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1.
Acta Anatomica Sinica ; (6): 88-97, 2024.
Article in Chinese | WPRIM | ID: wpr-1015151

ABSTRACT

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

2.
Chinese Pharmacological Bulletin ; (12): 285-291, 2024.
Article in Chinese | WPRIM | ID: wpr-1013632

ABSTRACT

Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

3.
Article in English | WPRIM | ID: wpr-1010324

ABSTRACT

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.


Subject(s)
Mice , Animals , Mitogen-Activated Protein Kinase 14/metabolism , Wolfiporia , Lipopolysaccharides/pharmacology , Sepsis/complications , Signal Transduction , Inflammation/drug therapy , Oxygen Radioisotopes
4.
Chinese Journal of Hepatology ; (12): 77-83, 2023.
Article in Chinese | WPRIM | ID: wpr-970955

ABSTRACT

Objective: To explore the pathogenic mechanism of the miR-340/high mobility group box 1 (HMGB1) axis in the formation of liver fibrosis. Methods: A rat liver fibrosis model was established by injecting CCl(4) intraperitoneally. miRNAs targeting and validating HMGB1 were selected with gene microarrays after screening the differentially expressed miRNAs in rats with normal and hepatic fibrosis. The effect of miRNA expressional changes on HMGB1 levels was detected by qPCR. Dual luciferase gene reporter assays (LUC) was used to verify the targeting relationship between miR-340 and HMGB1. The proliferative activity of the hepatic stellate cell line HSC-T6 was detected by thiazolyl blue tetrazolium bromide (MTT) assay after co-transfection of miRNA mimics and HMGB1 overexpression vector, and the expression of extracellular matrix (ECM) proteins type I collagen and α-smooth muscle actin (SMA) was detected by western blot. Statistical analysis was performed by analysis of variance and the LSD-t test. Results: Hematoxylin-eosin and Masson staining results showed that the rat model of liver fibrosis was successfully established. Gene microarray analysis and bioinformatics prediction had detected eight miRNAs possibly targeting HMGB1, and animal model validation had detected miR-340. qPCR detection results showed that miR-340 had inhibited the expression of HMGB1, and a luciferase complementation assay suggested that miR-340 had targeted HMGB1. Functional experiments results showed that HMGB1 overexpression had enhanced cell proliferation activity and the expression of type I collagen and α-SMA, while miR-340 mimics had not only inhibited cell proliferation activity and the expression of HMGB1, type I collagen, and α-SMA, but also partially reversed the promoting effect of HMGB1 on cell proliferation and ECM synthesis. Conclusion: miR-340 targets HMGB1 to inhibit the proliferation and ECM deposition in hepatic stellate cells and plays a protective role during the process of liver fibrosis.


Subject(s)
Animals , Rats , Cell Proliferation , Collagen Type I/metabolism , Fibrosis , Hepatic Stellate Cells , HMGB1 Protein/genetics , Liver Cirrhosis/pathology , MicroRNAs/metabolism
5.
Article in Chinese | WPRIM | ID: wpr-970899

ABSTRACT

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1).@*METHODS@#A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing.@*RESULTS@#The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously.@*CONCLUSION@#Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.


Subject(s)
Female , Humans , Child , Gas Chromatography-Mass Spectrometry , Genetic Testing , Mutation , Phenotype , Prenatal Diagnosis , Tyrosinemias/genetics
6.
Journal of Modern Urology ; (12): 50-58, 2023.
Article in Chinese | WPRIM | ID: wpr-1005465

ABSTRACT

【Objective】 To evaluate the value of platelet-to-lymphocyte ratio (PLR) in the prognosis of prostate cancer. 【Methods】 Relevant studies were searched in CNKI, Wanfang, CBM, VIP, PubMed, Web of Science, Cochrane Library and Embase databases from inception to Dec.2021. The literature was screeded, data were extracted, and the quality was evaluated according to the inclusion and exclusion criteria. A meta-analysis by using the hazard risk (HR) and 95% confidence interval (CI) was adopted to assess the prognostic value of PLR. The data were analyzed with STATA 16.0 software. 【Results】 A total of 10 studies were included, involving 1 802 patients. For patients with high level of PLR, the overall survival (OS) (HR=1.70, 95%CI:1.25-2.30, P=0.001) and disease-free survival (DFS)(HR=1.44, 95%CI:1.15-1.81, P=0.002) were significantly shorter. 【Conclusion】 PLR is an independent risk factor affecting the long-term prognosis of prostate cancer patients. Pretreatment detection of PLR is meaningful in determining the prognosis.

