ABSTRACT
Aim To investigate the mechanism by which formononetin (FN) inhibits mitochondrial dynamic-related protein 1 (DRP1) -NLRP3 axis via intervening the generation of ROS to reduce allergic airway inflammation. Methods In order to establish allergic asthma mouse model, 50 BALB/c mice aged 8 weeks were divided into the control group, model group, FN treatment group and dexamethasone group after ovalbumin (OVA) induction. Airway inflammation and collagen deposition were detected by HampE and Masson staining. Th2 cytokines and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, ROS in BEAS-2B cells was assessed by DCFH-DA staining, DRP1 expression in lung tissue and BEAS-2B cells was detected by immunohistochemistry and immunofluorescence, and the DRP1-NLRP3 pathway was analyzed by immunoblotting. Results FN treatment could effectively ameliorate the symptoms of asthmatic mouse model, including reducing eosinophil accumulation, airway collagen deposition, decreasing Th2 cytokine and IgE levels, reducing ROS and MDA production, increasing SOD and CAT activities, and regulating DRP1-NLRP3 pathway-related protein expression, thereby relieving inflammation. Conclusion FN ameliorates airway inflammation in asthma by regulating DRP1-NLRP3 pathway.
ABSTRACT
Objective:To investigate the effect of problem-solving therapy (PST) on clinical efficacy, cognitive and social function in senile patients with first episode depression.Methods:From March 2020 to August 2021, a total of 86 patients with first onset elderly depression treated in the geriatric department of Qingdao Mental Health Center were selected. According to the random number table method, totally 86 patients were randomly divided into a study group and a control group, with 43 cases in each group. The control group was treated with antidepressant drugs and basic psychiatric nursing intervention. The study group received PST treatment on the basis of the control group for 8 weeks. The Hamilton depression scale-17 items(HAMD-17), Montreal cognitive assessment scale (MoCA), and social dysfunction screening scale (SDSS) were used to assess the degree of depression, cognitive function and social function in both groups. SPSS 18.0 was used for statistical analysis. Independent sample t-test was used for comparison between groups, paired sample t-test was used for comparison before and after treatment. Results:After 8 weeks of intervention, HAMD-17 scores and SDSS scores in the two groups were both significantly decreased compared with before intervention, and the differences between pre intervention and post intervention had statistical significance( t=3.067, 22.543, both P<0.05), while MoCA scores were significantly increased, and the difference between pre intervention and post intervention had statistical significance ( t=9.623, P<0.05). Compared with the control group after 8 weeks of intervention, the HAMD-17 score ((14.44±1.97), (15.58±2.66), t=2.260, P=0.026) and SDSS score((9.44±2.24), (13.00±1.73), t=8.242, P<0.001) of the study group were lower, and the score of MoCA ((25.44±1.28), (23.84±1.56), t=5.223, P<0.001) was higher. Conclusion:In addition to conventional antidepressant therapy, PST not only reduces the severity of depression in elderly patients with first episode depression, but also significantly improves their cognitive and social function.
ABSTRACT
OBJECTIVE@#To analyze the effect of local unstable atherosclerotic plaque on plaque formation in the carotid and aortic arteries of rabbits.@*METHODS@#Thirty New Zealand white rabbits were randomly divided into atherosclerosis model group, highfat diet feeding group, and normal chow feeding group (blank control group). In the model group, carotid artery balloon injury was induced after 4 weeks of high-fat diet feeding. Eight weeks later, all the rabbits were euthanized for histopathological examination of the carotid artery and abdominal aorta, and the mean intimal thickness and plaque to lumen area ratio were measured using image analysis software. Venous blood samples were collected from the rabbits for blood lipid analysis.@*RESULT@#At the ends of 4, 8 and 12 weeks, the rabbits in the model group and high-fat feeding group, but not those in the blank control group, all showed significant weight gain compared with their body weight at 0 week (P < 0.05). The mean intimal thickness was significantly greater in atherosclerosis model group than in the other two groups (P < 0.05). In atherosclerosis model group, the mean intimal thickness and plaque to lumen area ratio in the injured carotid artery were significantly greater than those in the contralateral carotid artery and abdominal aorta (P < 0.05). At the end of the 12 weeks, the levels of triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and highsensitivity C-reactive protein (CRP) were all significantly higher in the model group and high-fat feeding group than in the blank control group (P < 0.05); the levels of TG, TC, LDL-C, or HDL-C did not differ significantly between the model group and high-fat feeding group (P>0.05), but the level of CRP was significantly higher in arteriosclerosis model group (P < 0.05).@*CONCLUSION@#Local unstable atherosclerotic plaque can increase the level of CRP and promote the formation of atherosclerotic plaques in the carotid artery and abdominal aorta in rabbits.
