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Objective To evaluate the immunoprotective effect of active immunization with recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice. Methods Female BALB/c mice at 6 weeks of age, each weighing approximately 20 g, were divided into the recombinant protein immunization group, the infection control group and the normal control group, of 25, 18, 15 mice in each group, respectively. Mice in the recombinant protein immunization group were given active immunization with recombinant BmPPIase protein, and 18 mice with the highest antibody titers were intraperitoneally injected with 100 μL of B. microti-infected whole blood 2 weeks after the last immunization. Mice in the infection control group were intraperitoneally injected with 100 μL of B. microti-infected whole blood, while 15 mice in the normal control group received no treatment. Blood samples were collected from mice in the recombinant protein immunization group and the infection control group on days 0 to 30 post-immunization for detection of B. microti infection, and blood samples were collected on days 0, 7, 14, 21, and 28 post-immunization for routine blood tests with a blood cell analyzer and for detection of serum cytokines using cytometric bead array. Results Anti-BmPPIase antibodies were detected in 25 mice in the recombinant protein immunization group 2 weeks after the last immunization, with titers of 5 × 103 to 8 × 104. B. microti infection rate peaked in mice in both the recombinant protein immunization and the infection control group on day 7 post-immunization, with positive infection rates of 13.3% and 50.0%, and there were significant differences between the two groups in terms of B. microti infection rate on days 3 (χ2= 113.18, P < 0.01), 5 (χ2 = 475.22, P < 0.01), 7 (χ2 = 465.98, P < 0.01) and 9 post-infection (χ2= 18.71, P < 0.01), while the B. microti infection rate tended to be 0 in both groups on day 11 post-immunization. Routine blood tests showed higher red blood cell counts [(5.30 ± 0.50) × 1012 to (9.87 ± 0.24) × 1012 counts/L)] and hemoglobin levels [(89.67 ± 22.80) to (148.60 ± 3.05) g/L)] in the recombinant protein immunization group than in the infection control group on days 0 to 28 post-immunization. Cytometric bead array detected higher serum interferon-γ [(748.59 ± 17.56) to (3 858.28 ± 1 049.10) fg/mL], tumor necrosis factor-α [(6 687.34 ± 1 016.64) to (12 708.13 ± 1 629.79) fg/mL], interleukin (IL)-6 [(611.05 ± 75.60) to (6 852.68 ± 1 554.00) fg/mL] and IL-17a [(167.68 ± 185.00) to (10 849.27 ± 355.40) fg/mL] and lower IL-10 levels [(247.65 ± 138.00) to (18 787.20 ± 2 830.22) fg/mL] in the recombinant protein immunization group than in the infection control group during the study period. Conclusions Recombinant BmPPIase protein induces up-regulation of interferon-γ, tumor necrosis factor-α and presents a high immunoprotective activity against B. microti infection in mice, which is a potential vaccine candidate protein.
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Objective To investigate the prevalence and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City. Methods Children with diarrhea under 5 years of age admitted to Guangzhou Children’s hospital, Guangzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children’s Medical Center during the period between January 1 and December 31, 2020, were enrolled. Participants’ demographics, living environments and health status were collected using questionnaire surveys. Stool samples were collected from participants and nucleic acid was extracted. B. hominis infection was identified using PCR assay and sequence alignment, and the factors affecting B. hominis infection among children with diarrhea under 5 years of age were identified using univariate analysis and multivariate logistic regression analysis. Results A total of 684 children with diarrhea under 5 years of age were enrolled, including 468 male children and 216 female children, with a mean age of (1.79 ± 1.12) years. The overall prevalence of B. hominis infection was 4.97% [34/684, 95% confidential interval (CI): (3.59%, 6.86%)] among participants, and there was no significant difference in the prevalence of B. hominis infection between children with chronic [7.52% (20/266), 95% CI: (4.92%, 11.33%)] and acute diarrhea [3.35% (14/418), 95% CI: (2.01%, 5.54%)] (χ2 = 5.983, P = 0.014). Multivariate logistic regression analysis identified keeping pet [odds ratio (OR) = 6.298, 95% CI: (2.711, 14.633)], drinking non-tap water [OR = 4.522, 95% CI: (1.769, 11.561)], lactose intolerance [OR = 4.221, 95% CI: (1.043, 17.087)], antibiotic use [OR = 0.125, 95% CI: (0.017, 0.944)] and chronic diarrhea [OR = 2.172, 95% CI: (1.018, 4.637)] as factors affecting B. hominis infection among children with diarrhea under 5 years of age in Guangzhou City. Conclusions B. hominis infections is detected in children with diarrhea under five years of age in Guangzhou City. Improving home environments and pet-keeping hygiene is recommended to reduce the likelihood of B. hominis infection among children.