7.
Chinese Journal of School Health ; (12): 1894-1897, 2023.
Article in Chinese | WPRIM | ID: wpr-1004914

ABSTRACT

Objective@#To understand the prevalence and associated factors of functional constipation(FC) among primary and middle school students in Shaanxi Province, in order to provide a basis for preventing FC in students.@*Methods@#A stratified cluster random sampling method was used to conduct a questionnaire survey on 9 133 primary and middle school students aged 10-18 in eight primary and secondary schools in Shaanxi Province from March to September,2017. Chi square test and multivariate Logistic regression were used to analyze the associated factors of FC among primary and middle school students in Shaanxi Province.@*Results@#There were a total of 364 students meeting the FC Rome IV diagnostic criteria, with a prevalence rate of 3.99%. Among them, there were 155 male students with a prevalence rate of 3.43%, and 209 female students with a prevalence rate of 4.53%. Univariate analysis showed that gender, breastfeeding, separation from parents, long term school meals, types of staple foods, breakfast frequency, cold foods eating frequency, spicy foods eating frequency, fried food eating frequency, pickled food eating frequency, desserts eating frequency, vegetables eating frequency were related to FC, and the differences were statistically significant ( χ 2=7.30,18.75, 20.89,35.54,22.43,16.05,21.31,13.97,10.33,23.96,16.25,17.74, P <0.05). Multivariate Logistic regression analysis showed that female, non breastfeeding, separation from parents, long term school meals, low consumption of staple food/staple food dominated by rice, and never eating vegetables were positively correlated with FC( OR =1.37,1.96,1.52,2.07,1.76,1.58,2.31, P < 0.05 ).@*Conclusions@#The prevalence of functional constipation is higher in primary and middle school students. Attention should be paid to factors related to students dietary habits and food classification to prevent the occurrence of FC in primary and middle school students.

8.
Article in Chinese | WPRIM | ID: wpr-996809

ABSTRACT

ObjectiveTo investigate the mechanism of icariin in ameliorating efferocytosis dysfunction and inflammatory response of alveolar macrophages induced by cigarette smoke extract via the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway. MethodThe untreated rat alveolar macrophages (NR8383) were taken as the blank group. The NR8383 cells treated with 10% cigarette smoke extract were divided into model, low-, medium-, and high-dose (10, 20, 40 μmol·L-1) icariin, PPARγ inhibitor, and PPARγ inhibitor + low-, medium-, and high-dose icariin groups. Alamar blue colorimetry was employed to examine the proliferation and toxicity of icariin on NR8383 cells. The efferocytosis rate of NR8383 cells was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), and milk fat globule-epidermal growth factor 8 (MFG-E8). Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were employed to determine the protein and mRNA levels, respectively, of PPARγ, CD36, and RAS-related C3 botulinum toxin substrate 1 (Rac1). ResultThe efferocytosis dysfunction model of NR8383 was established with the cigarette smoke extract. Compared with the blank control group, the model group showed decreased efferocytosis rate (P<0.05), elevated TNF-α level (P<0.05), lowered TGF-β1 and MFG-E8 levels (P<0.01), and down-regulated mRNA and protein levels of PPARγ, CD36, and Rac1 (P<0.05, P<0.01). Compared with the model group, the treatment with icariin increased the efferocytosis rate (P<0.05, P<0.01), lowered the TNF-α level (P<0.01), elevated TGF-β1 and MFG-E8 levels (P<0.05), and up-regulated the protein and mRNA levels of PPARγ, CD36, and Rac1 (P<0.05, P<0.01). Compared with icariin alone, PPARγ inhibitor + icariin decreased the efferocytosis rate (P<0.05) and down-regulated the protein and mRNA levels of PPARγ (P<0.05, P<0.01). In addition, PPARγ inhibitor + low-dose icariin down-regulated the protein level of CD36 (P<0.01) and PPARγ inhibitor + low-/medium-dose icariin up-regulated the protein level of Rac1 (P<0.05). ConclusionIcariin ameliorates the cigarette smoke extract-induced efferocytosis dysfunction of alveolar macrophage by regulating the PPARγ signaling pathway and cytoskeletal structure rearrangement.

