输精管结扎对家兔心功能及心肌NE含量的影响

本实验用日本大耳白兔复制输精管结扎的长期动物模型，分为结扎２５月组（ＶＧ２５），同龄假手术２５月组（ＳＯＧ２５）；结扎６月组（ＶＧ６），同龄假手术６月组（ＳＯＧ６）。记录各组家兔心功能，检测心肌及血清ＮＥ含量，称取心重（ＷＨ）。结果表明，左心室收缩期末压（ＬＶＳＰ），ＶＧ略高于ＳＯＧ；左心室舒张末压（ＬＶＥＤＰ），Ｖ６２５显著的低于ＳＯＧ２５Ｐ＜０．０５），ＶＧ６与５ＯＧ６比较虽无显著差异，也呈低值；±ｄｐ／ｄｔｍａｘ，ＶＧ均明显高于ＳＯＧ（Ｐ＜０．０１）。相关检验表明，＋ｄｐ／ｄｔｍａｘ与血清及心肌ＮＥ含量无相关性；心重与＋ｄｐ／ｄｔｍａｘ呈明显正相关，Ｐ＜０．０５；在２５月组，ＬＶＳＰ与＋ｄｐ／ｄｔｍａｘ呈正相关，Ｐ＜０．０５。提示输精管结扎可提高心肌收缩功能。     

Pygmaeoherin: A Novel Coumarin from Pygmaeopremna herbacea

A new 6-oxygenated coumarin, pygmaeoherin, was isolated from roots of PYGMAEOPREMNA HERBACEA. Its structure was determined by spectroscopic methods. An NOE experiment played an important role in confirming the structure.     

中性粒细胞/淋巴细胞比值对冠状动脉旁路移植术后心肌损伤的影响

探讨患者术前中性粒细胞/淋巴细胞比值（NLR）对非体外循环下冠状动脉旁路移植术（OPCABG）后心肌损伤以及临床预后的影响。方法 选取2014年1月—2019年12月我院收治的314名行OPCABG的患者,依据患者术前NLR的三分位数分为高比值组（NLR＞2.8,n=102）、中比值组（2.8≥NLR≥1.6,n=106）以及低比值组（NLR＜1.6,n=106）。分别检测患者术前基线、术后8 h及术后24 h肌酸激酶同工酶（CKMB）及肌钙蛋白（CTnI）水平。结果 高比值组患者术后心肌损伤发生率显著高于中比值组及低比值组（P＜0.05）。高比值组术后CKMB峰值显著高于中比值组［2.1(1.2～13.0) ng/mL vs2.0(1.0～7.3) ng/mL, P=0.047］及低比值组［2.1(1.2～13.0) ng/mL vs1.1(0.9～1.6) ng/mL, P＜0.001］。且高比值组患者术后CTnI峰值同样显著高于中比值组［0.075(0.010～0.185) ng/mL vs 0.020(0.000～0.103) ng/mL, P=0.011］,以及低比值组［0.075(0.010～0.185) ng/mL vs0.010(0.000～0.030) ng/mL, P＜0.001］。术前NLR较高是术后患者CTnI升高的独立危险因素（OR：2.809; 95%CI:1.326～5.954; P=0.007）。高比值组患者1年不良心血管事件发生率显著高于中比值组及低比值组（HR：1.80; 95%CI:1.16～2.79; Log Rank P=0.021）。结论 患者术前中性粒细胞/淋巴细胞比值升高是非体外循环冠状动脉旁路移植术后心肌损伤的独立危险因素,而且会增加患者不良心血管事件     

