Objective： The intoxications caused by 2,4-dinitrophenol （2,4-DNP）, even death, have been frequently reported in recent years. This study aims to investigate the dynamic changes of plasma toxin concentration and ex...Objective： The intoxications caused by 2,4-dinitrophenol （2,4-DNP）, even death, have been frequently reported in recent years. This study aims to investigate the dynamic changes of plasma toxin concentration and explore the clinical value of resin hemoperfusion （HP） in the treatment of patients with acute 2,4-DNP poisoning. Methods We reported 16 cases of acute 2,4-DNP poisoning through occupational exposure due to ignoring the risk of poisoning. The blood samples were collected from the 14 survivors. According to the different treatments of resin HP, the survivors were divided into routine HP （n=5） and intensive HP （n=9） groups. Ultra high performance liquid chromatography/ tandem mass spectroscopy （UPLC-MS/MS） was used to detect the 2,4-DNP concentration in plasma in this study. Results： The 14 survivors recovered very well after treatment. The initial plasma 2,4-DNP concentrations （C1） of survivors ranged from 0.25 to 41.88 pg/ml （mean （12.56＋13.93） pg/ml）. A positive correlation existed between initial plasma 2,4-DNP concentration （C1） and temperature. The elimination of 2,4-DNP was slow and persistent, and the total clearance rates of plasma toxin from the 1st to 3rd day （R3）, the 3rd to 7th day （R3-7）, and the 1st to 7th day （RT）, were only （53.03±14.04）%, （55.25±10.50）%, and （78.29±10.22）%, respectively. The plasma toxin was cleared up to 25 d after poisoning in most of the patients. The R3, R3-7, and R7 in the intensive HP group were all apparently higher than those in the routine HP group, with statistical significance （P〈0.05）. Simultaneously, the elimination half-life （tl/2） of 2,4-DNP in the intensive HP group was apparently shorter than that in the routine HP group, with statistical significance （P〈0.05）. Conclusions： The clinicians should be aware of this slow and persistent process in the elimination of plasma 2,4-DNP. Higher initial plasma toxin concentration resulted in a more severe fever for the patient. According to the limited data, longer and more frequent resin HP may accelerate to eliminate the poison.展开更多
Objective： To investigate the effects of resuscitation with normal saline（NS）, hypertonic saline（HTS）, and hydroxyethyl starch（HES） on regulatory T cells（Tregs）, helper T 1（Th1）/Th2 and cytotoxic T 1（Tc1）...Objective： To investigate the effects of resuscitation with normal saline（NS）, hypertonic saline（HTS）, and hydroxyethyl starch（HES） on regulatory T cells（Tregs）, helper T 1（Th1）/Th2 and cytotoxic T 1（Tc1）/Tc2 profiles in the treatment of hemorrhagic shock. Methods： Rats subjected to severe hemorrhagic shock were resuscitated for 30 min with NS（n=8）, HTS（n=8）, or HES（n=8）; sham（n=8） and naive control（n=8） groups were used for comparison. Following fluid resuscitation, the whole shed blood was reinfused for 30 min, and the rats were observed with continuous hemodynamic monitoring for 120 min. CD4^＋CD25^＋Foxp3^＋ Treg proportions, Th1/Th2 and Tc1/Tc2 profiles in spleen were analyzed by three-color flow cytometry. Results： The proportion of CD4^＋CD25^＋Foxp3^＋ Tregs and ratios of Th1/Th2 and Tc1/Tc2 did not differ among control, sham, and HTS groups, but were significantly lower in NS and HES groups（both P0.05 vs. sham）; NS and HES levels were similar. The level of Tc1 was significantly increased in HTS（P0.05 vs. sham）, and levels of Tc2 were increased in NS, HES, and HTS groups compared to sham（all P0.05）, but did not differ from each other. Conclusions： HTS resuscitation has a greater impact on immune system recovery than NS or HES by preserving the proportion of Tregs and maintaining the balance between Th1/Th2 and Tc1/Tc2 cells in the spleen. Thus, HTS resuscitation provides potential immunomodulatory activity in the early stage after hemorrhagic shock.展开更多
