23 例1 型糖尿病初发患儿免疫学改变与胰岛β细胞功能的关系

目的:观察1型糖尿病(T1DM)初发患儿细胞免疫与胰岛β细胞功能之间的关系。方法:T1DM组23例初发患儿均测定淋巴细胞亚群(T细胞、B细胞及NK细胞)、HbA1c、INS、C-P,正常对照组20例,测定淋巴细胞亚群。结果:T1DM组CD4、CD4/CD8较正常对照组升高(P<0.05);CD8、CD3-CD56+较对照组降低(P<0.05);CD4/CD8比值与HbA1c呈正相关(r=0.9451,P<0.01),而与INS呈负相关(r=-0.1020,P<0.01),与C-P呈负相关(r=-0.6174,P<0.01);CD3-CD56+与HbA1c呈正相关(r=0.1320,P<0.01),而与INS呈正相关(r=-0.0846,P<0.01),与C-P呈负相关(r=-0.3224,P<0.01)。结论:T1DM初发患者CD4、CD4/CD8明显增高,CD8、CD3-CD56+明显降低,提示细胞免疫功能改变与胰岛β细胞功能损伤密切相关。     

脐带间充质干细胞不同模式干预对2型糖尿病大鼠胰岛细胞凋亡的作用比较

目的对比脐带间充质干细胞(UCMSC)不同模式干预对2型糖尿病(T2DM)大鼠胰岛细胞凋亡的作用及其与TLR4/NF-κB炎症通路的关系。方法将SD大鼠分为正常对照组(NC组)、T2DM组、UCMSC A组和UCMSC B组,每组8只,予相应干预8周:UCMSC以尾静脉输注方式干预,其中UCMSC A组采用单次大量模式(细胞数20×106个);UCMSC B组采用多次足量序贯模式(每次细胞数5×106个,每两周干预1次共4次)。定期检测各组大鼠空腹血糖(FBG)、胰岛素(INS)、C肽(C-P);观察胰腺组织形态变化;TUNEL法检测胰岛细胞凋亡;Western blot法检测胰腺组织TLR4、NF-κB及IL-6蛋白表达水平。组间比较采用单因素方差分析。结果治疗8周末,与T2DM组比较,UCMSC A组和UCMSC B组大鼠FBG均呈明显下降,其中UCMSC B组明显低于UCMSC A组[(20.0±3.5)比(13.1±1.7)、(7.2±2.2)],P0.05;与T2DM组比较,两个治疗组大鼠INS和C-P水平呈不同程度增高;T2DM组大鼠胰腺组织形态紊乱,仅见少量胰岛细胞团存在,而两个治疗组大鼠胰腺组织形态呈不同程度改善;与T2DM组比较,两个治疗组大鼠胰岛细胞凋亡指数明显降低,以UCMSC B组为甚;与T2DM组比较,两个治疗组大鼠胰腺组织TLR4、NF-κB及IL-6蛋白表达降低,以UCMSC B组为甚,分别为(1.58±0.43)比(1.15±0.27)、(0.96±0.20),(1.06±0.22)比(0.80±0.15)、(0.62±0.10),(0.91±0.10)比(0.77±0.09)、(0.60±0.16),均P0.05。结论多次足量序贯输注干预模式对2型糖尿病大鼠糖代谢和胰岛分泌功能具有较好的改善作用,其机制可能与其下调TLR4/NF-κB炎症通路抑制胰岛β细胞凋亡相关。     

23例1型糖尿病初发患儿免疫学改变与胰岛β细胞功能的关系

目的：观察1型糖尿病（T1DM）初发患儿细胞免疫与胰岛β细胞功能之间的关系。方法：T1DM组23例初发患儿均测定淋巴细胞亚群（T细胞、B细胞及NK细胞）、HbA1c、INS、C-P,正常对照组20例,测定淋巴细胞亚群。结果：T1DM组CD4、CD4/CD8较正常对照组升高（P〈0.05）;CD8、CD3-CD56＋较对照组降低（P〈0.05）;CD4/CD8比值与HbA1c呈正相关（r=0.9451,P〈0.01）,而与INS呈负相关（r=-0.1020,P〈0.01）,与C-P呈负相关（r=-0.6174,P〈0.01）;CD3-CD56＋与HbA1c呈正相关（r=0.1320,P〈0.01）,而与INS呈正相关（r=-0.0846,P〈0.01）,与C-P呈负相关（r=-0.3224,P〈0.01）。结论：T1DM初发患者CD4、CD4/CD8明显增高,CD8、CD3-CD56＋明显降低,提示细胞免疫功能改变与胰岛β细胞功能损伤密切相关。     

