血清炎性因子在骨折延迟愈合患者富血小板血浆治疗中的变化

探讨血清炎性因子在骨折延迟愈合患者富血小板血浆治疗中的变化。方法 选取2020年4月—2021年4月我院收治的98例骨折患者,均予以富血小板血浆联合钢板内固定手术治疗,根据术后6个月内是否发生骨折延迟愈合分为延迟愈合组（37例）和正常愈合组（61例）。分别于骨折后1、4、8、12周采集患者血清样本,采用酶联免疫吸附法检测血清人可溶性细胞间粘附分子-1（sICAM-1）、人可溶性血管细胞粘附分子-1（sVCAM-1）、肿瘤坏死因子-α（TNF-α）等炎症因子水平,并绘制ROC曲线,评估其对骨折延迟愈合的预测价值。采用酶联免疫双抗体夹心法检测血清骨钙素（BGP）、Ⅰ型胶原氨基端肽原（PINP）、碱性磷酸酶（ALP）、胰岛素样生长因子-1（IGF-1）等骨生化代谢指标水平,并采用Pearson分析骨生化代谢指标与炎症因子的关系。结果 骨折1周时,两组患者血清sICAM-1、sVCAM-1、TNF-α等炎症因子水平比较差异无统计学意义（P＞0.05）;骨折4、8、12周时,延迟愈合组患者血清sICAM-1、sVCAM-1、TNF-α等炎症因子水平均高于正常愈合组（P＜0.05）,且随着时间推移,两组患者血清sICAM-1、sVCAM-1、TNF-α水平先升高后降低,但延迟愈合组炎症因子水平波动较正常愈合组更明显（P＜0.05）。骨折1周时,两组患者血清BGP、PINP、ALP、IGF-1等骨生化代谢指标水平比较差异无统计学意义（P＞0.05）,且两组各时间点血清ALP水平比较差异无统计学意义（P＞0.05）; 骨折4、8、12周时延迟愈合组患者血清BGP水平逐渐升高并高于正常愈合组,血清IGF-1水平逐渐升高但低于正常愈合组,骨折8、12周时延迟愈合组患者血清PINP水平低于正常愈合组（P＜0.05）。Pearson相关性分析结果显示,血清sICAM-1、sVCAM-1、TNF-α等炎症因子水平与血清BGP呈正相关（r=0.523,P＜0.001）,与血清IGF-1呈负相关（r=-0.467,P＜0.001）。ROC曲线分析结果显示,骨折8周时,血清炎症因子水平诊断骨折延迟愈合的曲线下面积高于0.7,提示其具有较好诊断价值,且联合检测对骨折延迟愈合诊断的灵敏度更高（P＜0.05）。结论 延迟愈合骨折患者血清sICAM-1、sVCAM-1、TNF-α等炎症因子指标水平随骨折时间增加呈现先升高后降低变化,炎症因子指标水平波动明显,且术后8周时血清炎症因子对预测骨折延迟愈合具有一定参考意义     

中国汉族人群APOE等位基因频率的初步研究

载脂蛋白Ｅ（ａｐｏｌｉｐｏｐｒｏｔｅｉｎＥ，ＡＰＯＥ）基因是一个多功能基因，除调节脂类及脂蛋白代谢之外，近年来还发现它与Ａｌｚｈｅｉｍｅｒ病及Ⅲ型高血脂症等病之间有密切关系。为对上述疾病进行病因学研究，作者采用一步法ＰＣＲ技术对４３８名无亲缘关系的中国汉族健康受试者的ＡＰＯＥ基因进行分型，并计算其基因频率分布，结果表明，中国治疗人群ＡＰＯＥ３种等位基因的频率分别为：Ｅ２＝０．０４００，Ｅ３＝０．８     

Association of DAAO with schizophrenia in the Chinese population

Recently, the gene called DAAO was reported to be associated with schizophrenia in the French Canadian populations. Here, we report a result obtained in the study of our large collection of 547 schizophrenia cases and 536 controls in the Chinese population. Six single-nucleotide polymorphisms (SNPs) were genotyped at and around the DAAO locus, covering a 10-kb region entirely encompassing the complementary DNA sequences of DAAO. We found statistically significant differences in allele distributions on one marker: SNP rs3741775 (P = 0.0000001). In the haplotype analysis based on the information of linkage-disequilibrium block across this gene locus, we demonstrated a highly significant association between schizophrenia and a DAAO haplotype (P = 2.0173 x 10(-21)), which therefore provides an independent statistical support for association of the DAAO gene with schizophrenia and indicates that the DAAO gene may play a significant role in the etiology of schizophrenia in the Han Chinese.     

A family-based association study of PLP1 and schizophrenia

Recently, proteolipid protein 1 (PLP1) has been identified as downregulated in schizophrenia by quantitative PCR and other technologies. In this work we attempted to investigate the role of PLP1 in the etiology of schizophrenia using a family based association study in 487 Chinese Han family trios. The TDT for allelic association demonstrated that, in male, a weak association was detected in SNP rs475827 with p=0.0294, suggesting that the genetic polymorphisms within PLP1 in male are likely to confer an increased susceptibility to schizophrenia in the Chinese population.     