Objective: To provide comprehensive data to understand mechanisms of vascular endothelial cell(VEC) response to hypoxia/re-oxygenation. Methods: Human umbilical vein endothelial cells(HUVECs) were employed to construc...Objective: To provide comprehensive data to understand mechanisms of vascular endothelial cell(VEC) response to hypoxia/re-oxygenation. Methods: Human umbilical vein endothelial cells(HUVECs) were employed to construct hypoxia/re-oxygenation-induced VEC transcriptome profiling. Cells incubated under 5% O2, 5% CO2, and 90% N2 for 3 h followed by 95% air and 5% CO2 for 1 h were used in the hypoxia/re-oxygenation group. Those incubated only under 95% air and 5% CO2 were used in the normoxia control group. Results: By using a well-established microarray chip consisting of 58 339 probes, the study identified 372 differentially expressed genes. While part of the genes are known to be VEC hypoxia/re-oxygenation-related, serving as a good control, a large number of genes related to VEC hypoxia/re-oxygenation were identified for the first time. Through bioinformatic analysis of these genes, we identified that multiple pathways were involved in the reaction. Subsequently, we applied real-time polymerase chain reaction(PCR) and western blot techniques to validate the microarray data. It was found that the expression of apoptosis-related proteins, like pleckstrin homology-like domain family A member 1(PHLDA1), was also consistently up-regulated in the hypoxia/re-oxygenation group. STRING analysis found that significantly differentially expressed genes SLC38A3, SLC5A5, Lnc-SLC36 A4-1, and Lnc-PLEKHJ1-1 may have physical or/and functional protein–protein interactions with PHLDA1. Conclusions: The data from this study have built a foundation to develop many hypotheses to further explore the hypoxia/re-oxygenation mechanisms, an area with great clinical significance for multiple diseases.展开更多
Objective： To investigate the distribution and differentiation of myeloid-derived suppressor cells （MDSCs） in hemorrhagic shock mice, which are resuscitated with normal saline （NS）, hypertonic saline （HTS）, and...Objective： To investigate the distribution and differentiation of myeloid-derived suppressor cells （MDSCs） in hemorrhagic shock mice, which are resuscitated with normal saline （NS）, hypertonic saline （HTS）, and hydroxyethyl starch （HES）. Methods： BALB/c mice were randomly divided into control, NS, HTS, and HES resuscitation groups. Three subgroups （n=8） in each resuscitation group were marked as 2, 24, and 72 h. Flow cytometry was used to detect the MDSCs, monocytic MDSCs （M-MDSCs）, and granulocytic/neutrophilic MDSCs （G-MDSCs） in peripheral blood nucleated cells （PBNCs）, spleen single-cell suspension, and bone marrow nucleated cells （BMNCs）. Results： The MDSCs in BMNCs among three resuscitation groups were lower 2 h after shock, in PBNCs of the HTS group were higher, and in spleen of the NS group were lower （all P〈0.05 vs. control）. The M-MDSC/G-MDSC ratios in PBNCs of the HTS and HES groups were lower （both ,P〈0.05 vs. control）. At 24 h, the MDSCs in PBNCs of the NS and HTS groups were higher, while the spleen MDSCs in the HTS group were higher （all P〈0.05 vs. control）. The M-MDSC/ G-MDSC ratios were all less in PBNCs, spleen, and BMNCs of the NS and HTS groups, and were lower in BMNCs of the HES group （all P〈0.05 vs. control）. At 72 h, the elevated MDSCs in PBNCs were presented in the HTS and HES groups, and in spleen the augment turned up in three resuscitation groups （all P〈0.05 vs. control）. The inclined ratios to M-MDSC were exhibited in spleen of the NS and HTS groups, and in PBNCs of the NS group; the inclination to G-MDSC in BMNCs was shown in the HES group （all P〈0.05 vs. control）. Conclusions： HTS induces the earlier ele- vation of MDSCs in peripheral blood and spleen, and influences its distribution and differentiation, while HES has a less effect on the distribution but a stronger impact on the differentiation of MDSCs, especially in bone marrow.展开更多
