Metabolomics comparison of metabolites and functional pathways in the SH-SY5Y cell model of Parkinson's disease under PEMF exposure.

Objective: PEMF is an emerging technique in the treatment of Parkinson's disease (PD) due to its potential improvement of movement speed. The aim of this study was to investigate the metabolic profiles of pulsed electromagnetic fields (PEMFs) in an SH-SY5Y cell model of PD. Methods: The SH-SY5Y cell model of PD was induced by 1-methyl-4-phenylpyridinium (MPP+). Liquid chromatography mass spectrometry (LC‒MS)-based untargeted metabolomics was performed to examine changes in the PD cell model with or without PEMF exposure. We conducted KEGG pathway enrichment analysis to explore the potentially related pathways of the differentially expressed metabolites. Results: A total of 275 metabolites were annotated, and 27 significantly different metabolites were found between the PEMF treatment and control groups (VIP >1, P < 0.05), mainly including 4 amino acids and peptides, 4 fatty acid esters, 2 glycerophosphoethanolamines, 2 ceramides and 2 monoradylglycerols; among them, 12 metabolites were upregulated, and 15 were downregulated. The increased expression levels of glutamine, adenosine monophosphate and taurine were highly associated with PEMF stimulation in the PD model. The enrichment results of differentially abundant metabolite functional pathways showed that biological processes such as the mTOR signaling pathway, PI3K-Akt signaling pathway, and cAMP signaling pathway were significantly affected. Conclusion: PEMFs affected glutamine, adenosine monophosphate and taurine as well as their functional pathways in an in vitro model of PD. Further functional studies regarding the biological effect of these changes are required to evaluate the clinical efficacy and safety of PEMF treatment in PD.

Intravascular papillary endothelial hyperplasia of the spleen in a child: a case report.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a vascular tumor characterized by the proliferation of endothelial cells with papillary formation. It is a rare benign condition affecting the head and neck. Currently, no cases of IPEH of the spleen have been reported. Here, we report a case of IPEH of the spleen in a child and discuss its clinical manifestations, imaging features, and surgical treatment. CASE PRESENTATION: A 5-year-old female presented with a 4-month-old tumor in the left upper abdomen, abdominal pain, and constipation. She underwent radiography, barium enema, US, and MRI. A solid space-occupying mass was found in the left abdominal cavity on preoperative imaging, and it was diagnosed as angiosarcoma. The lesion was surgically resected. Histopathological analysis was consistent with IPEH. CONCLUSION: Clinicians should consider the possibility of IPEH in patients presenting with tumors in the spleen, which is curable by surgical resection. Malignant vascular tumors must be excluded in the differential diagnosis of IPEH to prevent misdiagnosis and inappropriate overtreatment.

Chiral Assembly and Recognition of Seven Copper (II) Coordination Polymers from Tartaric Acid Derivative Ligands.

A pair of enantiomeric ligands, (2R,3R)-dibenzyl-2,3-bis(isonicotinoyloxy)succinate ((R,R)-L) and (2S,3S)-dibenzyl-2,3-bis(isonicotinoyloxy)succinate ((S,S)-L), are designed and synthesized. Seven copper (II) coordination polymers {[Cu((R,R)-L)Br2 (THF)] ⋅ CH3 CN} n (1 a) and {[Cu((S,S)-L)Br2 (THF)] ⋅ CH3 CN}n (1 b), {[Cu((R,R)-L)Cl2 (THF)] ⋅ CH3 CN}n (2 a) and {[Cu((S,S)-L)Cl2 (THF)] ⋅ CH3 CN}n (2 b), {[Cu((R,R)-L)(NO3 )2 (CH3 CN)]}n (3 a) and {[Cu((S,S)-L)(NO3 )2 (CH3 CN)]}n (3 b), {[Cu((R,R)-L)2 (CH3 CN)2 ](ClO4 )2 ⋅ 3CH3 CN}n (4) were obtained through the assemblies with CuBr2 , CuCl2 ⋅ 2H2 O, Cu(NO3 )2 ⋅ 3H2 O, Cu(ClO4 )2 ⋅ 6H2 O, respectively. Single-crystal X-ray diffraction and circular dichroism analysis demonstrate that 1 a-3 a, 1 b-3 b have a mono chiral one-dimensional (1D) chain-like spiral structure, while 4 have 1D chain-like structure whose metal centers have chiral propeller coordination environment. Ligand structure, anions and solvent systems have a regulatory effect on the formation of chiral helical structure. Further investigation has proved that 1 a can be used as circular dichroism spectrum probe for monitoring L-/D-cysteine and L-/D-penicillamine configuration and concentration in aqueous media based on ligand interchange mechanism.

