2型糖尿病患者血清PTX3、sTWEAK水平与非酒精性脂肪性肝病的关系研究

目的探讨2型糖尿病(T2DM)患者血清正五聚蛋白3(PTX3)、可溶性肿瘤坏死因子样凋亡弱诱导因子(sTWEAK)水平与非酒精性脂肪性肝病(NAFLD)的关系。方法选取北部战区总医院152例新诊断为T2DM的患者为研究对象,根据是否合并NAFLD将患者分为NAFLD组(92例)和非NAFLD组(60例);根据肝脏超声检查结果,将NAFLD患者分为轻度组、中度组和重度组。另选取35例健康人作为对照(对照组)。采用酶联免疫吸附试验检测血清PTX3、sTWEAK水平。采用Pearson相关分析T2DM患者PTX3和sTWEAK水平与总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)的关系。采用多因素Logistic回归分析T2DM合并NAFLD的影响因素;采用受试者工作特征(ROC)曲线分析PTX3、sTWEAK对NAFLD的预测价值,计算曲线下面积(AUC)。比较轻度组、中度组、重度组血清PTX3、sTWEAK水平。结果与对照组比较,NAFLD组和非NAFLD组血清PTX3、sTWEAK水平较高(P<0.05)。与非NAFLD组比较,NAFLD组血清PTX3、sTWEAK水平较高(P<0.05)。体质量指数(BMI,OR=3.387)、TG(OR=1.958)、HOMA-IR(OR=3.040)、PTX3(OR=4.836)、sTWEAK(OR=4.133)是T2DM合并NAFLD的影响因素(P<0.05)。T2DM患者血清PTX3水平分别与BMI、LDL-C、FPG、HbA1c、HOMA-IR呈正相关(P<0.05),而与HDL-C呈负相关(P<0.05)。血清sTWEAK水平分别与LDL-C、FPG、HOMA-IR呈正相关(P<0.05)。血清PTX3、sTWEAK预测T2DM患者发生NAFLD的AUC分别为0.873和0.821,二者联合可将AUC提高至0.915。轻度组、中度组、重度组血清PTX3和sTWEAK水平比较,差异有统计学意义(P<0.05),病情越重,患者血清PTX3和sTWEAK水平越高。结论PTX3、sTWEAK是T2DM患者发生NAFLD的影响因素,并且血清PTX3、sTWEAK水平越高,NAFLD病情越重。

特发性血小板减少性紫癜患儿血清PTX3、SDC-1水平及临床意义

目的探究特发性血小板减少性紫癜(ITP)患儿血清正五聚蛋白3(PTX3)、多配体蛋白聚糖1(SDC-1)水平及临床意义。方法选取2021年10月—2022年10月沧州市中心医院儿内科收治的ITP患儿95例为研究组;同期医院体检的健康儿童100例作为健康对照组。采用酶联免疫吸附法(ELISA)检测2组血清PTX3、SDC-1水平;采用Pearson相关分析血清PTX3、SDC-1水平的相关性;Logistic回归模型分析ITP患儿预后的相关影响因素;受试者工作特征(ROC)曲线分析血清PTX3、SDC-1水平对ITP的诊断价值和预后预测价值。结果与健康对照组比较,研究组ITP患儿血小板计数(PLT)水平显著下降,血清PTX3、SDC-1水平显著升高(t/P=76.639/<0.001、8.868/<0.001、8.483/<0.001)。与预后良好亚组比较,预后不良亚组ITP患儿血清PTX3、SDC-1水平显著升高(t/P=8.313/<0.001、7.851/<0.001)。Pearson相关分析显示,ITP患儿血清PTX3与SDC-1水平呈正相关(r/P=0.700/<0.001)。血清PTX3、SDC-1及二者联合诊断ITP的AUC分别为0.801、0.849、0.861,二者联合优于血清PTX3单独诊断(Z=2.708,P=0.007)。血清PTX3、SDC-1及二者联合预测ITP患儿预后的AUC分别为0.790、0.907、0.918,二者联合优于血清PTX3单独预测(Z=2.245,P=0.025)。Logistic回归分析显示,血清PTX3、SDC-1水平高是ITP患儿发生不良预后的危险因素[OR(95%CI)=5.463(3.193~9.347)、13.486(10.473~17.366)]。结论ITP患儿血清PTX3、SDC-1水平升高,对ITP诊断和预后评估具有重要临床意义。

The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma

Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ESCC.Methods: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model.Results: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.

