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Background and Objectives@#Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. @*Methods@#and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). @*Conclusions@#Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.
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Objective:To evaluate the feasibility of a predictire model composed of non-specific test indexes in early diagnosis of gastric cancer.Methods:From the database of electronic medical record system of Shanghai Changhai Hospital, a total of 24 615 case records were included from January 1, 2010 to April 30, 2019, including 10 497 cases of gastric cancer, 5 198 cases of precancerous diseases, and 8 920 cases of health examination. Through stratified random sampling, the study population was divided into validation set, training set and test set. After data processing and quality control for all laboratory variables, the optimal machine learning algorithm and diagnostic efficiency grouping were selected through four machine learning algorithms, induding the gradient boosting decision tree, random forest, support vector machine, and artificial neural network, and the data were trained by backward stepwise regression method to build the best feature model.Result:In this study, a diagnostic model V22 consisting of 22 routine testing parameters was established. V22 could distinguish early gastric cancer from control group composed of healthy group and precancerous disease, AUC was 0.808, the sensitivity was 85.7%, and the specificity was 91.9%. For CEA negative gastric cancer, V22 also showed high diagnostic accuracy, AUC was 0.801.Conclusion:V22 was a valuable model for the diagnosis of gastric cancer. V22 was an auxiliary diagnostic model of gastric cancer with clinical application value, which could well distinguish early gastric cancer from the control group composed of healthy group and precancerous disease, and the detection rate of early gastric cancer was better than the traditional tumor marker CEA.
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Purpose@#Sleep quality was considered a priority concern facing pregnant women. Conventional wisdom argues that good sleep quality benefits pregnant women and their fetuses. The aim of this study is to assess the effects of a specific exercise program on the sleep quality in pregnant women. @*Methods@#Searches were executed in seven databases since their inceptions until February 28, 2019, for randomized controlled trials evaluating the effects of an exercise program on the sleep quality and insomnia in pregnant women. A random-effects model was applied for meta-analysis, and odds ratio, mean differences (MDs), and 95% confidence intervals (CIs) are shown as parts of outcomes. @*Results@#Seven studies were included for meta-analysis. Compared with their not-exercising counterparts, analyses showed that regularly exercising women had significantly enhanced sleep quality, with an odds ratio of 6.21 (95% CI, 2.02–19.11;p = .001; I2 = 80.2%), with a standardized MD of −0.93 (95% CI, −1.19 to −0.67; p < .001; I2 = 30.0%). However, exercising women showed no significant insomnia improvement, with an standardized MD of −2.85 (95% CI, −7.67 to 1.98; p = .250; I2 = 97.0%), relative to their not-exercising counterparts. @*Conclusion@#This research indicated that exercise has a positive impact on the sleep quality of pregnant women. Despite the aforementioned positive impact on sleep quality, the present study did not find evidence to support that exercise may also improve insomnia for pregnant women.
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Purpose@#Sleep quality was considered a priority concern facing pregnant women. Conventional wisdom argues that good sleep quality benefits pregnant women and their fetuses. The aim of this study is to assess the effects of a specific exercise program on the sleep quality in pregnant women. @*Methods@#Searches were executed in seven databases since their inceptions until February 28, 2019, for randomized controlled trials evaluating the effects of an exercise program on the sleep quality and insomnia in pregnant women. A random-effects model was applied for meta-analysis, and odds ratio, mean differences (MDs), and 95% confidence intervals (CIs) are shown as parts of outcomes. @*Results@#Seven studies were included for meta-analysis. Compared with their not-exercising counterparts, analyses showed that regularly exercising women had significantly enhanced sleep quality, with an odds ratio of 6.21 (95% CI, 2.02–19.11;p = .001; I2 = 80.2%), with a standardized MD of −0.93 (95% CI, −1.19 to −0.67; p < .001; I2 = 30.0%). However, exercising women showed no significant insomnia improvement, with an standardized MD of −2.85 (95% CI, −7.67 to 1.98; p = .250; I2 = 97.0%), relative to their not-exercising counterparts. @*Conclusion@#This research indicated that exercise has a positive impact on the sleep quality of pregnant women. Despite the aforementioned positive impact on sleep quality, the present study did not find evidence to support that exercise may also improve insomnia for pregnant women.
