Collagen typeⅠ在胰腺癌发展中的作用

胰腺癌(PC)是高发病率、高死亡率的恶性肿瘤,尽管目前在胰腺癌的治疗策略中已取得了较大的进展,但胰腺癌的转移、复发及高耐药性仍是大部分患者预后不良的主要原因。Ⅰ型胶原蛋白(Col⁃I)是人体中主要的细胞外基质蛋白,在多种实体肿瘤中表达异常并参与肿瘤的形成。最近研究表明,Col⁃I在胰腺癌中高度表达与胰腺癌的生长、转移、侵袭、耐药以及治疗密切相关,是胰腺癌新的潜在治疗靶点。该文重点介绍了COl⁃I对胰腺癌发生发展的影响,为胰腺癌的诊断和靶向治疗提供新的思路。

Clinical efficacy of intradermal type Ⅰ collagen injections in treating skin photoaging in patients from high-altitude areas

BACKGROUND Photoaging,a result of chronic sun exposure,leads to skin damage and pigmentation changes.Traditional treatments may have limitations in high-altitude areas like Yunnan Province.Intradermal Col Ⅰ injections stimulate collagen production,potentially improving skin quality.This study aims to assess the efficacy and safety of this treatment for photoaging.AIM To evaluate the efficacy and safety of intradermal typeΙcollagen(ColΙ)injection for treating photoaging.METHODS This prospective,self-controlled study investigated the impact of intradermal injections of ColΙon skin photodamage in 20 patients from the Yunnan Province.Total six treatment sessions were conducted every 4 wk±3 d.Before and after each treatment,facial skin characteristics were quantified using a VISIA skin detector.Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector.The Face-Q scale was used for subjective evaluation of the treatment effect by the patients.RESULTS The skin thickness of the right cheek consistently increased after each treatment session compared with baseline.The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline.The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions,whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions.The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline(P<0.05).These findings were also supported by skin ultrasound images.The feature count for the red areas and wrinkle feature count decreased following the treatment(P<0.05).VISIA assessments also revealed a decrease in the red areas after treatment.The Face-QSatisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session.The overall appearance of the patients improved after treatment.CONCLUSION Intradermal ColΙinjection improves photoaging,with higher patient satisfaction and fewer adverse reactions,and could be an effective treatment method for populations residing in high-altitude areas.

氧化苦参碱对皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的影响

目的探讨氧化苦参碱对小鼠皮肤创面愈合中血清增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)及细胞Ⅰ型胶原蛋白(Type Ⅰ collagen)的影响。方法昆明小鼠背部手术制备1.5 cm×1.5 cm全层皮肤缺损创面模型。自第1 d始,除对照组给予等量生理盐水外,余各组分别按20、40、80 mg/kg给予氧化苦参碱。Van Gieson纤维胶原染色法观察小鼠背部皮肤创面组织胶原纤维的表达;免疫组学法评价创面组织中PCNA、α-SMA及Type Ⅰ collagen的表达。结果Van Gieson纤维胶原染色显示,氧化苦参碱可促进新生肉芽组织、毛细血管及新生纤维胶原生长。免疫组学研究显示,在第7 d时,氧化苦参碱20、40、80 mg/kg使小鼠皮肤创面组织中PCNA表达明显升高(P<0.05);在第9 d、11 d时,氧化苦参碱20 mg/kg使小鼠皮肤创面组织中α-SMA显著增加;氧化苦参碱20 mg/kg在第3 d、11 d,氧化苦参碱40 mg/kg在第3 d,氧化苦参碱80 mg/kg在第3 d、7 d引起Type Ⅰ collagen的表达显著升高(P<0.05)。结论氧化苦参碱能增加皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的表达。

