Hypercalcemia Associated with the Ectopic Expression of 25-hydroxyvitamin D3-1α-hydroxylase in Diffuse Large B-cell Lymphoma

An 82-year-old man was transferred to our hospital due to impaired consciousness. His albumin-corrected calcium level was 14.2 mg/dL, intact parathyroid hormone (PTH) and PTH-related protein levels were reduced, and his 1,25-dihydroxyvitamin D [1,25(OH)₂VitD] level was elevated at 71.5 pg/mL. Computed tomography revealed masses on the bilateral ribs. The mass on the rib was biopsied and diagnosed as diffuse large B-cell lymphoma (DLBCL). Immunostaining of the biopsy sample with the anti-CYP27B1 antibody revealed the ectopic expression of 1α-hydroxylase in the lesion. We herein report a rare case of hypercalcemia induced by the overproduction of 1,25(OH)₂VitD in DLBCL ectopically expressing 1α-hydroxylase.     

肝细胞癌患者肝组织中JAB1和P27kip1的表达变化及其临床意义

目的 研究肝细胞癌（HCC）组织中c-Jun激活域连接蛋白1（c-Jun activation domain binding protein 1,JAB1）的表达及与P27kip1(P27)间的关系,探讨JAB1与临床病理及预后的关系。方法 免疫组化检测HCC及 相应癌旁肝组织中JAB1和P27的表达。Western blot及免疫沉淀检测JAB1和P27的表达及相互作用。结果 HCC中,JAB1的表达高于癌旁肝组织,P27表达低于癌旁组织。JAB1的表达与组织分化程度、AFP值及转移相关（P<0.05）。HCC中JAB1与P27的表达呈负相关(r=－0.7077, P<0.001),并且能免疫共沉淀。结论 JAB1的表达与P27负相关,JAB1作为P27的负性调控因子,可能与HCC的恶性进展及预后相关。     

应用于新生儿缺氧缺血性脑病的脑电背景分析新方法

目的探讨一种新的新生儿缺氧缺血性脑病（hypoxic-ischemic encephaloapthy，HIE）脑电背景评价方法，以及其与临床分度和头部磁共振成像（magnetic resonance imaging，MRI）分度的关系。方法回顾性分析2016年1月—2022年8月诊断为HIE患儿的出生24 h内视频脑电图（video electroencephalography，vEEG）和同步振幅整合脑电图（amplitude-integrated electroencephalography，aEEG）的监测资料。将脑电背景分析有关项目全部纳入评估系统，按严重程度分层赋分，汇总得到脑电图（electroencephalography，EEG）总分。对EEG总分与头部MRI总分和Sarnat总分（total Sarnat score，TSS；用于评估临床分度）做相关分析。比较不同临床分度组和不同头部MRI分度组间EEG总分是否存在差异。采用受试者工作特征曲线的曲线下面积（area under the curve，AUC）评估EEG总分法对头部MRI中-重度异常和临床中-重度异常的诊断价值，并与aEEG分度法相比较。结果共收集50例HIE患儿。EEG总分与头部MRI总分、TSS均呈正相关（分别r_s =0.840、0.611，P<0.001）。不同临床分度组和不同头部MRI分度组间EEG总分比较差异均有统计学意义（P<0.05）。EEG总分法和aEEG分度法判断头部MRI中-重度异常的AUC分别为0.936和0.617（P<0.01），判断临床中-重度异常的AUC分别为0.887和0.796（P>0.05）。界定EEG总分≤6分、7~13分、≥14分分别为EEG轻度、中度和重度异常，与临床分度和头部MRI分度一致性最佳（P<0.05）。结论新的脑电背景评分方法可以定量化反映脑损伤的严重程度，适用于新生儿HIE的脑功能判断。     

27‐gauge microincision vitrectomy surgery compared with 25‐gauge microincision vitrectomy surgery on wound closure and need for wound suture and other postoperative parameters in the treatment of vitreoretinal disease: A meta‐analysis