9.
Article in Chinese | WPRIM | ID: wpr-993070

ABSTRACT

Objective:To investigate the effect of radiofrequency radiation (RF) from 5G mobile phone communication frequency bands (3.5 GHz and 4.9 GHz) on the permeability of the blood-brain barrier (BBB) in mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into Sham, 3.5 GHz RF and 4.9 GHz RF groups, and 8 mice in each group. Mice in the RF groups were systemically exposed to 5G cell phone radiation for consecutive 35 d(1 h/d) with 50 W/m 2 power density. The BBB permeability of mice was detected by Evans Blue (EB) fluorescence experiment. The expression levels of the BBB tight junction-related proteins (ZO-1, occludin and claudin-11) and the gap junction-related protein Connexin 43 were determined by Western blot. Results:The number of spots, fluorescence intensity and comprehensive score of EB were significantly increased in 3.5 GHz RF group and 4.9 GHz RF group compared with the Sham group ( t=12.98, 17.82, P<0.001). Compared with the Sham group, the content of S100B in mouse serum was significantly increased in 3.5 GHz RF group and 4.9 GHz RF group ( t=19.34, 14.68, P<0.001). The BBB permeability was increased in the RF group. The expression level of occludin protein was significantly reduced in the 3.5 GHz RF group ( t=-3.13, P<0.05), and this decrease was much profound in the 4.9 GHz RF group ( t=-6.55, P<0.01). But the protein levels of ZO-1, Claudin-11 and Connexin 43 in the cerebral cortex of the RF groups had no significantly difference in comparison with the Sham group( P>0.05). Conclusions:The continuous exposure of mobile phone RF at 3.5 GHz or 4.9 GHz for 35 d (1 h/d) induces an increase of BBB permeability in the mouse cerebral cortex, perhaps by reducing the expression of occludin protein.

10.
Article in Chinese | WPRIM | ID: wpr-1013876

ABSTRACT

Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K

11.
Article in Chinese | WPRIM | ID: wpr-989906

ABSTRACT

Objective:To analyze the effects of umbilical laparoendoscopic single-site surgery (U-LESS) and conventional laparoscopic appendectomy (CLS) on the treatment of acute appendicitis in children by using Meta-analysis. To evaluate the effectiveness and safety of U-LESS in treating acute appendicitis in children.Methods:The English databases Pubmed, Web of Science, the Cochrane Library, Clinical trials, CNKI, Weipu Database, Wanfang Medical Network Database, CBM literature and other Chinese databases were retrieved, and the relevant literature of the comparative study of U-LESS and CLS in the treatment of pediatric acute appendicitis was found, and the quality analysis and application of the selected comparative studies were carried out. RevMan5.3 and stata software were employed to compare the operation time, intraoperative blood loss, postoperative exhaust time, postoperative intestinal recovery time, incision length, postoperative hospital stay time, postoperative complications, etc. of different surgical procedures.Results:A total of 19 literature were included in this study, and a total of 2133 cases were included, including 1021 cases in the U-LESS group and 1112 cases in the CLS group, all of which were retrospective case-control studies. Meta analysis showed that the operation time in U-LESS was shorter than that in CLS (95%CI [-9.05, -3.17], Z=4.07, P<0.001) , and the intraoperative bleeding volume of U-LESS was less than that of CLS (95%CI [-15.28, -5.01], Z=3.87, P<0.001) , incision length was shorter in U-LESS than in CLS (95%CI [-1.40, -1.27], Z=39.30, P<0.001) , the postoperative exhaust time of U-LESS was shorter than that of CLS (95%CI [-8.63, -5.89], Z=10.37, P<0.001) , and the recovery time after U-LESS was shorter than that after CLS (95% CI, 95% CI, P<0.001) . U-LESS and CLS did not differ significantly in postoperative length of stay (95%CI [-1.33, -0.64], Z=5.61, P<0.001) . U-LESS had fewer postoperative complications compared with CLS (95%CI [0.24,0.52], Z=5.27, P<0.001) . Conclusion:For pediatric acute appendicitis, U-LESS is safe and feasible, and has the advantages of shortening the operation time and reducing intraoperative bleeding.

