The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overloa...The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal degeneration.Cyclophilin D is an important component of the mitochondrial permeability transition pore.Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear.In this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent protein.We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin.We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening.We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage.We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury.In addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage.Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage.Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.展开更多
BACKGROUND Venous thromboembolism(VTE)is a common neurosurgical complication after brain tumor resection,and its prophylaxis has been widely studied.There are no effective drugs in the clinical management of venous th...BACKGROUND Venous thromboembolism(VTE)is a common neurosurgical complication after brain tumor resection,and its prophylaxis has been widely studied.There are no effective drugs in the clinical management of venous thromboembolism,and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.AIM To explore whether ulinastatin(UTI)can prevent VTE after brain tumor resection.METHODS The present research included patients who underwent brain tumor resection.Patients received UTIs(400,000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were the incidence of VTE,coagulation function,pulmonary emboli,liver function,renal function,and drug-related adverse effects.RESULTS A total of 405 patients were evaluated between January 2019 and December 2021,and 361 of these were initially enrolled in the study to form intention-to-treat,which was given UTI(n=180)or placebo(n=181)treatment in a random manner.There were no statistically significant differences in baseline clinical data between the two groups.The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group.UTI can improve coagulation dysfunction,pulmonary emboli,liver function,and renal function.No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea,vomiting,hospital stays,or hospitalization costs.The incidence of allergies was higher in the UTI group than in the placebo group.CONCLUSION The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.展开更多
Objective:To investigate risk factors of gastroparesis syndrome(PGS) after abdominal nongastroduodenal operation and its prevention.Methods:Clinical data of 22 patients with PGS after abdominal non-gastroduodenal oper...Objective:To investigate risk factors of gastroparesis syndrome(PGS) after abdominal nongastroduodenal operation and its prevention.Methods:Clinical data of 22 patients with PGS after abdominal non-gastroduodenal operation was analyzed retrospectively,and compared with the patients of non-PGS after abdominal non-gastroduodenal operation during the same time.The possible influencing factors of PCS were analyzed by single factor analysis and logistic regression analysis.Results:All t3 selected factors related with PGS,including age,disease category (benign and malignant),operation time,intraoperative blood loss,postoperative analgesic pump, postoperative enteral nutrition time,postoperative parenteral nutrition time,perioperative blood glucose level,perioperative nutrition status(anaemia or lower proleinemia),pylorus obstruction before surgery,intra-abdominal infection after surgery,and spiritual factor were related with PGS.The statistical analysis showed that the difference was statistical significant(P【0.05),and gender had no correlation with PCS(P】0.05);non-conditional multivariate analysis showed that malignant tumor,perioperative nutrition status,pylorus obstruction,operation time,blood loss, intra-abdominal infection after surgery,and mental factor were significant related with PGS as dependent variable and related risk factors in single factor analysis as independent variables (P 【0.05).Conclusions:PGS is a result of multiple factors,and among these factors,malignant tumor,poor nutrition status,pylorus obstruction before surgery,longer operation—time,more blood loss,intra-abdominal infection after surgery,and mental factor are major risk factors of PGS.展开更多
Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury ti...Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.展开更多
AIM: To determine the impact of partial reimbursement for antivirals on antiviral utilization and adherence for chronic hepatitis B patients.METHODS: This was a retrospective cohort study. Two separate cohorts were en...AIM: To determine the impact of partial reimbursement for antivirals on antiviral utilization and adherence for chronic hepatitis B patients.METHODS: This was a retrospective cohort study. Two separate cohorts were enrolled, including 14163 and 16288 chronic hepatitis B outpatients, respectively. These patients were referred to Beijing You'an Hospital before and after the new partial reimbursement for antivirals, which was implemented on July 1, 2011. Demographic characteristics(including medical insurance status), routine biochemical, virological and serology laboratory test results, and antiviral agents' prescriptioninformation were collected from an electronic database. Patients were also defined as new and existing patients according to treatment