胃转流术治疗非肥胖T2DM 术后1 年血糖代谢变化的研究

目的:评价胃转流术(RYGP)治疗非肥胖2型糖尿病(T2DM)的1年血糖代谢变化,并探讨术前T2DM病史对术后1年效果的影响。方法:收集我科2009年6月～2010年4月期间60例行RYGP的非肥胖T2DM患者术前及术后1年内的一般资料,临床及实验室检查数据等。根据T2DM病史分为两组:Ⅰ组:≤5年;Ⅱ组:5-10年,两组体质指数(BMI)均<30 kg/m2。术后6M、12M主要随访:空腹血糖(FPG)、餐后2h血糖(2hPG)、体重、BMI、糖化血红蛋白(HbA1c)、空腹血清胰岛素(Fins)、空腹C肽(C-P)、胰岛素抵抗指数和用药情况,采用SPSS17.0软件进行手术前后对照与组间对照分析。结果:与术前相比,Ⅰ组术后6M、12M时FPG,2hPG,体重,BMI,C-P,HbA1c,Fins均明显改善(P<0.05),HOMA-IR在术后6M无显著差异(P>0.05),术后12M有显著差异(P<0.05);Ⅱ组术后6M、12M时与术前相比,FPG,2hPG,体重,BMI,C-P,HbA1c,HOMA-IR均明显改善(P<0.05),Fins在术后6M、12M与术前相比无显著差异(P>0.05)。Ⅰ组和Ⅱ组于术后6M、12M在FPG、2hPG、体重、BMI、C肽、Fins、HbA1c、HOMA-IR、用药以及手术缓解率方面均无显著差异(P>0.05)。结论:非肥胖T2DM患者胃转流术后1年血糖代谢明显改善,术后完全缓解率逐步增高,术前T2DM病史(≤5年与5-10年)对术后1年效果的影响无显著差异。     

双歧杆菌三联活菌及常规疗法在老年2型糖尿病中的应用观察

目的探讨双歧杆菌三联活菌及常规疗法在老年2型糖尿病中的应用效果。方法选取2017年3月-2019年12月我院老年T2DM患者118例,依据简单随机数字表法分为研究组与对照组,各59例。对照组采取常规治疗,研究组在对照组基础上采取双歧杆菌三联活菌治疗。检测两组治疗前后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2h PG)、糖化血红蛋白(HbA1c)]水平、胰岛功能指标[胰岛素抵抗指数(HOMA IR)、胰岛β细胞功能指数(HOMA β)、空腹胰岛素(FINS)、餐后2 h胰岛素(PINS)]、微炎症状态指标[白介素 1β(IL 1β)、肿瘤坏死因子 α(TNF α)、高敏C 反应蛋白(hs CRP)]、肠道菌群(肠杆菌、酵母菌、乳杆菌、拟杆菌、双歧杆菌)、丙二醛(MDA)、8 异前列腺素F2α(8 iso PGF2α)和不良反应。结果治疗后研究组FPG、2h PG、HbA1c水平低于对照组(P<0.05),HOMA β、FINS、PINS水平高于对照组,HOMA IR水平低于对照组(P<0.05),血清IL 1β、TNF α、hs CRP水平低于对照组(P<0.05),拟杆菌、乳杆菌、双歧杆菌数量高于对照组,酵母菌、肠杆菌数量低于对照组(P<0.05);MDA、8 iso PGF2α水平低于对照组(P<0.05)。研究组不良反应发生率(10.17%)与对照组(6.78%)差异无统计学意义(P>0.05)。结论双歧杆菌三联活菌辅助常规疗法治疗老年T2DM,可改善患者肠道菌群构成,降低血糖水平,改善胰岛β细胞功能,提高胰岛素敏感性,减轻机体微炎症状态,抑制氧化应激反应,安全可靠。     