组织桥接整合因子1、Ⅰ型胶原蛋白基因、核转运蛋白基因2与三阴性乳腺癌术后复发关系

目的探究组织桥接整合因子1(BIN1)、Ⅰ型胶原蛋白基因(COL1A1)、核转运蛋白基因2(KPNA2)表达与三阴性乳腺癌(TNBC)术后复发关系及联合检测意义。方法选取2019年5月至2020年5月上海市第八人民医院行手术治疗的TNBC病人80例,根据术后2年是否复发分为复发组、未复发组,比较两组临床资料、组织BIN1、COL1A1、KPNA2基因表达,复发的相关影响因素采用单因素与多因素logistic回归分析,组织BIN1、COL1A1、KPNA2基因表达预测术后复发的价值采用受试者操作特征曲线(ROC曲线)分析,组织BIN1、COL1A1、KPNA2基因表达与复发时间关系采用Pearson分析,比较不同组织BIN1、COL1A1、KPNA2基因表达病人无复发生存期(RFS)。结果复发组T分期、N分期与未复发组比较,差异有统计学意义(P<0.05);复发组组织BIN1mRNA表达为0.24±0.07,低于未复发组的0.35±0.10(P<0.05),复发组组织COL1A1mRNA、KPNA2mRNA表达分别为2.07±0.62、2.91±0.84,高于未复发组的1.48±0.43、1.85±0.60(P<0.05);T分期、N分期、COL1A1 mRNA、KPNA2 mRNA均是复发相关独立危险因素,BIN1 mRNA是复发相关独立保护因素(P<0.05);BIN1 mRNA、COL1A1 mRNA、KPNA2 mRNA的AUC分别为0.76、0.80、0.78,三者联合的AUC为0.94;BIN1mRNA与复发时间呈负相关(r=-0.79,P<0.001),COL1A1mRNA、KPNA2mRNA与复发时间呈正相关(r=0.77、0.78,均P<0.001);BIN1mRNA高水平病人RFS长于低水平病人,COL1A1mRNA、KPNA2mRNA高水平病人RFS短于低水平病人(P<0.05)。结论BIN1mRNA、COL1A1mRNA、KPNA2mRNA与TNBC术后复发风险、复发时间有关,联合检测可作为早期预测术后复发的一个可靠方案,为临床治疗提供重要的参考信息。

辽东兰花岭地区古元古代Ⅰ型花岗岩类与辽吉A型花岗岩对比研究

辽东半岛是华北克拉通胶-辽-吉古元古代活动带的重要组成部分,古元古代经历了复杂的构造演化过程,并记录了多期岩浆-变质作用,约2.2 Ga的辽吉A型花岗岩和1.89~1.85 Ga的巨斑状花岗岩、正长岩分别标志着辽东古元古代造山作用的开端和结束。最新研究显示,2.20~2.15 Ga的岩浆作用形成了2种不同类型的花岗岩,它们可能具有不同的岩石成因和构造意义。在青城子铅锌矿集区北部采集的兰花岭、白砬子花岗闪长岩和黄泊辉绿岩,锆石U-Pb年龄分别为2177±19 Ma、2129±36 Ma、1876±29 Ma。花岗闪长岩的岩石成因类型、地球化学特征与典型的约2.2 Ga的辽吉A型花岗岩明显不同,属于弱过铝质、低钾钙碱性—碱性岩石,Zr、Hf、Nb、Rb含量较低,K_(2)O/Na_(2)O值、稀土元素总量极低,为典型的Ⅰ型花岗岩类。根据锆石Lu-Hf同位素分析,ε_(Hf)(t)值为-5.1~9.0,二阶段Hf模式年龄t_(DM2)为2089~2817 Ma,岩浆源区为约2.5 Ga的太古宙地壳物质和少量软流圈地幔物质。兰花岭地区花岗闪长岩具备岛弧或活动大陆边缘的地球化学亲缘属性,可能形成于弧岩浆俯冲挤压环境;结合形成于伸展环境的A型条痕状花岗岩特征,认为约2.2 Ga辽东地区古元古代活动带呈现总体伸展、局部挤压的构造环境,为洋壳板块向龙岗地块俯冲碰撞过程中或碰撞后的弧后盆地。

Effects of Icariin on Expression of OPN mRNA and Type ⅠCollagen in Rat Osteoblasts in Vitro

To study the effects of Icariin on expression of osteopontin （OPN） mRNA and type Ⅰ collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley （SD） rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase （ALP） staining. Different concentration （0.1μg/mL, 1.0 μg/mL, 10 μ/mL） of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type l collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction （RT-PCR）. The expression of OPN mRNA and type Ⅰ collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 μg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type Ⅰ collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type Ⅰ collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.

