[Progress and prospects of liquid-liquid phase separation in developmental diseases].

Membrane-bound organelles as well as membrane-free compartments exist in eukaryotic cells, which divide the nucleus and cytoplasm into distinct subregions and allow specific biochemical reactions to occur. The physiological mechanisms of membrane-bound organelles have been extensively characterized, but the formation and function of membrane-free compartments have not been thoroughly studied. Over the past decade, significant progress had been made in the studies about the role of liquid-liquid phase separation (LLPS) in the formation of membrane-free organelles. LLPS which serves as an aggregated separation mechanism for cellular biochemical reactions, is associated with a variety of physiological processes such as signal transduction and gene transcriptional regulation; while aberrant LLPS may contribute to the occurrence of developmental diseases. The present review investigates the role of LLPS as a mechanism of aggregation and segregation of cellular biochemical responses. The mechanisms of LLPS development and recent advances in the relationships between aberrant LLPS and developmental diseases are forward discussed, as well as how these advances may aid in the development of LLPS-based therapies.

[Layer-specific strain assessment on left ventricular function before and after PCI in patients with ST segment elevation myocardial infarction].

Objective: To evaluate the changes of left ventricular function in patients with ST segment elevation myocardial infarction (STEMI) before PCI and within 24 hours after PCI by layer-specific strain, and to explore the value of this new assessment method for quantitative monitoring on the myocardial function in STEMI patients. Methods: A total of 40 patients with acute anterior wall myocardial infarction, who underwent PCI in Affiliated Hospital of Jiangsu University during July 2017 to July 2018, were included in this prospective cohort study. According to the symptom to balloon time (STB), the patients were divided into STB ≤6 hours group (26 cases) and STB 6-12 hours group (14 cases). Echocardiography was performed before, immediately, 3 hours and 24 hours after PCI. Echocardiographic indexes including endocardial myocardial longitudinal strain (LS-endo), 18-segment full-thickness myocardial longitudinal strain (LS) of left ventricle and left ventricular global longitudinal strain (GLS) were measured. The mean LS-endo and LS values of myocardial segments in infarcted area (IALS-endo, IALS) and the mean LS-endo and LS values of myocardial segments in non-infarcted area (NIALS-endo, NIALS) were calculated. Results: There were 34 males and 6 females in this cohort and age was (62±10) years. In STB≤6 hours group, the IALS-endo value ((13.7±4.9)% vs. (10.0±2.7)%, P<0.05) and NIALS-endo value ((17.0±2.9)% vs. (14.6±2.9)%, P<0.05) were significantly higher at 24 hours after PCI than those before PCI. In the group of STB 6-12 hours, IALS-endo decreased immediately after PCI ((6.7±3.3)% vs. (11.9±6.5)%, P<0.05), and there was a rising trend at 3 hours after PCI (P>0.05). At 24 hours after PCI, the index was higher than that immediately after PCI ((13.6±8.4)% vs. (6.7±3.3)%, P<0.05). The NIALS-endo value was significantly higher at 24 hours after PCI than that before PCI ((17.1±2.1)% vs. (14.5±3.2)%, P<0.05). In the STB 6-12 hours group, the decrease rate of IALS-endo immediately after PCI was higher than that in the STB ≤6 hours group (93% (13/14) vs. 35% (9/26), P<0.001). In STB ≤6 hours group, the NIALS value at 24 hours after PCI was higher than that before PCI (P<0.05), and there was no significant difference in IALS, NIALS and GLS at other time points (P>0.05). Conclusions: Layered LS is superior to full-thickness LS and GLS in evaluating left ventricular function in STEMI patients. LS measured by echocardiography can continuously and quantitatively evaluate the changes of left ventricular myocardial function in STEMI patients before and after PCI.

[Mechanisms and regulations in tooth root development].

Tooth loss caused by trauma, periodontitis or inherited disorders severely affects human physical and mental health. As an essential part of the tooth, tooth root is connected to periodontal tissues to maintain the tooth in the alveolar socket. To figure out the molecular mechanisms regulating tooth root development will contribute to the discovery of new approaches in tooth root regeneration. The development of tooth root is a complicated process involving communication between the epithelial and mesenchymal tissues and the regulation of multiple signaling pathways. The present article reviewed the research progress of the signaling pathways in tooth root development.

MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway, by J.-H. Fu, S. Yang, C.-J. Nan, C.-C. Zhou, D.-Q. Lu, S. Li, H.-Q. Mu, published in Eur Rev Med Pharmacol Sci 2018; 22 (2): 351-357-DOI: 10.26355/eurrev_201801_14179-PMID: 29424922" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14179.

MiRNA-20a-5p accelerates the proliferation and invasion of non-small cell lung cancer by targeting and downregulating KLF9.

OBJECTIVE: To uncover the role of microRNA-20a-5p (miRNA-20a-5p) in the progression of Non-small cell lung cancer (NSCLC) and the underlying mechanism. PATIENTS AND METHODS: MiRNA-20a-5p level in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Its level in NSCLC patients with larger or smaller tumor size, and either with lymphatic metastasis or not was examined as well. Regulatory effects of miRNA-20a-5p on viability, cell cycle, and invasiveness of A549 and PC9 cells were assessed. The interaction between miRNA-20a-5p and KLF9 was explored by Dual-Luciferase Reporter Gene Assay and Spearman correlation test. At last, the role of miRNA-20a-5p/KLF9 axis in influencing the progression of NSCLC was determined. RESULTS: MiRNA-20a-5p was upregulated in NSCLC tissues and cell lines. Its level was much pronounced in NSCLC patients with larger tumor size or accompanied with lymphatic metastasis. Overexpression of miRNA-20a-5p in A549 cells enhanced viability, cell ratio in S phase, and invasiveness, while the knockdown of miRNA-20a-5p in PC9 cells achieved the opposite trends. KLF9 was confirmed to be the direct target of miRNA-20a-5p. There was a negative correlation between the expression levels of miRNA-20a-5p and KLF9 in NSCLC tissues. In addition, KLF9 overexpression could reverse the promotive effects of upregulated miRNA-20a-5p on the proliferation and invasiveness of A549 cells. On the contrary, the knockdown of KLF9 reversed the inhibitory effects of downregulated miRNA-20a-5p on cellular behaviors of PC9 cells. CONCLUSIONS: MiRNA-20a-5p stimulates NSCLC to proliferate and invade by targeting KLF9.

The potential of ciRS-7 for predicting onset and prognosis of cervical cancer.

Considering the potency of circRNAs in manifesting neoplastic progression, we attempted to explore the feasibility of applying ciRS-7 for diagnosis and prognosis estimation of cervical cancer (CC). Here 352 CC patients, 204 cervical intraepithelial neoplasia (CIN) patients and 227 healthy controls were recruited. The Kaplan-Meier survival curves were fitted to estimate associations of ciRS-7 expression with CC prognosis, and we also adopted receiver operating characteristic (ROC) curves to assess the diagnostic performance of ciRS-7 for CC. Meanwhile, endometrial stromal cell line (ESC) and 4 human CC cell lines (i.e. Hela, CaSki, C33A and SiHa) were also gathered. After transfection of pcDNA3.1-ciRS-7, impacts of overexpressed ciRS-7 on proliferation, apoptosis, invasion and migration of CC cells were assessed through performing colony formation assay, flow cytometry, transwell assay and wound healing assay. The results demonstrated that CC patients that highly expressed ciRS-7 were associated with high odds of large tumor size, advanced FIGO stage, deep invasion, metastatic lymph nodes and HPV infection (p<0.05). Furthermore, ciRS-7 excelled in differentiating CC patients from healthy controls and CIN patients than CEA and CA125 (p<0.05), and ciRS-7 combined with CA125 and CEA generated an optimum efficacy in diagnosing CC patients and CIN patients from healthy controls (p<0.05). Concerning in vitro experiments, elevating ciRS-7 expression significantly intensified proliferation and epithelial-mesenchymal transition (EMT) of CC cells (p<0.05), and also markedly suppressed apoptosis of the cells (p<0.05). In conclusion, ciRS-7 possessed great potential in clinical diagnosis of CC, given its involvement in modulating the activity of CC cells.

Investigation of Streptococcus agalactiae using pcsB-based LAMP in milk, tilapia and vaginal swabs in Haikou, China.

