Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, alth...Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine.展开更多
Background:Nalbuphine has been suggested to be used for post-cesarean section(CS)intravenous analgesia.However,ideal concentration of nalbuphine for such analgesia remains unclear.The present study was conducted to ex...Background:Nalbuphine has been suggested to be used for post-cesarean section(CS)intravenous analgesia.However,ideal concentration of nalbuphine for such analgesia remains unclear.The present study was conducted to explore an ideal concentration of nalbuphine for post-CS intravenous analgesia by evaluating the analgesic effects and side-effects of three different concentrations of nalbuphine combined with hydromorphone for post-CS intravenous analgesia in healthy parturients.Methods:One-hundred-and-fourteen parturients undergoing elective CS were randomly allocated to one of three groups(38 subjects per group)according to an Excel-generated random number sheet to receive hydromorphone 0.05 mg/mL+nalbuphine 0.5 mg/mL(group LN),hydromorphone 0.05 mg/mL+nalbuphine 0.7 mg/mL(group MN),and hydromorphone 0.05 mg/mL+nalbuphine 0.9 mg/mL(group HN)using patient-controlled analgesia(PCA)pump.Visual analog scale(VAS)for pain,PCA bolus demands,cumulative PCA dose,satisfaction score,Ramsay score,and side-effects such as urinary retention were recorded.Results:The number of PCA bolus demands and cumulative PCA dose during the first 48 h after CS were significantly higher in group LN(21±16 bolus,129±25 mL)than those in group MN(15±10 bolus,120±16 mL)(both P<0.05)and group HN(13±9 bolus,117±13 mL)(both P<0.01),but no difference was found between group HN and group MN(both P>0.05).VAS scores were significantly lower in group HN than those in group MN and group LN for uterine cramping pain at rest and after breast-feeding within 12 h after CS(all P<0.01)and VAS scores were significantly higher in group LN than those in groupMNand group HN when oxytocin was intravenously infused within 3 days after CS(all P<0.05),whereas VAS scores were not statistically different among groups for incisional pain(all P>0.05).Ramsay sedation scale score in groupHNwas significantly higher than that in group MN at 8 and 12 h after CS(all P<0.01)and group LN at 4,8,12,24 h after CS(all P<0.05).Conclusions:Hydromorphone 0.05 mg/mL+nalbuphine 0.7 mg/mL for intravenous PCA could effectively improve the incisional pain and uterine cramping pain management and improve comfort in patients after CS.展开更多
Background： Spinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated, and there is no indwelling epidural catheter or contraindication to spinal an...Background： Spinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated, and there is no indwelling epidural catheter or contraindication to spinal anesthesia. However, the ideal dose of intrathecal bupivacaine has not been quantified for cesarean delivery for severe preeclamptic patients. This study aimed to determine the ED50 and ED95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery. Methods： Two hundred severely preeclamptic patients are undergoing elective cesarean delivery under combined spinal-epidural anesthesia enrolled in this randomized, double-blinded, dose-ranging study. Patients received 4 rag, 6 mg, 8 mg, or 10 mg intrathecal hyperbaric bupivacaine with 2.5 μg sufentanil. Successful spinal anesthesia was defined as a T6 sensory level achieved within 10 minutes after intrathecal drug administration and/or no epidural supplement was required during the cesarean section. The ED50 and ED95 were calculated with a logistic regression model. Results： ED90 and ED95 ofintrathecal bupivacaine for successful spinal anesthesia were 5.67 mg （95% confidence interval [C/]： 5.20-6.10 mg） and 8.82 mg （95% CI： 8.14-9.87 mg） respectively. The incidence of hypotension in Group 8 mg and Group 10 mg was higher than that in Group 4 mg and Group 6 mg （P 〈 0.05）. The sensory block was significantly different among groups 10 minutes after intrathecal injection （P 〈 0.05）. The use of lidocaine in Group 4 mg was higher than that in other groups （P 〈 0.05）. The use of phenylephrine in Group 8 mg and Group 10 mg was higher than that in the other two groups （P 〈 0.05）. The lowest systolic blood pressure before the infant delivery of Group 8 mg and Group 10 mg was lower than the other two groups （P 〈 0.05）. The satisfaction of muscle relaxation in Group 4 mg was lower than other groups （P 〈 0.05）. There was no significant difference in patients＇ satisfaction and the newborns＇ Apgar score and the blood gas analysis of umbilical artery serum （P 〉 0.05）. Conclusion： Our study showed that the EDs0 and ED~ of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery were 5.67 mg and 8.82 mg, respectively. In addition, decreasing the dose of intrathecal bupivacaine could reduce the incidence of maternal hypotension.展开更多