Malignant giant cell tumor in the left upper arm soft tissue of an adolescent: A case report.

BACKGROUND: Giant cell tumor of soft tissue (GCT-ST) is an extremely rare low-grade soft tissue tumor that is originates in superficial tissue and rarely spreads deeper. GCT-ST has unpredictable behavior. It is mainly benign, but may sometimes become aggressive and potentially increase in size within a short period of time. CASE SUMMARY: A 17-year-old man was suspected of having a fracture, based on radiography following left shoulder trauma. One month later, the swelling of the left shoulder continued to increase and the pain was obvious. Computed tomography (CT) revealed a soft tissue mass with strip-like calcifications in the left shoulder. The mass invaded the adjacent humerus and showed an insect-like area of destruction at the edge of the cortical bone of the upper humerus. The marrow cavity of the upper humerus was enlarged, and a soft tissue density was seen in the medullary cavity. Thoracic CT revealed multiple small nodules beneath the pleura of both lungs. A bone scan demonstrated increased activity in the left shoulder joint and proximal humerus. The mass showed mixed moderate hypointensity and hyperintensity on T1-weighted images, and mixed hyperintensity on T2-weighted fat-saturated images. The final diagnosis of GCT-ST was confirmed by pathology. CONCLUSION: GCT-STs should be considered in the differential diagnosis of soft tissue tumors and monitored for large increases in size.

Epidemiology of traumatic brain injury-associated epilepsy in western China: An analysis of multicenter data.

OBJECTIVES: This study aims to explore the probability of developing posttraumatic epilepsy (PTE) in the following 8 years after traumatic brain injury (TBI), the risk factors associated with PTE and its cumulative prevalence. METHODS: This is a retrospective follow-up study of patients with traumatic brain injury (TBI) discharged from the West China Hospital between January 1, 2011 and December 31, 2017, Chengdu Shang Jin Nan Fu Hospital and Sichuan Provincial People's Hospital from January 1, 2013 to March 1, 2015. We used forward stepwise method to build the final multivariate cox proportional hazard regression model to obtain estimates of hazard ratio (HR) of PTE and 95% confidence intervals (CI). We also conducted Kaplan-Meier survival analysis to investigate the cumulative prevalence of PTE. RESULTS: The cumulative incidence of PTE rose from 6.2% in one year to 10.6% in eight years. There were more male patients in PTE group and generally older. Besides, patients with PTE tended to have abnormal CT scan results. The risk factors of PTE were male (HR = 1.6, 95% CI: 1.1-2.2, P = 0.009), early posttraumatic seizures (HR = 2.9, 95% CI: 2.2-4.1, P < 0.001), TBI severity (moderate TBI: HR = 3.0, 95% CI: 1.8-5.0, P = 0.001; severe TBI: HR = 4.3, 95% CI: 2.3-7.6, P < 0.029), loss of consciousness (LOC) more than 30 min (30 min-24 h: HR = 1.8, 95% CI: 1.02-3.1, P = 0.041; >24 h: HR = 2.4, 95% CI: 1.4-2.4, P = 0.001), subdural hematoma (SDH) (HR = 1.9, 95% CI: 1.4-2.5, P < 0.001), brain contusion sites (frontal-temporal lobe: HR = 2.7, 95% CI: 1.9-3.9, P < 0.001; other sites: HR = 1.5, 95% CI: 1.01-2.3, P = 0.042) and cranial surgery (HR = 1.7, 95% CI: 1.3-2.3, P < 0.001). SIGNIFICANCE: The probability of developing PTE increased during the study period. In addition, the risk of developing PTE was significantly associated with gender, EPTS, LOC time, SDH, brain contusion sites, surgery and TBI severity. However, further researches may be needed to predict the risk of PTE in combination with quantitative factors.

The tolerability and safety profile of eslicarbazepine acetate in neurological disorders.