Chondrogenesis of periodontal ligament stem cells by transforming growth factor-β3 and bone morphogenetic protein-6 in a normal healthy impacted third molar

The periodontal ligament-derived mesenchymal stem cell is regarded as a source of adult stem cells due to its multipotency.However, the proof of chondrogenic potential of the cells is scarce.Therefore,we investigated the chondrogenic differentiation capacity of periodontal ligament derived mesenchymal stem cells induced by transforming growth factor(TGF)-p3 and bone morphogenetic protein(BMP)-6.After isolation of periodontal ligament stem cells(PDLSCs) from human periodontal ligament,the cells were cultured in Dulbecco’s modified Eagle’s medium(DMEM) with 20%fetal bovine serum(FBS).A mechanical force initiated chondrogenic differentiation of the cells.For chondrogenic differentiation,10μg·LTGF-β3 or 100μg·LBMP-6 and the combination treating group for synergistic effect of the growth factors.We analyzed the PDLSCs by fluorescence-activated cell sorting and chondrogenesis were evaluated by glycosaminoglycans assay,histology,immunohistochemistry and genetic analysis.PDLSCs showed mesenchymal stem cell properties proved by FACS analysis.Glycosaminoglycans contents were increased 217%by TGF-β3 and 220%by BMP-6. The synergetic effect of TGF-β3 and BMP-6 were shown up to 281%compared to control.The combination treatment increased Sox9, aggrecan and collagen II expression compared with not only controls,but also TGF-P3 or BMP-6 single treatment dramatically.The histological analysis also indicated the chondrogenic differentiation of PDLSCs in our conditions.The results of the present study demonstrate the potential of the dental stem cell as a valuable cell source for chondrogenesis,which may be applicable for regeneration of cartilage and bone fracture in the field of cell therapy.

Serum measurements of testosterone, insulin-like growth factor 1, and insulin-like growth factor binding protein-3 in the diagnosis of prostate cancer among Korean men

Aim： To investigate the relationships of serum testosterone, insulin-like growth factor （IGF）- 1 and IGF-binding protein （IGFBP）-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy （RRP） for clinically-localized prostate cancer. Methods： Serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer （n = 159） and those who were not diagnosed with prostate cancer from biopsy （control group, n = 433）. Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen （PSA）, pathological T stage and pathological Gleason score. Results： Prostate cancer patients and the control group demon- strated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-I and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Oleason score and preoperative PSA. Conclusion： Our data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men. （Asian J Androl 2008 Mar; 10： 207-213）

Interplay between micro RNA-17-5p, insulin-like growth factor-Ⅱ through binding protein-3 in hepatocellular carcinoma