内质网应激蛋白激酶RNA样ER激酶(PERK)通路对肝星状细胞激活及Ⅰ型胶原蛋白表达的影响

目的探讨内质网应激蛋白激酶RNA样ER激酶(PERK)/真核生物翻译起始因子2α(eIF2α)信号通路对肝星状细胞(HSC)活化的影响。方法收集11例肝穿刺病理提示S1~S4肝纤维化患者和9例肝血管瘤、肝腺瘤患者术后周围正常肝组织病理切片,进一步行组织免疫组化检测PERK、eIF2α、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)表达情况;使用不同浓度的内质网应激诱导剂毒胡萝卜素(0、125、250、500、1000 nmol/L)作用于人HSC-LX2,使用qRT-PCR检测PERK mRNA及Western Blot检测PERK、肌醇需要酶1(IRE1)、激活转录因子6(ATF6)、CHOP及α平滑肌肌动蛋白(α-SMA)表达水平。使用慢病毒转染构建PERK稳定过表达LX-2组及对照组,并通过qRT-PCR检测PERK、eIF2α、α-SMA mRNA,Western Blot检测PERK、p-eIF2α、α-SMA蛋白表达,免疫荧光检测胶Ⅰ型原蛋白(COL1A1)表达。符合正态分布的计量资料两组间比较采用成组t检验,多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验;不符合正态分布的计数资料,两组间比较采用Mann-Whitney U秩和检验。结果与正常肝组织相比,肝纤维化患者肝组织中PERK、eIF2α及CHOP表达升高,差异均有统计学意义(Z=−3.56、t=−5.75、Z=−3.52,P值均<0.001)。不同浓度毒胡萝卜素作用后,与溶媒组相比,内质网相关蛋白PERK、CHOP、IRE1、ATF6及α-SMA蛋白表达显著升高(P值均<0.05)。与对照空载慢病毒组相比,PERK稳定过表达组PERK mRNA、eIF2αmRNA、α-SMA mRNA表达及PERK、p-eIF2α、α-SMA蛋白表达明显升高(P值均<0.05)。细胞免疫荧光结果提示,PERK过表达组COL1A1表达升高(P<0.05)。结论PERK过表达可诱导LX-2细胞α-SMA、胶原蛋白COL1A1表达,提示PERK信号通路可能是HSC活化的重要机制之一。

Effects of gentiana scabra bage on expression of hepatic type Ⅰ,Ⅲ collagen proteins in Paragonimus skrjabini rats with liver fibrosis

Objective:To exploit- the effects of gentiana scabra bage on the expression of hepatic collagen proteins in Paragonimus skrjabini rats with liver fibrosis.Methods:Immunohistochemical technique was used to observe the changes of content of hepatic type Ⅰ,Ⅲ collagen proteins in Paragonimus skrjabini rats with Liver fibrosis before and after the gentiana scabra bage treatmeat.Results:Comparing with the model group,changes of hepatic tvpe Ⅰ and type Ⅲ collagen proteins in gentiana scabra bage treated group were significantly weakened.Conclusions:Gentiana scabra bage treatment can reduce the content of hepatic type Ⅲ and type Ⅰ collagen protein significantly in Paragonimus skrjabini rats with liver fibrosis,thereby,playing the role against hepatic fibrosis.

The Effects of Tetrandrine (TT) and Polyvinylpyridine-N-Oxide (PVNO) on Gene Expression of Type Ⅰand Type ⅢCollagens during Experimental Silicosis

In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis

Detection of Ⅴ,Ⅲ and Ⅰ Type Collagens of Dermal Tissues in Skin Lesions of Patients with Systemic Sclerosis and Its Implication

This study investigated the contents and distribution of collagen Ⅴ （Col Ⅴ） in skin lesions of the patients with systemic sclerosis （SSc） and its roles in the pathogenesis. The contents and distribution for α1 chain of collagen type Ⅰ, Ⅲ and V [α1 （Ⅰ）, α1 （Ⅲ） and α1 （Ⅴ）] in skin lesions of 36 patients with SSc （9 cases of mild fibrosis, 14 moderate, and 13 severe） were detected by using im- munohistochemical SP method. Six cases of normal skin tissues served as controls. The results showed that there was diffuse distribution for three kinds of collagens in dermis. The deep staining α1 （Ⅰ） and α1 （Ⅲ） masses or bands were seen in reticular layer, while α1 （Ⅴ） was distributed more ho- mogeneously. From control to weak, moderate and severe fibrosis stages, α1 （Ⅰ）, α1 （Ⅲ） and α1 （V） showed a gradually increased trend in skin lesions （P〈0.05）. α1 （Ⅴ） was obviously elevated in skin lesions at early stage and persisted in whole fibrotic process and risen in greater contents, while α1 （Ⅰ） and α1 （Ⅲ） were to go higher late and were apparently elevated at moderate and late stages. Com- pared with α1 （Ⅰ）, α1 （Ⅴ） took leading increase at early stage in skin lesions （P〈0.01）, and had more elevated contents than α1 （Ⅲ） at moderate and late stages. The fibrotic changes in dermal reticular layer occurred earlier than those in papillary layer, and the abnormalities of α1 （Ⅴ）/α1 （I） ratio ap- peared before α1 （Ⅲ）/α1 （Ⅰ） ratio. It was concluded that a lot of α1 （Ⅴ） began to deposit in greater contents prior to α1 （Ⅰ） and α1 （Ⅲ） at early stage in SSc and persisted in whole fibrotic process. The changes of α1 （Ⅴ） contents in reticular layer occurred earlier than those in papillary layer, and it sug- gested that the fibrosis in reticular layer appeared earlier.