Subject(s)
Rabbits , Animals , Plaque, Atherosclerotic , Aorta, Abdominal , Cholesterol, LDL , Atherosclerosis , Carotid ArteriesABSTRACT
OBJECTIVE@#Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness.@*METHODS@#A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected.@*RESULTS@#Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin+/CD31+ ratio, rather than the number of CD31+ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group.@*CONCLUSION@#Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.
Subject(s)
Humans , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Proliferating Cell Nuclear Antigen/therapeutic use , Mice, Nude , Glycogen Synthase Kinase 3 beta/genetics , beta Catenin/therapeutic use , Liver Neoplasms/drug therapy , Desmin/therapeutic use , Ki-67 Antigen , Cell Line, Tumor , Hypoxia , RNA, Messenger/therapeutic use , Cell ProliferationABSTRACT
Thirteen isoflavones were separated and purified from an ethanol extract of the rhizome of Dalbergia benthamii Prain by using silica gel, Sephadex LH-20, recrystallization et al. Their structures were identified by physicochemical properties and spectral analysis such as MS, 1D/2D-NMR as dalbergibenthamin (1), butesuperin A (2), xanthocercin A (3), butesuperin B (4), di-O-methylalpinum isoflavone (5), 2′-deoxgisoaunculutin (6), robustone (7), 4′-hydroxy-5,7-dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (8), formononetin (9), 6″-O-rhamnosyldaidzin (10), 3′,4′-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (11), derrubone dimethyl enter (12), and derrubone (13). Compound 1 is a pair of new isoflavonoid enantiomers, compound 12 is a new natural product and compounds 1-7 and 10-13 were obtained from D. benthamii Prain for the first time. In vitro cytotoxic activities of the compounds were explored by MTS testing with HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines. Results show that compound 8 significantly inhibited cellular proliferation. The IC50 of compound 8 in A-549 and SW480 cells was 16.68 ± 0.19 and 15.21 ± 0.60 μmol·L-1.
ABSTRACT
Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were -0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and -0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were -0.071 years and 0.006 years, respectively, while those in rural areas were -0.082 years and -0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were -0.064, -0.099, -0.091, -0.080, -0.096 and -0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and -0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.
Subject(s)
Female , Humans , Child , Adolescent , Menarche , Probability , East Asian PeopleABSTRACT
Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.