AIM: To investigate the effect of microR NA on insulinlike growth factor binding protein-3(IGFBP-3) and hence on insulin-like growth factor-Ⅱ(IGF-Ⅱ) bioavailability in hepatocellular carcinoma(HCC).METHODS: Bioinformatic analysis was performed using microrna.org, DIANA lab and Segal lab softwares. Total RNA was extracted from 23 HCC and 10 healthy liver tissues using mir Vana mi RNA Isolation Kit. microR NA-17-5p(miR-17-5p) expression was mimicked and antagonized in Hu H-7 cell lines using Hi Per Fect Transfection Reagent, then total RNA was extracted using Biozol reagent then reverse transcribed into cD NA followed by quantification of mi R-17-5p and IGFBP-3 expression using Taq Man real-time quantitative PCR. Luciferase reporter assay was performed to validate the binding of miR-17-5p to the 3'UTR of IGFBP-3. Free IGF-Ⅱ protein was measured in transfected Hu H-7 cells using IGF-Ⅱ ELISA kit. RESULTS: Bioinformatic analysis revealed IGFBP-3 as a potential target for miR-17-5p. Screening of miR-17-5p and IGFBP-3 revealed a moderate negative correlation in HCC patients, where mi R-17-5p was extensively underexpressed in HCC tissues(P = 0.0012), while IGFBP-3 showed significant upregulation in the same set of patients(P = 0.0041) compared to healthy donors. Forcing mi R-17-5p expression in Hu H-7 cell lines showed a significant downregulation of IGFBP-3 mR NA expression(P = 0.0267) and a significant increase in free IGF-Ⅱ protein(P = 0.0339) compared to mock untransfected cells using unpaired t-test. Luciferase assay validated IGFBP-3 as a direct target of mi R-17-5p; luciferase activity was inhibited by 27.5% in cells co-transfected with miR-17-5p mimics and the construct harboring the wild-type binding region 2 of IGFBP-3 compared to cells transfected with this construct alone(P = 0.0474).CONCLUSION: These data suggest that regulating IGF-Ⅱ bioavailability and hence HCC progression can be achieved through targeting IGFBP-3 via manipulating the expression of miR NAs.

Tribulus terrestris extracts alleviate muscle damage and promote anaerobic performance of trained male boxers and its mechanisms： Roles of androgen, IGF-1, and IGF binding protein-3

Purpose: To investigate the effects of Tribulus terrestris(TT) extracts on muscle mass, muscle damage, and anaerobic performances of trained male boxers and its mechanisms: roles of plasma androgen, insulin growth factor 1(IGF-1), and IGF-1 binding protein-3(IGFBP-3).Methods: Fifteen male boxers were divided into exercise group(E, n = 7) and exercise plus TT group(E + TT, n = 8). The 2 groups both undertook3-week high-intensity and 3-week high-volume trainings separated by a 4-week rest. TT extracts(1250 mg/day) were orally administered by boxers in E + TT group. TT extract compositions were detected by UHPLC–Q-TOF/MS. Before and at the end of the 2 trainings, muscle mass, anaerobic performance, and blood indicators were explored.Results: Compared with E group, decreases of plasma CK(1591.5 ± 909.6 U/L vs. 2719.9 ± 832.5 U/L) and IGFBP-3(3075.5 ± 1072.5 ng/m L vs. 3950.8 ± 479.3 ng/m L) as well as increases of mean power(MP, 459.4 ± 122.3 W vs. 434.6 ± 69.5 W) and MP/body weight(MP/BW, 7.5 ± 0.9 W/kg vs. 7.1 ± 1.1 W/kg) were detected in E + TT group after a high-intensity training. For high-volume training, reduction of IGFBP-3(2946.4 ± 974.1 ng/m L vs. 3632.7 ± 470.1 ng/m L) and increases of MP(508.7 ± 103.2 W vs. 477.8 ± 49.9 W) and MP/BW(8.2 ± 0.3 W/kg vs.7.5 ± 0.9 W/kg) were detected in E + TT group, compared with E group. Muscle mass, blood levels of testosterone, dihydrotestosterone(DHT),and IGF-1 were not signifiantly changed between the 2 groups.Conclusion: Taking 1250 mg capsules containing TT extracts did not change muscle mass and plasma levels of testosterone, DHT, and IGF-1 but significantly alleviated muscle damage and promoted anaerobic performance of trained male boxers, which may be related to the decrease of plasma IGFBP-3 rather than androgen in plasma.

Increased expression of insulin-like growth factor-binding protein-3 is implicated in erectile dysfunction in two-kidney one-clip hypertensive rats after propranolol treatment