Apoptotic pathways of macrophages within osteolytic interface membrane in periprosthestic osteolysis after total hip replacement

Macrophage apoptosis in interface membrane, which occurs through either death receptor, mitochondrion, or endoplasmic reticulum (ER) stress pathways, has been suggested to play an important role in promoting osteolysis. However, how and why macrophage apoptosis originates and the correlation among these apoptotic pathways is not yet clear. The objective of this study was to identify the apoptotic mechanism of macrophages, and to explore the relationship between the apoptotic pathways and progression of osteolysis. Transmission electron microscopy (TEM) was utilized to analyze the tissue ultrastructure of wear particles, and in situ apoptotic macrophage identification was performed by TUNEL staining. We analyzed the expression of the key biomarkers of apoptotic pathways via immunohistochemistry and Western blotting. Our results demonstrated that the majority of wear particles within osteolytic interface membrane was in the 30–60 nm range, and that macrophage apoptotic ratio increased along with osteolysis progression. Normal hip dysplasia and mechanical loosening of tissues showed low expression levels of biomarkers for ER stress (Ca²⁺, JNK, cleaved Caspase‐4, IRE1‐α, Grp78/Bip, and CHOP), mitochondrion (Bcl‐2, Bax, and Cytochrome c), and death receptor (Fas and cleaved Caspase‐8) pathways, while osteolytic interface membrane tissues expressed high levels of these biomarkers. In addition, we found that the ER stress intensity was in complete conformity with mitochondrial dysfunction and was consistent with the results of death receptor activation. Thus, our findings suggested that wear particles generated at implant interface can accelerate macrophage apoptosis through changes in apoptotic pathways and ultimately aggravate the symptom of osteolysis. These data represent a preferential apoptotic signaling pathway of macrophages as specific target points for the prevention and therapeutic modulation of periprosthetic osteolysis.     

Comparison of Water Immersion Versus Air Insufflation Colonoscopy Under Various Bowel Preparation Conditions

Background: To investigate the differences between water immersion (WI) and air insufflation (AI) for colonoscopy under various bowel preparation conditions. Methods: In this study, 526 outpatients were randomly assigned to two groups, namely a WI group (n = 263) and an AI group (n = 263). During the procedure, the quality of bowel preparation, abdominal pain score, cecal intubation rate (CIR), adenoma detection rate (ADR), the intubation times, and other indicators were recorded. After reaching the cecum, each group of patients was subdivided into one of four grades (excellent, good, fair, and poor) according to the quality of bowel preparation.Results: Under various bowel preparation conditions, the pain scores of the AI group were higher than those of the WI group (P < .05), but there was no significant difference between the two groups in CIR (P > .05). For the WI group compared with the AI group, the cecal intubation time (CIT) was prolonged under good bowel preparation (P = .045) and fair bowel preparation (P < .001). No significant differences were observed between the two groups on ADR in all patients (P = .476).Conclusion: Compared with AI colonoscopy, WI colonoscopy can decrease colonoscopy-related pain in patients for unsedated colonoscopy under various bowel preparation conditions, but there is no significant difference in CIR. WI colonoscopy requires longer CIT in patients with good and fair bowel preparation conditions. WI colonoscopy does not significantly increase ADR.     

Pharacogenetic effects of dopamine transporter gene polymorphisms on response to chlorpromazine and clozapine and on extrapyramidal syndrome in schizophrenia

A number of studies have investigated the effectiveness of the dopamine transporter (SLC6A3) Gene as an antipsychotic target. However, the focus has mainly been on a 40-bp variable number of a tandem repeat (VNTR) in the 3′-region and results have been inconsistent. To fully evaluate SLC6A3 as a therapeutic antipshycotic target we investigated association of the gene with responses to chlorpromazine and clozapine and with chlorpromazine-induced extrapyramidal syndrome (EPS) in the Chinese schizophrenia population. Six polymorphisms across the whole region of this gene were analyzed, namely rs2652511 (T-844C) and rs2975226 (T-71A) in the 5′-regulatory region, rs2963238 (A1491C) in intron 1, a 30-bp VNTR in intron 8, rs27072 and the 40-bp VNTR in the 3′-region. We found that the polymorphic marker, rs2975226, showed significant association of allele and genotype frequencies with response to clozapine (allele-wise: adjusted p = 0.00404; genotype-wise: adjusted p = 0.024), and that patients with the T allele had a better response to the drug. The haplotype block constructed from the first three markers near the 5′-region showed significant association with response to clozapine (for haplotype T-T-A: p = 0.0085; for haplotype C-A-C: p = 0.0092). We did not identify any significant association of the six genetic variants or haplotypes with EPS after Bonferoni correction. Our findings suggest that the 5′-regulatory region of SLC6A3 plays an important role in response to clozapine and that its role in EPS needs to be replicated in a large-scale well designed study.     

Engineering tropane biosynthetic pathway in Hyoscyamus niger hairy root cultures

Scopolamine is a pharmaceutically important tropane alkaloid extensively used as an anticholinergic agent. Here, we report the simultaneous introduction and overexpression of genes encoding the rate-limiting upstream enzyme putrescine N-methyltransferase (PMT) and the downstream enzyme hyoscyamine 6 beta-hydroxylase (H6H) of scopolamine biosynthesis in transgenic henbane (Hyoscyamus niger) hairy root cultures. Transgenic hairy root lines expressing both pmt and h6h produced significantly higher (P < 0.05) levels of scopolamine compared with the wild-type and transgenic lines harboring a single gene (pmt or h6h). The best line (T(3)) produced 411 mg/liter scopolamine, which was over nine times more than that in the wild type (43 mg/liter) and more than twice the amount in the highest scopolamine-producing h6h single-gene transgenic line H(11) (184 mg/liter). To our knowledge, this is the highest scopolamine content achieved through genetic engineering of a plant. We conclude that transgenic plants harboring both pmt and h6h possessed an increased flux in the tropane alkaloid biosynthetic pathway that enhanced scopolamine yield, which was more efficient than plants harboring only one of the two genes. It seems that the pulling force of the downstream enzyme (the faucet enzyme) H6H plays a more important role in stimulating scopolamine accumulation in H. niger whereas the functioning of the upstream enzyme PMT is increased proportionally. This study provides an effective approach for large-scale commercial production of scopolamine by using hairy root culture systems as bioreactors.