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Under the national policy background of traditional Chinese medicine（TCM）registration review and approval reform， TCM preparations in medical institutions（hereinafter referred to as medical institution preparations） have human use experience， conform to the characteristics of TCM clinical practice， and have advantages in the research and development of innovative Chinese medicines. Therefore， the research and development mode based on clinical experience prescription-medical institution preparations-innovative Chinese medicines has attracted widespread attention from the industry. However， in the process of development and use of medical institution preparations， there are generally clinical problems that restrict their transformation into innovative Chinese medicines， resulting in a relatively weak collection basis of human use experience and insufficient clinical evidence for supporting the research and development of new TCM medicines. In this paper， on the basis of sorting out the supporting regulations and relevant technical requirements of human use experience， and analyzing the clinical problems restricting the transformation of medical institution preparations， it provides suggestions for medical institutions to carry out high-quality research on human use experience of preparations in the process of TCM clinical practice from the aspects of continuously exploring clinical value， improving the construction of information system， focusing on the TCM clinical practice and giving full play to the advantages of discipline cooperation. By realizing the whole life cycle management of medical institution preparations based on three-combination evaluation evidence system， we can promote the transformation of medical institution preparations into innovative Chinese medicines.
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@#Objective To introduce a new method for identifying intersegmental planes during thoracoscopic segmentectomy using pulmonary circulation single-blocking in the target segment. Methods To retrospectively analyze the clinical data of 83 patients who underwent thoracoscopic pulmonary segmentectomy from January 2019 to March 2020 using the pulmonary circulation single-blocking method. There were 33 males and 50 females, with a median age of 54 (46-65) years, and they were divided into a single vein group (SVG, n=31) and a single artery group (SAG, n=52), and the clinical data of two groups were compared. Results The intersegmental planes were identified successfully in both groups and there were no statistically significant differences between the two groups in terms of intersegmental plane management (P=0.823), operating time (P=0.786), intraoperative blood loss (P=0.775), chest drainage time (P=0.659), postoperative hospital stay (P=0.824) or the incidence of postoperative complications (P=1.000). Conclusion The use of pulmonary circulation single-blocking for intersegmental plane identification during thoracoscopic segmentectomy is safe and feasible, and the intersegmental plane can be satisfactorily identified by the single-blocking of arteries or veins.
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Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections.
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Objective:To assess the changes of cardiac output (CO)-related indices in healthy term reproductive age pregnant women during labor.Methods:A prospective longitudinal study was conducted, involving 208 pregnant women at term who were at an reproductive age and admitted to the labor ward of Tianjin Central Hospital of Obstetrics and Gynecology from October 2020 to March 2021. The internal diameter of the aortic root, velocity-time integral of aortic valve flow, and heart rate were obtained through transthoracic echocardiography during uterine contractions period and the intervals between contractions in the latent phase, active phase, and the second stage of labor, as well as at one hour after delivery. Stroke volume (SV), CO, and cardiac index (CI) were then calculated. Comparisons among groups were performed using t-test, analysis of variance, or Wilcoxon test. CO-related indices during contractions periods and intervals between contractions were compared using paired t-test, those in each stage of labor using repeated measurement analysis of variance. Results:(1) CO-related indices in contractions periods vs intervals between contractions during labor: In the latent phase, maternal heart rate [79(72 -84) vs 76(70 -85) bpm, Z=－2.03, P<0.05], SV [(77.9±13.4) vs (71.1±12.8) ml, t=－13.98, P<0.05], CO [(6.1 ±1.2) vs (5.5 ±1.1) L/min, t=－14.19, P<0.05], and CI [(3.5 ±0.7) vs (3.1 ±0.6) L/(min·m 2), t=－14.29, P<0.05] during contractions were higher than those during the intervals. These parameters during contractions in the active phase and the second stage of labor were all higher than those during the intervals in the same stage (all P<0.05). (2) CO-related indices in each period of labor: Heart rate, CO, and CI during the intervals between contractions gradually increased along with labor progression and reached the peak at the second stage followed by a decrease at one hour after delivery, and a similar trend was also observed for these parameters during contractions in the whole labor (all P<0.05). No significant changes in the maternal SV during intervals between contractions were observed during the labor( P=0.366), while the figure during contractions showed a decreased trend along with the course of labor and declined to a nadir in the second stage (all P<0.05). Conclusions:Cardiac output related indices change significantly in healthy term reproductive age pregnant women during labor, especially in the second stage of labor. Therefore, correct monitoring and management of hemodynamic changes during labor are of great importance in the stability of cardiovascular function throughout labor.