文摘Objective： The intoxications caused by 2,4-dinitrophenol （2,4-DNP）, even death, have been frequently reported in recent years. This study aims to investigate the dynamic changes of plasma toxin concentration and explore the clinical value of resin hemoperfusion （HP） in the treatment of patients with acute 2,4-DNP poisoning. Methods We reported 16 cases of acute 2,4-DNP poisoning through occupational exposure due to ignoring the risk of poisoning. The blood samples were collected from the 14 survivors. According to the different treatments of resin HP, the survivors were divided into routine HP （n=5） and intensive HP （n=9） groups. Ultra high performance liquid chromatography/ tandem mass spectroscopy （UPLC-MS/MS） was used to detect the 2,4-DNP concentration in plasma in this study. Results： The 14 survivors recovered very well after treatment. The initial plasma 2,4-DNP concentrations （C1） of survivors ranged from 0.25 to 41.88 pg/ml （mean （12.56＋13.93） pg/ml）. A positive correlation existed between initial plasma 2,4-DNP concentration （C1） and temperature. The elimination of 2,4-DNP was slow and persistent, and the total clearance rates of plasma toxin from the 1st to 3rd day （R3）, the 3rd to 7th day （R3-7）, and the 1st to 7th day （RT）, were only （53.03±14.04）%, （55.25±10.50）%, and （78.29±10.22）%, respectively. The plasma toxin was cleared up to 25 d after poisoning in most of the patients. The R3, R3-7, and R7 in the intensive HP group were all apparently higher than those in the routine HP group, with statistical significance （P〈0.05）. Simultaneously, the elimination half-life （tl/2） of 2,4-DNP in the intensive HP group was apparently shorter than that in the routine HP group, with statistical significance （P〈0.05）. Conclusions： The clinicians should be aware of this slow and persistent process in the elimination of plasma 2,4-DNP. Higher initial plasma toxin concentration resulted in a more severe fever for the patient. According to the limited data, longer and more frequent resin HP may accelerate to eliminate the poison.
基金supported by the National Natural Science Foundation of China(No.81272075)
文摘Objective： To investigate the effects of resuscitation with normal saline（NS）, hypertonic saline（HTS）, and hydroxyethyl starch（HES） on regulatory T cells（Tregs）, helper T 1（Th1）/Th2 and cytotoxic T 1（Tc1）/Tc2 profiles in the treatment of hemorrhagic shock. Methods： Rats subjected to severe hemorrhagic shock were resuscitated for 30 min with NS（n=8）, HTS（n=8）, or HES（n=8）; sham（n=8） and naive control（n=8） groups were used for comparison. Following fluid resuscitation, the whole shed blood was reinfused for 30 min, and the rats were observed with continuous hemodynamic monitoring for 120 min. CD4^＋CD25^＋Foxp3^＋ Treg proportions, Th1/Th2 and Tc1/Tc2 profiles in spleen were analyzed by three-color flow cytometry. Results： The proportion of CD4^＋CD25^＋Foxp3^＋ Tregs and ratios of Th1/Th2 and Tc1/Tc2 did not differ among control, sham, and HTS groups, but were significantly lower in NS and HES groups（both P0.05 vs. sham）; NS and HES levels were similar. The level of Tc1 was significantly increased in HTS（P0.05 vs. sham）, and levels of Tc2 were increased in NS, HES, and HTS groups compared to sham（all P0.05）, but did not differ from each other. Conclusions： HTS resuscitation has a greater impact on immune system recovery than NS or HES by preserving the proportion of Tregs and maintaining the balance between Th1/Th2 and Tc1/Tc2 cells in the spleen. Thus, HTS resuscitation provides potential immunomodulatory activity in the early stage after hemorrhagic shock.