This study aimed to investigate the role of insulin-like growth factor-binding protein-3 （IGFBP-3） in erectUe dysfunction （ED） in two-kidney one-clip （2K-1C） hypertensive rats treated with the β-blocking agent propranolol. Adult male Wistar rats were randomly divided into three groups： a normal control group, a hypertensive control group and a propranolol treatment group （n=9）. After 4 weeks of propranolol treatment, intracavemous pressure （ICP） responses to electrical stimulation of the cavernous nerves were evaluated. The expression of IGFBP-3 and insulin-like growth factor-1 （IGF-1） mRNA and protein in the rat cavernous tissue were detected by quantitative real-time PCR and Western blot, respectively. The concentration of cyclic guanosine monophosphate （cGMP） in the cavernous tissue was determined by enzyme-linked immunosorbent assay （ELISA）. Cavernosal pressure in response to cavernous nerve stimulation was decreased 4 weeks after propranolol treatment （P〈0.01, compared to the hypertensive control group）. IGFBP-3 mRNA and protein expression was increased in the propranolol treatment group compared to the hypertensive control group （P〈O.01）, whereas IGF-1 expression was decreased in the propranolol treatment group compared to the hypertensive control group （P〈0.01）. In addition, cavernous cGMP concentration was decreased in the prepranolol treatment group compared to the hypertensive control group （P〈0.01）. Taken together, these results suggest that the upregulation of IGFBP-3 may play a role in the development of ED in hypertensive rats.

Improved Osteointegration of Ti-6Al-4V-implants of Different Surface Texture by the Use of Bone Morphogenetic Protein-3 (BMP-3)

Half of altogether 60 cylindrical implant devices made of titanium-aluminum-vanadium alloy （ Ti-6Al-4V） were plusna-sprayed with a hydroxyapatite-couting and the other half had a corundum blasted porous surface. 15 implants of each group of the titanium test buplants were coated with 230 μg porcine, high-purified BMP- 3-precipitute per implant. In each case a BMP- 3-couted and an uncoated control-device were implanted into the femoral part of the putellofemoral joint of the right and left leg of 30 adult giant rabbits. Histomorphological and histomorphometrical we found in both groups with BMP- 3-coated test devices an improved osteointegrution. Stutistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of tony formed bone of the BMP- 3-coated corundum- blasted or hydroxyapathe- coated Ti- 6Al- 4 V test devices compared to the non-couted controls of the same t）pe （p 〈 0.01, t-test for matched samples）. In both implant groups with BMP-couting a synergetic effect was verifiable although the bone ongrowth in the hydroxyaputite coated implants was more extensive than in the corundum blasted implants. Light microscopy demonstrated osteointegrution without connective tissue membrane around the surface of the implants. Our results indicate that composite metal implants,as used in endoprosthetics and implantology , are suitable carriers for BMP- 3 and im proved fixation of the implants can be achieved. The hydroxyapatite surface is superior to the corundum-blasted surface with regards to the observed parameters because of its pronounced bioactivity and its osteoconductive characteristics.

Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

BACKGROUND： Recent studies have found that insulin-like growth factors （IGFs） and insulin-like growth factor binding protein-3 （IGFBP-3） have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear. OBJECTIVE： To explore the changes of insulin-like growth factor-Ⅱ （IGF-Ⅱ ） and IGFBP-3 in cerebrospinal fluid （CSF） of children with tuberculous meningitis and the significance of the changes. DESIGN： A non-randomized concurrent controlled study. SETTING： Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College. PARTICIPANTS： Thirty children with tuberculous meningitis （14 males and 16 females） were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children （13 males and 17 females） with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children （13 males and 17 females） without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children. METHODS： ①The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid （3 mL）. The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined with a dry-chemical method. The number of white blood cells was counted by Fushi Method. ②The Pearson correlation analysis was used to analyze the correlation of the contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. MAIN OUTCOME MEASURES： The contents of IGF- Ⅱ and IGFBP-3 in cerebrospinal fluid, and their correlation with the leucocyte counting and the concentrations of glucose and protein in cerebrospinal fluid. RESULTS： ①Contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid： The contents of IGF-Ⅱ and IGFBP-3 in cerebrospinal fluid in the tuberculous meningitis group were significantly higher than those in the encephalitis virus group and control group （P 〈 0.05）. There was no significant difference in the contents of IGF- Ⅱ and IGFBP-3 in cerebrospinal fluid between the viral encephalitis group and control group （P 〉 0.05）. ②Correlation： The IGF- Ⅱ and IGFBP-3 contents in cerebrospinal fluid were positively correlated with the protein concentration in cerebrospinal fluid （r =0.821, 0.855, P 〈 0.01）, but negatively with the glucose （r =0.742, - 0.605, P 〈 0.01）. CONCLUSION- ①IGFs and IGVBPs are involved in the pathophysiological process of tuberculous meningitis, as well as the glucose and protein metabolism in cerebrospinal fluid. ②The IGF-Ⅱ and IGFBP-3 contents in cerebrospinal fluid can be used as the auxiliary indicators to differentially diagnose tuberculous meningitis and viral enceohalitis.

