Hippocampal size may contribute to prospective diagnosis of age-related dementia

Background: The hippocampus is a center of cognitive function and therefore hippocampal atrophy is the major factor in cognitive decline. Analysis of hippocampal size may make it possible to predict progression in cognitive impairment. To address this point, the present study investigated the relationship between hippocampal atrophy and dementia using magnetic resonance (MR) images and the Hasegawa Dementia Scale‐Revised (HDS‐R). Methods: The present study was performed on 274 subjects (14–97 years old; average, 66 years; 106 male and 168 female) who had no focal neurological deficit. Hippocampal area and whole brain area were measured in three series of coronal MR images taken from a 5‐mm slice rostrally along dorsal edge of the pons, and hippocampal size normalized by calculating summated hippocampal areas as percentages of summated whole brain areas. Dementia was screened for using HDS‐R. Results: Hippocampal size decreased and HDS‐R reduced with age. Hippocampal atrophy was highly correlated with cognitive deterioration; a critical normalized hippocampal size for HDS‐R of less than 20, which corresponds with mild cognitive impairment and dementia, was found in 65% of over 60‐years old subjects and 98% of subjects with HDS‐R of less than 20 were over 60 years old. Conclusion: There is a high probability that over 60‐year‐old people with a normalized hippocampal size of less than 1.0 would develop dementia in the future, even though their HDS‐R might presently be over 20. Measurement of hippocampal size with coronal MR imaging may therefore contribute to prospective diagnoses of age‐related dementia.     

从调理脾胃升降之枢论治糖尿病

糖尿病的发生，发展及其发症的发生均与脾胃功能失调有密切关系，对糖尿病的治疗，必须从调理脾胃着手，以健脾和胃为基本法则，主要从脾胃失调是糖尿病发生的基本病机，脾胃失调是糖尿病发展的病理根源，糖尿病从调理脾胃进行辨证施治等方面进行了论述。     

Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma

Podoplanin, a mucin-like transmembrane sialoglycoprotein, promotes platelet aggregation and may be involved in cancer cell migration, invasion, metastasis, and malignant progression. Podoplanin/aggrus is highly expressed in testicular seminoma, suggesting that it may be a sensitive marker for testicular seminomas. Here we investigated the expression of podoplanin in central nervous system (CNS) germ cell tumors (GCTs) by immunohistochemical staining of tumor samples from 62 patients. In 40 of 41 (98%) germinomas (including germinomatous components in mixed GCTs), podoplanin was diffusely expressed on the surface of germinoma cells; lymphocytes, interstitial cells, and syncytiotrophoblastic giant cells were negative for podoplanin. Except for immature teratomas (12/17; 71%), podoplanin expression was absent in non-germinomatous GCTs, including seven teratomas, seven embryonal carcinomas, seven yolk sac tumors, and seven choriocarcinomas. In immature teratomas, focal podoplanin staining was observed in fewer than 10% of immature squamous and columnar epithelial cells. Thus, podoplanin expression may be a sensitive immunohistochemical marker for germinoma in CNS GCTs. As such, it may be useful for diagnosis, for monitoring the efficacy of treatment, and as a potential target for antibody-based therapy.Kazuhiko Mishima and Yukinari Kato contributed equally to this work.     

Lenvatinib in combination with golvatinib overcomes hepatocyte growth factor pathway‐induced resistance to vascular endothelial growth factor receptor inhibitor

Vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for the treatment of several tumor types; however, some tumors show intrinsic resistance to VEGFR inhibitors, and some patients develop acquired resistance to these inhibitors. Therefore, a strategy to overcome VEGFR inhibitor resistance is urgently required. Recent reports suggest that activation of the hepatocyte growth factor (HGF) pathway through its cognate receptor, Met, contributes to VEGFR inhibitor resistance. Here, we explored the effect of the HGF/Met signaling pathway and its inhibitors on resistance to lenvatinib, a VEGFR inhibitor. In in vitro experiments, addition of VEGF plus HGF enhanced cell growth and tube formation of HUVECs when compared with stimulation by either factor alone. Lenvatinib potently inhibited the growth of HUVECs induced by VEGF alone, but cells induced by VEGF plus HGF showed lenvatinib resistance. This HGF‐induced resistance was cancelled when the Met inhibitor, golvatinib, was added with lenvatinib. Conditioned medium from tumor cells producing high amounts of HGF also conferred resistance to inhibition by lenvatinib. In s.c. xenograft models based on various tumor cell lines with high HGF expression, treatment with lenvatinib alone showed weak antitumor effects, but treatment with lenvatinib plus golvatinib showed synergistic antitumor effects, accompanied by decreased tumor vessel density. These results suggest that HGF from tumor cells confers resistance to tumor endothelial cells against VEGFR inhibitors, and that combination therapy using VEGFR inhibitors with Met inhibitors may be effective for overcoming resistance to VEGFR inhibitors. Further evaluation in clinical trials is warranted.     

