Rs4265085 in GPER1 gene increases the risk for unexplained recurrent spontaneous abortion in Dai and Bai ethnic groups in China.

Oestrogen receptors are implicated in the pathogenesis of recurrent spontaneous abortion (RSA). Non-genomic oestrogen responses can be mediated by GPER. The prevalence of polymorphisms in GPER1 gene in RSA was assessed in 747 Chinese women from Yunnan province (171 Bai, 258 Chinese Han, 234 Dai, 33 Achang and 51 Jingpo patients). Snapshot technology was used for genotyping the polymorphisms of the GPER1 gene. The rs4265085G was significantly increased in the Dai and Bai groups versus controls (Dai: P < 0.0001, Padj < 0.0001, OR 95% CI 2.34 [1.79 to 3.05]; Bai: P = 0.0004, Padj = 0.0012, OR 95% CI 1.71 [1.27 to 2.31]); recessive model of rs4265085 in the Dai (P = 0.003, Padj = 0.009, OR 95% CI 2.71 [1.38 to 5.30]); Bai (P < 0.0001, Padj < 0.0001, OR 95% CI 3.37 [1.93 to 5.91]). Haplotype frequencies containing rs10269151G-rs4265085G-rs11544331C were separately significantly different in Dai and Bai ethnic groups (Dai: P = 0.0002, Padj = 0.001, OR 95% CI = 2.12 [1.43 to 3.17]; Bai: P = 0.005, Padj = 0.025, OR 95% CI = 1.82 [1.18 to 2.78]) compared with controls. The intron variant rs4265085 may confer risk for RSA in Dai and Bai ethnic groups.

Lithium down-regulates histone deacetylase 1 (HDAC1) and induces degradation of mutant huntingtin.

Lithium is an effective mood stabilizer that has been clinically used to treat bipolar disorder for several decades. Recent studies have suggested that lithium possesses robust neuroprotective and anti-tumor properties. Thus far, a large number of lithium targets have been discovered. Here, we report for the first time that HDAC1 is a target of lithium. Lithium significantly down-regulated HDAC1 at the translational level by targeting HDAC1 mRNA. We also showed that depletion of HDAC1 is essential for the neuroprotective effects of lithium and for the lithium-mediated degradation of mutant huntingtin through the autophagic pathway. Our studies explain the multiple functions of lithium and reveal a novel mechanism for the function of lithium in neurodegeneration.

[Identification of null and duplicated alleles for forensic DYS549, DYS527 and DYS459 in male infertility population].

DYS549, DYS527, and DYS459 loci, located on the azoospermia factor (AZF) region and widely used in forensic and pedigree analysis, may be specifically altered in infertile patients, which will obscure the result of individual identification using Y-STR (Y chromosome short tandem repeat). In this study, we determined the AZF polymorphism by STS(-/-) (sequence tagged site) and DAZ, CDY1 gene copy numbers, and screened the samples by 14 Y-STR loci to disclose the unusual genotype of Y-STR in male infertility population. The 240 infertile males including non-obstructive azoospermia, severe oligozoospermia and congenital bilateral absence of vas deferens (CBVAD) were analyzed with a modified multiplex PCR system for AZF microdeletion STSs. AZF microdeletions were found in 40 cases (16.67%) (AZFa deletion, two cases; AZFb deletion, two cases; AZFc deletion, 30 cases; AZFb+c deletion, six cases). Further screening by the 14 Y-STR loci in samples with microdeletions, we found DYS549 allelic loss in all the cases with AZFb deletion, DYS527 and DYS459 allelic loss in all the cases with AZFc deletion, DYS549, DYS527, and DYS459 allelic loss in all the cases with AZFb+c deletion. Ten patients (4.17%) with AZFc partial duplication (one CBVAD case, two non-obstructive azoospermia cases, seven severe oligozoospermia cases) were found by DAZ and CDY1 gene dosage analysis. In conclusion, the unusual patterns of DYS549, DYS527, and DYS459 are caused by genetic defects rather than experimental bias. Revealing the locus heterogeneity in male infertility population can enrich the Y-STR database and assist in interpreting abnormal STR genotype in forensic DNA testing.

Cloning, bioinformatics and the enzyme activity analyses of a phenylalanine ammonia-lyase gene involved in dragon's blood biosynthesis in Dracaena cambodiana.