Background:Cell salvage has recently been recommended for obstetric use in cases with a high risk of massive hemorrhage during cesarean section(CS).However,limited data are available to support the use of one suction ...Background:Cell salvage has recently been recommended for obstetric use in cases with a high risk of massive hemorrhage during cesarean section(CS).However,limited data are available to support the use of one suction device to collect lost blood.This study aimed to investigate the volume of red blood cells(RBCs)salvaged and the components of amniotic fluid(AF)in blood salvaged by one suction device or two devices during CS in patients with placenta previa and/or accrete.Methods:Thirty patients with placenta previa and/or accrete undergoing elective CS in the Women's Hospital of Zhejiang University School of Medicine were recruited for the present study from November 1,2017 to December 1,2018.The patients were randomly assigned to one of the two groups according to an Excel-generated random number sheet:Group 1(w=15),in which only one suction device was used to aspirate all blood and AF,and Group 2(w=15),in which a second suction device was mainly used to aspirate AF before the delivery of the placenta.Three samples of blood per patient(pre-wash,post-wash,and post-filtration)were collected to measure AF components.The salvaged RBC volumes were recorded.Continuous data of pre-wash,post-wash,and postfiltration samples were analyzed by using one-way analysis of variance with Tukey5s test for multiple comparisons,or Kruskal-Wallis test with Dunn test for multiple comparisons.Comparisons of continuous data between Group 1 and Group 2 were conducted using Student's t test or Mann-Whitney U test.Results:The salvaged RBC volume was significantly higher in Group 1 than that in Group 2(401.6±77.2 mL vs.330.1土53.3 mL,?=4.175,P<0.001).In both groups,squamous cells,lamellar bodies,and fat were significantly reduced by washing(all P<0.001)and squamous cells were further reduced by filtering(P<0.001).Squamous cells were found in six post-filtration samples(three from each group).Lamellar bodies and fat were completely removed by filtering.Insulin-like growth factor binding protein 1,alphafetoprotein,albumin,lactate dehydrogenase,and potassium were significantly reduced post-wash(all P<0.05),with no further significant reduction after filtration in either group(all P>0.05).The mean percentage of fetal RBCs post-filtration was(1.8±0.8)%with a range of 1.0%to 3.5%and(1.9±0.9)%with a range of 0.7%to 4.0%in Groups 1 and 2,respectively,showing no significant difference between the two groups(U=188.5,P=0.651).Conclusion:Cell salvage performed by one suction device could result in higher volume of salvaged RBCs and can be used safely for CS in patients with placenta previa and/or accrete when massive hemorrhage occurs.Trial registration number:ChiCTR-INR-17012926,http://www.chictr.org.cn/Chinese Clinical Trial Registry.展开更多
It is commonly accepted that females and males differ in their experience of pain. Gender differences have been found in the prevalence and severity of pain in both clinical and animal studies. Sex-related hormones ar...It is commonly accepted that females and males differ in their experience of pain. Gender differences have been found in the prevalence and severity of pain in both clinical and animal studies. Sex-related hormones are found to be involved in pain transmission and have critical effects on visceral pain sensitivity. Studies have pointed out the idea that serum estrogen is closely related to visceral nociceptive sensitivity. This review aims to summarize the literature relating to the role of estrogen in modulating visceral pain with emphasis on deciphering the potential central and peripheral mechanisms.展开更多
The photoplethysmogram(PPG) of a pulse wave,similar in appearance to the arterial blood pressure(ABP) waveform,contains rich information about the cardiovascular system.The decay time constant RC,equal to the product ...The photoplethysmogram(PPG) of a pulse wave,similar in appearance to the arterial blood pressure(ABP) waveform,contains rich information about the cardiovascular system.The decay time constant RC,equal to the product of peripheral resistance R and total arterial compliance C,is a meaningful cardiovascular model parameter in vascular assessment.Using or ameliorating the existing ABP methods does not achieve a satisfactory estimation of RC from the PPG volume pulse(VRC).Thus,a novel non-iterative shape method(NSM) of evaluating VRC is introduced in this paper.The mathematic expression between a novel,readily available morphological parameter called the area difference ratio(ADR) and VRC was established.As it was difficult to calculate VRC from the complicated expression analytically,we recommend estimating it using a piecewise linear interpolation criterion.Also,since the effect of the PPG magnitude is eliminated in the calculation of ADR,precaliberation or normalization is dispensable in the NSM.Results of human experiments indicated that the NSM was computationally efficient,and the simulation experiments confirmed that the NSM was theoretically available for ABP.展开更多
基金supported by the National Natural Science Foundation of China,No.81471126(to XZC)and 81771216(to XZC)the Natural Science Foundation of Zhejiang Province of China,No.LY17H090005(to JLP)a grant from the Medical Science and Technology Plan Project of Zhejiang Province of China,No.2016KYB119(to JLP)
文摘Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine.