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Objective To observe the effect of speech therapy in group on children with autism spectrum disorders(ASD). Methods From July,2014 to July,2015,60 children with ASD were randomly divided into control group(n=30)and ex-perimental group(n=30).Both groups accepted regular rehabilitation training,while the experimental group ac-cepted speech therapy in group in addition,for six months.They were assessed with Autism Behavior Checklist (ABC)and Autism Treatment Evaluation Checklist(ATEC)before and after training,. Results The scores of ABC in both groups decreased after training(t>3.079,P<0.01),and decreased more in the experi-mental group(t=3.149,P<0.01).The score of Health/Physical/Behavior and total score of ATEC decreased in the control group(t>3.018,P<0.01),while the scores of all the items of ATEC decreased in the experimental group (t>2.498,P<0.05)after treatment.The scores of all the items of ATEC decreased more in the experimental group than in the control group(t>2.027,P<0.05). Conclusion The addition of speech therapy in group can further improve the behavior in children with ASD.
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Objective To explore the effect of dronedaronel on hyperpolarization-activated cyclic-nucleotide-gated(HCN) channel expression by detecting the change of HCN channel mRNA and protein level before and after giving dronedarone in neonatal rat ventricular myocytes.Methods Neonatal rat ventricular myocytes were separated and digested by type Ⅱ collagenase,and then single ventricular myocytes were collected through differential sticking wall separation method.According to the concentrations (0.1,0.5,1.0,5.0,10.0,20.0 μmol/L of dronedaronel for treating myocytes for 48 h) and time(10 μmol/L of dronedaronel for treating myocytes for 1,6,12,24,48 h)the gradient grouping was conducted.The levels of HCN2 and HCN4 channel mRNA and protein level were determined by real-time PCR and Western blot.Results The HCN2 mRNA and HCN4 mRNA expression levels in concentration gradient group and time gradient group were lower than those in the control group(P＜0.05);compared with the control group,the protein level in the 10 umol/L dronedaronel treatment for 12 h group was significantly down-regulated(P＜ 0.01).Conclusion Dronedaronel could inhibit the expression of HCN2/HCN4 channel mRNA and protein,moreover its action shows the concentration dependency and reaches the maximum at 12 h after medication.
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Objective To study the association of early prognosis and risk factors about early neurological deterioration (END) in aged patients with cerebral hemorrhage in basal ganglia. Methods One hundred and thirty-nine aged patients with cerebral hemorrhage in basal ganglia were selected. The patients were divided into END group (59 cases) and non-END group (80 cases), the clinical data were retrospectively analyzed. The patients were followed up 3 months after discharge, the prognosis was evaluated by modified Rankin scale. Logistic regression analysis was used to determine the independent risk factors of END. Results The incidence of END was 42.4%(59/139). The incidence of unfavourable prognosis in END group was significantly higher than that in non-END group:78.0%(46/59) vs. 30.0%(24/80), and there was statistical difference (P0.05). The Logistic regression analysis results showed that brain ventricle hemorrhage and white blood cell count at admission were independent risks factor for END in aged patients with cerebral hemorrhage in basal ganglia(P < 0.05 or < 0.01). Conclusions The aged patients with cerebral hemorrhage in basal ganglia will be prone to END, the brain ventricle hemorrhage and white blood cell count at admission are independent risks factor for END, and the early prognosis is poor.