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ObjectiveTo observe the effects of Hedysarum polysaccharides（HPS）on the signaling pathways of B-cell lymphoma 2 （Bcl-2）， cysteinyl aspartate-specific protease 3 （Caspase-3）， and Bcl-2-associated X protein （Bax） in Schwann cells（SCs）cultured in high glucose，and explore the possible mechanism of HPS against diabetic peripheral neuropathy（DPN）. MethodFour SD suckling mice aged 5-7 days were randomly divided into a normal group，a high-glucose group，an HPS + high-glucose group，and an α-lipoic acid（α-LA）+ high-glucose group. SCs were extracted from the sciatic nerve and cultured in a 37 ℃，5% CO2 incubator. After the cells reached 80% confluence，Cell Counting Kit-8（CCK-8）was used to screen the experimental concentrations suitable for high glucose，HPS， and α-LA interventions. Western blot and Real-time polymerase chain reaction （Real-time PCR）were used to detect the protein and mRNA expression of Bcl-2，Bax，and Caspase-3. The apoptosis rate of SCs was detected by flow cytometry using Annexin V-fluorescein isothiocyanate （FITC）/propidium iodide （PI）. ResultAs revealed by Western blot and real-time PCR，compared with the normal group，the high-glucose group showed reduced protein and mRNA expression of Bcl-2 and increased protein and mRNA expression of Bax and Caspase-3（P<0.01）. Compared with the high-glucose group，the HPS + high-glucose group and the α-LA + high-glucose group showed increased protein and mRNA expression of Bcl-2 and decreased protein and mRNA expression of Bax and Caspase-3（P<0.01）. As displayed by the results of flow cytometry using Annexin V/PI， compared with the normal group，the high-glucose group showed increased apoptosis rate；compared with the high-glucose group，the HPS + high-glucose group and the α-LA + high-glucose group showed reduced apoptosis rate（P<0.01）. ConclusionHPS can alleviate the apoptotic response of SCs，and its mechanism may be related to the inhibition of the activation of the Bcl-2/Caspase-3 signaling pathway.
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OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Adiponectin/metabolism , Animals , Antidepressive Agents/pharmacology , China , Depression/drug therapy , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Glucose , Hypothalamus/metabolism , Mice , Receptors, Adiponectin/metabolismABSTRACT
Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
Subject(s)
Child , Child, Preschool , Consensus , Dental Caries/prevention & control , Dental Caries Susceptibility , Humans , Oral HealthABSTRACT
Objective:To explore the effect of Aspergillus fumigatus ( A. fumigatus) on the autophagic flux in murine bone marrow-derived macrophages (BMDM) . Methods:Murine BMDM were in vitro cultured with heat-killed A. fumigatus for 0, 0.5, 4, and 12 hours. Then, cellular proteins were extracted, and Western blot analysis was performed to detect the conversion of the key autophagy protein microtubule-associated protein 1 light chain 3 (LC3) -Ⅰ to LC3-Ⅱ, and to determine the protein expression of phosphorylated mammalian target of rapamycin (p-mTOR) Ser2481. Additionally, murine BMDM were in vitro cultured with A. fumigatus alone or in combination with different lysosomal inhibitors, including the cysteine cathepsin inhibitor E-64d + pepstatin, bafilomycin-A1 (BAF-A1) , ammonium chloride (NH 4Cl) , and chloroquine, for 4 or 12 hours. Then, Western blot analysis was performed to investigate the effect of A. fumigatus on newly formed LC3-Ⅱ and basal autophagic flux, and confocal laser scanning fluorescence microscopy to analyze the colocalization of A. fumigatus with LC3 and Rubicon (a RUN domain Beclin-1-interacting and cysteine-rich-domain-containing protein) . Experimental results at different treatment time points were analyzed by using unpaired t test, and results of experiments evaluating the effect of two factors ( A. fumigatus spores and autophagosome inhibitors) were analyzed by 2 × 2 factorial analysis. Results:After in vitro co-culture with A. fumigatus for 0.5, 4, 12 hours, Western blot analysis showed that the conversion of LC3-Ⅰ to LC3-Ⅱ increased over time in murine BMDM compared with the control (0 hour) group ( t = 6.58, 3.28, 3.02, respectively, all P < 0.05) , but the protein expression level of p-mTOR (Ser2481) did not significantly differ at different treatment time points ( t = 0.441, 0.477, 0.382, P = 0.682, 0.660, 0.722, respectively) . After 4- and 12-hour in vitro treatment, the accumulation levels of LC3-Ⅱ in BMDM significantly increased in the A. fumigatus + chloroquine group compared with the chloroquine-alone group ( t = 2.13, 2.78, respectively, both P < 0.05) , in the A. fumigatus + NH 4Cl group compared with the NH 4Cl-alone group ( t = 2.92, 2.92, respectively, both P < 0.05) , in the A. fumigatus + BAF-A1 group compared with the BAF-A1-alone group ( t = 2.13, 2.13, respectively, both P < 0.05) , and in the A. fumigatus + E-64d + pepstatin group compared with the E-64d + pepstatin group ( t = 2.13, 2.92, respectively, both P < 0.05) . After 8-hour treatment with calcofluor white-labeled A. fumigatus spores, confocal laser scanning fluorescence microscopy showed that LC3 and Rubicon mainly surrounded A. fumigatus, suggesting their colocalization with A. fumigatus. Conclusion:A. fumigatus can in vitro increase the basal autophagic flux in murine BMDM.
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OBJECTIVE To study the mechanism of curcumol inhibiting the pro liferation of breast cancer cells T 47D. METHODS MTT assay was used to detect the inhibitory effects of different doses of curcumol （0，6.25，12.5，25，50，100 μg/mL）on the proliferation of T 47D cells. After treated with curcumol （12.5，25，50，100 μg/mL），the morphology of T 47D cells was observed by inverted phase contrast microscope. The cell cycle and the levels of reactive oxygen species （ROS）were detected by flow cytometry. Quantitative real-time PCR （qRT-PCR）was used to detect the expressions of proliferating cell nuclear antigen （PCNA），cell cycle regular p 21 and cyclin-dependent kinase 2（CDK2）mRNA. Western blot assay was used to detect the protein expression of CDK 2，CDK6，Cyclin D ，PCNA，nucler transcription factor E 2-related factor （Nrf2）and Kelch-like ECH associated protein 1（Keap1）. Breast cancer cells T 47D were divided into 2 groups，one group was given different doses of curcumol ，and another group was given curcumol 33 μg/mL for 6，12，24，48 h. After the optimal oxidation time and administration concentration were determined according to the results of the above two groups ，the blank control group ，N-acetylcysteine（NAC）group（ROS antioxidant NAC alone ），curcumol group （curcumol alone ），curcumol combined with NAC group （pretreatment with ROS antioxidant NAC ，and then adding into curcumol ）. Cell cycle and fluorescence intensity of ROS were detected. RESULTS Curcumol could significantly increase the inhibitory rate of the proliferation of T 47D cells （P＜0.05 or P＜0.01），and showed a certain dose and time dependent trend. Curcumol blocked the ， cycle in the G 1 phase and significantly increased the level of ROS （P＜0.05 or P＜0.01）；ROS antioxidant NAC could significantly reverse above inductive effect of curcumol （P＜ 0.01）. qRT-PCR showed that curcumol down-regulated the com expression of PCNA and CDK 2 mRNA and up-regulated the expression of p 21 mRNA（P＜0.05 or P＜0.01）. Western blot assay showed that curcumol significantly down-regulated the edu.cn protein expression of Keap 1，Nrf2，CDK2，CDK6 and Cyclin D（P＜0.05，P＜0.01）；ROS antioxidant NAC could reverse the down-regulation effects of curcumol on the expression of these proteins（P＜0.05 or P＜0.01）. CONCLUSIONS Curcumol may induce oxidative stress and cell arrest in G 1 phase to inhibit the proliferation of T 47D cells.