AIMS: To develop a pcsB-based Loop-mediated isothermal amplification (LAMP) method for the detection of Streptococcus agalactiae (GBS) in milk, tilapia and vaginal swabs. METHODS AND RESULTS: The sensitivity of the LAMP method using real-time turbidity monitoring was 1 pg of template within 1 h at 64°C, 100-fold higher than conventional PCR. The sensitivity of visual detection dropped an order of magnitude using SYBR Green I or hydroxynaphthol blue. The validity of the visual LAMP assay was assessed by the detection of GBS in 180 vaginal swabs from one hospital, 14 brain tissues samples of diseased tilapias from two fishponds and fresh milk of 67 dairy cattle from one farm. In total, 17 samples (4 vaginal swabs, 13 tilapia brain tissues but no milk sample) tested positive for GBS. Subsequent bacterial identification confirmed the specificity and reliability of the LAMP method. Molecular serotyping and multilocus sequence typing demonstrated that all 13 tilapia GBS isolates were identical (serotype Ia, ST7), whereas the four human GBS isolates were more diverse and could be classified into two serotypes (Ia, III) and four sequence types (ST19, ST23, ST24, ST862). Virulence gene testing showed that only the bac, rib and lmb genes were not present in all isolates. Antimicrobial susceptibility profiles of the isolates were basically consistent with their genotypes, except for sulphonamide and fluoroquinolone. CONCLUSIONS: We developed a reliable pcsB-based LAMP assay for GBS detection. Our results demonstrated that the prevalence of GBS was 92·9% among diseased tilapia, 2·2% among female patients and 0% on a dairy farm in Hainan. SIGNIFICANCE AND IMPACT OF THE STUDY: The pcsB-based LAMP method is suitable for GBS detection and contains great potential of application in dairy industry, aquiculture and clinical.

[Clinical analysis of 555 outpatients with hand, foot and mouth diseases caused by different enteroviruses].

Objective: To study the clinical characteristics of outpatients with hand, foot and mouth disease (HFMD) caused by different serotypes of enteroviruses. Methods: This was a prospective study. From February 2017 to March 2018, 563 outpatients with HFMD were enrolled by systematic sampling in the Department of Infectious Diseases, Henan Children's Hospital. Throat swabs were collected to determine the serotypes via PCR. Demographic, clinical, and laboratory data were collected by standard questionnaire. All cases were followed up twice at 2 and 9 weeks after the initial outpatient visit through telephone interview. A total of 563 cases were enrolled and 555 (98.6%) cases were positive for human enteroviruses, including 338 (60.9%) males. Analyses were stratified by enterovirus serotypes, Chi square test or Fisher's exact test, Rank sum test was used for comparison among different groups. Results: The age of 555 cases was 24.2 (16.4, 41.3) months. Among them 44.0% (224 cases) were identified as coxsackievirus (CV)-A6, while 189 cases, 35 cases, 14 cases and 73 cases were identified as CV-A16, enterovirus (EV)-A71, CV-A10 and other serotypes, respectively. Fever (≥37.5 ℃) was present in 51.4% (285/555) of laboratory confirmed cases. The proportions of fever in cases of CV-A6 (68.9%(168/244)) and CV-A10 (12/14) were significantly higher than those in cases of CV-A16 (31.7%(60/189),χ(2)=57.344,14.313,both P=0.000), other serotypes (43.8%(32/73),χ(2)=15.101 and 8.242, P=0.000 and 0.004) and EV-A71 (37.1%(13/35), χ(2)=13.506 and 9.441, P=0.000 and 0.002) respectively. There was no significant difference between CV-A6 and CV-A10 in presentation of fever (χ(2)=1.785, P=0.182). There were 359 cases (64.7%) with eruptions in mouth, hands, feet and buttocks. Cases infected with EV-A71 had the highest proportions (74.3%(26/35)) of rash emerging simultaneously in mouth, hands, feet, and buttocks. The proportion in cases of CV-A16, CV-A6, CVA10 and other serotype were 73.5% (139/189), 61.9% (151/244), 7/14 and 49.3% (36/73), respectively. The proportion of rash on other parts of body, such as face, limbs or torso in cases infected with CV-A6 (16.8% (41/244)) was the higherest and the proportion in cases of CV-A16, EV-A71, CV-A10 or other serotypes were 8.5% (16/189) , 5.7% (2/35) , 1/14, 6.8% (5/73) , respectively. None of these cases developed serious complications. Desquamation occurred in 45.5% (179/393) cases 7.5 (5.0, 9.0) days after disease onset and 13.5% (53/393) cases showed onychomadesis 31.0 (18.0, 33.5) days after disease onset. The proportion of desquamation and onychomadesis associated with CV-A6 (64.2% (95/148) and 31.8% (47/148)) was significantly higher than CV-A16 (31.8% (49/154) and 1.3% (2/154), χ(2)=33.601 and 52.482, both P=0.000) and other serotypes (38.0%(19/50) and 6.0%(3/50),χ(2)=10.236 and 12.988, P=0.001 and 0.000). Desquamation appeared more in cases of CV-A6 than in cases of CV-A10 (2/11,χ(2)=9.386, P=0.002), with the proportion of onychomadesis higher in CV-A6 than in EV-A71 (3.3% (1/30),χ(2)=11.088, P=0.001). Conclusion: Clinical manifestation such as fever, rash emerging parts, desquamation and onychomadesis are different among outpatient HFMD cases infected with CV-A16, CV-A6, EV-A71, CV-A10 and other enteroviruses.