OBJECTIVES: This study aimed to assess the tolerability and safety profile of eslicarbazepine acetate (ESL). METHODS: Placebo controlled, double-blind randomized controlled trials (RCTs) were enrolled by searching Pubmed, Embase, Cochrane Online Library, and clinicaltrial.gov. Studies evaluating the safety of ESL on any neurological disorders were included. Adverse events (AEs), serious AEs and AEs-related withdrawals were pooled by direct or indirect meta-analysis. RESULTS: A total of 4067 patients in 13 RCTs (5 for refractory partial epilepsy, 2 for bipolar I disorder, 1 for migraine, 1 for fibromyalgia, 2 for diabetic neuropathic pain, and 2 for post-herpetic neuralgia) were included. Meta-analysis revealed that ESL treatment had a higher incidence of serious AEs and AEs-related withdrawals than the placebo. Of 35 reported AEs, 13 were significantly associated with ESL treatment, including blurred vision, diplopia, vertigo, nausea, vomiting, fatigue, dizziness, somnolence, headache, rash, hyponatraemia, increased gamma-glutamyl transferase, and dysarthria. Subgroup analysis revealed that dizziness was the only AE significant at 400 mg/day, while diplopia, nausea, vomiting, dizziness, somnolence, rash, and hyponatremia at 800 mg/day, and blurred vision, diplopia, vertigo, nausea, vomiting, fatigue, dizziness, somnolence, headache, rash, and hyponatremia at 1200 mg/day were significant. Adjunctive use of ESL in refractory epilepsy significantly led to higher risk for vestibulocerebellar AEs than other disorders. CONCLUSIONS: ESL treatment was related to a range of AEs, especially at high doses or when used as adjunctive therapy in epilepsy. While the majority of AEs of ESL were related to the vestibulocerebellar system, hyponatremia and rash should also be noted by clinicians.

Green Layer-by-Layer Assembly of Porphyrin/G-Quadruplex-Based Near-Infrared Nanocomposite Photosensitizer with High Biocompatibility and Bioavailability.

A simple and green layer-by-layer assembly strategy is developed for the preparation of a highly bioavailable nanocomposite photosensitizer by assembling near-infrared (NIR) light-sensitive porphyrin/G-quadruplex complexes on the surface of a highly biocompatible nanoparticle that is prepared via Zn2+-assisted coordination self-assembly of an amphiphilic amino acid. After being efficiently delivered to the target site and internalized into tumor cells via enhanced permeability and retention effect and interactions between aptamers and tumor markers, the as-prepared nanoassembly can be directly used as an NIR light-responsive photosensitizer for tumor photodynamic therapy (PDT) since the porphyrin/G-quadruplex complexes are exposed on the nanoassembly surface and kept in an active state. It can also disassemble under the synergistic stimuli of an acidic pH environment and overexpressed glutathione, leasing more efficient porphyrin/G-quadruplex composite photosensitizers while reducing the interference caused by glutathione-dependent 1O2 consumption. Since the nanoassembly can work no matter if it is disassembled or not, the compulsory requirement for in vivo photosensitizer release is eliminated, thus resulting in the great improvement of the bioavailability of the photosensitizer. The PDT applications of the nanoassembly were well demonstrated in both in vitro cell and in vivo animal experiments.

A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer.

PURPOSE: We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify the best strategy for HER2+ metastatic breast cancer (MBC). METHODS: Pubmed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials that evaluated any taxanes+HER2-targeted agents in the treatment of HER2+ MBC. The primary outcome was overall survival (OS). The secondary outcomes included overall response rate (ORR) and progression-free survival (PFS). RESULTS: A total of 13 RCTs were eligible, involving 4941 patients and 10 regimens. The result showed that single-HER2-targeted agent+a taxane did improve the effect on ORR and PFS than taxane alone, but only trastuzumab+a taxane had a significant improvement in OS outcomes. Single-HER2-targeted agent (trastuzumab) combined with taxane-based doublets (taxane+carboplatin/capecitabine/doxorubicin/bevacizumab) showed no further benefit than trastuzumab+a taxane. Doublet-HER2-targeted agents combined with a taxane(trastuzumab+pertuzumab+a taxane) showed further improvement in ORR, PFS, and all OS outcomes than single-HER2-targeted agent+a taxane. Ranking analysis based on their P-scores suggested that trastuzumab+pertuzumab+a taxane was the best combination treatment for all the efficacy outcomes. CONCLUSIONS: These findings demonstrate that combining two HER2-targeted agents (trastuzumab+pertuzumab) with a taxane is much more beneficial for the treatment of HER2+ MBC. Dual HER2-targeted agents combined with a taxane appears to be the preferred application of HER2+ MBC.