history. Antiviral utilization, medication possession ratio and persistence rate were calculated and compared among the patients with different characteristics. A questionnaire survey was conducted among 212 randomly sampled outpatients from the same hospital to confirm the validity of the electronic database. Propensity score matching was used to adjust the distribution of patient's characteristics which may influence the antiviral utilization. χ2 test or ANOVA was adopted and multivariate logistic regression was used to determine the factors associated with antiviral utilization and good adherence. RESULTS: A total of 13364 outpatients from each cohort were enrolled after the propensity score matching. The antiviral utilization rate for the insured patients increased from 57.4% to 75.9%(P < 0.0001) after the reimbursement, and the rate among those who paid out-of-pocket increased from 54.9% to 56.7%(P = 0.028). Approximately 71% of the patients had a medication possession ratio of more than 80% in each cohort before reimbursement. This increased to 79.2% and 73.1% for insured patients and those who paid out-of-pocket, respectively(P < 0.0001). Insured patients and those who paid out-of-pocket had the similar persistence rates before reimbursement. But after reimbursement, insured patients had higher persistence rates than those who paid out-of-pocket at 6(86.5% vs 81.5%, P < 0.0001), 9(79.7% vs 69.9%, P < 0.0001), 12(73.4% vs 61.9%, P < 0.0001), and 15 mo(66.6% vs 53.1%, P < 0.0001). The reimbursement could significantly improve adherence for the insured patients than those who paid out-of-pocket even after adjusting other covariates, with an interaction odds ratio of 1.422(95%CI: 1.220-1.657, P < 0.0001). The questionnaire survey supported the validity of the electronic database.CONCLUSION: The reimbursement policy shows a positive impact on antiviral utilization as well as adherence for insured chronic hepatitis B patients.展开更多
Trauma-induced coagulopathy(TIC)is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage.Previous...Trauma-induced coagulopathy(TIC)is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage.Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC,while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2%–85.1%of trauma patients,in whom it can increase the risk of thrombotic events and mortality by 2-to 4-fold.Therefore,the Chinese People’s Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition,pathophysiological mechanism,assessment,prevention,and treatment of trauma-induced hypercoagulopathy.展开更多
BACKGROUND Forniceal deep brain stimulation(DBS)has been proposed as an alternative treatment for Alzheimer's disease(AD).Previous studies on mild to moderate AD patients demonstrated improvements in cognitive fun...BACKGROUND Forniceal deep brain stimulation(DBS)has been proposed as an alternative treatment for Alzheimer's disease(AD).Previous studies on mild to moderate AD patients demonstrated improvements in cognitive functions brought about by forniceal DBS.Here,we report our longitudinal findings in one severe AD patient for whom the activities of daily living(ADL)rather than cognitive function significantly improved after 3 mo of continuous stimulation.CASE SUMMARY In 2011,a 62-year-old Chinese male with no previous history of brain injury or other neuropsychological diseases and no family history of dementia developed early symptoms of memory decline and cognitive impairment.Five years later,the symptoms had increased to the extent that they affected his daily living.He lost the ability to work as a businessman and to take care of himself.The patient was given a clinical diagnosis of probable AD and was prescribed donepezil and subsequently memantine,but no improvement in symptoms was observed.The patient then received DBS surgery.After 3 mo of continuous stimulation,the patient's ADL score decreased from 65 points to 47 points,indicating the quality of the patient's daily living improved distinctly.Other scores remained unchanged,suggesting no significant improvement in cognitive function.A follow-up positron emission tomography scan demonstrated perceivable increased glucose metabolism in the classical AD-related brain regions.CONCLUSION Based on this case we hypothesize that forniceal DBS may improve ADL through elevating regional glucose metabolism in the brain.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81901267(to YY),82001263(to WXC),81901193(to HLZ)a grant from State Key Laboratory of Trauma,Burn and Combined Injury,No.SKLYQ202002(to YJC)+1 种基金a grant from Wuxi Municipal Health Commission No.2020ZHYB19(to YY)a grant from Wuxi Science and Technology Bureau,No.Y20212045(to LKY)。
文摘The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal degeneration.Cyclophilin D is an important component of the mitochondrial permeability transition pore.Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear.In this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent protein.We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin.We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening.We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage.We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury.In addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage.Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage.Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.