口腔骨增量种植修复患者龈沟液PTX3、Nrg4水平与种植体预后的关系

目的分析口腔骨增量种植修复患者龈沟液正五聚蛋白3(PTX3)、神经调节素-4(Nrg4)水平与种植体预后的关系。方法选取2021年4月—2022年4月华中科技大学同济医学院附属协和医院口腔科收治口腔骨增量种植修复患者92例为研究组,根据种植后1个月复诊时X线检查结果分为预后不良亚组56例,预后良好亚组36例;同期在医院体检牙周健康志愿者92例为健康对照组。采用酶联免疫吸附法(ELISA)法测定龈沟液PTX3、Nrg4的表达水平,Pearson相关性分析口腔骨增量种植修复患者龈沟液PTX3、Nrg4表达水平的相关性,Logistic回归分析影响骨增量种植修复患者种植牙预后的因素。结果与健康对照组比较,研究组CRP、TNF-α及龈沟液PTX3表达水平升高(t/P=30.695/<0.001、18.994/<0.001、8.383/<0.001),Nrg4表达水平降低(t/P=10.988/<0.001)。与预后良好亚组比较,预后不良亚组PTX3、CRP、TNF-α水平升高(t/P=4.706/<0.001、17.480/<0.001、9.410/<0.001),Nrg4表达水平降低(t/P=9.033/<0.001)。骨增量种植修复患者龈沟液PTX3和Nrg4表达水平呈负相关(r/P=-0.349/0.001)。Logistic回归分析显示,PTX3高、Nrg4低、CRP高是骨增量种植修复患者种植体预后的危险因素[OR(95%CI)=3.542(1.742~7.201)、2.524(1.121~5.682)、4.767(2.056~11.051)]。结论PTX3在口腔骨增量种植修复患者龈沟液中呈高表达,Nrg4呈低表达,二者与种植体预后相关。

Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells

OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.

PTX3在子宫内膜癌组织中的表达及与肿瘤发生发展的关系

目的探讨五聚素3(PTX3)在子宫内膜癌组织中的表达及与肿瘤发生发展的关系。方法选取2017年1月至2018年1月我院经病理检查确诊的子宫内膜癌组织60例、60例正常子宫内膜组织,采用RT-qPCR法检测两组标本中的PTX3表达水平,并分析在不同年龄、FIGO分期、病理学类型、病理学分级、淋巴结转移、肌层浸润患者中的表达差异。结果子宫内膜癌组织中的PTX3基因表达强度显著的高于正常子宫内膜组织,差异有统计学意义(P<0.05);不同FIGO分期、是否发生淋巴结转移、不同肌层浸润深度的子宫内膜癌组织中的PTX3基因表达强度组间分别比较,差异有统计学意义(P<0.05);不同年龄、不同病理学分型、不同病理学分级的子宫内膜癌组织中的PTX3基因表达强度组间比较,差异无统计学意义(P>0.05)。结论PTX3在子宫内膜癌组织中表达显著上调,并且与肿瘤分期、淋巴结转移及肿瘤浸润深度具有一定的关系。

