analysis showed that compared with the middle aged and elderly people without MS, the risk for ADL impairments was 1.29 times higher (95%CI: 1.12-1.50) for those with one component of MS, 1.32 times higher (95%CI:1.07-1.64) for those with hyperlipemia complicated with diabetes, 1.78 times higher (95%CI: 1.22-2.59) for those with obesity and one component of MS, 2.48 times higher (95%CI:1.59-3.85) for those with hypertension complicated with hyperlipemia, 3.51 times higher (95%CI:1.66-7.43) for those with hypertension complicated with diabetes, 1.80 times higher (95%CI: 1.40-2.32) for those with ≥3 MS, respectively. Compared with the middle-aged and elderly population without MS, the risk for impaired ADL increased by 30% (HR=1.30, 95%CI: 1.13-1.51), 54% (HR=1.54, 95%CI: 1.28-1.85) and 87% (HR=1.87, 95%CI:1.45-2.41), respectively, in the middle-aged and elderly with one, two, and more than three components of MS, with a significant dose-response relationship that ADL impaired risks increased as the number of MS components increased (P<0.001). Conclusions: Our findings suggested that MS is a risk factor for ADL impairment in middle-aged and elderly population in China. Prevention and early intervention of obesity, hypertension, hyperlipemia, diabetes and metabolic syndrome could help to reduce or delay the incidence of ADL impairment.


Subject(s)
Activities of Daily Living , Aged , China/epidemiology , Humans , Longitudinal Studies , Metabolic Syndrome/epidemiology , Middle Aged , Prospective Studies
19.
Article in Chinese | WPRIM | ID: wpr-935238

ABSTRACT

The risk of plague epidemics and relapse of various types of plague foci persists in Inner Mongolia Autonomous Region. For Marmota sibirica plague foci, the animal plague has not been found but antibody has been detected positive. Nowadays, Marmota sibirica has been increasing in population and distribution in China. In bordering countries Mongolia and Russia, the animal plague has been continuously prevalent. For Spermophilus dauricus plague foci, the animal plague has been taken place now and then. Compared to the above foci, the animal plague is most prevalent in Meriones unguiculatus plague foci and frequently spread to humans. Due to higher strain virulence and historical disaster in Marmota sibirica plague foci and Spermophilus dauricus plague foci, plague prevention and control should be strengthened on these foci. In addition to routine surveillance, epidemic dynamics need to be further monitored in these two foci, in order to prevent their relapse and spread to humans.


Subject(s)
Animals , China/epidemiology , Epidemics , Humans , Plague/prevention & control , Prevalence , Sciuridae , Yersinia pestis
20.
Article in Chinese | WPRIM | ID: wpr-934114

ABSTRACT

Objective:To evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt.Methods:Data of 24 patients with gastric fundal varices with large spontaneous shunt (the smallest diameter was 5-15 mm) treated by EUS-guided coil embolization combined with endoscopic cyanoacrylate injection in Renmin Hospital of Wuhan University from December 2016 to December 2020 were retrospectively analyzed. The short-term efficacy (the rates of technical success, five-day rebleeding and six-week mortality) and long-term efficacy (the rates of one-year rebleeding, one-year mortality and three-year mortality) and safety (ectopic embolism) were evaluated.Results:The technical success rate was 91.7% (22/24), and the five-day rebleeding rate was 0 (0/22). Computed tomography angiography of portal vein reexamined 2 days after the treatment showed embolism of splenic vein in 1 patient (4.5%). The median follow-up time was 14.9 months (ranging 1.0-48.6 months) and 2 patients were lost during follow-up. The six-week mortality was 0 (0/20), and the one-year rebleeding rate was 35.0% (7/20). Among 12 patients who underwent endoscopy in the follow-up, 5 had aggravation of esophageal varices, and 5 had aggravation of portal hypertension gastropathy. The one-year and three-year mortalities were 5.0% (1/20) and 20.0% (4/20), respectively, neither of which was related to such events as bleeding or ectopic embolism.Conclusion:EUS-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt is effective and safe in short term, with a low rate of ectopic embolism. Long-term efficacy and safety need to be further confirmed.

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