CD18 inhibits progression of kidney cancer by down-regulating Treg cell levels.

OBJECTIVE: Gene mutation is closely related to the occurrence of tumor. Renal cell carcinoma is a malignant tumor, seriously threatening patients' life quality. Regulatory T cells (Treg) play important roles in the development of several cancers. This study aimed to investigate whether CD18 affects renal carcinoma cell proliferation. MATERIALS AND METHODS: Thirty mice with renal cell carcinoma were constructed using gene-engineering mouse with CD18 deficiency, and another 30 normal C57 mice were used as control. Ki67 and micro-vessel density were detected by using immunohistochemistry (IHC) and immunofluorescence, respectively. The expression of CD3, CD4 and CD8 were detected in blood and spleen by quantitative PCR (q-PCR). Flow cytometry was used to detect the changes of Treg cells. RESULTS: The expression of Ki67 in C57 was significantly higher than that in CD18-/- mice (p<0.05). IHC results showed that CD31 was also significantly downregulated in CD18-/- group compared to control group (p<0.05). It was found that only high expression of CD4 in mesenteric lymph nodes of CD18-/- was considered as non-tumor-bearing. Flow cytometry results showed that Treg cells were significantly decreased in CD18-/- compared to C57 group (p<0.05). CONCLUSIONS: CD18-/- down-regulates Treg cells and inhibits the pathogenesis of renal cell carcinoma.

MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: PI3K/AKT/mTOR signaling pathway plays a crucial role in tumorigenesis and development. It was shown that mTOR overexpression was associated with the pathogenesis of renal cancer. Down-regulation of MiR-182 was found in renal carcinoma tissue. This study thus aims to investigate the influence of miR-182 in regulating mTOR expression and renal carcinoma cell proliferation, invasion, and apoptosis. PATIENTS AND METHODS: The targeted regulatory relationship between miR-182 and mTOR was tested by dual luciferase assay. Renal carcinoma tissue and benign renal tissue were collected to detect miR-182 and mTOR expressions. MiR-182, mTOR, p-mTOR, and Survivin levels were compared between HK-2 and A498 cells. Renal carcinoma A498 cells were divided into four groups, including miR-NC, anti-miR-182 mimic, si-NC, and si-mTOR groups. Cell apoptosis and proliferation were evaluated by flow cytometry. Cell invasion was determined by transwell assay. RESULTS: Bioinformatics analysis revealed the complementary relationship between miR-182 and the 3'-UTR of mTOR mRNA. The level of miR-182 was significantly reduced, while mTOR expression was upregulated in renal carcinoma tissue compared with that in benign lesion, which was associated with TNM stage. MiR-182 expression was markedly declined, whereas mTOR, p-mTOR, and Survivin levels were apparently upregulated in A498 cells compared with that in HK-2 cells. The treatment of miR-182 mimic or si-mTOR transfection significantly downregulated mTOR, p-mTOR, and Survivin expressions, restrained cell proliferation and invasion, and enhanced cell apoptosis. CONCLUSIONS: The decreasing level of miR-182 plays a role in enhancing mTOR expression and promoting renal carcinoma pathogenesis. Overexpression of miR-182 inhibited mTOR expression and weakened cell proliferation and invasion, which provides leads to the future therapy of renal cancer.

[Mechanism and clinical efficacy of third-generation epidermal growth factor receptor tyrosine kinase inhibitor in non-small cell lung cancer].