妊娠期糖尿病孕妇血清CST、humanin、VAP-1与糖脂代谢及胰岛素抵抗的关系研究

目的:探讨妊娠期糖尿病(GDM)孕妇血清皮质醇激素抑制素(CST)、humanin、血管黏附蛋白-1(VAP-1)与糖脂代谢及胰岛素抵抗的关系。方法:选择2017年1月至2019年10月我院妇产科门诊收治的79例GDM患者(GDM组),另选取同期到我院行产检的52例正常妊娠孕妇(NGT组)。检测并比较血清CST、humanin、VAP-1水平,分析CST、humanin、VAP-1与GDM患者糖脂代谢、胰岛素抵抗的相关性,并作二元Logistic回归分析探讨GDM发病的危险因素。结果:GDM组血清CST、humanin、空腹C肽(FC-P)、C-P峰值/FC-P、胰岛素β细胞功能指数[HOMA-β(C-P)]水平低于NGT组(P<0.05),VAP-1、空腹血糖(FPG)、胰岛素抵抗指数[HOMA-IR(C-P)]、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平高于NGT组(P<0.05)。Pearson相关性分析结果显示血清CST水平与FPG、HOMA-IR(C-P)呈负相关(P<0.05),与FC-P、C-P峰值/FC-P、HOMA-β(C-P)呈正相关(P<0.05)。humanin水平与TG、FPG、HOMA-IR(C-P)呈负相关,与FC-P、C-P峰值/FC-P、HOMA-β(C-P)呈正相关(P<0.05)。VAP-1与TG、FPG、HOMA-IR(C-P)呈正相关(P<0.05),与FC-P、C-P峰值/FC-P、HOMA-β(C-P)呈负相关(P<0.05)。二元Logistic回归分析结果显示CST、humanin、HOMA-β(C-P)水平降低,年龄、BMI、LDL-C、VAP-1、HOMA-IR(C-P)水平升高是GDM发病的危险因素(P<0.05)。结论:GDM患者血清CST、humanin水平降低,VAP-1水平升高,三者均参与GDM发病和胰岛素抵抗。CST与糖代谢紊乱有关,humanin、VAP-1与糖脂代谢异常有关。     

短期胰岛素泵强化治疗对2 型糖尿病患者脂糖代谢及胰岛β细胞功能的影响

目的:探讨短期胰岛素泵强化治疗对2型糖尿病患者脂糖代谢及胰岛β细胞功能的影响。方法:选择2013年10月到2015年10月我院收治的2型糖尿病患者86例,随机分为对照组(n=43)和实验组(n=43)。对照组患者给予门冬胰岛素常规治疗,实验组患者给予胰岛素泵强化治疗,两组疗程均为2周。检测并比较两组患者治疗前后血糖、血脂、糖化血红蛋白(Hb A1c)及口服葡萄糖刺激后胰岛β细胞功能指标。结果:治疗后两组患者空腹血糖(FPG)、Hb A1c、总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白胆固醇(LDL-C)、稳态模型评价-胰岛素抵抗(HOMA-IR)较治疗前均明显下降(P0.05),高密度脂蛋白胆固醇(HDL-C)、胰岛素曲线下面积(AUC)、稳态模型评价-胰岛β细胞功能(HOMA-β)及0.5h胰岛素浓度/血糖浓度(I30/G30)较治疗前明显升高(P0.05),且实验组患者以上各指标变化均优于对照组(P0.05)。结论:短期胰岛素泵强化治疗能明显纠正2型糖尿病患者血糖、血脂水平,改善胰岛β细胞功能,值得在临床上推广应用。     