小儿肾积水术后分肾功能水平与血清PTX3、IgA/C3水平的相关性

目的研究小儿肾积水术后分肾功能(DRF)水平与血清正五聚素-3(PTX3)、免疫球蛋白A(IgA)/补体C3(C3)水平的相关性。方法采用回顾性研究,选择2019年1月至2021年12月新疆医科大学第一附属医院收治的144例肾积水患儿作为研究对象,患儿均行肾盂输尿管成形术,将DRF≥45%定义为肾功能正常,根据术后DRF将患儿分为DRF≥45%组(54例)和DRF<45%组(90例)。收集所有患儿一般资料,包括患儿性别、手术时年龄、发病侧别、手术方式;进行肾脏超声,检测患儿术前患侧肾皮质厚度、术前患侧肾盏大小、术前肾盂前后径、术前长径比、术前横径比;进行肾核素显像检查,评估患儿的术前DRF。以受试者工作特征(ROC)曲线分析术前患侧DRF、PTX3、IgA、IgA/C3预测小儿肾积水术后DRF<45%的价值;采取非条件Logistic逐步回归分析小儿肾积水术后DRF<45%的危险因素;以Spearman系数检验小儿肾积水术后DRF与血清PTX3、IgA/C3水平的相关性。结果与DRF≥45%组相比,DRF<45%组术前患侧DRF较低,PTX3、IgA、IgA/C3水平较高,差异均有统计学意义(P<0.05)。经ROC分析,术前患侧DRF≤40.911%、PTX3≥1.461 ng/mL、IgA≥2.513 g/L、IgA/C3≥2.449是小儿肾积水术后DRF<45%的最佳截断值,均有P<0.05。多因素Logistic回归性分析显示,术前患侧DRF≤40.911%、PTX3≥1.461 ng/mL、IgA≥2.513g/L、IgA/C3≥2.449是小儿肾积水术后DRF<45%的危险因素。经相关性分析,小儿肾积水术后DRF与PTX3、IgA、IgA/C3呈负相关(P<0.05);小儿肾积水术后DRF与C3水平无明显相关性(P>0.05)。结论肾积水患儿术后DRF可能受术前DRF、血清PTX3、IgA及IgA/C3等因素影响,并且PTX3、IgA、IgA/C3与患儿术后DRF呈负相关,临床可在术前检测以上指标以预测患儿术后DRF。

动脉粥样硬化型ACI患者血清Lp-PLA2、MCP-1、VE-cadherin、PTX3变化及与IMT的关系

目的探讨动脉粥样硬化型(AT型)急性脑梗死(ACI)患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)、单核细胞趋化蛋白1(MCP-1)、血管内皮细胞钙黏蛋白(VE-cadherin)、五聚素3(PTX3)水平变化及其与颈动脉内-中膜厚度(IMT)之间的关系。方法选取AT型ACI患者104例(ACI组),根据ACI程度分为轻度组(n=46)、中度组(n=34)和重度组(n=24),根据颈动脉粥样硬化斑块(CASP)性质分为非CASP组(n=23)、CASP稳定组(n=38)与CASP不稳定组(n=43)。另选同期健康体检者40例为正常对照组(n=40)。测定并比较各组的血清Lp-PLA2、MCP-1、VE-cadherin、PTX3水平及与IMT的关系。结果ACI患者的血清Lp-PLA2、MCP-1、VE-cadherin、PTX3水平及IMT显著高于对照组(P<0.05),且随着病情程度加重呈显著增高趋势(P<0.05),CASP稳定组和CASP不稳定组显著高于非CASP组,CASP不稳定组显著高于CASP稳定组(P<0.05)。ACI患者的血清Lp-PLA2、MCP-1、VEcadherin、PTX3水平与IMT呈显著正相关性(均P<0.05)。结论AT型ACI患者具有明显IMT增厚及血清Lp-PLA2、MCP-1、VE-cadherin、PTX3高表达,且Lp-PLA2、MCP-1、VE-cadherin、PTX3水平与IMT厚度密切相关。

Expression of albumin, IGF-1, IGFBP-3 in tumor tissues and adjacent non-tumor tissues of hepatocellular carcinoma patients with cirrhosis