Novel electrospun poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits for repair of peripheral nerve injury

Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury.Natural biopolymers have received much attention because of their biocompatibility.To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type I collagen nanofiber conduits(biopolymer nanofiber conduits)on the repair of peripheral nerve injury,we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits,poly(ε-caprolactone)or silicone conduits in Sprague-Dawley rats.Rat neurologica1 function was weekly evaluated using sciatic function index within 8 weeks after repair.Eight weeks after repair,sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining,hematoxylin-eosin staining,and transmission electron microscopy.S-100(Schwann cell marker)and CD4(inflammatory marker)immunoreactivities in sciatic nerve were detected by immunohistochemistry.In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits,no serious inflammatory reactions were observed in rat hind limbs,the morphology of myelin sheaths in the injured sciatic nerve was close to normal.CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone)or silicone.Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone)or silicone repair.These results suggest that electrospun absorbable poly(ε-caprolactone)/type I collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility.All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital,Taiwan,China(La-1031218)on October 2,2014.

Is type Ⅰ alpha 2 collagen gene responsible for intracranial aneurysm in Northeast China?

In this study, we investigated whether a single nucleotide polymorphism （rs42524 G 〉 C） in the type I alpha 2 collagen gene was associated with sporadic ruptured intracranial aneurysm or its clinical characteristics in patients from Northeast China. Genotyping of the rs42524 G 〉 C polymorphism was carried out using a polymerase chain reaction-restriction fragment length polymorphism assay. The data showed that the frequency of the rs42524 GC ＋ CC genotype was significantly higher than the GG genotype among intracranial aneurysm patients whose Hunt and Hess grading scale was 〉 3. In addition, the rs42524 G 〉 C genotype was found to have a statistically significant association with intracranial aneurysm risk. These findings indicate that the type I alpha 2 collagen gene gene may be involved in a predisposition to intracranial aneurysm in the Northeast Chinese population. Crucially, the rs42524 C allele may be an important risk factor for increased severity of the condition in patients with ruptured intracranial aneurysms.

重组Ⅰ型人源化胶原蛋白“福活因子”的生物合成及其结构表征研究

目的:筛选获得含胶原蛋白保守序列hCol.1基因的重组人源化Ⅰ型胶原蛋白高效表达基因工程菌和高产创新融合蛋白,并通过检测其理化特征验证表达产物。方法:将His6-SUMO-hCol.1重组基因大肠杆菌高密度发酵后经镍亲和层析和离子交换层析两步纯化浓缩获得重组蛋白,检测理化测试特征。结果:测序证明克隆基因与hCol.1序列高度一致,Blast比对蛋白序列与人Ⅰ型胶原蛋白高度同源,折叠结构与人Ⅲ型胶原蛋白高度类似。表观分子量55~60kD,产量36.4mg/L,纯度>95%。等电点检测、氨基酸组成和圆二色谱等实验结合高级结构预测分析,证明其理化性状与蛋白结构符合胶原蛋白特征。结论:成功将人Ⅰ型胶原蛋白保守功能结构域hCol.1与SUMO等肽段重组融合表达并命名为福活因子(FHTFF),筛选出基因工程菌pET21a(+)-FHTFF/BL21,纯化产物“福活因子”的理化特性、序列和结构与人Ⅰ、Ⅲ型胶原蛋白肽段高度相似,属于重组人源化胶原蛋白新生物材料。