基金supported by the grant from National Natural Science Foundation of China(No.81471126).
文摘Background:Nalbuphine has been suggested to be used for post-cesarean section(CS)intravenous analgesia.However,ideal concentration of nalbuphine for such analgesia remains unclear.The present study was conducted to explore an ideal concentration of nalbuphine for post-CS intravenous analgesia by evaluating the analgesic effects and side-effects of three different concentrations of nalbuphine combined with hydromorphone for post-CS intravenous analgesia in healthy parturients.Methods:One-hundred-and-fourteen parturients undergoing elective CS were randomly allocated to one of three groups(38 subjects per group)according to an Excel-generated random number sheet to receive hydromorphone 0.05 mg/mL+nalbuphine 0.5 mg/mL(group LN),hydromorphone 0.05 mg/mL+nalbuphine 0.7 mg/mL(group MN),and hydromorphone 0.05 mg/mL+nalbuphine 0.9 mg/mL(group HN)using patient-controlled analgesia(PCA)pump.Visual analog scale(VAS)for pain,PCA bolus demands,cumulative PCA dose,satisfaction score,Ramsay score,and side-effects such as urinary retention were recorded.Results:The number of PCA bolus demands and cumulative PCA dose during the first 48 h after CS were significantly higher in group LN(21±16 bolus,129±25 mL)than those in group MN(15±10 bolus,120±16 mL)(both P<0.05)and group HN(13±9 bolus,117±13 mL)(both P<0.01),but no difference was found between group HN and group MN(both P>0.05).VAS scores were significantly lower in group HN than those in group MN and group LN for uterine cramping pain at rest and after breast-feeding within 12 h after CS(all P<0.01)and VAS scores were significantly higher in group LN than those in groupMNand group HN when oxytocin was intravenously infused within 3 days after CS(all P<0.05),whereas VAS scores were not statistically different among groups for incisional pain(all P>0.05).Ramsay sedation scale score in groupHNwas significantly higher than that in group MN at 8 and 12 h after CS(all P<0.01)and group LN at 4,8,12,24 h after CS(all P<0.05).Conclusions:Hydromorphone 0.05 mg/mL+nalbuphine 0.7 mg/mL for intravenous PCA could effectively improve the incisional pain and uterine cramping pain management and improve comfort in patients after CS.
基金This study was supported partly by the fund from National Natural Science Foundation of China （NSFC, No. 81271237 and No. 81471126） and the fund from Jiaxing Science and Technol- ogy Bureau in Zhejiang Province, China （No. 2013AY21050-2）.ACKNOWLEDGMENTS The authors would like to thank all staffs in the Department of Anesthesia and Operating Room of Jiaxing Maternity and Child Care Hospital for their help in this study.
文摘Background： Spinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated, and there is no indwelling epidural catheter or contraindication to spinal anesthesia. However, the ideal dose of intrathecal bupivacaine has not been quantified for cesarean delivery for severe preeclamptic patients. This study aimed to determine the ED50 and ED95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery. Methods： Two hundred severely preeclamptic patients are undergoing elective cesarean delivery under combined spinal-epidural anesthesia enrolled in this randomized, double-blinded, dose-ranging study. Patients received 4 rag, 6 mg, 8 mg, or 10 mg intrathecal hyperbaric bupivacaine with 2.5 μg sufentanil. Successful spinal anesthesia was defined as a T6 sensory level achieved within 10 minutes after intrathecal drug administration and/or no epidural supplement was required during the cesarean section. The ED50 and ED95 were calculated with a logistic regression model. Results： ED90 and ED95 ofintrathecal bupivacaine for successful spinal anesthesia were 5.67 mg （95% confidence interval [C/]： 5.20-6.10 mg） and 8.82 mg （95% CI： 8.14-9.87 mg） respectively. The incidence of hypotension in Group 8 mg and Group 10 mg was higher than that in Group 4 mg and Group 6 mg （P 〈 0.05）. The sensory block was significantly different among groups 10 minutes after intrathecal injection （P 〈 0.05）. The use of lidocaine in Group 4 mg was higher than that in other groups （P 〈 0.05）. The use of phenylephrine in Group 8 mg and Group 10 mg was higher than that in the other two groups （P 〈 0.05）. The lowest systolic blood pressure before the infant delivery of Group 8 mg and Group 10 mg was lower than the other two groups （P 〈 0.05）. The satisfaction of muscle relaxation in Group 4 mg was lower than other groups （P 〈 0.05）. There was no significant difference in patients＇ satisfaction and the newborns＇ Apgar score and the blood gas analysis of umbilical artery serum （P 〉 0.05）. Conclusion： Our study showed that the EDs0 and ED~ of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery were 5.67 mg and 8.82 mg, respectively. In addition, decreasing the dose of intrathecal bupivacaine could reduce the incidence of maternal hypotension.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81471126 and No.81870868).