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment for non-small cell lung cancer (NSCLC) patients with EGFR activating mutations. However, most of patients will develop resistance to TKIs treatment due to the emergence of the T790M mutation. The third-generation EGFR-TKI is highly selective and efficient for activating mutants (EGFR sensitive mutations) and resistance mutant (T790M+ ). This review summarizes the mechanism and clinical efficacy of the third-generation EGFR-TKI in NSCLC patients.

[Application strategies of the third-generation EGFR-TKI in the context of precision medicine].

With the advances in molecular detection technology and the emergence of various targeted agents, we have entered the era of precision medicine across the whole process of cancer diagnosis and treatment. Tyrosine kinase inhibitors targeting epidermal growth factor receptor gene mutation, the most common driver, have been developed from the first generation to the third generation, improving the survival and life quality of patients with advanced non-small cell lung cancer. It is critically important how to rank these targeted agents and arrange combination therapies, and this review will focus on the strategies of the third-generation EGFR-TKI in the context of precision medicine.

Long noncoding RNA FTX inhibits hepatocellular carcinoma proliferation and metastasis by binding MCM2 and miR-374a.

It has long been known that males are more susceptible than females to hepatocellular carcinoma (HCC), but the reason remains elusive. In this study, we investigated the expression and function of the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome inactivation center, in both HCC and HCC gender disparity. lnc-FTX is expressed at higher levels in female livers than in male livers and is significantly downregulated in HCC tissues compared with normal liver tissues. Patients with higher lnc-FTX expression exhibited longer survival, suggesting that lnc-FTX is a useful prognostic factor for HCC patients. lnc-FTX inhibits HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, lnc-FTX represses Wnt/ß-catenin signaling activity by competitively sponging miR-374a and inhibits HCC cell epithelial-mesenchymal transition and invasion. In addition, lnc-FTX binds to the DNA replication licensing factor MCM2, thereby impeding DNA replication and inhibiting proliferation in HCC cells. In conclusion, these findings suggest that lnc-FTX may act as a tumor suppressor in HCC through physically binding miR-374a and MCM2. It may also be one of the reasons for HCC gender disparity and may potentially contribute to HCC treatment.

Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

BACKGROUND: Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. METHODS: Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. RESULTS: The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (<9 %). No new safety signals were reported. Objective response rate in 195 evaluable Chinese patients was 68.8 %, including four complete responses (2.1 %). Time to disease progression (TTP) and overall survival were 8.8 and 18.5 months, respectively. CONCLUSIONS: The safety and efficacy of first-line bevacizumab-based treatment in Chinese population with advanced NS-NSCLC are consistent with those in previous studies as well as in Asian subgroup population from SAiL study. No new safety signals were reported.

Comparison of tumor neovasculature-targeted paramagnetic nanoliposomes for MRI in mice xenograft models.

INTRODUCTION: Neovasculature imaging is a promising approach for tumor diagnosis. We constructed tumor neovasculature targeted paramagnetic nanoliposomes with RGD10, F56, and K237 peptides, which can bind to Integrin αvß3 and VEGFR-1, VEGFR-2, respectively, and compared their potential value as MRI contrast agents for detecting small tumors in animal models. MATERIALS AND METHODS: Peptide-Ahx-palmitic acid conjugate was synthesized using Fmoc solid-phase synthesis chemistry. Targeted paramagnetic nanoliposomes were prepared by the thin film dispersion-sonication method. The tumor signal enhancements of liposome particles were evaluated by MRI in a xenograft mice model. RESULTS: The apparent affinity constants of RGD10, K237, and F56 peptides binding to their cell receptors were 9.15 × 10(7), 6.01 × 10(7), and 3.85 × 10(7) mol/L, respectively. RGD10 and K237 targeted paramagnetic nanoliposomes have shown much greater tumor-specific MRI signal enhancement in xenograft of the nude mice compared to F56 targeted paramagnetic nanoliposome. Tumor signal enhancement rate (SER %) increased 2.21 ± 0.09 and 1.82 ± 0.05 fold, respectively, for RGD10 and K237 compared to non-targeted control in T1 weighted MR image. CONCLUSION: RGD10 and K237 targeted paramagnetic nanoliposomes can be developed as potential tumor-specific MRI contrast agents and are helpful for tumor detection.

Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study.

INTRODUCTION: This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives. METHODS: Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500 mg/m(2); 107 randomized; 106 treated) or docetaxel (75 mg/m(2); 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded. RESULTS: The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P>0.025 (efficacy retained=97.9% [95% CLs: 47.1, 141.9]; P=0.0276), in the combined population (pemetrexed: n=390, docetaxel: n=392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P=0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n=107, docetaxel: n=104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P=0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P=0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P=0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P=0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P=0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients). CONCLUSION: The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274.