ABSTRACT
Objective: To analyze the prevalence trend of malnutrition among Chinese Han children and adolescents aged 7-18 years from 2010 to 2019. Methods: Based on the data from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019, about 215 102, 214 268 and 212 713 Han students aged 7-18 years were included in this study. According to the National Screening Standard for Malnutrition of School-age Children and Adolescents, the detection rate of malnutrition among Chinese Han children and adolescents aged 7-18 was calculated, and the prevalence trend of malnutrition from 2010 to 2019 was analyzed. Results: In 2019, the detection rate of malnutrition among Chinese Han students aged 7-18 years was 8.64% (18 381/212 713), of which the rate of growth retardation, moderate-to-severe wasting and mild wasting was 0.50% (1 062/212 713), 3.25% (6 914/212 713) and 4.89% (10 405/212 713), respectively. In 2019, the detection rate of malnutrition in these boys was higher than that of girls (9.97% vs. 7.31%), and the detection rate in rural areas was higher than that in cities (9.30% vs. 7.98%). The detection rates were 9.74% (5 252/53 916), 8.17% (4 408/53 937), 7.29% (3 885/53 310), and 9.38% (4 836/51 550) in 7-9, 10-12, 13-15, and 16-18 years groups, and 8.14% (6 563/80 618), 7.61% (4 237/55 694) and 9.92% (7 581/76 401) in the eastern, central, and western regions. Malnutrition among students in China was mainly caused by mild wasting, and the detection rate of growth retardation accounted for only 5.78% (1 062/18 381). Malnutrition was mostly concentrated in the southwest region, and the rate was relatively low in eastern provinces. In three surveys from 2010 to 2019, the detection rate of malnutrition among Han students aged 7-18 in China decreased gradually, and the differences were statistically significant (P<0.05). Among them, the detection rates in western rural areas decreased significantly, as well as the gap between urban and rural areas. Compared with that in 2014, the detection rate of malnutrition in Shandong, Hunan, Qinghai and Hainan provinces in 2019 decreased significantly (P<0.05). Conclusion: In 2019, the malnutrition of Chinese children and adolescents aged 7-18 years is dominated by wasting malnutrition. The detection rate shows a downward trend from 2010 to 2019, with regional differences.
ABSTRACT
Objective To evaluate the performance of contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) LR-5 in the diagnosis of hepatocellular carcinoma (HCC). Methods The clinical research reports with the application of CEUS LI-RADS in the diagnosis of HCC were collected from PubMed,Embase,Cochrane Library,CNKI,and Wanfang Data from inception to November 14,2021.Two researchers respectively screened the literature and extracted relevant information.The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to evaluate the quality of all the included articles.RevMan 5.4,Meta disc 1.4,and Stata 16.0 were employed to analyze the diagnostic performance of LR-5 for HCC in high-risk patients. Results Twenty original studies were included,involving a total of 6131 lesions,of which 5142 were HCC.The results of meta-analysis showed that the LR-5 in CEUS LI-RADS for diagnosing HCC in the high-risk population had the overall sensitivity of 0.72 (95%CI=0.66-0.77),the overall specificity of 0.93 (95%CI=0.87-0.96),the overall positive likelihood ratio of 9.89 (95%CI=5.31-18.41),the overall negative likelihood ratio of 0.30 (95%CI=0.25-0.37),and the area under the summary receiver operating characteristic curve of 0.88 (95%CI=0.85-0.91).There was heterogeneity among the included studies (I2=95.31,P<0.001).The funnel plot indicated the existence of publication bias (P=0.04). Conclusion The CEUS LI-RADS can effectively diagnose HCC in high-risk patients based on the LR-5 criteria.
Subject(s)
Humans , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Diagnostic Imaging , UltrasonographyABSTRACT
An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.
ABSTRACT
The secondary metabolites of plants are important sources of natural drugs. Betula plants have abundant pharmacological value, complex mechanism and wide applications, which are closely related to the triterpenoids of theirs. Triterpenoids in Betula species are mainly divided into dammarane-type, ocotillol-type, oleanane-type, lupane-type and cycloaltunane-type. The extracts of Betula species have varieties of activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial, etc. And the biosynthetic pathways of triterpenoids after 2,3-oxidosqualene are split into four branches of dammarenediol-II, lupeol, cycloartenol and amyrin according to the different oxidosqualene cyclases. This review summarizes the chemical constituents, pharmacological activities and biosynthetic pathways of triterpenoids in Betula plants. It provides a reference for the research and development of new drugs and the production of these triterpenoids in microbial cell factories by synthetic biology methods.