Phenylalanine ammonia-lyase (PAL) is the key enzyme of the phenylpropanoid pathway, playing an important role in plant development and defence. We cloned a partial cDNA of PAL gene, DcPAL1, from Dracaena cambodiana seedlings using RT-PCR with degenerate primers that were designed based on a multiple sequence alignment of known PAL genes from other plant species. DcPAL1 shows highly homologous to other known PAL genes registered in GenBank, being closest to that of Musa acuminata. DcPAL1 has a relatively high GC content and most of the GC is in the third codon position. It has 768 bp in size with a maximum open reading frame (ORF) of 765 bp, encoding a 255 amino acid-polypeptide. The deduced PAL protein is a stable protein, having classical PAL domains and consisting of three major hydrophobic domains. Analysis of effective number of codons (ENC) shows that DcPAL1 codons are used at equal frequency. Relatively higher usage frequency appears randomly in codons ended with any of the four bases; six codons have no usage bias. There are 45 codons showing distinct usage preference between DcPAL1 and E. coli, 20 between DcPAL1 and yeast. Therefore, the yeast system may be more suitable for the expression of DcPAL1. Upon the elicitation of Fusarium proliferatum, a potent elicitor of dragon's blood, the PAL enzyme activity in the leaves and stems of D. cambodiana and other two Dracaena spp. significantly increased, accompanying with the formation of dragon's blood, indicating the involvement of PAL in the biosynthesis of dragon's blood, a precious traditional medicine.

Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model.

AIM: The tumor suppressor in lung cancer-1 (TSLC1) is a candidate tumor suppressor of lung cancer, and frequently inactivated in primary non-small cell lung cancer (NSCLC). In this study, we investigated the effects of TSLC1 mediated by a dual-regulated oncolytic adenovirus on lung cancer, and the mechanisms underlying the antitumor actions. METHODS: The recombinant virus Ad·sp-E1A(Δ24)-TSLC1 was constructed by inserting the TSLC1 gene into the dual-regulated Ad·sp-E1A(Δ24) vector, which contained the survivin promoter and a 24 bp deletion within E1A. The antitumor effects of Ad·sp-E1A(Δ24)-TSLC1 were evaluated in NCI-H460, A549, and H1299 lung cancer cell lines and the normal fibroblast cell line MRC-5, as well as in A549 xenograft model in nude mice. Cell viability was assessed using MTT assay. The expression of TSLC1 and activation of the caspase signaling pathway were detected by Western blot analyses. The tumor tissues from the xenograft models were examined using H&E staining, IHC, TUNEL, and TEM analyses. RESULTS: Infection of A549 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced high level expression of TSLC1. Furthermore, the Ad·sp-E1A(Δ24)-TSLC1 virus dose-dependently suppressed the viability of NCI-H460, A549, and H1299 lung cancer cells, and did not affect MRC-5 normal fibroblast cells. Infection of NCI-H460, A549, and H1299 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced apoptosis, and increased activation of caspase-8, caspase-3 and PARP. In A549 xenograft model in nude mice, intratumoral injection of Ad·sp-E1A(Δ24)-TSLC1 significantly suppressed the tumor volume, and increased the survival rate (from less than 15% to 87.5% at d 60). Histological studies showed that injection of Ad·sp-E1A(Δ24)-TSLC1 caused tumor cell apoptosis and virus particle propagation in tumor tissues. CONCLUSION: The oncolytic adenovirus Ad·sp-E1A(Δ24)-TSLC1 exhibits specific antitumor effects, and is a promising agent for the treatment of lung cancer.

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest.

AIM: Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP were explored. METHODS: Human osteosarcoma cell line MG63 and human MDR osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was examined using a cell proliferation assay with the Cell Counting Kit-8 (CCK-8). The distribution of cells across the cell cycle was determined with flow cytometry. The expression of cell cycle-regulated genes cyclin B1 and Cdc2 (CDK1), and the phosphorylated Cdc2 and Cdc25C was examined using Western blot analyses. RESULTS: MG63/DOX cells were highly resistant to doxorubicin (ADM) and gemcitabine (GEM), but were sensitive or lowly resistant to THP, methotrexate (MTX) and cisplatin (DDP). Treatment of MG63/DOX cells with THP (200-1000 ng/mL) inhibited the cell proliferation in time- and concentration-dependent manners. THP (50-500 ng/mL) induced MG63/DOX cell cycle arrest at the G(2)/M phase in time- and concentration-dependent manners. Furthermore, the treatment of MG63/DOX cells with THP (200-1000 ng/mL) downregulated cyclin B1 expression, and decreased the phosphorylated Cdc2 at Thr(161). Conversely, the treatment increased the phosphorylated Cdc2 at Thr(14)/Tyr(15) and Cdc25C at Ser(216), which led to a decrease in Cdc2-cyclin B1 activity. CONCLUSION: The cytotoxicity of THP to MG63/DOX cells may be in part due to its ability to arrest cell cycle progression at the G(2)/M phase, which supports the use of THP for managing patients with MDR osteosarcoma.