基金The registration number for the study was CWXH-IPR-2018004(date:January 11,2019).
文摘BACKGROUND Venous thromboembolism(VTE)is a common neurosurgical complication after brain tumor resection,and its prophylaxis has been widely studied.There are no effective drugs in the clinical management of venous thromboembolism,and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.AIM To explore whether ulinastatin(UTI)can prevent VTE after brain tumor resection.METHODS The present research included patients who underwent brain tumor resection.Patients received UTIs(400,000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were the incidence of VTE,coagulation function,pulmonary emboli,liver function,renal function,and drug-related adverse effects.RESULTS A total of 405 patients were evaluated between January 2019 and December 2021,and 361 of these were initially enrolled in the study to form intention-to-treat,which was given UTI(n=180)or placebo(n=181)treatment in a random manner.There were no statistically significant differences in baseline clinical data between the two groups.The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group.UTI can improve coagulation dysfunction,pulmonary emboli,liver function,and renal function.No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea,vomiting,hospital stays,or hospitalization costs.The incidence of allergies was higher in the UTI group than in the placebo group.CONCLUSION The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.
基金supported by 2011Mandatory Planning Projeet of Scientifieand Teehologieal Bureau of Zhangjiakou City(111100111)
文摘Objective:To investigate risk factors of gastroparesis syndrome(PGS) after abdominal nongastroduodenal operation and its prevention.Methods:Clinical data of 22 patients with PGS after abdominal non-gastroduodenal operation was analyzed retrospectively,and compared with the patients of non-PGS after abdominal non-gastroduodenal operation during the same time.The possible influencing factors of PCS were analyzed by single factor analysis and logistic regression analysis.Results:All t3 selected factors related with PGS,including age,disease category (benign and malignant),operation time,intraoperative blood loss,postoperative analgesic pump, postoperative enteral nutrition time,postoperative parenteral nutrition time,perioperative blood glucose level,perioperative nutrition status(anaemia or lower proleinemia),pylorus obstruction before surgery,intra-abdominal infection after surgery,and spiritual factor were related with PGS.The statistical analysis showed that the difference was statistical significant(P【0.05),and gender had no correlation with PCS(P】0.05);non-conditional multivariate analysis showed that malignant tumor,perioperative nutrition status,pylorus obstruction,operation time,blood loss, intra-abdominal infection after surgery,and mental factor were significant related with PGS as dependent variable and related risk factors in single factor analysis as independent variables (P 【0.05).Conclusions:PGS is a result of multiple factors,and among these factors,malignant tumor,poor nutrition status,pylorus obstruction before surgery,longer operation—time,more blood loss,intra-abdominal infection after surgery,and mental factor are major risk factors of PGS.
基金supported by the National Natural Science Foundation of China,No.81571939(to KX),81601719(to JZ)and 81772134(to KX)Key Research and Development Program of Hunan Province of China,No.2018SK2091(to KX)+1 种基金Wu Jie-Ping Medical Foundation of the Minister of Health of China,No.320.6750.14118(to KX)Teacher Research Foundation of Central South University of China,No.2014JSJJ026(to KX)
文摘Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.