基金Project supported by the National Natural Science Foundation of China(Nos.81801572 and 81272075)the Foundation of Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine(No.2017-XKA36)+5 种基金the Foundation of Key Research Project of Zhejiang Province for Traditional Chinese Medicine(No.2019ZZ014)the Medical and Health Science Foundation of Zhejiang Province(No.2019327552)the Key Research and Development Program of Zhejiang Province(No.2019C03076)the General Research Program of Zhejiang Provincial Department of Medical and Health(No.2013KYA066)the Opening Foundation of State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases(Nos.2018KF02 and 2019KF06)the Program of Education Department of Zhejiang Province(No.Y201738150),China。
文摘Objective: To provide comprehensive data to understand mechanisms of vascular endothelial cell(VEC) response to hypoxia/re-oxygenation. Methods: Human umbilical vein endothelial cells(HUVECs) were employed to construct hypoxia/re-oxygenation-induced VEC transcriptome profiling. Cells incubated under 5% O2, 5% CO2, and 90% N2 for 3 h followed by 95% air and 5% CO2 for 1 h were used in the hypoxia/re-oxygenation group. Those incubated only under 95% air and 5% CO2 were used in the normoxia control group. Results: By using a well-established microarray chip consisting of 58 339 probes, the study identified 372 differentially expressed genes. While part of the genes are known to be VEC hypoxia/re-oxygenation-related, serving as a good control, a large number of genes related to VEC hypoxia/re-oxygenation were identified for the first time. Through bioinformatic analysis of these genes, we identified that multiple pathways were involved in the reaction. Subsequently, we applied real-time polymerase chain reaction(PCR) and western blot techniques to validate the microarray data. It was found that the expression of apoptosis-related proteins, like pleckstrin homology-like domain family A member 1(PHLDA1), was also consistently up-regulated in the hypoxia/re-oxygenation group. STRING analysis found that significantly differentially expressed genes SLC38A3, SLC5A5, Lnc-SLC36 A4-1, and Lnc-PLEKHJ1-1 may have physical or/and functional protein–protein interactions with PHLDA1. Conclusions: The data from this study have built a foundation to develop many hypotheses to further explore the hypoxia/re-oxygenation mechanisms, an area with great clinical significance for multiple diseases.
基金Project supported by the National Natural Science Foundation of China(No.81272075)
文摘Objective： To investigate the distribution and differentiation of myeloid-derived suppressor cells （MDSCs） in hemorrhagic shock mice, which are resuscitated with normal saline （NS）, hypertonic saline （HTS）, and hydroxyethyl starch （HES）. Methods： BALB/c mice were randomly divided into control, NS, HTS, and HES resuscitation groups. Three subgroups （n=8） in each resuscitation group were marked as 2, 24, and 72 h. Flow cytometry was used to detect the MDSCs, monocytic MDSCs （M-MDSCs）, and granulocytic/neutrophilic MDSCs （G-MDSCs） in peripheral blood nucleated cells （PBNCs）, spleen single-cell suspension, and bone marrow nucleated cells （BMNCs）. Results： The MDSCs in BMNCs among three resuscitation groups were lower 2 h after shock, in PBNCs of the HTS group were higher, and in spleen of the NS group were lower （all P〈0.05 vs. control）. The M-MDSC/G-MDSC ratios in PBNCs of the HTS and HES groups were lower （both ,P〈0.05 vs. control）. At 24 h, the MDSCs in PBNCs of the NS and HTS groups were higher, while the spleen MDSCs in the HTS group were higher （all P〈0.05 vs. control）. The M-MDSC/ G-MDSC ratios were all less in PBNCs, spleen, and BMNCs of the NS and HTS groups, and were lower in BMNCs of the HES group （all P〈0.05 vs. control）. At 72 h, the elevated MDSCs in PBNCs were presented in the HTS and HES groups, and in spleen the augment turned up in three resuscitation groups （all P〈0.05 vs. control）. The inclined ratios to M-MDSC were exhibited in spleen of the NS and HTS groups, and in PBNCs of the NS group; the inclination to G-MDSC in BMNCs was shown in the HES group （all P〈0.05 vs. control）. Conclusions： HTS induces the earlier ele- vation of MDSCs in peripheral blood and spleen, and influences its distribution and differentiation, while HES has a less effect on the distribution but a stronger impact on the differentiation of MDSCs, especially in bone marrow.