ABSTRACT
Objective This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials(RCTs)assessing the clinical efficacy of acupuncture for chronic stable angina(CSA).Methods PubMed,The Cochrane Library,Embase,CNKI,VIP,WanFang Data,CBM databases,ClinicalTrial.gov and Chinese Clinical Trial Registry were electronically searched to collect randomized controlled trials(RCTs)of acupuncture for CSA and only RCTs that included acupuncture as the sole or combination of acupuncture in the treatment of CSA.The retrieval period was from the establishment of the database to May 19,2022.The primary outcome measure was the frequency of angina attacks,and the secondary outcome measures were angina efficacy,total effective rate of ECG improvement,nitroglycerin use after treatment,patient-perceived overall effectiveness,performance on the Six-Minute Walk Test(6-MWT),depression as measured by the anxiety as measured by the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),adverse effects.Results Twelve studies with a total of 1605 case subjects were included and grade quality of evidence reviews had 1 outcomes as medium quality evidence,5 outcomes as low quality evidence and 4 outcomes as very low quality evidence.Acupuncture treatment resulted in significantly greater reductions in angina attacks,visual analog scale(VAS),6-minute walk test,angina efficacy,electrocardiogram improvement rate,angina efficacy,total clinical response rate.Conclusion The efficacy of acupuncture combined with western medicine in treating CSA is better than that of Western medicine alone,thanks to restricted by the number and quality of included researchs,higher quality studies are required to prove above conclusions.
ABSTRACT
Objective:To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency (ECHS1D) caused by enoyl-CoA hydratase short chain 1 ( ECHS1) gene mutation. Methods:The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed, and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results:The child was a 6 months and 4 days old male, with acute onset, the main clinical manifestation being limb movement disorder after admission. The child had slow motor development, his head was still upright and cannot turn over, the child also cannot sit alone, follow up and make a laugh, and the muscle tension of limbs was increased. The child′s blood lactate was increased to 6.2 mmol/L, which suggested metabolic acidosis, and magnetic resonance imaging (MRI) of the head showed abnormal signals in the basal ganglia on both sides, abnormal enhancement of the meninges of the left cerebral hemisphere. Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene, c.563C>T (p.A188V) and c.5C>T (p.A2V), respectively. The child′s father carried c.563C>T mutation, the mother carried c.5C>T mutation, all of which were missense mutations. Conclusions:ECHS1 gene mainly has missense mutations, most of which are compound heterozygous mutations, and a few are homozygous mutations. The ECHS1D caused by ECHS1 gene mutation often affects infants and young children. MRI suggests abnormal signals in the basal ganglia; for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI, genetic testing should be considered to confirm the diagnosis.
ABSTRACT
Antrodia cinnamomea, an edible and medicinal fungus with significant economic value and application prospects, is rich in terpenoids, benzenoids, lignans, polysaccharides, and benzoquinone, succinic and maleic derivatives. In this study, the transcriptome of A. cinnamomea cultured on the wood substrates of Cinnamomum glanduliferum (YZM), C. camphora (XZM), and C. kanehirae (NZM) was sequenced using the high-throughput sequencing technology Illumina HiSeq 2000, and the data were assembled by de novo strategy to obtain 78,729 Unigenes with an N50 of 4,463 bp. Compared with public databases, about 11,435, 6,947, and 5,994 Unigenes were annotated to the Non-Redundant (NR), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genome (KEGG), respectively. The comprehensive analysis of the mycelium terpene biosynthesis-related genes in A. cinnamomea revealed that the expression of acetyl-CoA acetyltransferase (AACT), acyl-CoA dehydrogenase (MCAD), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), mevalonate pyrophosphate decarboxylase (MVD), and isopentenyl diphosphate isomerase (IDI) was significantly higher on NZM compared to the other two wood substrates. Similarly, the expression of geranylgeranyltransferase (GGT) was significantly higher on YZM compared to NZM and XZM, and the expression of farnesyl transferase (FTase) was significantly higher on XZM. Furthermore, the expressions of 2,3-oxidized squalene cyclase (OCS), squalene synthase (SQS), and squalene epoxidase (SE) were significantly higher on NZM. Overall, this study provides a potential approach to explore the molecular regulation mechanism of terpenoid biosynthesis in A. cinnamomea.