12.
Article in Chinese | WPRIM | ID: wpr-989749

ABSTRACT

Objective:To explore the molecular mechanism of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease (AD) with the same treatment through network pharmacology. Methods:Effective components of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were retrieved from TCMSP, TCMID and ETCM databases. The disease targets of depression and AD were retrieved from GeneCards, TTD and CTD databases. Targets of action of drugs on active components were predicted through SwissTargetPrediction, and then the intersection targets of medicinal pair and the diseases were taken. Cytoscape 3.6.1 was used to construct the interaction network of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair on "component-common target-disease". The enrichment analysis of GO function and KEGG pathway was carried out with the help of Metascape platform, and molecular docking verification was carried out. Results:Through searching the databases and literature, 78 compounds in Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were obtained, corresponding to 41 targets of different diseases with the same treatment. The GO function was mainly concentrated in response to lipopolysaccharide and cellular response to nitrogen compound. The KEGG pathway was mainly concentrated in lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on. The core targets were PTGS2, ESR2, etc. Molecular docking showed that most of the core components could form stable conformation with the core targets. Conclusions:Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair has the characteristics of multi-component, multi-target and multi-pathway in the same treatment of depression and AD. Through their core components of senegenin, 1-carbobutoxy-β-carboline, 6-hydroxy-1,2,3,7-tetramethoxyxanthone, kaempferol and etc., the pair can act on PTGS2 and other targets, regulate lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on, and play a therapeutic role in depression and Alzheimer's disease with the same treatment.

13.
Article in Chinese | WPRIM | ID: wpr-989541

ABSTRACT

The emergence of immune checkpoint inhibitors holds new promise for patients with small cell lung cancer. Studies have found that PD-L1 expression, tumor mutation burden, genomic characteristics, peripheral blood parameters and other indicators can be used as prognostic predictors in patients with small cell lung cancer receiving immunotherapy. Further exploration and evaluation of relevant predictors can provide a reference for screening patients with potential benefits of immunotherapy.

14.
Article in Chinese | WPRIM | ID: wpr-986929

ABSTRACT

Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%,Z=-3.46,P<0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z=-1.98,P<0.05]. At the genus level, the relative abundance of Prevotella, Lactobacillus, Parascardovia and Sphingobium in the study group was higher than that in the control group(Z values were-2.92, -2.69, -2.05, -2.31, respectively, P<0.05).And the relative abundance of Streptococcus, Cardiobacterium, Klebsiella and Uruburuella of study group was lower than that of control group(Z values were -2.43, -2.32, -2.17, -2.32, respectively, P<0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella, which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group(P<0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.


Subject(s)
Male , Female , Humans , Laryngopharyngeal Reflux/diagnosis , Case-Control Studies , Microbiota , Outpatients , Saliva/microbiology
15.
Article in Chinese | WPRIM | ID: wpr-1008606