Comparative Effectiveness of Taxane-Containing Regimens for Treatment of HER2-Negative Metastatic Breast Cancer: A Network Meta-analysis.

STUDY OBJECTIVES: To compare the effectiveness of different taxane-containing regimens and to identify the best strategy for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). DESIGN: Network meta-analysis of 20 randomized controlled trials (RCTs). PATIENTS: A total of 6577 patients with HER2-negative MBC who received treatment (20 different regimens) with taxanes (paclitaxel [4267 patients] or docetaxel [2310 patients]). MEASUREMENTS AND MAIN RESULTS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched (through March 2019) for RCTs that evaluated any taxane-containing regimens for the treatment of HER2-negative MBC. A network meta-analysis in a Bayesian framework was performed using the random-effects model. We compared the surface under the cumulative ranking (SUCRA) curve for each regimen. Overall, paclitaxel-based combinations were superior to paclitaxel alone in objective response rate (ORR) (odds ratio 1.60, 95% credible interval [CrI] 1.15-2.16) and overall survival (OS) (hazard ratio 1.08, 95% CrI 1.01-1.15). Docetaxel-based combinations were also superior to paclitaxel alone in ORR. Among the paclitaxel-based regimens, based on the results of SUCRA, paclitaxel + bevacizumab + capecitabine was likely to be the most efficacious in improving ORR, OS, and progression-free survival (PFS), whereas paclitaxel + gemcitabine was likely to be the most efficacious in 1-year OS rate. Among the docetaxel-based regimens, based on the results of SUCRA, docetaxel + gemcitabine was likely to be the most efficacious in improving PFS and OS. CONCLUSION: These findings demonstrated that paclitaxel-based combinations can provide significant improvement in ORR and OS compared with paclitaxel alone. The regimens of paclitaxel + bevacizumab + capecitabine, docetaxel + gemcitabine, and paclitaxel + gemcitabine may be superior to other regimens for the treatment of HER2-negative MBC.

G-Quadruplex/Porphyrin Composite Photosensitizer: A Facile Way to Promote Absorption Redshift and Photodynamic Therapy Efficacy.

Photosensitizer is one of the most important elements of photodynamic therapy (PDT). Herein, we reported a novel strategy to prepare a new series of composite photosensitizers. The composite photosensitizer was prepared by simply mixing DNA G-quadruplexes with a hydrophilic porphyrin (TMPipEOPP)4+·4I-. Compared with the conventional porphyrin photosensitizers, the excitation wavelength of the composite one has been ∼50 nm redshifted (from 650 to 700 nm), which is beneficial to the penetration of the light. Moreover, the composite photosensitizer showed an about 7.4-fold increase of light absorption efficiency, thus greatly enhancing the singlet oxygen (1O2) generation capacity and PDT efficacy. What is more, the introduction of nucleic acids in the composite photosensitizer could also provide some extra charming properties, such as the targeted recognition ability conferred by aptamer and high capability to assemble with various drug carriers. We demonstrated that the composite photosensitizer could be easily assembled with MnO2 nanosheet. The obtained nanodevice integrated the merits of a composite photosensitizer and MnO2 nanosheet, thus showing strong near-infrared absorption, high 1O2 generation efficiency, avoidance of nonideal 1O2 consumption by glutathione, and in situ O2 generation to relieve tumor hypoxia. This nanodevice showed greatly improved PDT efficacy both in vitro and in vivo, presenting a huge potential for applications in clinical therapy for tumors.

Predictors of seizure reduction outcome after vagus nerve stimulation in drug-resistant epilepsy.