Single nucleotide polymorphisms in NOS2A and NOS3 genes are not associated with treatment response of non-small cell lung cancer patients following the definitive radiochemotherapy.

Nitric oxide (NO), is endogenously synthesized from L-arginine by nitric oxide synthase (NOS), exhibits a dual role in sensitivity to radiotherapy and chemotherapy of cancer cells. The aim of this study was to evaluate the influence of polymorphisms in NOS genes on treatment response of non-small-cell lung cancer (NSCLC) patients after radiochemotherapy. A cohort of 198 NSCLC patients treated with radiochemotherapy between 2009 and 2011 were included in this study. Genotyping analyses of 35 SNPs ( NOS2A, 21 and NOS3, 14) in each sample were conducted by using the Sequenom MassArray system. Unconditional logistic regression was performed to assess the association between treatment response and each genotype while adjusting or not for other covariates. Of 198 patients, 87 (43.9%) had objective responses, and 111(56.1%) did not respond. We observed no significant associations between treatment response and each genotype. While adjusting for other covariates, the associations were also not significant. Our results suggest that genetic variations within the NOS2A and NOS3 genes may not influence the treatment response in NSCLC patients with radiochemotherapy. Future studies in this problem are required to confirm our findings.

The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats.

UNLABELLED: Ovariectomized (OVX) rats with tibial fracture received vehicle, ZA, PTH, or ZA plus PTH treatment for 4 and 8 weeks. Bone metabolism, callus formation, and the mass of undisturbed bone tissue were evaluated by serum analysis, histology, immunohistochemistry, radiography, micro-computerized tomography, and biomechanical test. INTRODUCTION: Previous studies have demonstrated the effect of ZA or PTH on osteoporotic fracture healing. However, reports about effects of ZA plus PTH on callus formation of osteoporotic fracture were limited. This study was designed to investigate the impact of combined treatment with ZA and PTH on fracture healing in OVX rats. METHODS: Twelve weeks after bilateral ovariectomy, all rats underwent unilateral transverse osteotomy on tibiae. Animals then randomly received vehicle, ZA (1.5 µg/kg weekly), PTH (60 µg/kg, three times a week), or ZA plus PTH until death at 4 and 8 weeks. The blood and bilateral tibiae of rats were harvested for evaluation. RESULTS: All treatments increased callus formation and strength other than the control; ZA + PTH showed the strongest effects on percent bone volume (BV/TV), trabecular thickness, total fluorescence-marked callus area, and biomechanical strength. Additionally, inhibited RANKL and enhanced osteoprotegerin expression were observed in the ZA + PTH group. But no difference in bone mineral density and BV/TV of the contralateral tibiae was observed between treated groups. CONCLUSION: Findings in this study suggested an additive effect of ZA and PTH on fracture healing in OVX rats, and this additive effect was specific to callus formation, not to undisturbed bone tissue.

[Anti-inflammatory and anti-allergic action of aloperine].

Aloperine, an alkaloid isolated from Sophora alopecuroides L, showed a marked suppressive effect on the swelling of the rat's hind paw induced by injecting carrageenin, macostatin, PGE2, histamine, 5-HT, on the rat's scald oedema induced by scalding its hind paw, and on the increased permeability of capillaries caused by histamine and the leukocytic migratory response. The swelling induced by injecting carrageenin into the hind paw of adrenolectomized rats was still significantly inhibited. Noticeably, aloperine reduced the content of PGE and histamine in the exudate formed after injecting carrageenin and dextran into the rat's hind paw, and increased the stability of red cell membranes, the activity of catalase (CAT) in hepatic tissue of mice, and reduced the content of malondialdehyde (MDA) in hepatic tissue of intoxicated mice. It had no apparent effect either on the activity of superoxide dismutase (SOD) in mice serum or on the phagocytosis of the monocyte-macrophage system, or on Forssman cutaneous vasculitis and the content of immune complex in serum of rats with Arthus reaction. But it had certain inhibitory effect on the PCA reaction and significant inhibitory effect upon such allergic reaction as Arthus reaction, reversible passive Arthus reaction, the delayed hypersensitivity reaction induced by tuberculin in rats, and adjuvant arthritis.