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Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d<DOT≤15.0 d), Q 3 (15.0 d<DOT≤27.0 d) and Q 4 (DOT>27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%<breast milk intake ratio≤50%), medium-ratio breastfeeding group (50%<breast milk intake ratio≤75%) and high-ratio breastfeeding group (breast milk intake ratio>75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.
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Objective:To explore functional brain region changes and their correlation with behavioral variables based on amplitude of low-frequency fluctuation (ALFF) analysis using resting-state functional MRI (rs-fMRI) in patients with spinocerebellar ataxia type 3 (SCA3).Methods:In this prospective study, patients with SCA3 and healthy controls (HC) were recruited by Southwest Hospital, Army Medical University from May 2017 to March 2022. All subjects completed the scale for assessment and rating of ataxia (SARA), the international cooperative ataxia rating scale-posture and gait (ICARS-p&g), the rapid verbal retrieval (RVR) and Montreal cognitive assessment (MoCA). Meanwhile, the subjects underwent structural MRI and rs-fMRI scans. The MRI data were processed by DPABI software based on MATLAB. The normalized ALFF values of the two groups were compared using two-sample t-test, and the changes of ALFF values in the brain regions of SCA3 and HC groups were analyzed with the t-test of partial correlation coefficient. Spearman correlation analysis was used to evaluate the relationship between the ALFF values of abnormal brain area and the score of neurobehavioral scale in SCA3. Results:Compared with HC group, ALFF significantly increased in the left cerebellum (Crus1, Crus2, 4_5, 6, 7b, 8, 9), right cerebelum_9, left fusiform gyrus and vermis_8; while ALFF significantly decreased in the vermis_4_5 in patients with SCA3. Correlation analysis showed that ALFF values in the left cerebellar_8 were negatively correlated with RVR scores ( r=-0.293, P=0.035), ALFF values in the left cerebellar_9 were negatively correlated with MoCA scores ( r=-0.324, P=0.019), ALFF values in the right cerebellar_9 were negatively correlated with RVR scores ( r=-0.401, P=0.003) in the SCA3 patients. ALFF in the vermis_8 was positively correlated with SARA scores ( r=0.308, P=0.026) and ICARS-p&g scores ( r=0.313, P=0.024) in the SCA3 patients. Conclusion:There are significant changes in ALFF values in the cerebellum and left fusiform gyrus in patients with SCA3, and the changes of ALFF values are closely related with communication, cognitive and movement disorders.
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According to the current situation of professional ethics education for pediatric medical students and the needs of social industries, we focus on the construction of a systematic comprehensive curriculum knowledge system and training plan based on child development, formulate specific goals and training systems for pediatric medical students that are in line with the development of modern medicine, clarify the content and education path of pediatric professional ethics education, strengthen the requirements for students' knowledge, ability and quality, improve the process management and policy implementation of talent training, and improve the pertinence and effectiveness of professional ethics education for pediatric medical students, thereby making pediatric medical students to be used to the development trend and environment of the industry.