PURPOSE: To evaluate the predictors of seizure reduction outcome after vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE). METHODS: A meta-analysis was performed using relevant research from databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to predefined inclusion and exclusion criteria. The quality of studies was evaluated by using the Newcastle-Ottawa Scale (NOS) scale. All data was pooled by STATA 12.0 software for meta-analysis. RESULTS: The review considered 1281 articles, and 16 articles with NOS score ≥6 were included in the analysis. The meta-analysis showed that at 6 m, 1, 2, 3, 4, 6 and 12 years after implantation, 33.99, 43.42, 46.50, 63.31, 52.71, 54.64, 70.37 and 82.90% of patients exhibited >50% reduction of seizure frequency after VNS. The duration of epilepsy showed a significant difference between the good responders and poor responders (p = 0.038), whereas age at VNS implantation (p = 0.305), age at seizure onset (p = 0.530), seizure type (p = 0.11), etiology (p = 0.187), and history of previous epilepsy surgery (p = 0.075) were not predictors of seizure reduction outcome after VNS. Several features about the electroencephalogram (EEG) feature and heart rhythm complexity (HRV) have not been analyzed by a sufficient number of studies. CONCLUSIONS: DRE patients with shorter duration of epilepsy may be better candidates for VNS rather than those who are younger at onset and implantation. Several EEG or HRV features may have predictive value but more research is needed.

Curcumin intervention for cognitive function in different types of people: A systematic review and meta-analysis.

Curcumin is a polyphenolic natural compound with diverse and attractive biological activities, which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia, or mood disorders. However, clinical trials and animal studies have yielded conflicting conclusions regarding its effectiveness for cognition in different individuals. The aim of this review is to meta-analytically assess the effectiveness of curcumin for cognitive function in different types of people. A preliminary search on PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang Data and China Biology Medicine disc was performed to identify randomized controlled trials investigating the effect of curcumin on cognition. Six clinical trials with a total of 289 subjects met inclusion criteria for this review. We used a random-effects model to calculate the pooled standardized difference of means (SMD). For older adults who received curcumin, scores on measures of cognitive function (SMD = 0.33, 95% confidence interval [CI] [0.05, 0.62]; p = 0.02), occurrence of adverse events (odds ratio [OR] = 5.59, 95% CI [0.96, 36.80]; p = 0.05), and measures of depression (SMD = -0.29, 95% CI [0.64, 0.05]; p = 0.09) indicated significant memory improvement. In patients with Alzheimer's disease (AD), scores in measures of cognition status (SMD = -0.90, 95% CI [1.48, -0.32]; p = 0.002) indicated that there was a trend for treated subjects to do worse than placebo-treated subjects on the Mini-Mental State Examination. The occurrence of adverse events (OR = 0.87, 95% CI [0.10, 7.51]; p = 0.90) was similar to those who received placebo. Due to insufficient data, it was impossible to provide a narrative account of only the outcomes for schizophrenia. Curcumin appears to be more effective in improving cognitive function in the elderly than in improving symptoms of AD and schizophrenia. Curcumin is also safe and tolerated among these individuals. Because of the small number of studies available, a funnel plot or sensitivity analysis was not possible. Further high-quality trials with larger sample sizes or bioavailability-improved curcumin formulations may be considered for reliable assessment.

Asymmetric Cationic Porphyrin as a New G-Quadruplex Probe with Wash-Free Cancer-Targeted Imaging Ability Under Acidic Microenvironments.

Porphyrins are promising candidates for nucleic acid G-quadruplex-specific optical recognition. We previously demonstrated that G-quadruplex recognition specificity of porphyrins could be improved by introducing bulky side arm substituents, but the enhanced protonation tendency limits their applications in some cases, such as under acidic conditions. Here, we demonstrated that the protonation tendency of porphyrin derivatives could be efficiently overcome by increasing molecular asymmetry. To validate this, an asymmetric, water-soluble, cationic porphyrin FA-TMPipEOPP (5-{4-[2-[[(2 E)-3-[3-methoxy-4-[2-(1-methyl-1-piperidinyl)ethoxy]phenyl]-1-oxo-2-propenyl]oxy]ethoxy]phenyl},10,15,20-tri{4-[2-(1-methyl-1-piperidinyl)ethoxy]-phenyl}porphyrin) was synthesized by introducing a ferulic acid (FA) unit at one side arm, and its structure was well-characterized. Unlike its symmetric counterpart TMPipEOPP that has a tendency to protonate under acidic conditions, FA-TMPipEOPP remained in the unprotonated monomeric form under the pH range of 2.0-8.0. Correspondingly, FA-TMPipEOPP showed better G-quadruplex recognition specificity than TMPipEOPP and thus might be used as a specific optical probe for colorimetric and fluorescent recognition of G-quadruplexes under acidic conditions. The feasibility was demonstrated by two proof-of-concept studies: probing structural competition between G-quadruplexes and duplexes and label-free and wash-free cancer cell-targeted bioimaging under an acidic tumor microenvironment. As G-quadruplex optical probes, FA-TMPipEOPP works well under acidic conditions, whereas TMPipEOPP works well under neutral conditions. This finding provides useful information for G-quadruplex probe research. That is, porphyrin-based G-quadruplex probes suitable for different pH conditions might be obtained by adjusting the molecular symmetry.