文摘Background:Cell salvage has recently been recommended for obstetric use in cases with a high risk of massive hemorrhage during cesarean section(CS).However,limited data are available to support the use of one suction device to collect lost blood.This study aimed to investigate the volume of red blood cells(RBCs)salvaged and the components of amniotic fluid(AF)in blood salvaged by one suction device or two devices during CS in patients with placenta previa and/or accrete.Methods:Thirty patients with placenta previa and/or accrete undergoing elective CS in the Women's Hospital of Zhejiang University School of Medicine were recruited for the present study from November 1,2017 to December 1,2018.The patients were randomly assigned to one of the two groups according to an Excel-generated random number sheet:Group 1(w=15),in which only one suction device was used to aspirate all blood and AF,and Group 2(w=15),in which a second suction device was mainly used to aspirate AF before the delivery of the placenta.Three samples of blood per patient(pre-wash,post-wash,and post-filtration)were collected to measure AF components.The salvaged RBC volumes were recorded.Continuous data of pre-wash,post-wash,and postfiltration samples were analyzed by using one-way analysis of variance with Tukey5s test for multiple comparisons,or Kruskal-Wallis test with Dunn test for multiple comparisons.Comparisons of continuous data between Group 1 and Group 2 were conducted using Student's t test or Mann-Whitney U test.Results:The salvaged RBC volume was significantly higher in Group 1 than that in Group 2(401.6±77.2 mL vs.330.1土53.3 mL,?=4.175,P<0.001).In both groups,squamous cells,lamellar bodies,and fat were significantly reduced by washing(all P<0.001)and squamous cells were further reduced by filtering(P<0.001).Squamous cells were found in six post-filtration samples(three from each group).Lamellar bodies and fat were completely removed by filtering.Insulin-like growth factor binding protein 1,alphafetoprotein,albumin,lactate dehydrogenase,and potassium were significantly reduced post-wash(all P<0.05),with no further significant reduction after filtration in either group(all P>0.05).The mean percentage of fetal RBCs post-filtration was(1.8±0.8)%with a range of 1.0%to 3.5%and(1.9±0.9)%with a range of 0.7%to 4.0%in Groups 1 and 2,respectively,showing no significant difference between the two groups(U=188.5,P=0.651).Conclusion:Cell salvage performed by one suction device could result in higher volume of salvaged RBCs and can be used safely for CS in patients with placenta previa and/or accrete when massive hemorrhage occurs.Trial registration number:ChiCTR-INR-17012926,http://www.chictr.org.cn/Chinese Clinical Trial Registry.
基金Project supported by the National Natural Science Foundation of China(No.81471126)
文摘It is commonly accepted that females and males differ in their experience of pain. Gender differences have been found in the prevalence and severity of pain in both clinical and animal studies. Sex-related hormones are found to be involved in pain transmission and have critical effects on visceral pain sensitivity. Studies have pointed out the idea that serum estrogen is closely related to visceral nociceptive sensitivity. This review aims to summarize the literature relating to the role of estrogen in modulating visceral pain with emphasis on deciphering the potential central and peripheral mechanisms.
基金Project (No.81070885) supported by the National Natural Science Foundation of China
文摘The photoplethysmogram(PPG) of a pulse wave,similar in appearance to the arterial blood pressure(ABP) waveform,contains rich information about the cardiovascular system.The decay time constant RC,equal to the product of peripheral resistance R and total arterial compliance C,is a meaningful cardiovascular model parameter in vascular assessment.Using or ameliorating the existing ABP methods does not achieve a satisfactory estimation of RC from the PPG volume pulse(VRC).Thus,a novel non-iterative shape method(NSM) of evaluating VRC is introduced in this paper.The mathematic expression between a novel,readily available morphological parameter called the area difference ratio(ADR) and VRC was established.As it was difficult to calculate VRC from the complicated expression analytically,we recommend estimating it using a piecewise linear interpolation criterion.Also,since the effect of the PPG magnitude is eliminated in the calculation of ADR,precaliberation or normalization is dispensable in the NSM.Results of human experiments indicated that the NSM was computationally efficient,and the simulation experiments confirmed that the NSM was theoretically available for ABP.