We performed a meta‐analysis to evaluate the effect of 27‐gauge microincision vitrectomy surgery compared with 25‐gauge microincision vitrectomy surgery on wound closure and the need for wound suture and other postoperative parameters in the treatment of vitreoretinal disease. A systematic literature search up to June 2022 was performed and 1264 subjects with the vitreoretinal disease at the baseline of the studies; 562 of them were using the 27‐gauge microincision vitrectomy surgery, and 722 were using 25‐gauge microincision vitrectomy surgery. Odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of 27‐gauge microincision vitrectomy surgery compared with 25‐gauge microincision vitrectomy surgery on wound closure and the need for wound suture and other postoperative parameters in the treatment of vitreoretinal disease using the dichotomous, and contentious methods with a random or fixed‐effect model. The 27‐gauge microincision vitrectomy surgery subjects had a significantly lower intraoperative and postoperative wound complication (OR, 6.66; 95% CI, 0.46‐0.95, P = .02), and wound suture number (OR, 0.38; 95% CI, 0.20‐0.71, P = .002), and best corrected visual acuity (MD, −0.03; 95% CI, −0.05 to −0.001, P = .02) compared with 25‐gauge microincision vitrectomy surgery in subjects with vitreoretinal disease. However, 27‐gauge microincision vitrectomy surgery subjects had no significant difference in the wound closure time (MD, −8.45; 95% CI, −23.44 to 6.55, P = .27), operation time (MD, 0.85; 95% CI, −1.17 to 2.86, P = .41), intraocular pressure at postoperative day 1 (MD, 0.42; 95% CI, −1.45‐2.28, P = .66), primary anatomical success rate (OR, 0.83; 95% CI, 0.42‐1.63, P = .58), and central macular thickness (MD, 1.81; 95% CI, −21.76 to 25.37, P = .88) compared to 25‐gauge microincision vitrectomy surgery in subjects with vitreoretinal disease. The 27‐gauge microincision vitrectomy surgery subjects had a significantly lower intraoperative and postoperative wound complication, wound suture number, and best corrected visual acuity, and no significant difference in the wound closure time, operation time, intraocular pressure at postoperative day 1, primary anatomical success rate, and central macular thickness compared to 25‐gauge microincision vitrectomy surgery in subjects with vitreoretinal disease. The analysis of outcomes should be with caution because of the low sample size of 12 out of 15 studies in the meta‐analysis and a low number of studies in certain comparisons.     

增殖细胞核抗原和p53蛋白在胆囊癌中的表达

本文应用PCNA和p53抑癌基因蛋白的免疫络化方法，对11例胆囊上皮良性病变和33例胆囊癌进行了研究，结果发现胆囊良性病变和胆囊癌的平均PCNA指数分别为：良性病变为24．1％（n＝11．x±24．6），高分化癌为48．0％（n＝13，x±12．8），中分化癌为49．5％（n＝11，x±15．4）．低分化癌为76．4％（n＝9，x±18．1）；高分化胆囊癌平均PCNA指数明显高于良性病变（P＜0．05）；低分化癌的平均PCNA指数明显高于高分化癌（P＜0．05）；11例胆囊上皮良性病变均无p53蛋白阳性表达；33例胆囊癌p53阳性表达12例（36．4％），高分化癌p53阳性率为15．4％（2／13）．中分化癌45．5％（5／11）．低分化癌55．6％（5／9）：各组阳性率比较无显著性差异（P＞0．05）；PCNA指数≥50％的胆囊癌其p53蛋白阳性率明显高于PCNA指数＜50％的胆囊癌（P＜0．05）。结果提示：PCNA指数与胆囊癌的分化程度有关．PCNA及p53蛋白的免疫组化染色对胆囊上皮良、恶性病变的鉴别论断有帮助。本文还就胆囊癌p53蛋白表达与PCNA指数的关系进行了讨论。     

158例非小细胞肺癌中3p25杂合性丢失研究

目的　探讨非小细胞肺癌组织 (NSCLC)中 3p2 5位点上等位基因的杂合性丢失 (LOH)与肺癌发生、发展的相关性。方法　采用银染聚合酶链反应结合二核苷酸 (CA)n重复程序出现多态性评价LOH ,分析 1 58例NSCLC癌组织中 3p2 5等位基因的LOH。结果　 1 58例NSCLC组织中 80例出现 3p2 5LOH ,总的杂合性丢失率为 50 .6%。腺癌组织中 3p2 5杂合性丢失率为 62 .0 % ,鳞癌为 43 .2 % ,两者间差异有显著性 (P <0 .0 5)。 3p2 5LOH与NSCLC临床分期关系不明显 ,Ⅰ、Ⅱ及Ⅲ期分别为 52 .2 %、45.0 %及 52 .8% ,4例良性肺肿瘤和 5例正常胎儿肺组织均未出现 3p2 5LOH。结论　本研究结果表明 3p2 5LOH在NSCLC中普遍存在 ,从而说明 3p2 5位点处可能存在着某些与肺癌发生、发展有关的抑癌基因     

Rb基因和p53基因表达与胃癌预后的关系

目的　探讨Rb基因和p53基因表达与胃癌临床病理学特点及预后的关系。　方法　采用原位杂交和免疫组织化学技术对85例进展期胃癌切除标本中Rb基因和p53基因产物表达和p53基因突变进行检测和分析。　结果　p53基因突变率为30%(6/20);Rb基因和p53基因产物表达为7294%(62/85)和4941%(42/85),其阳性分级与胃癌术后生存期呈显著相关(P<001和P<005),与淋巴结转移呈显著正相关(P<001),后者还与浸润深度呈显著正相关(P<005)。　结论　Rb基因和p53基因表达与淋巴结转移、浸润深度和胃癌术后生存期有关     

A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells

Background

Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.

Methods

P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.

Results

The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.

Conclusions

Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.