[Association between IL-6 C-572G and susceptibility to spontaneous preterm birth].

OBJECTIVE: To investigate the association between the genetic polymorphism of IL-6 C-572G and susceptibility to spontaneous preterm birth (SPTB). METHODS: The subjects were from Beijing and the surrounding areas of Beijing. This case-control study enrolled 569 SPTB infants, including 56 extremely preterm (<28 weeks of gestation), 166 very preterm (28-31+6 weeks of gestation) and 347 moderate to late preterm infants (32 to 36+6 weeks of gestation). A total of 673 term infants were enrolled as the control group. The latest Sequenom MassARRAY®SNP detection technique was used for the typing of single nucleotide polymorphism of IL-6 C-572G. RESULTS: Compared with the CC genotypes, the IL-6 C-572G G-positive genotype (CG+GG genotype) was significantly associated with an increased susceptibility to moderate to late SPTB (OR=1.35, 95%CI: 1.01-1.80, P=0.04). CONCLUSIONS: Among the Chinese population, IL-6 C-572G polymorphism is associated with susceptibility to moderate to late SPTB.

Sensitive fluorescent detection of DNA methyltransferase using nicking endonuclease-mediated multiple primers-like rolling circle amplification.

Sensitive and reliable detection of DNA methyltransferase (MTase) is of great significance for both early tumor diagnosis and therapy. In this study, a simple, label-free and sensitive DNA MTase-sensing method was developed on the basis of a nicking endonuclease-mediated multiple primers-like rolling circle amplification (RCA) strategy. In this method, a dumbbell RCA template was prepared by blunt-end ligation of two molecules of hairpin DNA. In addition to the primer-binding sequence, the dumbbell template contained another three important parts: 5'-CCGG-3' sequences in double-stranded stems, nicking endonuclease recognition sites and C-rich sequences in single-stranded loops. The introduction of 5'-CCGG-3' sequences allows the dumbbell template to be destroyed by the restriction endonuclease, HpaII, but is not destroyed in the presence of the target MTase-M.SssI MTase. The introduction of nicking endonuclease recognition sites makes the M.SssI MTase-protected dumbbell template-mediated RCA proceed in a multiple primers-like exponential mode, thus providing the RCA with high amplification efficiency. The introduction of C-rich sequences may promote the folding of amplification products into a G-quadruplex structure, which is specifically recognized by the commercially available fluorescent probe thioflavin T. Improved RCA amplification efficiency and specific fluorescent recognition of RCA products provide the M.SssI MTase-sensing platform with high sensitivity. When a dumbbell template containing four nicking endonuclease sites is used, highly specific M.SssI MTase activity detection can be achieved in the range of 0.008-50U/mL with a detection limit as low as 0.0011U/mL. Simple experimental operation and mix-and-detection fluorescent sensing mode ensures that M.SssI MTase quantitation works well in a real-time RCA mode, thus further simplifying the sensing performance and making high throughput detection possible. The proposed MTase-sensing strategy was also demonstrated to be applicable for screening and evaluating the inhibitory activity of MTase inhibitors.

[Association between tumor necrosis factor-α G-308A polymorphisms and genetic susceptibility to spontaneous preterm birth].

OBJECTIVE: To study the association between tumor necrosis factor-α (TNF-α) G-308A polymorphisms and genetic susceptibility to spontaneous preterm birth (SPTB). METHODS: The case group enrolled 753 SPTB infants and the control group included 681 term infants. TNF-α G-308A polymorphisms were genotyped using Sequenom MassARRAY®SNP. RESULTS: The frequencies of the allele (G and A) in the case and control groups were not significantly different (P=0.35). The frequencies of the genotypes (GG, GA and AA) in the case and control groups were not significantly different (P=0.64). The logistic regression analysis found that TNF-α G-308A was not associated with genetic susceptibility to SPTB (OR=0.85; 95%CI: 0.61-1.19; P=0.35). CONCLUSIONS: There is no association between the polymorphisms of TNF-α G-308A and the genetic susceptibility to SPTB.