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Objective To compare the clinical effects and characteristics between hypertensive intracerebral hemorrhage (HICH) and haematoma clearance by craniotomy for basal ganglia.Methods Clinical data of 50 patients with HICH in basal ganglia were collected,including operation duration,amount of intraoperative bleeding,cleared amount of haematoma,postoperative intracranial infection,and GOS at the sixth month after operation.The patients were divided into endoscopic group and craniotomy group.Clinical effects were analyzed by using GOS at the sixth month as a prognosis index.Results Preoperatively,the two groups showed no significant difference in any type of clinical materials(all P ＞ 0.05).Operation durations were (1.5 ± 0.8) h and (3.5 ± 1.1) h (P ＜ 0.05),respectively; amounts of intraoperative bleeding were (40.0 ± 19.7) rnl and (40.6 ± 13.2) ml (P ＜ 0.05),respectively; clearance rates of haematoma were (92.6 ± 9.4) ％ and (73.1 ± 21.1) ％ (P ＜ 0.05),respectively; cases of postoperative intracranial infections were 0 and 3 (P ＜ 0.05),respectively,for the endoscopy group and the craniotomy group.GOS prognosis at 6 months showed 7 cases of good recovery,12 cases of slight disability,2 cases of severe disability,1 case of vegetative state,and 1 death in the endoscopy group;6 cases of good recovery,9 cases of slight disability,6 cases of severe disability,3 case of vegetative state,and 1 death in the craniotomy group.Prognosis was better in the endoscopy group than in the craniotomy group(P ＜ 0.05).Conclusion Endoscopic surgery is an efficient and minimally invasive and operating technique for the treatment of hypertensive basal ganglia intracerebral hemorrhage.
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Spontaneous transient outward currents (STOCs) play an important role in the myogenic regulation of small artery tone, such as coronary artery. In the present study, we investigated the electrophysiological properties and the regulation of STOCs in vascular smooth muscle cells (VSMCs) of porcine coronary artery by perforated patch-clamp technique. Our data showed that STOCs were dependent on voltage and extracellular calcium and they were highly variable in amplitudes and frequencies. STOCs superimposed stochastically onto whole-cell K(+) currents induced by step and ramp protocols. STOCs were completely abolished by ChTX [inhibitor of large-conductance Ca(2+)-activated potassium (BK(Ca)) channels], removal of extracellular Ca(2+), or addition of ryanodine (50 mumol/L) respectively. In contrast, CdCl2 and verapamil, inhibitors of voltage-dependent L-type Ca(2+) channels, had little effect on STOCs. Caffeine (5 mmol/L) transiently increased STOCs (hump), followed by a temporary inhibition. Ca(2+) ionophore A23187 increased both amplitude and frequency of STOCs. Na(+) ionophore monensin increased the frequency of STOCs. STOCs were strongly inhibited by KB-R7943, a selective inhibitor of the reverse mode of the Na(+)/Ca(2+) exchanger. Based on these observations, we conclude that STOCs are mediated by BK(Ca) channels. The generation and activation of STOCs depend upon Ca(2+) influx through Na(+)/Ca(2+) exchange and release of Ca(2+) from sarcoplasmic reticulum (SR) via ryanodine receptors. This suggests that Na(+)/Ca(2+) exchange determines calcium store refilling. Recycling of entering Ca(2+) from superficial SR may locally elevate Ca(2+) concentration at the plasma membrane, thereby activating BK(Ca) channels and then initiating STOCs.
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Animais , Vasos Coronários , Biologia Celular , Fisiologia , Fenômenos Eletrofisiológicos , Fisiologia , Músculo Liso Vascular , Biologia Celular , Fisiologia , Miócitos de Músculo Liso , Biologia Celular , Fisiologia , Técnicas de Patch-Clamp , Canais de Potássio Cálcio-Ativados , Fisiologia , Trocador de Sódio e Cálcio , Fisiologia , SuínosRESUMO
Objective To investigate the role of a cis-acting element,cell cycle genes homology region (CHR),in the transcriptional regulation of human NFBD1 gene (a nuclear factor with BRCT domain 1) by conducting a site-directed mutagenesis analysis on the element in human NFBD1 promoter region.Methods Wild type of NFBD1 promoter reporter,NFBD1-PS1-325,was used as template to make CHR mutant by using PCR based site-directed mutagenesis.Dual luciferase reporter assay was used to determine promoter reporter activity.Adiamycin treatment was employed to investigate the role of CHR in the transcriptional downregulation of NFBD1 after DNA damage.Results Site-directed mutagenesis of CHR caused a significant decrease in NFBD1 promoter activity,and also attenuated the transcriptional down-regulation of NFBD1 after DNA damage.Conclusion CHR element might be involved in both basic transcriptional regulation and transcriptional downregulation of NFBD1 after DNA damage.