ABSTRACT
Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ2=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Acute Kidney Injury/epidemiology , Cohort Studies , Critical Illness , Prospective Studies , Risk FactorsABSTRACT
Aim To investigate the protective effect and mechanism of JTE-013 on allergic rhinitis (AR) by regulating mitochondrial injury and apoptosis through RhoA/ROCKl/Drpl pathway. Methods AR model was established by ovalbumin (OVA) in mice. Nasal tissue sections were then stained with HE, TUNEL and DHE. Western blot assay. In vitro, human nasal epithelial cells (HNEpCs) were stimulated with human recombinant interleukin-13 (IL-13), and the effects of JTE-013 and Y27632-related protein expression were detected by Western blot. Immunofluorescence was used to observe the effects of JTE-013 and Y 27632 on total ROS, mitochondrial membrane potential and mitochondrial ROS generation, Drpl translocation and Cyt-c expression in cells. Results JTE-013 reduced the frequency of nose rubbing and sneezing, reduced nasal mucosal thickening and decreased eosinophil infiltration in AR mice. TUNEL and DHE staining results suggested that JTE-013 could inhibit apoptosis and reduce ROS expression in mouse nasal epithelial cells. Western blot showed that both JTE-013 and Y 27632 could significantly reduce RhoA, ROCK1, Drpl and p-Drpl(616), inhibit the expression of apoptotic proteins Bax, cleaved-caspase-3, Cyt-c, cleavedcaspase-9 and up-regulate the expression of p-Drpl (637) and Bcl-2. Immunofluorescence showed that inhibitors of JTE-013 or ROCK1 almost blocked IL-13mediated increase in ROS and mtROS production, inhibited decrease in mitochondrial membrane potential, and blocked Cyt-c expression and Drpl translocation in nasal mucosal epithelial cells. Conclusion JTE-013 can regulate the morphology and function of mitochondria by inhibiting RhoA/ROCKl/Drpl signaling axis, thereby alleviating nasal epithelial cell inflammation in mice with allergic rhinitis.
ABSTRACT
Natural products are an important source for the development of antitumor lead compounds, but the pharmacological effects and regulatory mechanisms of natural products in osimertinib resistance in non-small cell lung cancer (NSCLC) are not well understood. The natural product ligustroflavone was used as the research object to analyze its efficacy in osimertinib-resistant NSCLC cells by cell proliferation assay and cell cycle detection. The potential targets of ligustroflavone in osimertinib-resistant NSCLC cells were screened by public databases and bioinformatics, molecular docking and microscale thermophoresis were used to identify the interaction between privet and target molecules. Western blot was used to detect the effect of privet on the target molecules and their downstream pathways. Ligustroflavone reduced the proliferation of osimertinib-resistant NSCLC cells, and could arrest the cell cycle. Cyclin-dependent kinase 6 (CDK6) was the potential target of ligustroflavone in osimertinib-resistant NSCLC cells. Ligustroflavone inhibited the activation of CDK6-Rb axis. Together, ligustroflavone could regulate osimertinib resistance in NSCLC cells by binding cell cyclin-related molecules. This study provides a theoretical basis for the targeted drug resistance of NSCLC with natural products, and also provides a new idea for the development of clinical drug combination.
ABSTRACT
Objective:To investigate the safety and efficacy of Belintoumab on the treatment of children with acute B-lymphoblastic leukemia (B-ALL).Methods:The clinical data of 10 children with CD 19+ B-ALL who were admitted to the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from September 2021 to May 2022 and treated with Belintoumab were analyzed retrospectively. Results:Among the 10 cases, there were 6 recurrent cases, 3 cases with persistent minimal residual disease (MRD) positive after an initial treatment, and 1 case complicated with invasive candidiasis.Before treatment, bone marrow blasts ≥0.25, and that ranged 0.05-<0.25 were detected in 2 cases and 1 case, respectively.Seven cases had a complete remission (CR) of bone marrow, 6 of which were MRD positive and 1 case was MRD negative.After treatment with Belintoumab, the CR rate was 66.7% (2/3). The overall MRD negative rate was 88.9% (8/9), and the negative rate in previously MRD positive children was 100% (6/6). The median follow-up time was 4.1 (1.6-10.0) months after the application of Belintoumab.The overall survival (OS) rate was 70.0% (7/10). Eight MRD negative children received hematopoietic stem cell transplantation, and the OS rate was 75% (6/8). Survived children did not relapse until the last follow-up visit.Fever (90%, 9/10) was the most common adverse events, followed by neutropenia (90%, 9/10). One case (10%, 1/10) of neurotoxicity was seizures (grade 2) and one case (10%, 1/10) suffered cytokine release syndrome (grade 2), which did not influence the therapeutic efficacy of Belintoumab after symptomatic treatment.Conclusions:Belintoumab is safe and effective on the treatment of children with recurrent/refractory CD 19+ B-ALL, and those with MRD positive who have achieved CR in bone marrow have a higher rate of turning negative.Belintoumab can also be used as a bridge scheme for CD 19+ B-ALL children who cannot tolerate chemotherapy.
