AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was i...AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.展开更多
The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response(including infectious and non-bacterial injuries).Nowadays,the interleukin-1 family mai...The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response(including infectious and non-bacterial injuries).Nowadays,the interleukin-1 family mainly includes 11 cytokines and has multiple roles in the pathology and physiology of inflammation.Moreover,accumulating number of research show that the interleukin-1 family and its receptors are involved in the occurrence and development of cardiovascular diseases.Therefore,we show here the review involving hotspots of the interleukin-1 family in the process of inflammation and its target therapy in cardiovascular diseases,including atherosclerosis,myocardial infarction and heart failure.展开更多
AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METH...AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.展开更多
Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunte...Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.展开更多
The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression...The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.展开更多
目的:探讨急性冠脉综合征(acute coronary syndrome,ACS)患者血清补体C1肿瘤坏死因子相关蛋白家族12(complement C1 tumor necrosis factor-associated protein family 12,CTRP12)水平与影响ACS及冠脉病变严重程度因素的关系。方法:选择...目的:探讨急性冠脉综合征(acute coronary syndrome,ACS)患者血清补体C1肿瘤坏死因子相关蛋白家族12(complement C1 tumor necrosis factor-associated protein family 12,CTRP12)水平与影响ACS及冠脉病变严重程度因素的关系。方法:选择2021年11月—2022年8月于江苏省丹阳市人民医院心血管内科行冠状动脉造影的患者共116例,其中ACS 81例,非ACS 35例。收集血液标本检测血清CTRP12及其他血液生化指标。心脏超声测量心外膜脂肪厚度(epicardial fat thickness,EFT)。比较两组血清CTRP12水平和EFT,分析CTRP12与其他因素的相关性。采用SYNTAX(Synergy between PCI with TAXUSTM and Cardiac Surgery)评分评估冠脉病变严重程度,将其分为SYNTAX评分≤22分和SYNTAX评分>22分,Logistic回归分析影响ACS及冠脉病变严重程度的因素。结果:ACS组患者男性比例、吸烟比例、EFT、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、WBC计数、中性粒细胞计数、单核细胞计数均高于非ACS组(均P<0.05),血清CTRP12水平低于非ACS组(P<0.05),EFT较非ACS组增加(P<0.05)。ACS组患者中SYNTAX评分≤22分者血清CTRP12水平高于SYNTAX评分>22分者(P<0.05),EFT小于SYNTAX评分>22分者(P<0.05)。相关性分析提示CTRP12与EFT呈负相关(r=-0.557,P<0.05)。Logistic回归提示CTRP12和EFT是ACS的独立影响因素(β=-2.107、1.607,均P<0.05)。CTRP12和EFT是ACS患者冠脉病变严重程度的影响因素(β=-1.085、1.740,均P<0.05),在校正年龄、性别、BMI、吸烟、糖尿病、高血压、LDL-C后,CTRP12和EFT仍是ACS患者冠脉病变严重程度的影响因素(β=-1.033、2.109,均P<0.05)。结论:ACS患者血清CTRP12水平显著降低,且与EFT呈负相关。EFT是ACS及冠脉病变严重程度的独立危险因素,而CTRP12为ACS的保护因素。展开更多
Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues follo...Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues following AKI will repair or fibrose and lead to chronic kidney disease (CKD) are not well defined. Numerous cytokines are activated at various times after injury and recruit inflammatory cells. Interleukin-8 (IL-8) is upregulated following activation of Gα12 by H2O2, a reactive oxygen species (ROS). Herein, we study this occurrence in vitro and in vivo. IL-8 was measured by ELISA in Gα12-silenced (si-Gα12) and inducible QLα12 (constitutively active Gα12) Madin-Darby Canine Kidney (QLα12-MDCK) cell lines after H2O2/catalase cell injury. QLα12- and si-Gα12 MDCK cells showed time-, agonist- and Gα12-dependent increases in IL-8 mRNA and protein. Gα12-silenced MDCK cells demonstrated lower IL-8 expression and blunted IL-8 increases. In transgenic mice (QLα12γGTCre+, proximal tubule Qα12 expression) ischemia reperfusion injury led to significant upregulation of CXCL-1 (IL-8 homologue) at 48 hours that was not observed in Gα12 knockout mice. Macrophages in renal cells from these mice were imaged by immunofluorescent microscopy and QLα12γGTCre+ showed increased macrophage infiltration. We demonstrate that IL-8 is a critical link between H2O2 stimulated Gα12 and renal injury. Gα12 activation led to increased IL-8 expression, a potent mediator of inflammation after injury. Future studies targeting Gα12 for inhibition after injury may blunt the IL-8 response and allow for organ recovery.展开更多
BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomar...BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomarkers in SLE.MicroRNA-125a(miR-125a)levels are decreased in T cells,B cells,and dendritic cells of SLE patients.MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha(TNF-α)and interleukin 12(IL-12),which are crucial pro-inflammatory cytokines in SLE pathogenesis.AIM To assess the levels of miR-125a,IL-12,and TNF-αin SLE patients’plasma,evaluating their diagnostic and prognostic value.METHODS The study included 100 healthy individuals,50 newly diagnosed(ND),and 50 SLE patients undergoing treatment.The patients were monitored for a duration of 24 wk to observe and record instances of relapses.MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction,while ELISA kits were used to assess IL-12 and TNF-αproduction.RESULTS The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals,with the lowest levels in ND patients.TNF-αand IL-12 expression levels were significantly elevated in SLE patients,especially in the early stages of the disease.Receiver operating characteristic curve analyses,and Cox-Mantel Log-rank tests indicated miR-125a,TNF-α,and IL-12 as proper diagnostic biomarkers for SLE.A negative correlation was found between plasma miR-125a expression and IL-12/TNF-αlevels in SLE patients.CONCLUSION Decreased miR-125a levels may be involved in the development of SLE,while elevated levels of IL-12 and TNF-αcontribute to immune dysregulation.These findings offer new diagnostic and prognostic markers for SLE.Moreover,the negative correlation observed suggests an interaction between miR-125a,TNF-α,and IL-12.Further research is necessary to uncover the underlying mechanisms that govern these relationships.展开更多
BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatme...BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.展开更多
AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divid...AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls(HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral Ld T daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array(CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97(123.26-492.79) pg/m L vs 184.50(135.56-292.16) pg/m L, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with Ld T [175.51(103.90-331.91) pg/m L vs 184.50(135.56-292.16) pg/m L, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB(r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to Ld T treatment at 24 wk(48.15% vs 15.79%, P = 0.023) and 52 wk(66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary nonresponse at week 12 after treatment initiation were lower than those in patients with primary response [64.44(49.85-172.08) pg/m L vs 190.54(121.35-355.28) pg/m L, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with Ld T. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to Ld T treatment.展开更多
基金Supported by the National Natural Science Foundation of China(No.82060183)Ningxia Natural Science Foundation(No.2022AAC03388)the Key Research and Development Project of Ningxia Hui Autonomous Region(No.2021BEG02045,No.2020BEG03044).
文摘AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
基金Key Research and Development Project of Hainan Province(No.ZDYF2021SHFZ089)Rapid Innovation Foundation for Key Laboratories of the Ministry of Education(No.KLET-202019)。
文摘The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response(including infectious and non-bacterial injuries).Nowadays,the interleukin-1 family mainly includes 11 cytokines and has multiple roles in the pathology and physiology of inflammation.Moreover,accumulating number of research show that the interleukin-1 family and its receptors are involved in the occurrence and development of cardiovascular diseases.Therefore,we show here the review involving hotspots of the interleukin-1 family in the process of inflammation and its target therapy in cardiovascular diseases,including atherosclerosis,myocardial infarction and heart failure.
文摘AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.
文摘Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.
文摘The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.