Cost-effectiveness analysis of 4 GLP-1RAs in the treatment of obesity in a US setting.

Background: The number of obese people continues to increase worldwide, and obesity-related complications add to every country's health burden. Consequently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), are attracting increasing attention. This study sought to assess the cost effectiveness for weight loss of 4 GLP-1RAs in adult patients with obesity in the United States. Methods: Four GLP-1RA groups that received Liraglutide (1.8 mg QD), Semaglutide (1.0 mg QW), Dulaglutide (1.5 mg QW), or Exenatide (10 µg BID), and one no-treatment group were compared using a decision-tree model. All the estimated parameters were derived from published articles. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were adopted as the study endpoints. We analyzed the results with the willingness-to-pay (WTP) threshold, and conducted deterministic and probabilistic sensitivity analyses. Results: The GLP-1RAs produced effective weight-loss results; however, not all the GLP-1RAs were cost effective compared to no treatment based on a WTP threshold of $195000/QALY. Among the 4 GLP-1RAs, Semaglutide provided a cost-effective strategy with an ICER of $135467/QALY. The sensitivity analyses showed that these results are reliable. Conclusions: Among the 4 GLP-1RAs, Semaglutide was the most cost-effective obesity medication.

[Simultaneous determination of trihexyphenidyl, chlorpromazine and clozapine in blood by GC-MS].

OBJECTIVE: To develop a method to measure trihexyphenidyl, chlorpromazine and clozapine in human blood with GC-MS. METHODS: The specimens were alkalized (pH > 10) and extracted with V (benzene):V(ethyl acetate) = 1:1, and qualitatively analyzed using GC-MS-Full Scan with internal standard SKF525A. The specimens were alkalized (pH > 10) and extracted with V(benzene):V(ethyl acetate) = 1:1, and quantitatively analyzed using GC-MS-SIM with internal standard diazepam-d5. RESULTS: The lowest detection limits of trihexyphenidyl, chlorpromazine and clozapine were 0.3, 0.3 and 0.7 ng/mL (S/N > or = 3) respectively. The calibration curve in 20-10 000 ng/mL showed a good linear distribution. The recovery rate was 79.9% to 85.5%. The RSDs of intraday and interday were less than 5.1%. CONCLUSION: The established method was simple, sensitive and accurate for simultaneous determination of trihexyphenidyl, chlorpromazine and clozapine in human blood, and can be applied in forensic toxicological cases.

Botrychium schaffneri Underw. extract acts via DIABLO to induce apoptosis and inhibit proliferation of non-small cell lung carcinoma in vitro and in vivo.

BACKGROUND: Botrychium schaffneri Underw. has been popularly consumed since ancient times as a traditional medicine in China to treat whooping cough, bronchial asthma, and febrile convulsive twitch disease. This led us to investigate whether Botrychium schaffneri Underw. extract (BSE) may be effective against lung cancer, especially non-small cell lung carcinoma (NSCLC). METHODS: In this study, we extracted the ethanolic root extract of the grass, Botrychium schaffneri Underw. In vitro study, the change of NCI-H1299 cell proliferation was observed with CCK8 and MTT assays. Cell apoptosis was assessed using a kit based on staining with FITC-conjugated annexin V. In vivo study, we establish a stable animal model of NSCLC in nude mice, tumor volume and weight was measured twice a week. We conduct gene microarray screened for differentially expressed genes (DEGs), between NCI-H1299 cells treated by BSE or not. Then the DEGs were functionally annotated and path enriched. RESULTS: It was revealed that BSE significantly suppressed NSCLC cell proliferation (IC50 134 µg/mL) and induced apoptosis. It also slowed tumor growth without affecting body weight, and a dose of 25 g/kg led to significantly smaller tumors than in control animals (13.85±3.36 vs. 23.40±6.05, P=0.044). Apoptosis-related protein direct IAP Binding protein with low PI (DIABLO) expression was up-regulated by BSE, and DIABLO knockdown significantly attenuated the anti-tumor effects of the extract. CONCLUSIONS: In conclusion, BSE reduces the viability of NSCLC cells and promotes apoptosis, and these effects may be mediated by DIABLO.