[Folic acid modified polyrotaxanes effectively transfer si RNA-CD47 to inhibit the proliferation of melanoma].

To investigate the effect that folic acid-modified polyrotaxanes(FPP) transfered siRNA CD47 to inhibit melanoma proliferation, the expression of CD47 in clinical melanoma patients was tested by Western blot and RT-PCR, respectively. Physical performance of FPP(siRNA-CD47: CD47) nanoparticles was tested by Malvern particle size instrument and scanning electron microscope. The clone formation experiment demonstrated that FPP(CD47) nanoparticles inhibited the growth of clones. Invasion assay revealed that FPP(CD47) inhibited migration of B16F10 cells. Tumor bearing mice were used in the experiment to test the efficacy of FPP(CD47) treatment. Compared with the control group, high expression of CD47 was observed in the clinical melanoma patients. FPP(CD47) nanoparticle size at 80 nm exhibited a potential of 10 m V; compared with FPP(Con), fluorescence intensity was significantly reduced to 4.2% and B16F10 cell clone formation was decreased by 91% in the FPP(CD47) treatment. Tumor volume of tumor-burdened mice was decreased by 90% with FPP(CD47) treatment. FPP(CD47) lowered CD47 protein and m RNA expression in the tumor. This study suggests that FPP may transfer siRNA CD47 into the cancer cells to inhibit melanoma growth effectively.

Antitumor Compounds from the Stout Camphor Mushroom Taiwanofungus camphoratus (Higher Basidiomycetes) Spent Culture Broth.

A known compound, 5-(hydroxymethyl) furan-2-carbaldehyde, and a novel compound, 3-isobutyl-1-methoxy-4-(4'-(3-methylbut-2-enyloxy)phenyl)-1H-pyrrole-2,5-dione were isolated from spent broth from submerged cultures of Taiwanofungus camphoratus. Their structures were elucidated by nuclear magnetic resonance (1H, 13C, and 2D) and mass spectra. These compounds inhibited the proliferation of K562 and HepG2 tumor cells in vitro.

Cisplatin-based chronotherapy for advanced non-small cell lung cancer patients: a randomized controlled study and its pharmacokinetics analysis.

PURPOSE: We intended to evaluate the superiority of cisplatin-based chronotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and investigate the relationship between the circadian rhythm and the variability of pharmacokinetics for cisplatin. METHODS: Forty-one patients with advanced NSCLC were divided into two groups with minimization randomization, including routine group (24 cases) and chronotherapy group (17 cases). The clinical effect and toxicity between the two groups were investigated. The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling method. RESULTS: There is no significant difference in total response rate between chronotherapy group (52.94%) and routine chemotherapy group (50.00%), p = 0.853. The rate of leucopenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy (37.50%), p < 0.05. The rate of neutropenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy group (33.33%), p < 0.05. The proportion of gastrointestinal toxicity (nausea, grade 1 vs 2) in chronotherapy group is significantly lower than that in routine chemotherapy, p < 0.05. When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (p < 0.05). CONCLUSIONS: Cisplatin-based chronotherapy has advantage in relieving side effects of chemotherapy, and circadian could influence the metabolism of cisplatin, and more clinical researches are needed.

[Analysis of MLC1 gene mutation in a Chinese family with megalencephalic leukoencephalopathy with subcortical cysts].

The clinical data of a patient with megalencephalic leukoencephalopathy (MLC) with subcortical cysts and her parents were collected. MLC1 gene mutation was detected by polymerase chain reaction and direct DNA sequencing. The patient presented with motor developmental delay and giant skull, and brain magnetic resonance imaging showed diffuse white matter swelling accompanied by subcortical cysts in bilateral frontal and parietal lobes. Gene sequencing identified two heterozygous mutations of MLC1, including missense mutation in exon 3 (c.217G>A, p.Gly73Arg) and splice site mutation in intron 9 (c.772-1G>C in IVS9-1). The patient's parents both had heterozygous mutation c.772-1G>C in IVS9-1 with normal phenotype. It can be presumed that c.772-1G>C in IVS9-1 comes from the parents, and c.217G>A (p.Gly73Arg) is a de novo mutation.