Role of vasoactive intestinal peptide in the progression of osteoarthritis through bone sclerosis and angiogenesis in subchondral bone

ObjectiveOsteoarthritis (OA) is a progressive joint disorder, with abnormal remodeling of subchondral bone linked to the disruption of cartilage metabolism. Nerves also play an important role in bone remodeling in OA progression, and vasoactive intestinal peptide (VIP), one of the neuropeptides, plays an important role in bone metabolism. The aim of this study was to analyze the expression pattern of VIP in subchondral bone, and its potential as a therapeutic target for OA progression.DesignThe pattern of VIP expression in the human tibia was histologically evaluated. The effect of VIP on angiogenesis was investigated using human umbilical vein endothelial cells (HUVECs). Knee OA was induced by the resection of the medial meniscotibial ligament in C57BL/6 mice. A VIP receptor antagonist was intraperitoneally administered postoperatively, and therapeutic effects were analyzed at 4 and 8 weeks.ResultsVIP expression in the subchondral bone increased as OA progressed in human tibia. VIP was also expressed in the vascular channels into the cartilage layer. The total length and branch points were significantly increased, due to the VIP receptor agonist in HUVECs. In OA mice, the VIP receptor antagonist could prevent cartilage degeneration and subchondral bone sclerosis. The Osteoarthritis Research Society International score in the VIP receptor antagonist group was significantly lower than in the control group.ConclusionVIP is involved in the progression of OA through its effect on subchondral bone sclerosis and angiogenesis. Inhibition of VIP signaling has the potential to be a therapeutic target to prevent OA progression.     

常染色体显性多囊肾病治疗药物的研究进展

常染色体显性多囊肾病(ADPKD)是一种遗传性肾囊肿性疾病,临床中缺乏特异性治疗药物,治疗重点在于缓解症状,若发展为肾功能衰竭则需采取透析、肾移植等替代治疗。为进一步开展治疗ADPKD的临床试验及应用提供参考,查阅最新国内外研究报道,分析总结了目前治疗ADPKD的药物主要有血管加压素V2受体(AVPV2R)拮抗剂托伐普坦、哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂西罗莫司和依维莫司、生长抑素类似物(SST)奥曲肽、他汀类药物洛伐他汀和普伐他汀进入临床试验阶段,其中AVPV2R拮抗剂托伐普坦已在日本被批准为世界首个用于延缓ADPKD进展的治疗药物,但由于其不良反应尚未被FDA正式批准,大规模临床试验和随后的风险–效益分析有待进一步深入研究。     

Effect of selective uterine artery embolization on symptomatic uterine fibroids

Objective： To evaluate the outcomes of selective uterine artery embolization （SUAE） in treatment of symptomatic uterine fibroids using Color Doppler ultrasonography （CDUS）. Methods： As the procedure SUAE for fibroids, prospective data of the initial 65 consecutive women treated from March 2007 to September 2009 were collected. The follow-up period from 1 week to 30 months, using questionnaires, we investigated the fibroid-related physical and psychological symptoms, and the cumulative rates of symptom control, gynecologic interventions, and complications. The volumes of uterine and uterine fibroids were calculated by CDUS pre- and post-SUAE for 6 months. And we tested the levels of internal hormone including FSH, LH and E2 before and after SUAE for 3, 6 months. Results： SUAE was performed successfully in all patients. There was no peri-operative morbidity in all procedures. Compared with pre-SUAE volumes of uterine [（322± 12） cm^3] and uterine fibroids [（125±46） cm^3], their volumes in post-SUAE were （144±72） cm^3 and （51 a：l 1） cm^3 （P〈0.01）, and reduction rate was 58% and 61%, respectively. At 3, 6 months after SUAE, levels of FSH, LH, and E2 were not decreased than that of in pre-SUAE （P〉0.05）. After SUAE for 24 months, the fibroids related physical and psychological symptoms such as bleeding, pain and quality of life were significantly improved （P〈0.01）. 90.8% （59/65） women had resolution of symptoms and no significant post-procedural symptoms. Parts of patients discharge necrotic fibroids. 86% （34/40） complications were minor, requiring no therapy. 9.2% （6/65） had significant post-procedural symptoms, requiring therapy in hospital or out-patient department. Conclusion： SUAE contributes to a long-term significant improvement of all investigated uterine fibroid-related symptoms and markedly improves women＇s health-related quality of life. SUAE that no impair on changes of internal hormone, under suitable conditions, represents an attractive alternative to hysterectomy for the treatment of symptomatic fibroids and is a minimally invasive, new method of good clinical prognosis. CDUS is an effective to investigate the outcome of SUAE.     