多囊性肾脏发育不良胎儿的遗传学病因、影像学表现及妊娠结局分析

目的 探究多囊性肾脏发育不良胎儿的遗传学病因、影像学表现及妊娠结局。方法 回顾性分析2017年5月—2023年5月扬州大学附属淮安市妇幼保健院收治的80例多囊性肾脏发育不良胎儿的临床资料,分析其遗传学病因、影像学表现及妊娠结局。结果 80例多囊性肾脏发育不良胎儿中检出11例（13.75%）染色体异常,其中染色体数目异常1例（1.25%）,10例（12.50%）存在染色体拷贝数变异（CNV）。80例多囊性肾脏发育不良胎儿中,39例（48.75%）为左侧多囊性发育不良肾,37例（46.25%）为右侧多囊性发育不良肾,剩余4例（5.00%）为双侧多囊性发育不良肾;单纯泌尿系统异常64例（80.00%）,合并其他系统异常16例（20.00%）,以心血管系统异常（8例）、肢体骨骼异常（3例）和、神经系统异常（3例）最常见。单纯性泌尿系统异常胎儿、合并其他系统异常胎儿的致病性CNV检出率分别为10.94%（7/64）和12.50%（2/16）,差异无统计学意义（P >0.05）。单纯性泌尿系统异常胎儿中,单侧多囊性发育不良胎儿、双侧多囊性发育不良胎儿的致病性CNV检出率分别为9.84%（6/61）和33.33%（1/3）,差异无统计学意义（P >0.05）。对80例多囊性肾脏发育不良胎儿进行随访,失访8例（10.00%）,人工终止妊娠31例（38.75%）,胎死宫内0例（0.00%）,活产41例（51.25%）,其中产后死亡1例（1.25%）。结论 多囊性肾脏发育不良胎儿采用染色体微阵列分析技术可提高遗传学检出率,影像学检查在多囊性肾脏发育不良诊断中具有一定价值,可为多囊性肾脏发育不良胎儿的产前诊断、遗传咨询、预后评估提供依据。     

GALC transduction leads to morphological improvement of the twitcher oligodendrocytes in vivo

Globoid cell leukodystrophy (GLD, Krabbe disease) is a severe demyelinating disease caused by a genetic defect of beta-galactocerebrosidase (GALC). To date treatment to GLD is limited to hematopoietic stem cell transplantation. Experimental approaches by means of gene therapy in twitcher mouse, an authentic murine model of human GLD, showed significant but only marginal improvements of the disease. To clarify whether the introduction of GALC could provide beneficial effects on the oligodendrocytes in GLD, we transduced twitcher oligodendrocytes by stereotactically injecting recombinant retrovirus encoding GALC-myc-tag fusion gene into the forebrain subventricular zone of neonatal twitcher mouse. In vivo effects of exogenous GALC on twitcher oligodendrocytes were studied histologically by combined immunostaining for the myc-epitope and the oligodendroglial specific marker, pi form of glutathione-S-transferase, at around 40 days of age. We show here that GALC transduction led to dramatic morphological improvement of the twitcher oligodendrocytes comparing with those in untreated twitcher controls. This study provided direct in vivo evidence that GALC transduction could prevent or correct aberrant morphology of oligodendrocytes in GLD which may be closely related to the dysfunction and/or degeneration of oligodendrocytes and the demyelination in this disease.     

Causal relationship between conformational change and inhibition of domain functions of glycoxidative fibronectin