Ⅰ型胶原编码基因突变致成骨不全症动物模型

成骨不全症(osteogenesis Imperfecta,OI)是一类以低骨量、骨脆性及骨骼畸形为特征的单基因遗传性骨病,研究其病理生理学机制和有效治疗方法的关键是动物模型的应用。绝大部分OI由编码Ⅰ型胶原相关基因突变引起,本文总结了COL1A1和COL1A2突变的主要动物模型,这些模型是研究致病机制、开发和测试新的治疗策略的宝贵工具。未来的研究将运用CRISPR/Cas9等新型基因编辑技术,结合多种生物类别,优化和拓展OI动物模型,更好地模拟人类疾病,有助于对OI及其治疗方法的深入探索。

扬子地块西缘峨山新元古代高分异Ⅰ型花岗岩地球化学特征及岩石成因

峨山高分异Ⅰ型花岗岩位于扬子地块西缘,是扬子地块新元古代岩浆岩带的重要组成部分,对其源区、成因及其构造背景进行系统研究能够揭示新元古代地壳演化历史。本文对峨山高分异Ⅰ型花岗岩开展了LA-MC-ICP-MS锆石U-Pb定年及岩石地球化学研究。研究结果表明,峨山花岗岩主要由肉红色中粗粒花岗岩和灰白色中粗粒花岗岩组成,它们的形成年龄分别为(746±34)Ma(MSWD=4.2)和(732±30)Ma(MSWD=3.3)。全岩地球化学显示峨山花岗岩具有高SiO_(2)(70.32%~78.41%)、Na_(2)O(3.09%~3.94%)、K_(2)O(5.13%~7.35%)含量,低CaO(0.52%~0.90%)、TiO 2(0.001%~0.025%)、P_(2)O_(5)(0.061%~0.097%)含量,富集K、Rb、Th等元素,亏损Nb、P、Ti等元素的特征,与高分异Ⅰ型花岗岩特征一致。全岩Sr-Nd同位素结果显示,ε_(Nd)(t)=-10.8~-7.5,两阶段Nd模式年龄(T DM2)为2.3~2.0 Ga。结合区域地质研究,本次研究认为峨山高分异Ⅰ型花岗岩是在伸展的构造背景下,地幔或年轻下地壳熔融形成的岩浆底侵由中高钾玄武质岩和黑云母片麻岩组成的古元古代上地壳,经部分熔融产生母岩浆,后经高程度的分离结晶作用而形成的。

8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ与T2MD患者血糖在目标范围内时间的相关性及预测糖尿病周围神经病变的价值

目的探讨8-异前列腺素F2α(8-isoPGF2α)、镍纹样蛋白(Metrnl)、微管相关蛋白3B-Ⅱ(LC3B-Ⅱ)/微管相关蛋白-Ⅰ(LC3B-Ⅰ)与2型糖尿病(T2MD)患者血糖在目标范围内时间(TIR)的相关性及对糖尿病周围神经病变(DPN)预测价值。方法选取2020年5月至2022年10月新乡医学院第一附属医院收治的187例T2DM患者进行前瞻性研究,根据是否合并DPN分为DPN组(n=48)和无DPN组(n=139)。比较两组患者及根据TIR四分位数分组的患者8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ水平,采用Pearson相关性分析8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ与TIR相关性,采用多因素Logistic回归分析DPN的相关影响因素;绘制受试者工作特征曲线(ROC)评价8-isoPGF2α、Metrnl、LC3B-Ⅱ预测DPN的价值。结果DPN组患者的TIR为(51.43±7.68)%,明显低于无DPN组的(56.94±8.12)%,差异有统计学意义(P<0.05);DPN组患者的8-isoPGF2α、Metrnl分别为(162.78±51.33)pg/mL、(259.18±74.42)pg/mL,明显高于无DPN组的(129.56±43.00)pg/mL、(208.37±65.61)pg/mL,LC3B-Ⅱ/LC3B-Ⅰ为0.89±0.27,明显低于无DPN组的1.15±0.31,差异均有统计学意义(P<0.05);根据TIR第25、50、75百分位数将全部患者分为Q1~Q4四组,8-isoPGF2α、Metrnl在Q4组最低,LC3B-Ⅱ/LC3B-Ⅰ在Q4组最高;8-isoPGF2α、Metrnl随着TIR降低逐渐升高,LC3B-Ⅱ/LC3B-Ⅰ随着TIR降低而降低,四组间比较差异均有统计学意义(P<0.05);Pearson相关性分析结果显示,8-isoPGF2α、Metrnl与TIR呈显著负相关(r=-0.786、-0.665,P<0.01),LC3B-Ⅱ/LC3B-Ⅰ与TIR呈显著正相关(r=0.711,P<0.01);多因素Logistic回归分析结果显示,TIR、LC3B-Ⅱ/LC3B-Ⅰ是DPN的独立相关保护因素(P<0.05),8-isoPGF2α、Metrnl是DPN的独立相关危险因素(P<0.05);ROC分析结果显示,单一指标中,Metrnl预测DPN的AUC最大(0.830),特异度最高(87.05%),8-isoPGF2α+Metrnl+LC3B-Ⅱ预测DPN的AUC为0.923(95%CI:0.875~0.957),大于Metrnl,预测敏感度为87.50%,特异度为85.61%(P<0.05)。结论8-isoPGF2α、Metrnl、LC3B-Ⅱ/LC3B-Ⅰ与T2MD患者TIR有关,均是患者并发DPN的预警因素。联合检测三者能为临床分层管理和早期识别DPN高风险人群提供参考。