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This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
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Rats , Animals , Doxorubicin/adverse effects , Nephrotic Syndrome , AMP-Activated Protein Kinases/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , ApoptosisABSTRACT
AIM: To investigate the effect of Shenqi fuzheng injection (SFI) on tumor immunity and its preliminary molecular mechanism. METHODS: The animal model of low glucose tumor microenvironment was established by B16-PKM2-OE; the level of interleukin-2(IL-2) and interferon-γ(IFN-γ), CD40L and transforming growth factor-β1(TGF-β1) were detected by ELISA kit; the expressions of glucose transporter-1 (Glut-1) and key enzymes of glycolysis ( HK, PFK and PK ) in CD4
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Objective:To explore the protective effect of vagus nerve stimulation (VNS) on the prognosis of rats suffering from cardiac arrest/cardiopulmonary resuscitation (CA/CPR) under different treatment timings.Methods:The method of percutaneous epicardial electrical stimulation was used to establish CA model of rat. Fifty-three male SD rats were randomly (random number) divided into the sham group ( n=5), CPR group ( n=12), PRE group ( n=12), POST5 group ( n=12) and POST30 group ( n=12). The sham group did not experience CA/CPR. VNS treatment was started at 30 min before CA (PRE group, n=12), 5 min after recovery of spontaneous circulation (ROSC) (POST5 group, n=12), and 30 min after ROSC (POST30 group, n=12) in different VNS-treated group, respectively. The electrical stimulation was applied to the vagus nerve for 30 min with a unified parameter. The neurological deficit scores at 24, 48, and 72 h after ROSC were recorded, and the survival rate in each group was observed. TUNEL staining was used to detect the apoptosis of cortical area and the expression of α7 nicotinic acetylcholine receptor (α7nAChR) in brain tissue was measured by immunofluorescence at 72 h after ROSC. Variables were compared with one-way analysis of variance, and survival for Kaplan-Meier curves were tested with the log-rank test. A P value less than 0.05 was considered statistically significant. Results:Compared with the CPR group (survival rate 33.33%), both pre-treatment (survival rate 75%) and post-treatment of VNS (POST5 group survival rate 75% and POST30 group survival rate 83.33%) significantly improved the 72 h survival rate after CPR ( P<0.05), mitigated neurological deficits after ROSC, reduced the positive rate of apoptosis neurons, and up-regulated the expression of α7nAChR in cerebral cortex. There was no significant difference among the VNS-treated groups (all P>0.05). Conclusions:Both pre-treatment and post-treatment of VNS can play a protective role in rats after CA/CPR, which may be related to the activation of α7nAChR-mediated anti-inflammatory and anti-apoptosis effects.
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During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood-brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1
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OBJECTIVES@#Lung cancer is one of the most common malignant tumors in the world, and its lethality ranks the first among many malignant tumors. For non-small cell lung cancer (NSCLC) patients, due to the high mortality rate, the overall 5-year survival rate is less than 15%. When NSCLC undergoes local invasion, the 5-year survival rate is only 20%, and it is even lower when distant metastasis occurs up to 4%. Almonertinib is an innovative drug independently researched and developed by China with independent intellectual property rights. As an epidermal growth factor receptor tyrosine kinase inhibitor, almonertinib is mainly used for locally advanced or metastatic NSCLC patients with epidermal growth factor receptor (EGFR) T790M mutation. This study aims to investigate the effects of almonertinib on the proliferation, invasion and migration of NSCLC cells in vitro.@*METHODS@#NSCLC cells H1975 and PC-9 were cultured in vitro. The effects of almonertinib on the proliferation, apoptosis, invasion, and migration of H1975 and PC-9 cells were detected by CCK-8 assay, apoptotic assay and Transwell assay. The expression of invasion and migration related proteins was detected by Western blotting.@*RESULTS@#The CCK-8 experiment showed that almonertinib inhibited the proliferation of H1975 and PC-9 cells in a time- and dose-dependent manner. The IC@*CONCLUSIONS@#Almonertinib can inhibit the proliferation, invasion, and migration of NSCLCH1975 and PC-9 cells in vitro and vivo, and promote the apoptosis of H1975 and PC-9 cells. The underlying mechanism may be related to the inhibition of tumor cell epithelial mesenchymal transformation and metalloproteinase expression.
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Animals , Humans , Mice , Acrylamides , Apoptosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , ErbB Receptors/genetics , Indoles , Lung Neoplasms , Mice, Nude , Mutation , Protein Kinase Inhibitors/pharmacology , PyrimidinesABSTRACT
BACKGROUND@#Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC.@*METHODS@#FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression.@*RESULTS@#FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality.@*CONCLUSIONS@#Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, disease burden became even severer in developing countries, especially for the population aged ≥40 years. Effective targeted preventive programs are strongly encouraged to reduce the FBC disease burden worldwide.