ABSTRACT
Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β(IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression.
Subject(s)
Animals , Male , Rats , Cytokines/metabolism , Disease Models, Animal , Ejaculation/physiology , Interleukin-1beta/metabolism , N-Methylaspartate/metabolism , Prostate/metabolism , Prostatitis/metabolism , Receptors, N-Methyl-D-Aspartate/metabolismABSTRACT
Objective:To investigate the clinical efficacy, safety and compliance of Voriconazole suspension formula on the prevention and treatment of invasive fungal infection (IFI) in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of 25 children treated Voriconazole suspension formula for the prevention and treatment of IFI during the period of allo-HSCT in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from August 1, 2020 to April 30, 2021 were retrospectively analyzed.The plasma trough concentration of Voriconazole was detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the genotype of CYP2C19 was detected by polymerase chain reaction-restriction fragment length polymorphism (RFLP). The effect of CYP2C19 genotype on Voriconazole trough concentration was analyzed by rank-sum test, and Fisher′ s accurate test was used to analyze the influence of severity of gastrointestinal mucositis on serum trough concentration of Voriconazole in children with allo-HSCT. Results:A total of 25 children, including 18 males and 7 females were recruited.The median age at allo-HSCT was 6 (2-13) years.After initial administration of conventional dose of Voriconazole suspension formula during transplantation, plasma trough concentration of Voriconazole was intermittently monitored.Only 13 cases (52.0%) reached the target plasma trough concentration, 11 cases(44.0%) reached the target plasma trough concentration after adjusting the dose according to the plasma concentration, and 1 cases(4.0%) failed to reach it after increasing the dose twice.Genotype detection of CYP2C19 was performed in 20 children, involving 4 cases of poor metabolizers (PM), 9 cases of intermediate metabolizers (IM), 6 cases of extensive metabolizers (EM), and 1 case of ultra extensive metabolizer (UEM). A significant difference in plasma trough concentration was detected among all groups ( F=24.012, P<0.01). During the transplantation, 12 cases developed mild to moderate gastrointestinal mucositis, and 7 cases had severe gastrointestinal mucositis.The stan-dard rate of plasma trough concentration in children with severe gastrointestinal mucositis (1/7 cases, 14.3%)was significantly lower than those with mild to moderate gastrointestinal mucositis (9/12 cases, 75.0%) ( P=0.02). Five children (71.4%) with severe gastrointestinal mucositis could reach the target trough concentration after increasing the drug dose, suggesting that severe gastrointestinal mucositis had a great influence on the plasma concentration of Vorico-nazole suspension.The incidence of IFI in 25 children with allo-HSCT was 0, and the compliance of children taking Voriconazole dry suspension was 100.0%.The incidence of adverse reactions was 24.0% and all adverse reactions were relieved after symptomatic treatment. Conclusions:The plasma concentration of Voriconazole varies greatly among children and in different states of the same patient.Therefore, it is necessary to monitor the trough concentration of the drug and adjust the drug dose.The use of Voriconazole suspension formula for the prevention and treatment of fungal infection during allo-HSCT in children is clinically safe and effective, with a good compliance in children.