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Sagittal translation(ST) was defined as any measurable sagittal displacement more than 5 mm between the posterior inferior edge of the cranial vertebral body and the posterior superior edge of the caudal body at the osteotomized vertebrae(OV). Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by enthesitis and heterotopic ossification affecting sacroiliac joints and vertebral column. In the late stage, the poor quality of life caused by inability to lie supine or look straight ahead were the chief reasons for spinal osteotomy. Intraoperative ST secondary to AS thoracolumbar kyphosis contributed to improvement of sagittal vertical axis (SVA) partly. However, severe ST leaded to a huge bony step in front of dura, which was prone to vascular injury, neurologic deficit and cerebrospinal fluid leakage, thus affecting surgical outcomes. Prior research indicated there were significant correlations between intraoperative ST and inappropriate maneuver, the degree of ankylosis, the kyphosis curve pattern and correction, early fracture of the anterior cortex of the OV, excessive or insufficient decancellation of the OV, mismatch between the center of correcting forces and the center of rotation, incorrect application of cantilever technique. The use of anti-ST appliances, intraoperative fluoroscopy and nerve monitoring could prevent the occurrence of ST effectively. For AS patients with ST, relevant measures or decompressive laminectomies could be taken on the basis of neurological function to prevent neurologic deficit. Due to the strong osteogenic ability in AS patients, favorable bony reconstruction and fusion could be available during follow-up after adopting corresponding treatment involving ST. A thorough understanding of mechanism and risk factors of sagittal translation was essentially instructional to spinal surgeons thereby the incidence of intraoperative ST and complications could be decreased.
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Objective:To observe the therapeutic effect of microwave ablation combined with anhydrous ethanol for cystic thyroid nodules.Methods:From Jan. 2019 to Dec. 2019, 56 patients with thyroid cystic nodules (≥2cm) underwent ultrasound guided thyroid cystic nodule ablation in Department of Thyroid and Breast Surgery, Nanjing Hospital of Traditional Chinese Medicine. According to different ablation methods, the patients were divided into microwave ablation combined with anhydrous ethanol group and microwave ablation group. There were 36 cases in microwave ablation combined with anhydrous ethanol group and 20 cases in microwave ablation group. The volume reduction rate of thyroid nodules, the incidence of postoperative complications and the changes of thyroid function were compared between the two groups after treatment. Statistical analysis were performed using SPSS, version 21.0, the mean±SD deviation ( ± s) was used to describe the statistics, t-test was performed, and the adoption rate of counting data (%) was expressed by χ 2 test. The difference was statistically significant with P<0.05. Results:The nodule volume reduction rates of the microwave ablation combined with anhydrous ethanol group and microwave ablation group were (49.86±6.78) % vs (22.84±1.88) %, (67.57±5.84) % vs (47.25±7.09) % and (75.70±4.51) % vs (71.14±4.65) % at 3 months, 6 months and 12 months after operation, respectively. There was significant difference between the two groups ( P<0.001) . The incidence of postoperative complications in the two groups was 38.89% and 45.00% respectively, and there was no significant difference between the two groups ( P>0.05) , and all complications were cured within 2 months. There was no significant difference in thyroid function (T3, T4, FT3, FT4, TSH) between the two groups before and 12 months after operation ( P>0.05) . Conclusions:Microwave ablation combined with anhydrous ethanol is more effective in treatment of cystic thyroid nodules (≥2cm) than microwave ablation alone. It can significantly improve patients’symptoms and nodule volume reduction, and does not affect thyroid function. It can be used as a recommended option for treatment of cysticthyroid nodules.
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OBJECTIVES@#To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO).@*METHODS@#A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk.@*RESULTS@#A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2.@*CONCLUSIONS@#Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.
Subject(s)
Administration, Inhalation , Child , Humans , Hypertension, Pulmonary/drug therapy , Infant , Infant, Newborn , Nitric Oxide , Persistent Fetal Circulation Syndrome/drug therapy , Retrospective Studies , Risk FactorsABSTRACT
The secondary metabolites from the dandelion-derived Epicoccum sorghinum 1-2 were isolated by silica gel and Sephadex gel column chromatography, and semi-preparative high performance liquid chromatography (HPLC). Their structures were identified by comprehensive NMR and MS methods. Their antibacterial activities were determined by filter paper method. Finally, seven compounds were isolated and identified from the fermentation product of E. sorghinum 1-2, including (4R*,5R*,6S*)-4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-methoxymethyl-2-cyclohexen-l-one (1), (4R*,5R*,6S*)-4,5-dihydroxy-6-(6′-methylsalicyloxy)-2-methyl-2-cyclohexen-1-one (2), (4R,5R,6S)-4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydroxymethyl-2-cyclohexen-1-one (3), (-)-gabosine E (4), theobroxide (5), 3-chlorogentisyl alcohol (6), and 3-hydroxybenzyl alcohol (7), of which 1-5 are epoxydons, and 6 and 7 are phenolics. Compounds 1 and 2 are new structures reported for the first time. Compound 6 showed significant antibacterial activity against Staphylococcus aureus.
