细胞周期素CyclinD1和CyclinE在鼻咽癌组织中的表达及意义

目的探讨CyclinD1和CyclinE在鼻咽癌中的表达及临床意义,并分析它们表达的相关性。方法用免疫组化S_P法分别检测CyclinD1和CyclinE在60例鼻咽癌组织中的表达。结果CyclinD1和CyclinE在鼻咽癌组织中的阳性表达率分别为60%(36/60)和66.7%(40/60);CyclinD1和CyclinE阳性和阴性病例的平均生存期、5年生存率和中位生存期存在显著性差异(P<0.05);鼻咽癌组织中CyclinD1和CyclinE的表达一致率为75%(45/60),存在显著相关性(P<0.01);CyclinD1和CyclinE阳性表达在鼻咽癌不同临床时期(Ⅱ、Ⅲ、Ⅳ)存在显著差异(P<0.01)。结论CyclinD1和CyclinE可能作为生物标志物预测鼻咽癌预后。     

国际教育推动中医药国际化研究进展

中医药在防治疾病养生保健方面有独特优势,在国际上逐渐被广泛接受。国际教育是实现中医药国际化的必要途径之一,本文通过对中医药国际化在教育方面遇到问题的论述,探讨国际教育推动中医药国际化的方式。     

弹性脂质囊泡在经皮给药系统的研究进展

目的 对近年来弹性脂质囊泡在经皮给药系统的研究与应用进行文献整理和归纳,为以后该领域的研究提供借鉴。方法 查阅近5年弹性脂质囊泡在经皮给药系统的相关文献,总结弹性脂质囊泡的分类、制备方法、促透机制、应用的研究进展,提出其今后研究的重点方向。结果 弹性脂质囊泡具有较好的变形性、皮肤渗透性,可以通过角质层,更利于药物到达毛细血管被吸收,提高生物利用度,更有利于皮肤用药。结论 弹性脂质囊泡经皮给药系统是一种安全、有效的给药途径,其顺应性更好,在经皮给药方面有很好的应用前景。     

N-cadherin and P-cadherin are biomarkers for invasion,metastasis, and poor prognosis of gallbladder carcinomas

Gallbladder cancer (GBC) is a rare, but highly aggressive cancer. The most common type of gallbladder cancer is adenocarcinoma (AC), while squamous cell/adenosquamous carcinoma (SC/ASC) is a rare type of gallbladder cancer. The clinicopathologic and biological characteristics of SC/ASC have not been well documented. In this study, the protein expression of N-cadherin and P-cadherin in 46 SC/ASCs and 80 ACs was measured using immunohistochemistry. We demonstrated that positive N-cadherin and P-cadherin expression were significantly associated with large tumor size, invasion, and lymph node metastasis of both SC/ASC and AC. In contrast, positive N-cadherin and P-cadherin expression were significantly associated with differentiation and TNM stage in only AC. Univariate Kaplan–Meier analysis showed that positive N-cadherin and P-cadherin expression, differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and surgical curability were significantly associated with overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive N-cadherin and P-cadherin expression are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive N-cadherin and P-cadherin expression closely correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer.     

The antitumor activity of 4,4′-bipyridinium amphiphiles

A series of 4,4′-bipyridinium amphiphiles were synthesized and their anticancer activities were further evaluated. MTT assay showed that the cytotoxicity first increased and then decreased with the growth of carbon chains (8–16 C) at both ends of bipyridyl. Specifically, compounds with saturated carbon chains consisting of 13 carbons at both ends of bipyridyl displayed the best cell inhibitory activity with IC₅₀ values in the low-micromolar range, which were even superior to that of cisplatin, against all the tested human cancer cells and cisplatin-resistant A549 cancer cells in vitro. In addition, compound 6 could evidently arrest the G2/M phase of the cell cycle in a dose-dependent manner. Moreover, this study demonstrates the potent performance of compound 6 in cell growth inhibition and apoptosis induction via a conceivable approach of membrane damage.

The cell growth inhibition and apoptosis induction of 4,4′-bipyridinium amphiphiles.     

Adiponectin Alleviates Diet-Induced Inflammation in the Liver by Suppressing MCP-1 Expression and Macrophage Infiltration

Adiponectin is an adipokine that exerts insulin-sensitizing and anti-inflammatory roles in insulin target tissues including liver. While the insulin-sensitizing function of adiponectin has been extensively investigated, the precise mechanism by which adiponectin alleviates diet-induced hepatic inflammation remains elusive. Here, we report that hepatocyte-specific knockout (KO) of the adaptor protein APPL2 enhanced adiponectin sensitivity and prevented mice from developing high-fat diet–induced inflammation, insulin resistance, and glucose intolerance, although it caused fatty liver. The improved anti-inflammatory and insulin-sensitizing effects in the APPL2 hepatocyte–specific KO mice were largely reversed by knocking out adiponectin. Mechanistically, hepatocyte APPL2 deficiency enhances adiponectin signaling in the liver, which blocks TNF-α–stimulated MCP-1 expression via inhibiting the mTORC1 signaling pathway, leading to reduced macrophage infiltration and thus reduced inflammation in the liver. With results taken together, our study uncovers a mechanism underlying the anti-inflammatory role of adiponectin in the liver and reveals the hepatic APPL2–mTORC1–MCP-1 axis as a potential target for treating overnutrition-induced inflammation in the liver.     

PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy

p21-Activated kinase 6 (PAK6) has been implicated in radiotherapy and docetaxel resistance. We have further evaluated PAK6 as a predictor of 5-fluorouracil (5-FU) treatment response in colon cancer. Here we report that in colon cancer PAK6 promotes tumor progression and chemoresistance both in vitro and in vivo. In the clinical analysis, PAK6 was overexpressed in 104 of 147 (70.75%) stage II and III patients who received 5-FU based chemotherapy after surgery. Multivariate Cox regression analysis indicated that PAK6 was an independent prognostic factor for overall survival (P < 0.001) and disease-free survival (P < 0.001). Colon cancer cell lines showed increased PAK6 expression upon 5-FU treatment. In PAK6-knockdown cells treated with 5-FU, cell viability and phosphorylation of BAD decreased, and the number of apoptotic cells, levels of cleaved caspase 3 and PARP increased compared to control cells. The opposite was observed in PAK6 overexpressing cells. Short hairpin RNA knockdown of PAK6 blocked cells in G2-M phase. Furthermore, Animal experiments results in vivo are consistent with outcomes in vitro. This study demonstrates that PAK6 is an independent prognostic factor for adjuvant 5-FU-based chemotherapy in patients with stage II and stage III colon cancer.     

Live births following preimplantation genetic testing for dynamic mutation diseases by karyomapping: a report of three cases

The preimplantation genetic testing for monogenic defects (PGT-M) is a beneficial strategy for the patients suffering from a Mendelian disease, which could protect their offspring from inheriting the disease. The purpose of this study is to report the effectiveness of PGT-M based on karyomapping for three cases of dynamic mutation diseases with trinucleotide repeat expansion. PGT-M was carried out on three couples, whose family members were diagnosed with Huntington’s disease or spinocerebellar ataxias 2 or 12. The whole genome amplification was obtained using the multiple displacement amplification (MDA) method. Then, karyomapping was performed to detect the allele that is carrying the trinucleotide repeat expansion using single nucleotide polymorphism (SNP) linkage analyses, and the copy number variations (CNVs) of the embryos were also identified. Prenatal diagnosis was performed to validate the accuracy of PGT-M. PGT-M was successfully performed on the three couples, and they accepted the transfers of euploid blastocysts without the relevant pathogenic allele. The clinical pregnancies were acquired and the prenatal diagnosis of the three families confirmed the effectiveness of karyomapping. The three born babies were healthy and free of the pathogenic alleles HTT, ATXN2, or PPP2R2B corresponding to Huntington’s disease, spinocerebellar ataxias 2 or 12, respectively. This study shows that karyomapping is a highly powerful and efficient approach for dynamic mutation detection in preimplantation embryos. In this work, we first report the birth of healthy babies that are free of the pathogenic gene for dynamic mutation diseases in patients receiving PGT-M by karyomapping.     

分析前列腺动脉栓塞治疗前列腺增生操作者学习曲线

目的分析前列腺动脉栓塞(PAE)治疗前列腺增生(PH)的操作者学习曲线。方法回顾分析由同一具有5年以上外周血管介入治疗经验医师行PAE治疗的第1～60例PH患者的资料,按治疗顺序分为A、B、C组,每组20例。比较各组间PAE手术时间、术中X线曝光时间、患者术后住院时间的差异;对比分析术前与术后3个月国际前列腺症状评分(IPSS)、生活质量评分(QOL)、前列腺体积、最大尿流率(Q_(max))及残余尿量(PVR)。结果 3组PAE术前前列腺体积、IPSS评分、QOL评分、Q_(max)及PVR差异均无统计学意义(P均0.05);手术时间及术中X线曝光时间差异均有统计学意义(F=32.74、13.57,P均0.01),其中A组手术时间及术中X线曝光时间明显长于B组(P均0.01)及C组(P均0.01),B组与C组间差异均无统计学意义(P=0.22、0.30)。3组患者术后住院时间差异无统计学意义(F=0.17,P=0.84)。PAE术后3个月,A、B、C组IPSS评分(t=14.66、11.74、29.02)、QOL评分(t=8.51、8.19、7.99)及PVR(t=11.68、12.71、16.80)均低于术前(P均0.01),Q_(max)均(t=-11.72、-10.80、-7.74)较术前明显升高(P均0.01),前列腺体积(t=14.75、17.45、27.42)均较术前明显减小(P均0.01)。结论 PAE治疗PH近期疗效确切。医师积累20例PAE手术经验后,后续手术时间及曝光时间明显缩短,学习曲线进入平台期。