P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis.

Yes-associated protein 1 (YAP1), a key player in the Hippo pathway, has been shown to play a critical role in tumor progression. However, the role of YAP1 in prostate cancer cell invasion, migration, and metastasis is not well defined. Through functional, transcriptomic, epigenomic, and proteomic analyses, we showed that prolyl hydroxylation of YAP1 plays a critical role in the suppression of cell migration, invasion, and metastasis in prostate cancer. Knockdown (KD) or knockout (KO) of YAP1 led to an increase in cell migration, invasion, and metastasis in prostate cancer cells. Microarray analysis showed that the EMT pathway was activated in Yap1-KD cells. ChIP-seq analysis showed that YAP1 target genes are enriched in pathways regulating cell migration. Mass spectrometry analysis identified P4H prolyl hydroxylase in the YAP1 complex and YAP1 was hydroxylated at multiple proline residues. Proline-to-alanine mutations of YAP1 isoform 3 identified proline 174 as a critical residue, and its hydroxylation suppressed cell migration, invasion, and metastasis. KO of P4ha2 led to an increase in cell migration and invasion, which was reversed upon Yap1 KD. Our study identified a novel regulatory mechanism of YAP1 by which P4HA2-dependent prolyl hydroxylation of YAP1 determines its transcriptional activities and its function in prostate cancer metastasis.

The expression of CRM1 is associated with prognosis in human osteosarcoma.

The nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) is involved in the nuclear export of proteins and messenger RNAs and, thus, mediates the subcellular distribution of important molecules. Osteosarcoma is a ubiquitous and highly aggressive malignant bone tumor. The expression of CRM1 protein in human osteosarcoma has not been reported to date. We investigated the expression of CRM1 in 57 human osteosarcoma and 5 normal cartilage tissues. Western blot investigation revealed expression of CRM1 was significantly increased in osteosarcoma compared with normal tissues. High expression of CRM1 was significantly associated with increased serum level of alkaline phosphatase (ALP, P=0.001) but did not associate with that of lactate dehydrogenase (LDH, P=0.06). In univariate analysis, a significant association between CRM1 expression and tumor size (P=0.014) as well as histological grade (P=0.003) was observed, while high CRM1 expression was not correlated with the other clinicopathological parameters. In Kaplan-Meier survival analysis, high CRM1 expression was a significant prognostic indicator for progression-free survival (P=0.016) as well as overall survival (P=0.008). Multivariate analysis demonstrated that expression of CRM1 was an independent prognostic parameter for longer overall survival (95% CI, 1.27-5.39). Additional prospective studies are required to investigate the prognostic role of high expression of CRM1.

Relationship of serum methotrexate concentration in high-dose methotrexate chemotherapy to prognosis and tolerability: A prospective cohort study in chinese adults with osteosarcoma.