西红花水提物对实验性糖尿病小鼠血糖水平的影响

目的：观察西红花水提物对链脲佐菌素（STZ）诱导的糖尿病小鼠血糖、血脂及胰腺组织的影响。方法：采用STZ （60 mg/kg）连续2 d腹腔注射建立糖尿病小鼠模型。将造模成功后的小鼠随机分为3组（n=10）：糖尿病模型（DM）组、西红花水提物（SE）组、阳性对照二甲双胍（MH）组。另取10只正常小鼠设为正常对照（NC）组。给药组每天灌胃1次,连续6周,模型组和正常对照组灌胃生理盐水。给药期间每周测定小鼠进食量、饮水量及体重,给药6周后测定空腹血糖（FBG）、口服糖耐量（OGTT）、糖化血清蛋白（GSP）、血清胰岛素（INS）和血脂等指标的变化情况;HE染色观察胰腺组织病理变化。结果：与NC组相比,DM组进食量、饮水量、线下曲线面积、FBG、GSP以及血脂中的总胆固醇（TC）均显著升高,空腹体重、血清胰岛素（INS）及高密度脂蛋白胆固醇（HDL-c）均显著降低;与DM组相比,SE组小鼠饮水量、FBG、线下曲线面积、TC显著降低,HDL-c以及INS显著升高。病理学显示DM组胰岛结构破坏、胰岛细胞数量明显减少、胰岛血管增生、形态不规则等变化,SE能明显修复受损胰腺组织。结论：SE对链脲佐菌素诱导的糖尿病小鼠有一定降血糖、降血脂作用,可以有效改善胰腺病变的情况,提示西红花可能用于糖尿病的防治。     

替米沙坦对2 型糖尿病合并高血压患者胰岛β 细胞功能影响 的临床观察

目的:观察替米沙坦对糖尿病合并高血压患者胰岛β细胞功能的影响,探索血管紧张素Ⅱ阻断剂降压以外的胰岛功能修复作用.方法:70例糖尿病合并轻、中度高血压的患者随机分为替米沙坦治疗组和氨氯地平治疗组,每组35例患者;替米沙坦治疗组在控制血糖的治疗上给予替米沙坦进行降压治疗;氨氯地平治疗组在控制血糖的治疗上给予氨氯地平进行降压治疗;两组的观察周期均12周,每2周观察1次血压、空腹血糖、并记录低血糖及其它不良反应.治疗前后测糖化血红蛋白(HbAlc)、餐后2小时血糖,并按照HOMA稳态模型公式计算胰岛β细胞功能指数(HOMA-β)和胰岛素抵抗指数(HOMA-IR).结果:两组患者在降压效果方面无显著性差异,收缩压、舒张压对比,P＞0.05;与氨氯地平组比较,替米沙坦组胰岛素峰值和HOMA-3显著升高,HOMA-IR则显著降低.结论:替米沙坦可更显著改善糖尿病合并高血压的患者的胰岛β细胞功能,具有降压以外的改善胰岛细胞功能的作用.     

短期胰岛素泵强化治疗对2型糖尿病患者血清C-反应蛋白水平的影响

目的:通过比较短期胰岛素泵持续皮下胰岛素输注(CSⅡ)治疗前后初诊2型糖尿病(T2DM)患者血清C反应蛋白(C-reactive protein,CRP),胰岛素抵抗水平(Insulin Resistance,IR)和胰岛β细胞功能(β-cell function)的变化,评价CSⅡ对初诊T2DM患者CRP的改善情况.方法:对空腹血糖(FPG)＞13mmol/L或餐后两小时血糖＞15 mmol/L的初诊T2DM患者63例(男33例,女30例)行为期2周的CSⅡ治疗,并于治疗前后测定血清CRP、FPG、空腹胰岛素(FINS)、餐后两小时血糖(2hPG),对各指标进行分析.结果:1.治疗后CRP和HOMA-IR明显低于治疗前,差异均有统计学意义(P＜0.01).2.治疗后HOMA-β明显高于治疗前,差异有统计学意义(P＜0.01).3.CRP水平与FPG(r=0.26,P＜0.05),HOMA-IR(r=0.21,P＜0.05)呈正相关.结论:对伴有明显高血糖的初诊T2DM患者,CSⅡ治疗可以改善CRP水平和胰岛素抵抗.     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Synthesis and antimicrobial studies of hydrazone derivatives of 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid and 4-[3-(3,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78?µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.

     

Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).