基金Supported by Foundation of Ministry of Science and Technology of China,No.2012ZX10004904 and No.2013ZX10002002006002Bristol-Myers Squibb Company,No.AI463-961Innovative Foundation of Beijing Union Medical College
文摘AIM: To determine the impact of partial reimbursement for antivirals on antiviral utilization and adherence for chronic hepatitis B patients.METHODS: This was a retrospective cohort study. Two separate cohorts were enrolled, including 14163 and 16288 chronic hepatitis B outpatients, respectively. These patients were referred to Beijing You'an Hospital before and after the new partial reimbursement for antivirals, which was implemented on July 1, 2011. Demographic characteristics(including medical insurance status), routine biochemical, virological and serology laboratory test results, and antiviral agents' prescriptioninformation were collected from an electronic database. Patients were also defined as new and existing patients according to treatment history. Antiviral utilization, medication possession ratio and persistence rate were calculated and compared among the patients with different characteristics. A questionnaire survey was conducted among 212 randomly sampled outpatients from the same hospital to confirm the validity of the electronic database. Propensity score matching was used to adjust the distribution of patient's characteristics which may influence the antiviral utilization. χ2 test or ANOVA was adopted and multivariate logistic regression was used to determine the factors associated with antiviral utilization and good adherence. RESULTS: A total of 13364 outpatients from each cohort were enrolled after the propensity score matching. The antiviral utilization rate for the insured patients increased from 57.4% to 75.9%(P < 0.0001) after the reimbursement, and the rate among those who paid out-of-pocket increased from 54.9% to 56.7%(P = 0.028). Approximately 71% of the patients had a medication possession ratio of more than 80% in each cohort before reimbursement. This increased to 79.2% and 73.1% for insured patients and those who paid out-of-pocket, respectively(P < 0.0001). Insured patients and those who paid out-of-pocket had the similar persistence rates before reimbursement. But after reimbursement, insured patients had higher persistence rates than those who paid out-of-pocket at 6(86.5% vs 81.5%, P < 0.0001), 9(79.7% vs 69.9%, P < 0.0001), 12(73.4% vs 61.9%, P < 0.0001), and 15 mo(66.6% vs 53.1%, P < 0.0001). The reimbursement could significantly improve adherence for the insured patients than those who paid out-of-pocket even after adjusting other covariates, with an interaction odds ratio of 1.422(95%CI: 1.220-1.657, P < 0.0001). The questionnaire survey supported the validity of the electronic database.CONCLUSION: The reimbursement policy shows a positive impact on antiviral utilization as well as adherence for insured chronic hepatitis B patients.
文摘Trauma-induced coagulopathy(TIC)is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage.Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC,while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2%–85.1%of trauma patients,in whom it can increase the risk of thrombotic events and mortality by 2-to 4-fold.Therefore,the Chinese People’s Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition,pathophysiological mechanism,assessment,prevention,and treatment of trauma-induced hypercoagulopathy.
文摘BACKGROUND Forniceal deep brain stimulation(DBS)has been proposed as an alternative treatment for Alzheimer's disease(AD).Previous studies on mild to moderate AD patients demonstrated improvements in cognitive functions brought about by forniceal DBS.Here,we report our longitudinal findings in one severe AD patient for whom the activities of daily living(ADL)rather than cognitive function significantly improved after 3 mo of continuous stimulation.CASE SUMMARY In 2011,a 62-year-old Chinese male with no previous history of brain injury or other neuropsychological diseases and no family history of dementia developed early symptoms of memory decline and cognitive impairment.Five years later,the symptoms had increased to the extent that they affected his daily living.He lost the ability to work as a businessman and to take care of himself.The patient was given a clinical diagnosis of probable AD and was prescribed donepezil and subsequently memantine,but no improvement in symptoms was observed.The patient then received DBS surgery.After 3 mo of continuous stimulation,the patient's ADL score decreased from 65 points to 47 points,indicating the quality of the patient's daily living improved distinctly.Other scores remained unchanged,suggesting no significant improvement in cognitive function.A follow-up positron emission tomography scan demonstrated perceivable increased glucose metabolism in the classical AD-related brain regions.CONCLUSION Based on this case we hypothesize that forniceal DBS may improve ADL through elevating regional glucose metabolism in the brain.