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Female , Humans , Breast Neoplasms/epidemiology , Global Health , Incidence , Registries , Risk FactorsABSTRACT
Objective:To investigate the prevalence and molecular characteristics of Escherichia coli ( E. coli) producing a novel Shiga toxin 2k subtype in goat in Lanling county, Shandong province. Methods:In November 2019, 512 goat fecal samples were collected from different households in Lanling county, Shandong province. After enriched with EC broth, stx-positive samples were detected by PCR and inoculated in CHROMagar? ECC agar and CHROMagar? STEC agar. The whole genomes of stx-positive strains were sequenced. Based on the genomic senquences, the stx subtype, serotype, multi-locus sequence type and virulence genes of each strain were analyzed. Results:Eighty-six strains of Shiga toxin-producing E. coli (STEC) were isolated from 512 goat fecal samples. Five stx subtypes were identified and 37 strains were positive for stx2k. The 86 STEC strains belonged to 20 O∶H serotypes and 18 different sequence types (STs). Conclusions:STEC strains circulating in goats in Lanling county, Shandong province were heterogeneous in stx subtypes, serotypes and virulence gene profiles, and a certain proportion of strains producing a novel Shiga toxin 2k subtype were detected.
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OBJECTIVE@#To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism.@*METHODS@#MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting.@*RESULTS@#HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells.@*CONCLUSIONS@#HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
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Humans , Apoptosis , Autophagy , Breast Neoplasms , Cell Line, Tumor , Cell Proliferation , ErbB Receptors , Phosphatidylinositol 3-Kinases , Protein Kinase InhibitorsABSTRACT
OBJECTIVE@#To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism.@*METHODS@#MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting.@*RESULTS@#HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells.@*CONCLUSIONS@#HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Autophagy , Breast Neoplasms , Drug Therapy , Cell Line, Tumor , Cell Proliferation , ErbB Receptors , Metabolism , Protein Kinase Inhibitors , Pharmacology , Signal TransductionABSTRACT
Objective To establish the cardiac arrest (CA) model in rats by modified transcutaneous electrical stimulation on epicardium. Methods This study was performed in the Emergency Medicine laboratory in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. After 10 Sprague-Dawley male rats weighing 330-380 g were anesthetized, two acupuncture needles connected to the anode and cathode of a stimulator were transcutaneously inserted into the epicardium as electrodes. The puncture points were located quantitatively according to the anatomical structure of the rat chest. The electrical stimulation was maintained for 3 minutes to induce ventricular fibrillation(VF). Cardiopulmonary resuscitation (CPR) included chest compressions, intravenous adrenaline and defi brillation operated at 6 min after a period of nonintervention. Results CA was induced after the implement of the effective electrical stimulation in all ten rats in this experiment. The average current intensity to induce VF was (1.80 ± 0.59) mA, the average time to induce CA was (5.07 ± 2.37)s,the average time of the total electrical stimulation was(187.50 ± 12.75)s and the total time of CA was 6 min. At the end of the electrical stimulation, 9 rats presented VF and 1 rat showed pulseless electrical activity. The restoration of spontaneous circulation was achieved in all 10 rats. The average time of CPR was(190.90±68.60) s, the mean numbers of defi brillation were(1.20 ± 0.63) , and he average number of adrenaline application were (1.20 ± 0.42) times. Neither visible hemorrhage on epicardium nor gross pulmonary congestion was observed. Conclusions The modified transcutaneous electrical stimulation on epicardium to produce CA model in rats is an easily applicable and effective technique. This model may provide an alternative for experimental research of CPR.
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Rapid development of MRI has gradually evolved from morphological imaging to functional imaging.Functional MRI can provide pathophysiological information more than morphological information,such as molecular and metabolic information.The application value of functional MRI in cervical cancer has become a hotspot in recent years.The research progresses of functional MRI in cervical cancer were reviewed in this article.
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Rapid development of MRI has gradually evolved from morphological imaging to functional imaging.Functional MRI can provide pathophysiological information more than morphological information,such as molecular and metabolic information.The application value of functional MRI in cervical cancer has become a hotspot in recent years.The research progresses of functional MRI in cervical cancer were reviewed in this article.