miRNA-15b和成纤维细胞生长因子2(FGF2)在增生型糖尿病视网膜病变患者玻璃体及视网膜增生膜组织中的表达

目的探讨增生型糖尿病视网膜病变(PDR)患者玻璃体、视网膜增生膜组织中miRNA-15b(miR-15b)和成纤维细胞生长因子2(FGF2)的表达情况,并进行相关性研究,初步探讨PDR发生原因。方法选取2016年9月至2019年10月期间在重庆市开州区人民医院眼科住院的PDR患者80例(80眼)作为PDR组,收集其玻璃体及视网膜增生膜组织;选取同期因眼外伤在本院眼科行眼球摘除术的2型糖尿病患者21例(21眼)作为对照组,收集其玻璃体及视网膜组织;通过实时荧光定量聚合酶链式反应(qRT-PCR)法检测玻璃体及视网膜组织/视网膜增生膜组织中miR-15b水平,分别通过酶联免疫吸附法(ELISA)、Western blot法检测玻璃体、视网膜组织/视网膜增生膜组织中FGF2蛋白水平表达;通过Pearson相关性分析法分析对照组玻璃体及视网膜组织以及PDR组患者玻璃体及视网膜增生膜组织中miR-15b与FGF2水平相关性;通过二元Logistic回归分析影响糖尿病患者发生PDR的危险因素。结果 PDR组糖尿病病程显著长于对照组(P<0.001)。PDR组玻璃体及视网膜增生膜组织中miR-...     

Polymerization Contraction Stress of Resin Composite Restorations in a Model Class I Cavity Configuration Using Photoelastic Analysis

Purpose: An important factor that contributes to deterioration of resin composite restorations is contraction stress that occurs during polymerization. The purpose of this article is to familiarize the clinician with the characteristics of contraction stress by visualizing the stresses associated with this invisible and complex phenomenon. Materials and Methods: Internal residual stresses generated during polymerization of resin composite restorations were determined using micro‐photoelastic analysis. Butt‐joint preparations simulating Class I restorations (2.0 mm ± 5.0 mm, 2.0 mm in depth) were prepared in three types of substrates (bovine teeth, posterior composite resin, and transparent composite resin) and were used to examine contraction stress in and around the preparations. Three types of composite materials (a posterior composite, a self‐cured transparent composite, and a light‐cured transparent composite) were used as the restorative materials. The self‐cured composite is an experimental material, and the others are commercial products. After treatment of the preparation walls with a bonding system, the preparations were bulk‐filled with composite. Specimens for photo‐elastic analysis, were prepared by cutting sections perpendicular to the long axis of the preparation. Fringe patterns for directions and magnitudes of stresses were obtained using transmitted and reflected polarized light with polarizing microscopes. Then, the photoelastic analysis was performed to examine stresses in and around the preparations. Results: When cavity preparations in bovine teeth were filled with light‐cured composite, a gap was formed between the dentinal wall and the composite restorative material, resulting in very low stress within the restoration. When cavity preparations in the posterior composite models were filled with either self‐cured or light‐cured composite, the stress distribution in the two composites was similar, but the magnitude of the stress was greater in the light‐cured material. When preparations in the transparent composite models were filled with posterior composite and light‐cured transparent composite material, significant stress was generated in the preparation models simulating tooth structure, owing to the contraction of both restorative materials. CLINICAL SIGNIFICANCE Polymerization contraction stress is an undesirable and inevitable characteristic of adhesive restorations encountered in clinical dentistry that may compromise restoration success. Clinicians must understand the concept of polymerization contraction stress and realize that the quality of composite resin restorations depends on successful management of these stresses.     