BACKGROUND: Cancer that originates in the bone, termed primary bone cancer, is rare. Osteosarcoma (OS) occurs primarily in growing bone tissue and is more prevalent in children and adolescents. OS in adults is rare, with 3 to 5 cases per million population per year worldwide. There are limited data on treatment-related prognosis and adverse reactions in adults reported in the literature. OBJECTIVES: The aims of this study were to investigate factors that influence serum methotrexate (MTX) concentrations used in chemotherapy in Chinese adult patients with OS, and to determine the correlations (based on age, sex, and dosage), if any, between MTX and prognosis, in terms of disease-free survival (DFS) and overall survival (OAS), and tolerability. METHODS: Adult patients aged ≥30 years with OS received ≥3 courses (2 courses before surgery and 3-4 courses postsurgery) of high-dose MTX (6 or 8 g/m(2)) combined chemotherapy. The regimen consisted of day 1: MTX + folinic acid (herein referred to as citrovorum factor rescue); day 8: cisplatin; days 21 to 25: ifosfamide + mesna; and day 21: doxorubicin. Serum MTX concentrations were assessed immediately after the end of infusion (baseline) and at 24 and 48 hours using high-performance liquid chromatography. Changes in serum MTX concentrations, factors that influence serum MTX concentrations, and the relationship between serum MTX concentrations and prognosis and tolerability (determined by adverse reactions) were analyzed. Patients received a second course of treatment after a 3-week period. RESULTS: Ninety patients (58 men, 32 women; age range, 30-67 years) with OS were included in the study. A total of 532 courses of combined chemotherapy were administered. The serum MTX concentrations ranged widely at baseline (244.31-929.68 mol/L, Cmin and Cmax, respectively) and at 24 hours (0.73-28.24 mol/L, respectively), suggesting that the serum MTX concentrations varied significantly between different individuals and within the same individual at different time points. The serum MTX concentrations in ~23% of cases (122/532) determined at 24 and/or 48 hours were numerically higher than the safety values (according to Nirenberg's reference: irreversible damage if MTX concentration was >10 umol/L and > 1 umol/L at 24 and 48 hours, respectively). No correlation was found between high serum MTX concentration at baseline and high serum MTX concentration at 24 hours (r = 0.401). The prevalences of the 3 most common adverse reactions in these patients were depressed white blood cell count (44.03%), dental ulcer (23.0%), and rash (18.0%). However, in the remaining 410 courses in which serum MTX concentrations were lower than the safety values, these prevalences were 14.6%, 3-9%, and 2.4%, respectively. Neither age nor sex was significantly associated with MTX Cmax, but dosage was (P < 0.05). Patients with a serum MTX Cmax concentration >500 µmol/L at baseline had a significantly longer DFS rate than those with ≤500 umol/L (P = 0.040). There were no significant between-group differences in the OAS rates. conclusions: In these Chinese patients with OS, serum MTX concentrations measured at different time points were varied. The findings suggest that adverse reactions occurred in patients whose serum MTX concentrations at 24 and/or 48 hours were higher than the safety values. The dosage appeared to have influenced MTX Cmax, while sex and age did not, and the Cmax was significantly related to DFS but not OAS.

Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells.

OBJECTIVE: To investigate the effects of curcumin on release of cytochrome c and expressions of Bcl-2, Bax, Bad, Bcl-xL, caspase-3, poly ADP-ribose polymerase (PARP), and survivin of HT-29 cells. METHODS: HT-29 cells were treated with curcumin (0 approximately 80 micromol/L) for 24 h. The release of cytochrome c from the mitochondria and the apoptosis-related proteins Bax, Bcl-2, Bcl-xL, Bad, caspase-3, PARP, and survivin were determined by Western blot analysis and their mRNA expressions by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Curcumin significantly induced the growth inhibition and apoptosis of HT-29 cells. A decrease in expressions of Bcl-2, Bcl-xL and survivin was observed after exposure to 10 approximately 80 micromol/L curcumin, while the levels of Bax and Bad increased in the curcumin-treated cells. Curcumin also induced the release of cytochrome c, the activation of caspase-3, and the cleavage of PARP in a dose-dependent manner. CONCLUSION: These data suggest that curcumin induced the HT-29 cell apoptosis possibly via the mitochondria-mediated pathway.

[Molluscicidal effect and toxicity of META-Li on Oncomelania snails in the mountain area].

The molluscicidal effect and toxicity of META-Li were evaluated and compared with niclosamide in Yushan county of Jiangxi Province in August 2008. There are four groups named as META-Li ridge group (1 g/m2), META-Li field group (1 g/m2), niclosamide group (2 g/m2) and control group. At 3 d, 7 d, 15 d and 2 months after drugs sprayed, the corrected mortalities of snails in the 3 groups were considerably higher than those of control (P<0.05). The corrected mortalities in META-Li field group were significantly lower than those of META-Li ridge group and niclosamide group (P<0.05). No adverse effect was observed to non-target organisms in META-Li groups, while fishes, snails and frogs all died at the first day after treated with niclosamide.

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice.

BACKGROUND: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models. METHODS: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group. RESULTS: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 109/L at the 28th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] µmol/L) at the 28th day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney. CONCLUSION: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

Poor prognostic role of the pretreatment platelet counts in colorectal cancer: A meta-analysis.