肺癌相关miRNAs研究进展

肺癌的发生发展为复杂的多基因事件,microRNAs（miRNAs）参与其中并发挥重要作用。miR-NAs为一系列长约19-25nt的内源性非编码微小RNA,可抑制靶基因转录或蛋白翻译从而沉默靶基因的表达。部分miRNAs在肺癌组织中表达上调,并证明可负性调节抑癌基因。亦有部分miRNAs在肺癌组织中表达下调,被认为是抑癌基因且其中一部分也已得到证实,在临床潜在应用方面,目前研究证实miR-101可发挥放疗增敏效应,而miR-134、miR-379与miR-495或有助于指导肺癌化疗用药的选择。通过回顾最新文献,本文对肺癌高度相关的miRNAs及其靶基因进行了总结,并在生物学效应、潜在靶基因、基因诊断、治疗、预测预后等方面进行探讨。     

Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: An analysis of Japan Multinational Trial Organisation LC00-03

We examined the impact of pretreatment neutrophil count on survival in patients with advanced non-small-cell lung cancer (NSCLC). A total of 388 chemo-naïve patients with stage IIIB or IV NSCLC from a randomised controlled trial were evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte and monocyte counts and neutrophil–lymphocyte ratio on survival were examined using the proportional hazards regression model to estimate hazard ratios after adjustment for covariates. The optimal cut-off value was determined by proportional hazards regression analysis with the minimum P-value approach and shrinkage procedure. After adjustment for prognostic factors, the pretreatment elevated neutrophil count was statistically significantly associated with short overall (P = 0.0008) and progression-free survival (P = 0.024), whereas no association was found between prognosis and lymphocyte or monocyte count. The cut-off value selected for neutrophil count was 4500 mm^–3 (corrected hazard ratio, 1.67; 95% confidence interval (CI), 1.09–2.54). The median survival time was 19.3 months (95%CI, 16.5–21.4) for the low-neutrophil group (?4500 mm^–3, n = 204) and was 10.2 months (95%CI, 8.0–12.3) for the high-neutrophil group (?4500 mm^–3, n = 184). We confirmed that pretreatment elevated neutrophil count is an independent prognostic factor in patients with advanced NSCLC receiving modern chemotherapy. Neutrophil count is easily measured at low cost, and it may be a useful indicator of patient prognosis.     

Multicenter cross‐sectional observational study of antibiotic resistance and the genotypes of Propionibacterium acnes isolated from Chinese patients with acne vulgaris

Antibiotics are widely applied in management of acne vulgaris, which raises the issue of antibiotic resistance. Due to improper application and supervision of antibiotics, antibiotic resistance has become a serious problem in China. So, the efficacy of antimicrobial therapy in acne is unclear without an objective monitor of antibiotic resistance of Propionibacterium acnes. This cross‐sectional, multicenter observational study is aimed at understanding the status of antibiotic resistance in P. acnes, investigating the measures of acne management in China and analyzing the genotypes of antibiotic‐resistant strains of P. acnes. Altogether, 312 strains of P. acnes were collected from patients in five medical centers across central China after reviewing the corresponding medical history in detail. The samples underwent antibiotic susceptibility assays by agar dilution method with a total of 11 classes of antibiotics being tested. The antibiotic‐resistant strains were screened and further analyzed by investigation of the genotypes regarding 23S rRNA, 16S rRNA and erm(X). The predominant resistance occurred in macrolides and lincomycin with an overall resistance rate of 47.8%. The resistance to tetracyclines was scarce with only two cases identified. The emergence of minimum inhibitory concentration elevation for tetracyclines is associated with its application history (P < 0.005). The genotypes of the reported macrolide–lincosamide–streptogramin B resistance strains were also spotted in Chinese subjects while other resistance determinants may also exist. The tetracyclines have been proved to be vastly susceptible while macrolides and lincomycin face a serious resistance status in China.     

Circular RNAs: The crucial regulatory molecules in colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Recent studies have shown that circular RNAs (circRNAs) play critical roles in the pathogenesis and progression of CRC. CircRNAs are a special class of endogenous non-coding RNAs (ncRNAs) that harbor covalently closed ring structure with high conservation and stability, which are expressed in a tissue- and developmental-stage-specific manner. A growing body of evidence suggests that circRNAs are abnormally expressed in CRC tissues, cell lines and plasma, and are closely linked with CRC clinical malignant features. CircRNAs participate in various biological processes of CRC cells, including cell proliferation, apoptosis, senescence, migration and invasion and so on, through acting as “microRNA (miRNA) sponges”, binding to protein and even translating protein. In the present review, we systematically introduce the CRC-related circRNAs and their functional mechanisms, as well as the potential applications for CRC diagnosis and prognosis.