文摘目的:探讨急性冠脉综合征(acute coronary syndrome,ACS)患者血清补体C1肿瘤坏死因子相关蛋白家族12(complement C1 tumor necrosis factor-associated protein family 12,CTRP12)水平与影响ACS及冠脉病变严重程度因素的关系。方法:选择2021年11月—2022年8月于江苏省丹阳市人民医院心血管内科行冠状动脉造影的患者共116例,其中ACS 81例,非ACS 35例。收集血液标本检测血清CTRP12及其他血液生化指标。心脏超声测量心外膜脂肪厚度(epicardial fat thickness,EFT)。比较两组血清CTRP12水平和EFT,分析CTRP12与其他因素的相关性。采用SYNTAX(Synergy between PCI with TAXUSTM and Cardiac Surgery)评分评估冠脉病变严重程度,将其分为SYNTAX评分≤22分和SYNTAX评分>22分,Logistic回归分析影响ACS及冠脉病变严重程度的因素。结果:ACS组患者男性比例、吸烟比例、EFT、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、WBC计数、中性粒细胞计数、单核细胞计数均高于非ACS组(均P<0.05),血清CTRP12水平低于非ACS组(P<0.05),EFT较非ACS组增加(P<0.05)。ACS组患者中SYNTAX评分≤22分者血清CTRP12水平高于SYNTAX评分>22分者(P<0.05),EFT小于SYNTAX评分>22分者(P<0.05)。相关性分析提示CTRP12与EFT呈负相关(r=-0.557,P<0.05)。Logistic回归提示CTRP12和EFT是ACS的独立影响因素(β=-2.107、1.607,均P<0.05)。CTRP12和EFT是ACS患者冠脉病变严重程度的影响因素(β=-1.085、1.740,均P<0.05),在校正年龄、性别、BMI、吸烟、糖尿病、高血压、LDL-C后,CTRP12和EFT仍是ACS患者冠脉病变严重程度的影响因素(β=-1.033、2.109,均P<0.05)。结论:ACS患者血清CTRP12水平显著降低,且与EFT呈负相关。EFT是ACS及冠脉病变严重程度的独立危险因素,而CTRP12为ACS的保护因素。
文摘Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues following AKI will repair or fibrose and lead to chronic kidney disease (CKD) are not well defined. Numerous cytokines are activated at various times after injury and recruit inflammatory cells. Interleukin-8 (IL-8) is upregulated following activation of Gα12 by H2O2, a reactive oxygen species (ROS). Herein, we study this occurrence in vitro and in vivo. IL-8 was measured by ELISA in Gα12-silenced (si-Gα12) and inducible QLα12 (constitutively active Gα12) Madin-Darby Canine Kidney (QLα12-MDCK) cell lines after H2O2/catalase cell injury. QLα12- and si-Gα12 MDCK cells showed time-, agonist- and Gα12-dependent increases in IL-8 mRNA and protein. Gα12-silenced MDCK cells demonstrated lower IL-8 expression and blunted IL-8 increases. In transgenic mice (QLα12γGTCre+, proximal tubule Qα12 expression) ischemia reperfusion injury led to significant upregulation of CXCL-1 (IL-8 homologue) at 48 hours that was not observed in Gα12 knockout mice. Macrophages in renal cells from these mice were imaged by immunofluorescent microscopy and QLα12γGTCre+ showed increased macrophage infiltration. We demonstrate that IL-8 is a critical link between H2O2 stimulated Gα12 and renal injury. Gα12 activation led to increased IL-8 expression, a potent mediator of inflammation after injury. Future studies targeting Gα12 for inhibition after injury may blunt the IL-8 response and allow for organ recovery.
基金the Department of Research and Technology at Golestan University of Medical Sciences,No.113017.
文摘BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomarkers in SLE.MicroRNA-125a(miR-125a)levels are decreased in T cells,B cells,and dendritic cells of SLE patients.MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha(TNF-α)and interleukin 12(IL-12),which are crucial pro-inflammatory cytokines in SLE pathogenesis.AIM To assess the levels of miR-125a,IL-12,and TNF-αin SLE patients’plasma,evaluating their diagnostic and prognostic value.METHODS The study included 100 healthy individuals,50 newly diagnosed(ND),and 50 SLE patients undergoing treatment.The patients were monitored for a duration of 24 wk to observe and record instances of relapses.MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction,while ELISA kits were used to assess IL-12 and TNF-αproduction.RESULTS The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals,with the lowest levels in ND patients.TNF-αand IL-12 expression levels were significantly elevated in SLE patients,especially in the early stages of the disease.Receiver operating characteristic curve analyses,and Cox-Mantel Log-rank tests indicated miR-125a,TNF-α,and IL-12 as proper diagnostic biomarkers for SLE.A negative correlation was found between plasma miR-125a expression and IL-12/TNF-αlevels in SLE patients.CONCLUSION Decreased miR-125a levels may be involved in the development of SLE,while elevated levels of IL-12 and TNF-αcontribute to immune dysregulation.These findings offer new diagnostic and prognostic markers for SLE.Moreover,the negative correlation observed suggests an interaction between miR-125a,TNF-α,and IL-12.Further research is necessary to uncover the underlying mechanisms that govern these relationships.
文摘BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.
文摘AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls(HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral Ld T daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array(CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97(123.26-492.79) pg/m L vs 184.50(135.56-292.16) pg/m L, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with Ld T [175.51(103.90-331.91) pg/m L vs 184.50(135.56-292.16) pg/m L, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB(r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to Ld T treatment at 24 wk(48.15% vs 15.79%, P = 0.023) and 52 wk(66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary nonresponse at week 12 after treatment initiation were lower than those in patients with primary response [64.44(49.85-172.08) pg/m L vs 190.54(121.35-355.28) pg/m L, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with Ld T. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to Ld T treatment.