ABSTRACT

This study aims to reveal the effects of different growth patterns and years on the quality of Saposhnikoviae Radix samples. The apparent colors of the powder samples were quantified by a colorimeter, and the total color values(E~*ab) were calculated. The content of prim-O-glucosylcimifugin, cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and 3'-O-angeloylhamaudol in the samples was simultaneously determined by high performance liquid chromatography(HPLC). Cluster analysis, principal component analysis, partial least squares discriminant analysis, and Pearson correlation analysis were performed to analyze the powder chromatic values and the content of 5 components. The results showed that the E~*ab values of the samples were in the order of wild group<multiple-year-old group<one-year-old group. The content of cimifugin, sec-O-glucosylhamaudol, and 3'-O-angeloylhamaudol in the wild group was significantly higher than that in the multiple-year-old and one-year-old groups. The results of multivariate statistical analysis showed that the quality of multiple-year-old group varied greatly. The quality of the multiple-year-old samples was close to that of the wild group and better than that of the one-year-old group. The variable importance in the projection(VIP) values of b~*, 3'-O-angeloylhamaudol content, E~*ab, and L~* were all larger than 1, and that of cimifugin content was close to 1. The E~*ab value was negatively correlated with the content of prim-O-glucosylcimifugin, cimifugin, sec-O-glucosylhamaudol, and 3'-O-angeloylhamaudol, while it had no linear correlation with the 4'-O-β-D-glucosyl-5-O-methylvisamminol content. The growth patterns and years had different effects on the quality of Saposhnikoviae Radix samples. The chromatic values of Saposhnikoviae Radix and the content of 5 components can be used to evaluate the quality of Saposhnikoviae Radix, and 3'-O-angeloylhamaudol and cinmifugin can be considered as markers for the quality control of Saposhnikovia divaricata during the growing process.


Subject(s)
Powders , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/analysis , Apiaceae , Plant Roots/chemistry
16.
Article in Chinese | WPRIM | ID: wpr-1008756

ABSTRACT

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.


Subject(s)
Pregnancy , Female , Mice , Humans , Animals , Spleen , Ghrelin , Fetal Weight , Cholesterol, LDL , Diarrhea
17.
Article in Chinese | WPRIM | ID: wpr-1008640

ABSTRACT

This study aimed to analyze the effect of matrine on tumor necrosis factor-α(TNF-α)-induced inflammatory response in human umbilical vein endothelial cells(HUVECs) and explore whether the underlying mechanism was related to the miR-25-3p-mediated Krüppel-like factor 4(Klf4) pathway. The HUVEC cell inflammation model was induced by TNF-α stimulation. After 24 or 48 hours of incubation with different concentrations of matrine(0.625, 1.25, and 2.5 mmol·L~(-1)), CCK-8 assay was used to detect cell proliferation. After treatment with 2.5 mmol·L~(-1) matrine for 48 h, the expression of TNF-α, interleukin-6(IL-6), interleukin-1β(IL-1β), and Klf4 mRNA and miR-25-3p was detected by real-time fluorescence-based quantitative PCR, and the protein expression of TNF-α, IL-6, IL-1β, and Klf4 was detected by Western blot. The anti-miR-25-3p was transfected into HUVECs, and the effect of anti-miR-25-3p on TNF-α-induced cell proliferation and inflammatory factors was detected by the above method. The cells were further transfected with miR-25-3p and incubated with matrine to detect the changes in proliferation and expression of related inflammatory factors, miR-25-3p, and Klf4. The targeting relationship between miR-25-3p and Klf4 was verified by bioinformatics analysis and dual luciferase reporter gene assay. The results displayed that matrine could inhibit TNF-α-induced HUVEC proliferation, decrease the mRNA and protein expression of TNF-α, IL-6, and IL-1β, increase the mRNA and protein expression of Klf4, and reduce the expression of miR-25-3p. Bioinformatics analysis showed that there were specific complementary binding sites between miR-25-3p and Klf4 sequences. Dual luciferase reporter gene assay confirmed that miR-25-3p negatively regulated Klf4 expression in HUVECs by targeting. The inhibition of miR-25-3p expression can reduce TNF-α-induced cell proliferation and mRNA and protein expression of TNF-α, IL-6, and IL-1β. MiR-25-3p overexpression could reverse the effect of matrine on TNF-α-induced cell proliferation and the mRNA and protein expression of TNF-α, IL-6, IL-1β, and Klf4. This study shows that matrine inhibits the inflammatory response induced by TNF-α in HUVECs through miR-25-3p-mediated Klf4 pathway.