Significance of elevated serum concentration of type Ⅰ collagen metabolites and its correlation with serum interleukin 6 activities in multiple myeloma

In this study, serum concentrations of carboxyterminal propeptide of type Ⅰ collagen(PICP) and carboxyterminal cross-linked telopeptide of type Ⅰ collagen (ICTP), which represent the rates of synthesis and degradation of type Ⅰ collagen, were determined by radioimmunoassay in 56 patients with multiple myeloma (MM) and 22 healthy controls. It was discovered that serum concentrations of both PICP and ICTP were higher in MM than those in healthy controls (P<0. 01 ). With the disease progressing and the number of bone lesions increasing,serum concentration of ICTP elevated while serum concentration of PICP showed no significant change. Neither serum PICP nor ICTP concentration was related to M-component classes. Our results indicated that serum ICTP concentration was a good serological marker to reflect severity of bone lesions in MM and elevated serum PICP concentration might be due to compensatory increase in type Ⅰ collagen synthesis. Moreover, we also found that serum ICTP concentrations in MM correlated with serum interleukin-6 (IL-6) activities (r= 0. 610, P< 0. 01),which confirms the effectiveness of IL-6 as an osteoclast activating factor.

Effects of connective tissue growth factor and collagen type Ⅰ scleroderma

Objective： To investigate the effects of connective tissue growth factor（CTGF） and collagen type I（COL-I） on the pathogenesis of scleroderma and explore the relationship between the level of COL-I and CTGF. Methods： 12 mice model of scleroderma was established by the injection of Bleomycin. The level of CTGF and COL-I were detected by immunohistochemical method. The relationship was analyzed between CTGF and COL-I level. As control group, 12 healthy mice were selected. Results： The levels of CTGF and COL-I in sclerotic models were higher than in normal controls （P 〈 0.05）. It was found that there was a correlation between the level of CTGF and COL-I. Conclusion： CTGF and COL-I played an important role in the hardening process of the skin lesions of the mice model, which may be involved in the pathogenesis of scleroderma.

Lentinula edodes extract inhibits matrix metalloproteinase expression and increases typeⅠprocollagen expression via the p38 MAPK/c-Fos signaling pathway in ultraviolet A and B-irradiated HaCaT keratinocytes

Objective:To determine the effect of Lentinula edodes extract on ultraviolet(UV)A and UVB-induced changes in matrix metalloproteinase(MMP)and type I procollagen expression using human immortalized HaCaT keratinocytes.Methods:Lentinula edodes ethanol extract(LEE)was obtained by extraction with 80%ethanol for 4 h at 80℃.Effect of LEE on UVinduced alteration on the expression and production of MMPs and type I procollagen in keratinocytes was investigated using ELISA,RT-PCR,and Western blotting assay.To determine the underlying mechanism of LEE-mediated effects,mitogen-activated protein kinase(MAPK)and activator protein 1 signaling pathways were analysed by Western blotting assay.Results:LEE significantly inhibited the expression of MMP-1 and MMP-9 and increased the expression of type I procollagen in UVA and UVB-irradiated HaCaT keratinocytes.The phosphorylation levels of p38 were significantly inhibited by LEE whereas it did not affect c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation.Suppression of p38 phosphorylation was also accompanied by downregulation of UVA and UVB-induced increase in c-Fos.Conclusions:LEE effectively inhibits the expression of MMP-1 and MMP-9 and increases type I procollagen production through the p38 MAPK/c-Fos signaling pathway in UVA and UVB-irradiated HaCaT keratinocytes.This findings suggest that Lentinula edodes may be developed as a cosmetic material to suppress UV exposuremediated skin aging.