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BACKGROUND@#Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China.@*METHODS@#A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed.@*RESULTS@#In 6204 participants, there are 1002 women (1002/6204,16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m2vs. 23.50 ± 3.52 kg/m2vs. 22.55 ± 3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further.@*CONCLUSIONS@#The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.
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Adult , Blood Glucose/metabolism , China/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes, Gestational , Female , Fetal Macrosomia , Glucose Intolerance , Humans , Male , Pregnancy , Retrospective StudiesABSTRACT
Objective:To understand the possible detected mosaicism chromosome karyotyping using uncultured chorionic villus samples.Methods:This study retrospectively analyzed the clinical data of singleton pregnant women who underwent fetal chromosome karyotyping of uncultured chorionic villus samples at the Prenatal Diagnosis Center of Tianjin Central Hospital of Gynecology and Obstetrics from January 2016 to January 2019. Prenatal diagnosis indicators, fetal karyotypes, the incidence of chromosomal mosaicism and subsequent diagnosis, and perinatal outcomes were analyzed. Amniocentesis was performed when chromosomal mosaicism was identified. Descriptive statistical analysis was used for data analysis.Results:(1) A total of 438 pregnant women with available follow-up data were enrolled. Increased nuchal translucency (56.6%, 248/438) was the major indication for prenatal diagnosis. The karyotype analysis indicated that 79.5% (348/438) were normal, and 2.7% (12/428) were mosaicism. (2) Of the 438 cases, 336 cases (76.7%) were delivered at term, of which 327 cases were uncomplicated. There was one case of premature rupture of membranes within one week after amniocentesis and eight cases of abortion/fetal death between one week after the amniocentesis and 28 weeks of gestation. Of these nine cases, four had chromosomal abnormalities, and five had normal karyotypes. Termination of pregnancy was selected in 65 cases (14.8%) and 28 cases (6.4%) delivered before term. (3) Among the 12 (2.7%) cases of chromosomal mosaicism verified by fetal karyotyping through amniocentesis, four were confined placental mosaicism; six were abnormal chromosomal karyotypes in chorionic villous and amniotic fluid; one was true fetal mosaicism; one was a false positive. Among the 12 cases, three continued to term, one was preterm delivered, and eight selected labor induction, including three cases each of trisomy-21 and ultrasonographic structure abnormalities, and one case each of fetal growth restriction and labor induction based on patient preference.Conclusions:Karyotype analysis of uncultured chorionic villus samples may detect a certain proportion of mosaicism. Therefore, combining fluorescence in situ hybridization to achieve an accurate diagnosis and a detailed and systematic ultrasonic scan are recommended.