Glycoxidative modification of various body proteins, including fibronectin (FN), has been shown to change their structural and functional properties, and be implicated in pathogenesis of diabetic complications. Little is known about the role of secondary structure of glycoxidative FN (gFN) in its domain functions. gFN was prepared by incubation with 25 and 200 mM glucose in 0.2 M sodium phosphate buffer at 37 degrees C on a shaking plate under aerobic and sterile conditions for various time intervals up to 49 days, being defined as gFN25 and gFN200, respectively. Unmodified FN (uFN) was prepared by incubation in 0.2 M sodium phosphate buffer without any glucose at 4 degrees C for 49 days. The extent of glycoxidative modification was examined using a noncompetitive enzyme-linked immunosorbent assay with an antibody against N(epsilon) -(carboxymethyl)lysine (CML), one of the major glycoxidation products. The binding activities of uFN and gFN to collagen, gelatin and heparin were determined by a solid phase enzyme immunoassay or heparin-affinity HPLC. Cell attachment was estimated by the extent of adhesion of FITC-labeled smooth muscle cells to uFN or gFN. Conformational change in gFN was detected by SDS-polyacrylamide gel electrophoresis and spectroscopy (circular dichroism). CML was detected in gFN25 and gFN200 after 49 and 21 days of incubation, respectively. Levels of CML were about six-fold higher in gFN200 than in gFN25 after 49 days. Both gFN25 and gFN200 showed a significant decrease in the ability of binding to collagen and gelatin after 7 days of incubation. The binding activity for heparin was significantly decreased in both gFN25 and gFN200 after one day. Cell attachment activity was reduced to 89% and 76% of the unmodified form in both gFN25 and gFN200 after 49 days, respectively. High molecular weight materials were found in gFN25 and gFN200 after 21 and 7 days, respectively. CD spectrum showed that gFN25 had lost its native conformation after 3 days of incubation, depending upon the concentration and incubation interval of the applied glucose. These in vitro results suggest that the loss of native conformation may reduce the domain functions of gFN, including binding activity to macromolecular ligands and cell attachment, and may play a major role in the pathogenesis of diabetic complications.     

多脏器恶性肿瘤术后肝黏膜相关淋巴组织淋巴瘤

目的 探讨肝黏膜相关淋巴组织淋巴瘤的临床病理特征。方法 对1例罕见多脏器恶性肿瘤术后肝黏膜相关淋巴瘤病例结合文献进行临床、病理和免疫组化分析。结果 患者于8年和3年前先后发生胃恶性间质瘤、阴囊阴茎皮肤湿疹样癌，有长期化疗史。肿瘤组织学以单核样B细胞为主，并有淋巴滤泡和淋巴上皮病变形成。免疫表型示瘤细胞CD45、CD79α、CD20阳性，CD5、CD10、ALK、TdT阴性，bcl—2、Ki—67少数肿瘤细胞阳性。结论 肝黏膜相关淋巴瘤可以发生于多脏器恶性肿瘤术后，其发病可能与长期使用免疫抑制剂有关，诊断本病时需与肝继发性淋巴瘤及肝的炎性假瘤鉴别。     

Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.     

Characterization of Hprt mutations in cDNA and genomic DNA of T-cell mutants from control and 1,3-butadiene-exposed male B6C3F1 mice and F344 rats

A multiplex PCR procedure for analysis of genomic DNA mutations in the mouse hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene was developed and then used with other established methods for the coincident identification of large- and small-scale genetic alterations in the Hprt gene of mutant T-cell isolates propagated from sham- and 1,3-butadiene (BD)-exposed mice and rats. The spectra data for RT-PCR/cDNA analysis and multiplex PCR of genomic DNA from Hprt mutants were combined, and statistical analyses of the mutant fractions for the classes of mutations identified in control versus exposed animals were conducted. Under the assumption that the mutant fractions are distributed as Poisson variates, BD exposure of mice significantly increased the frequencies of (1) nearly all types of base substitutions; (2) single-base deletions and insertions; and (3) all subcategories of deletions. Significantly elevated fractions of G:C-->C:G and A:T-->T:A transversions in the Hprt gene of BD-exposed mice were consistent with the occurrence of these substitutions as the predominant ras gene mutations in multiple tumor types increased in incidence in carcinogenicity studies of BD in mice. BD exposure of rats produced significant increases in (1) base substitutions only at A:T base pairs; (2) single-base insertions; (3) complex mutations; and (4) deletions (mainly 5' partial and complete gene deletions). Future coincident analyses of large- and small-scale mutations in rodents exposed to specific BD metabolites should help identify species differences in the sources of deletion mutations and other types of mutations induced by BD exposures in mice versus rats.