BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibito...BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.展开更多
Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we...Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.展开更多
BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its me...BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.展开更多
Background The genes encoding adiponectin receptor 1 （ADIPOR1） and small ubiquitin-like modifier 4 （SUM04） have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two g...Background The genes encoding adiponectin receptor 1 （ADIPOR1） and small ubiquitin-like modifier 4 （SUM04） have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease （CAD） without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms （SNPs） in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 （rs7539542-G, rs7514221-C and rs3737884-G） and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery （OR： 6.77, P = 0.009）, the right coronary artery （OR： 4.81, P = 0.028） or a relatively large number of vessels （P = 0.04）. Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles （OR： 5.82, 95% CI： 1.23-27.7, P= 0.013）. Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.展开更多
The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features an...The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.展开更多
AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomi...AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomized into three groups: normal chow (control), high fat diet (HD) and high fat diet with sleeve gastrectomy (SG). After surgery, the HD and SG groups were fed a high fat diet. Animals were sacrificed and plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) levels were determined. LOX-1 protein and LOX-1 mRNA expression was also measured. Aortas were stained with Nile red to visualize adipose tissue. RESULT: Body weights were higher in the HD group compared to the other groups. HDL levels in control,HD, and SG groups were 32.9 ± 6.2 mg/dL, 43.4 ± 4.0 mg/dL and 37.5 ± 4.3 mg/dL, respectively. LDL levels in control, HD, and SG groups were 31.8 ± 4.5 mg/dL, 53.3 ± 5.1 mg/dL and 40.5 ± 3.7 mg/dL, respectively. LOX-1 protein and LOX-1 mRNA expression was greater in the HD group versus the other groups. Staining for adipose tissue in aortas was greater in the HD group in comparison to the other groups. Thus, a high fat diet elevates LOX-1 protein and mRNA expression in aorta. CONCLUSION: Sleeve gastrectomy decreases plasma LDL levels, and downregulates LOX-1 protein and mRNA expression.展开更多
BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and...BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.展开更多
BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipo...BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipopolysaccharide （LPS） was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS： Thirty BALB/C mice were randomly divided into a normal control group （n=6） and an ALl group （n=24）. The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS： The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA （P=0.14）; the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score （r=0.795, P=0.001 ：r=0.499, P=0.034）, but not with the expression of TREM-1 mRNA （P=0.176）.CONCLUSION： The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.展开更多
Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system （CNS）. Nogo proteins, myelin-as- sociated glycoprotein （MAG）, oligodendrocyte myelin gl...Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system （CNS）. Nogo proteins, myelin-as- sociated glycoprotein （MAG）, oligodendrocyte myelin glycoprotein （OMgp） and B lymphocyte stimulator （BLyS）, are 4 inhibitors that commonly interact with the neuronal receptor, Nogo receptor-1 （NgR1）, lead- ing to inhibition of axonal growth. Here, we demon- strate that lateral olfactory tract usher substance （LOTUS） binds to NgR1 and blocks the binding of all four ligands to NgR1, resulting in the suppression of axonal growth inhibition induced by these NgR1 li- gands. LOTUS allows neurons to overcome NgRl-me- diated axonal growth inhibition, raising the possibility that LOTUS may be useful in future therapeutic ap- proaches as an endogenous potent inhibitor of NgR1 for promoting neuronal regeneration.展开更多
There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined w...There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 （FGF2） and fibroblast growth factor receptor-1 （FGFR1） protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.展开更多
基金Supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,No.2021-I2M-1-061 and 2021-I2M-1-003Chinese Society of Clinical Oncology-Hengrui Cancer Research Fund,No.Y-HR2019-0239+1 种基金Chinese Society of Clinical Oncology-MSD Cancer Research Fund,No.Y-MSDZD2021-0213National Ten-thousand Talent Program.
文摘BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.
基金supported by the Key Project of the National Natural Science Foundation of China,No.81930070(to SF)the National Natural Science Foundation of China,No.81972074(to XY)the Key Program of Natural Science Foundation of Tianjin,No.19JCZDJC34900(to XY)。
文摘Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.