Subject(s)
Humans , Tumor Necrosis Factor-alpha/metabolism , MicroRNAs/metabolism , Human Umbilical Vein Endothelial Cells , Matrines , Interleukin-6/genetics , Signal Transduction , Antagomirs , Inflammation/metabolism , Luciferases/pharmacology , RNA, Messenger , Apoptosis
18.
Journal of Clinical Hepatology ; (12): 843-849, 2023.
Article in Chinese | WPRIM | ID: wpr-971840

ABSTRACT

Objective To investigate the value of alpha-fetoprotein (AFP) response in evaluating the clinical efficacy and safety of sorafenib combined with camrelizumab in the treatment of advanced hepatocellular carcinoma (HCC). Methods Clinical data were collected from 48 patients with advanced HCC who were treated with sorafenib combined with camrelizumab in The First Affiliated Hospital of Xinjiang Medical University from September 2020 to February 2022, and according to the level of AFP response after treatment, they were divided into response group with 32 patients (AFP after 6-8 months of treatment was reduced by more than 20% compared with baseline AFP) and non-response group with 16 patients (AFP after 6-8 months of treatment was reduced by less than 20% compared with baseline AFP). The Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Survival curves were plotted, and univariate and multivariate Cox regression analyses were used to investigate the independent risk factors for overall survival (OS). Progression free survival (PFS) time, OS time, and treatment outcome were compared between the two groups. Results No patient achieved clinical remission in either group. Compared with the non-response group, the response group had significantly higher objective response rate (21.88% vs 0, χ 2 =2.530, P =0.112) and disease control rate (84.38% vs 43.75%, χ 2 =6.668, P =0.010). Compared with the non-response group, the response group had longer PFS time (9.9 months vs 6.8 months) and OS time (13.8 months vs 11.1 months). Early non-response of AFP (hazard ratio [ HR ]=2.624, 95% confidence interval [ CI ]: 1.097-6.277, P =0.030) and extrahepatic metastasis ( HR =0.392, 95% CI : 0.157-0.978, P =0.045) were independently associated with a shorter PFS time. No adverse event leading to drug withdrawal was observed in the study. Conclusion Early AFP response has a high clinical value in predicting the efficacy of sorafenib combined with camrelizumab in the treatment of advanced HCC and the prognosis of such patients.

19.
Frontiers of Medicine ; (4): 1170-1185, 2023.
Article in English | WPRIM | ID: wpr-1010819

ABSTRACT

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.


Subject(s)
Mice , Animals , Receptors, Tumor Necrosis Factor/physiology , Receptors, OX40 , Membrane Glycoproteins , Ligands , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacology
20.
Article in Chinese | WPRIM | ID: wpr-982140

ABSTRACT

OBJECTIVE@#To investigate the causes of ineffectiveness of platelet transfusion with monoclonal antibody solid phase platelet antibody test (MASPAT) matching in patients with allogeneic hematopoietic stem cell transplantation and explore the strategies of platelet transfusion.@*METHODS@#A case of donor-specific HLA antibodies (DSA) induced by transfusion which ultimately resulted in transplantation failure and ineffective platelet transfusion with MASPAT matching was selected, and the causes of ineffective platelet transfusion and platelet transfusion strategy were retrospectively analyzed.@*RESULTS@#The 32-year-old female patient was diagnosed as acute myeloid leukemia (high risk) in another hospital with the main symptoms of fever and leukopenia, who should be admitted for hematopoietic stem cell transplantation after remission by chemotherapy. In the course of chemotherapy, DSA was generated due to platelet transfusion, and had HLA gene loci incompatible with the donor of the first transplant, leading to the failure of the first transplant. The patient received platelet transfusion for several times before and after transplantation, and the results showed that the effective rate of MASPAT matched platelet transfusion was only 35.3%. Further analysis showed that the reason for the ineffective platelet transfusion was due to the missed detection of antibodies by MASPAT method. During the second hematopoietic stem cell transplantation, the DSA-negative donor was selected, and the matching platelets but ineffective transfusion during the primary transplantation were avoided. Finally, the patient was successfully transplanted and discharged from hospital.@*CONCLUSIONS@#DSA can cause graft failure or render the graft ineffective. For the platelet transfusion of patients with DSA, the platelet transfusion strategy with matching type only using MASPAT method will miss the detection of antibodies, resulting in invalid platelet transfusion.


Subject(s)
Female , Humans , Adult , Platelet Transfusion , Antibodies, Monoclonal , Retrospective Studies , HLA Antigens , Hematopoietic Stem Cell Transplantation
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