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Objective:To evaluate the effect of resveratrol on apoptosis and cell cycle of human epidermal keratinocytes (HEKs) after ultraviolet B (UVB) irradiation.Methods:After 12-hour treatment with 0 (control group) , 25, 50, 100, 150 and 200 μmol/L resveratrol, cell counting kit-8 (CCK8) assay, bromodeoxyuridine (BrdU) assay and lactate dehydrogenase (LDH) assay were performed to evaluate the effect of resveratrol on proliferative activity and death of HEKs. Some HEKs were divided into 4 groups: normal control group receiving no treatment, resveratrol group treated with 100 μmol/L resveratrol, UVB group irradiated with 50 mJ/cm 2 UVB, and UVB+resveratrol group irradiated with 50 mJ/cm 2 UVB followed by 12-hour treatment with 100 μmol/L resveratrol. Western blot analysis was conducted to determine the expression of apoptosis-related proteins poly (ADP-ribose) polymerase (PARP) and caspase-3, as well as cell cycle-related proteins cyclin B1 and cyclin E1, and flow cytometry to detect the apoptosis and determine cell cycle distribution. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference- t test for multiple comparisons. Results:The proliferative activity of HEKs significantly differed among the 25-, 50-, 100-, 150-, 200-μmol/L resveratrol groups and control group ( F=46.52, P < 0.001) , and was significantly lower in these resveratrol groups than in the control group (all P < 0.001) ; the DNA synthesis activity of HEKs was significantly lower in the 100-μmol/L resveratrol group (0.761 ± 0.141) than in the control group (2.226 ± 0.141, t=17.92, P < 0.001) ; there was no significant difference in cell death rate among the 25-, 50-, 100- and 200-μmol/L resveratrol groups ( F=1.938, P > 0.05) . After treatment with or without UVB and/or resveratrol, there were significant differences in the apoptosis rate, proportion of cells at G1, G2 and S phases, expression of PARP, caspase-3, cyclin B1 and cyclin E1 among the 4 groups (all P < 0.05) . The UVB group showed significantly increased apoptosis rates (24.69% ± 3.54%) and cleavage levels of PARP and caspase-3 (2.190 ± 0.349, 0.090 ± 0.016, respectively) compared with the normal control group and UVB+resveratrol group (4.00% ± 0.81%, 0.926 ± 0.040, 0.024 ± 0.019, respectively, all P < 0.05) ; the UVB group showed significantly decreased protein expression of cyclin E1 and cyclin B1 (0.116 ± 0.017, 0.775 ± 0.080, respectively) compared with the normal control group, and the UVB+resveratrol group showed significantly increased expression of cyclin E1 (0.287 ± 0.047) , but decreased expression of cyclin B1 (0.504 ± 0.009) compared with the UVB group (all P < 0.05) ; the UVB group showed significantly decreased proportion of S-phase cells, but increased proportion of G1- and G2-phase cells compared with the UVB+resveratrol group (all P < 0.05) . Conclusion:Resveratrol can decrease the proliferative activity of HEKs, inhibit apoptosis induced by UVB radiation, and regulate cell cycle progression.
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Objective:To evaluate the effect of Candida albicans ( C. albicans) hyphae on autophagic flux in murine bone marrow-derived macrophages (BMDM) . Methods:BMDM were in vitro stimulated with C. albicans hyphae for 0.5, 4 and 12 hours, and the 0-hour group treated without hyphae served as a control. Western blot analysis was performed to detect the conversion of microtubule-associated protein 1 light chain 3 (LC3) -Ⅰto LC3-Ⅱ, and determine the expression of phosphorylated mechanistic target of rapamycin (p-mTOR) at each time point. Some BMDM were divided into several groups: control group receiving no treatment, hyphae group treated with C. albicans hyphae, lysosomal inhibitor groups treated with different lysosomal inhibitors, including E-64d (a cysteine proteinase inhibitor) + pepstatin (a pepsin inhibitor) , bafilomycin-A1 (BAF-A1) , ammonium chloride and chloroquine, and hyphae combined with lysosomal inhibitor groups treated with lysosomal inhibitors immediately followed by C. albicans hyphae. After 4- or 12-hour treatment, the effect of C. albicans hyphae on basal autophagic flux in murine BMDM was evaluated. Statistical analysis was carried out by using unpaired t test, factorial design analysis of variance and least significant difference- t test. Results:After 0.5-, 4- and 12-hour in vitro treatment with C. albicans hyphae, the conversion of LC3-Ⅰ to LC3-Ⅱ significantly increased in murine BMDM (1.254±0.118, 1.629±0.391, 1.598±0.379, respectively) compared with the 0-hour group (0.983±0.030; t=3.875, 2.856, 2.804, respectively, all P< 0.05) , while there was no significant difference in the protein expression of p-mTOR among the 0-, 0.5-, 4- and 12-hour groups. After 4- and 12-hour in vitro treatment with C. albicans hyphae combined with lysosomal inhibitors E-64d and pepstatin, the accumulation level of LC3-Ⅱ significantly increased in BMDM compared with those treated with E-64d and pepstatin alone ( t=3.691, 6.648, respectively, both P< 0.05) . Compared with the corresponding lysosomal inhibitor groups, the accumulation level of LC3-Ⅱsignificantly increased in BMDM treated with C. albicans hyphae combined with BAF-A1, ammonium chloride or chloroquine for 4 and 12 hours (all P< 0.05) . Conclusion:In vitro treatment with C. albicans hyphae can increase the conversion of LC3-Ⅰto LC3-Ⅱ in the basal autophagic flux in murine BMDM.
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Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.