文摘目的 分析血清脂联素(APN)、摄食抑制因子(NSF)-1与妊娠糖尿病(GDM)患者不良妊娠结局的关系。方法 纳入郑州人民医院妇产科2019年2月至2021年1月收治的200例GDM患者进行研究,所有患者均随访至完成分娩,以随访期间是否发生孕妇、胎儿或新生儿不良事件定义妊娠结局。确诊后即检测患者血糖[空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)]、血清APN、NSF-1及性激素[雌二醇(E2)、黄体生成素(LH)、孕酮(P)、促卵泡生成素(FSH)]等指标,分析血清APN、NSF-1与GDM患者不良妊娠结局的关系,并检验血清APN、NSF-1对GDM患者不良妊娠结局的预测效能。结果 纳入的200例GDM患者,不良妊娠结局占31.00%;不良妊娠结局患者FBG、2 h PG、HbA1c及血清NSF-1表达均高于良好妊娠结局患者,血清APN表达低于良好妊娠结局患者(P<0.05)。logistic回归分析得出,血清APN低表达,NSF-1高表达与GDM患者不良妊娠结局有关(P<0.05)。绘制受试者工作特征(ROC)曲线,血清APN、NSF-1单独及联合预测GDM患者不良妊娠结局的曲线下面积(AUC)分别为0.782、0.785、0.850。结论 血清APN低表达、NSF-1高表达均与GDM患者不良妊娠结局有关,联合检测血清APN、NSF-1能够预测患者不良妊娠结局风险。
基金Supported by the National Natural Science Foundation of China,No.81570543 and No.81560104
文摘BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.
基金Acknowledgments This study was funded by the National Natural Science Foundation of China （81570323, 30972709, 81061120527, 81241082） and the 12th Five-Year National Program of the Ministry of Scientific Technology （2012BAI10B01）. We thank Liu M and Zhou L from Beijing Hospital for providing experimental data, the nurses from Beijing Anzhen Hospital for collecting specimens, and the study volunteers.
文摘Background The genes encoding adiponectin receptor 1 （ADIPOR1） and small ubiquitin-like modifier 4 （SUM04） have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease （CAD） without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms （SNPs） in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 （rs7539542-G, rs7514221-C and rs3737884-G） and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery （OR： 6.77, P = 0.009）, the right coronary artery （OR： 4.81, P = 0.028） or a relatively large number of vessels （P = 0.04）. Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles （OR： 5.82, 95% CI： 1.23-27.7, P= 0.013）. Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.
文摘The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.
基金Supported by A Grant from the National Natural Science Foundation of China, No. 81000158the Special Fund for Technology of Liaoning Province, No. L2010591
文摘AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomized into three groups: normal chow (control), high fat diet (HD) and high fat diet with sleeve gastrectomy (SG). After surgery, the HD and SG groups were fed a high fat diet. Animals were sacrificed and plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) levels were determined. LOX-1 protein and LOX-1 mRNA expression was also measured. Aortas were stained with Nile red to visualize adipose tissue. RESULT: Body weights were higher in the HD group compared to the other groups. HDL levels in control,HD, and SG groups were 32.9 ± 6.2 mg/dL, 43.4 ± 4.0 mg/dL and 37.5 ± 4.3 mg/dL, respectively. LDL levels in control, HD, and SG groups were 31.8 ± 4.5 mg/dL, 53.3 ± 5.1 mg/dL and 40.5 ± 3.7 mg/dL, respectively. LOX-1 protein and LOX-1 mRNA expression was greater in the HD group versus the other groups. Staining for adipose tissue in aortas was greater in the HD group in comparison to the other groups. Thus, a high fat diet elevates LOX-1 protein and mRNA expression in aorta. CONCLUSION: Sleeve gastrectomy decreases plasma LDL levels, and downregulates LOX-1 protein and mRNA expression.
基金Supported by Heilongjiang Provincial Health and Family Planning Commission Research Project,No.2017-413
文摘BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.
文摘BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipopolysaccharide （LPS） was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS： Thirty BALB/C mice were randomly divided into a normal control group （n=6） and an ALl group （n=24）. The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS： The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA （P=0.14）; the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score （r=0.795, P=0.001 ：r=0.499, P=0.034）, but not with the expression of TREM-1 mRNA （P=0.176）.CONCLUSION： The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.
基金supported by a grant-in-aid from the Ministry of Education,Culture,Sports,Science and Technology of Japangrants for Research and Development project of Yokohama City University
文摘Glia-derived axonal growth inhibitory proteins limit functional repair following damage to the adult cen- tral nervous system （CNS）. Nogo proteins, myelin-as- sociated glycoprotein （MAG）, oligodendrocyte myelin glycoprotein （OMgp） and B lymphocyte stimulator （BLyS）, are 4 inhibitors that commonly interact with the neuronal receptor, Nogo receptor-1 （NgR1）, lead- ing to inhibition of axonal growth. Here, we demon- strate that lateral olfactory tract usher substance （LOTUS） binds to NgR1 and blocks the binding of all four ligands to NgR1, resulting in the suppression of axonal growth inhibition induced by these NgR1 li- gands. LOTUS allows neurons to overcome NgRl-me- diated axonal growth inhibition, raising the possibility that LOTUS may be useful in future therapeutic ap- proaches as an endogenous potent inhibitor of NgR1 for promoting neuronal regeneration.
文摘There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 （FGF2） and fibroblast growth factor receptor-1 （FGFR1） protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.