糖尿病视网膜病变玻璃体切割术前康柏西普玻璃体腔注射时机对VEGF表达水平和视力恢复的影响

目的：探讨糖尿病视网膜病变（DR）玻璃体切割术前康柏西普玻璃体腔注射时机对新生血管膜血管内皮生长因子（VEGF）表达水平及患者视力恢复的影响。方法：前瞻性临床研究。将2015 年5 月至2017 年5 月重庆市开州区人民医院眼科收治的109 例DR患者按随机数余数法分为A组（32 例）、B组（43 例）、C组（34 例），3 组均行玻璃体切割术，A组术前不予玻璃体腔内注射康柏西普，B组术前3 d术眼玻璃体腔注射康柏西普，C组术前5 d术眼玻璃体腔注射康柏西普，观察3 组手术情况，记录手术时间、术中出血量及医源性裂孔发生情况，所有患者术中留取视网膜下新生血管膜标本，测定VEGF表达水平；观察各组并发症发生率，比较手术前后不同时间患者最佳矫正视力（BVCA）的变化情况。 数据采用单因素方差分析进行比较。结果：B、C组手术时间及术中出血量均少于A组（P<0.05），术中电凝止血率、医源性视网膜裂孔率均低于A组，术后玻璃体内出血发生率较A组低（P<0.05），术后角膜水肿、高眼压、前房炎性反应发生率均低于A组（P<0.05），但B、C组组间比较差异无统计学意义（P>0.05）。B、C组新生血管膜VEGF阳性率低于A组，但B、C组组间比较差异无统计学意义（P>0.05）。术后3、6个月，3组BCVA均上升（P<0.05），B、C组术后3、6个月BCVA高于A组（P<0.05），但组间比较差异无统计学意义（P>0.05）。结论：DR患者术前玻璃体腔内注射康柏西普均可缩短手术时间，降低术中、术后并发症发生率，降低新生血管膜VEGF表达水平，促进患者术后视力恢复，但术前3 d或5 d注射效果并无明显差别。     

Respiratory inhibition after crying in infants

BACKGROUND: Among full-term neonates, the authors discovered infants who showed respiratory inhibition after crying which involved a marked decrease in SpO2. The infants were found to present increased echogenicity or a cyst in a cranial region termed the ganglionic eminence, or to have a subependymal cyst. The authors prospectively examined the relationship between respiratory inhibition after crying and these changes to examine the prevention and treatment of the episode. METHODS: The authors conducted cranial ultrasonography to screen 381 full-term neonates who showed no abnormalities at birth and whose parents requested ultrasonographic screening of the head, followed by polygraphy of infants who showed increased echogenicity or a cyst in ganglionic eminence, or had a subependymal cyst. The authors similarly conducted polygraphy for 50 neonates without cranial ultrasound abnormalities; the former constituted the control group. Respiratory inhibition was defined to be central apnea immediately after crying with a decrease in SpO2 to <60%. RESULTS: Among 381 neonates examined, 104 showed cranial ultrasound abnormalities; 60 of the 104 neonates indicated respiratory inhibition after crying. Oxygenation failed to improve the episode in 17 neonates with severe respiratory inhibition. However, theophylline alleviated the episode, and SpO2 no longer decreased to <60%. Theophylline was discontinued successfully by 6 months after birth, while 50 neonates in the control group showed no respiratory inhibition after crying. CONCLUSION: Respiratory inhibition after crying which involved a marked decrease in SpO2 was observed in full-term neonates who showed no abnormalities after birth. These neonates could be screened by cranial ultrasonography.     

Normal values for KL-6 in cord venous plasma of neonates

BACKGROUND: KL-6 in umbilical cord blood, including from premature infants, and perinatal factors that may affect these values have not yet been adequately discussed. The authors investigated factors affecting cord venous plasma levels of KL-6 in neonates, and to establish a normal range of values for KL-6 in neonatal cord blood. METHODS: Cord plasma levels of KL-6 were measured in 75 neonates, and statistical analysis of factors affecting these levels was performed. A normal range for cord plasma KL-6 levels was calculated by statistical analysis methods based on guidelines by the National Committee for Clinical Laboratory Standards. RESULTS: Data from a total of 75 neonates was analyzed. Gestational age ranged from 25 to 40 weeks (median, 33.4 weeks), and birthweight ranged from 776 to 3760 g (median, 1944 g). There was no statistically significant correlation between cord plasma KL-6 levels with gender, gestational age, birthweight, method of delivery, Apgar score 1 min, and postnatal respiratory distress. The normal range of values for cord plasma KL-6 was 44.3-148.2 U/mL (median, 73.0 U/mL). CONCLUSION: The cord plasma levels of KL-6 were about half the normal values reported in children and healthy adults and were not affected by various perinatal factors. The authors' findings suggest that plasma KL-6 levels rise when respiratory function is established after birth and tend to further increase with age.