AIM： To explore the expression of albumin （ALB）, insulinlike growth factor （IGF）-I, and insulin-like growth factor binding protein （IGFBP）-3 in tumor tissues and adjacent non-tumor tissues of hepatocellular carcinoma （HCC） patients with cirrhosis.METHODS： Twenty-four HCC patients with cirrhosis who underwent hepatectomy were studied. ALB mRNA, IGF-1 mRNA, and IGFBP-3 mRNA in liver tissues （including tumor tissues and adjacent non-tumor tissues） were detected by reverse transcriptase-polymerase chain reaction（RT-PCR）. Liver Ki67 immunohistochemistry staining was studied. At the same time, 12 patients with cholelithiasis or liver angioma who underwent operation were segregated as normal control.RESULTS： In HCC patients with cirrhosis, hepatic ALB mRNA, IGF-1 mRNA, and IGFBP-3 mRNA of tumor tissues or adjacent non-tumor tissues were lower than the normal liver tissues, while in tumor tissues, hepatic ALB mRNA and IGFBP-3 mRNA were lower, hepatic IGF-1 mRNA was higher than in adjacent non-tumor tissues. Liver Ki67 labeling index （Ki67 LI） in tumor tissues or adjacent nontumor tissues were higher than that in the normal liver tissues, while in tumor tissues it was higher than that in adjacent non-tumor tissues.CONCLUSION： Imbalance of IGF-1 and IGFBP-3 may play a role in hepatocarcinogenesis and tumor development of liver cirrhosis patients.

RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39℃

Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.

病毒性心肌炎患儿血清PTX-3及IL-35水平及其与心功能、心肌损伤的相关性分析

目的探讨病毒性心肌炎(VMC)患儿血清正五聚体蛋白-3(PTX-3)及白细胞介素(IL)-35水平及其与心功能、心肌损伤的相关性。方法选取该院儿科收治的VMC患儿80例作为VMC组,选取同期于该院进行体检的50例健康儿童作为对照组。采用酶联免疫吸附试验比较两组血清中PTX-3、IL-35水平,采用放射免疫法检测VMC组患儿心肌酶谱表达,采用超声检测VMC组患儿心输出量(CO)、每搏输出量(SV)、射血分数(EF),采用Pearson相关分析血清PTX-3、IL-35水平与心肌酶谱及心功能的相关性。结果与对照组比较,VMC组患儿血清PTX-3水平升高,IL-35水平降低(P<0.05)。血清PTX-3水平与心肌肌钙蛋白I(cTnI)、肌酸激酶(CK)、肌酸磷激酶同工酶(CK-MB)、α-羟丁酸脱氢酶(α-HBDH)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)水平均呈正相关(r=0.816、0.671、0.861、0.869、0.913、0.603,P<0.05),与CO、SV、EF均呈负相关(r=-0.880、-0.836、-0.745,P<0.05)。血清IL-35水平与cTnI、CK、CK-MB、α-HBDH、AST、LDH均呈负相关(r=-0.539、-0.554、-0.589、-0.619、-0.531、-0.511,P<0.05),与CO、SV、EF均呈正相关(r=0.588、0.531、0.367,P<0.05)。结论VMC患儿血清中PTX-3水平升高,IL-35水平降低,且均与心肌损伤程度及心功能有相关性,PTX-3、IL-35水平检测对诊断VMC有一定的临床参考价值。

3D-QSAR and action mechanism of potential dual inhibitors towards AP-1 and NF-κB

Three-dimensional quantitative structure-activity relationship （3D-QSAR） and docking studies of a series of novel dioxopyrrolinyl-amino-pyrimidine derivatives, which are potential dual inhibitors mediating a transcriptional activation towards protein-1 （AP-1） and nuclear factor kappa B （NF-κB）, have been carried out. The QS, AR models established by comparative molecular field analysis （CoMFA） and comparative molecular similarity index analysis （CoMSIA） show a good predictive ability with cross-validated coefficients q2 of 0.644 and 0.636, respectively. The docking result shows that there are quite lower average values of the flexible and rigid energy scores on the selected binding sites, meanwhile, it further shows that the binding sites just fall on the joint regions between AP-1 （and NF-κB） and DNA. The reason that these analogues have inhibition function towards AP-I and NF-κB is that their existence on these joint regions can effectively prevent free AP-I and NF-κB from binding to DNA. These results can offer a valuable theoretical reference to the pharmaceutical molecular design as well as the action mechanism analysis.