BACKGROUND: Recently, a wide variety of studies have suggested that elevated platelet counts are associated with survival in patients with colorectal cancer. On one hand several studies suggest a negative connection in colorectal cancer patients with pre-operative thrombocytosis, on the other hand other studies contradicts this. However, it remains unknown whether elevated platelet counts are associated with survival in colorectal cancer patients. We therefore conducted this meta-analysis to evaluate the prognostic role of platelet counts in colorectal cancer. METHODS: PubMed, Embase, and the Cochrane Library databases were searched from their inception to October 15, 2016 to identify relevant studies that have explored the prognostic role of platelet counts in colorectal cancer. Studies that examined the association between platelet counts and prognoses in colorectal cancer and that provided a hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) and/or disease-free survival (DFS) were included. RESULTS: This meta-analysis included 9 retrospective cohort studies involving 3413 patients with colorectal cancer. OS was shorter in patients with elevated platelet counts than in patients with normal counts (HR 2.11, 95% CI: 1.68-2.65). For DFS, an elevated platelet count was also a poor predictor (HR 2.51, 95% CI: 1.84-3.43). CONCLUSION: In this meta-analysis, we suggest that an elevated platelet count is a negative predictor of survival in both primary colorectal cancer and resectable colorectal liver metastases.

Mechanical intestinal obstruction secondary to appendiceal mucinous cystadenoma: A case report and brief review.

BACKGROUND: Appendiceal mucinous cystadenoma can present in various ways, and it is most commonly encountered incidentally during appendectomy, but mechanical intestinal obstruction secondary to an appendiceal mucocele has been rarely reported. METHODS: We report a case of mechanical intestinal obstruction secondary to appendiceal mucinous cystadenoma. After nasogastric decompression and initial aggressive intravenous fluid resuscitation, an emergency operation was performed under the diagnosis of acute mechanical intestinal obstruction. RESULTS: We performed an appendectomy and intraoperative enteral decompression without anastomoses. The pathologic examination (PE) revealed appendiceal mucinous cystadenoma. After the operation, the patient's recovery went smoothly, and the patient was discharged on the fifth postoperative day. No tumor recurrence was recorded over an 8 month follow-up period. CONCLUSION: Early operative intervention should be recommended to the patient with acute mechanical complete intestinal obstruction, especially the patient who had no previous abdominal surgery. And it is vital to discriminate benign and malignantappendiceal mucocel in determining the extent of surgery.

The Association between 5HT2A T102C and Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease: A Meta-Analysis.

The serotonin receptor gene (5-HT2A) has been reported to be a susceptible factor in behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, previous results were conflicting. We aim to investigate the association of 5-HT2A T102C with BPSD in AD using a meta-analysis. Studies were collected using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI), and Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess associations. Nine studies with 1899 AD patients with/without BPSD were included in this meta-analysis. The 102C and CC genotypes were associated with psychosis in AD (102C: p < 0.00001, OR [95% CI] = 3.19 [2.12-4.79]; CC: p < 0.00001, OR [95% CI] = 7.24 [3.60-14.59]). The TT genotype was significantly associated with hallucinations, aberrant motor behavior, and psychosis in AD (hallucinations: p = 0.001, OR [95% CI] = 0.52 [0.36-0.77]; aberrant motor behavior: p = 0.03, OR [95% CI] = 0.58 [0.35-0.95]; and psychosis: p = 0.002, OR [95% CI] = 0.34 [0.17-0.67]). No association was observed between T102C alleles or genotypes and delusions, agitation/aggression, depression, and apathy (p > 0.05). Thus, the 5HT2A T102C might be a susceptible factor for hallucinations, aberrant motor behavior, and psychosis in AD. The potential mechanism of this polymorphism in BPSD in AD requires further exploration.

Prognostic role of the pre-treatment platelet-lymphocyte ratio in pancreatic cancer: a meta-analysis.

BACKGROUND AND AIMS: Recently, the pre-treatment platelet-lymphocyte ratio (PLR), which is based on blood parameters, was accepted as a prognostic factor for patients with various cancers. Numerous studies have investigated the prognostic role of the PLR in pancreatic cancer; however, it remains unclear. Therefore, we conducted this meta-analysis to evaluate the relationship between the pre-treatment PLR and overall survival (OS) in pancreatic cancer. MATERIALS AND METHODS: We performed a systematic literature search of the PubMed, Embase and Web of Science databases for relevant studies that explored the prognostic role of the pre-treatment PLR in pancreatic cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) related to OS were pooled using a random effects model. RESULTS: Fourteen retrospective cohort studies involving 2,260 patients were included in this meta-analysis. Compared with low PLR, high PLR was a predictor of shorter OS (HR = 1.24, 95% CI: 1.10-1.39, I2 = 74%). CONCLUSIONS: In this meta-analysis, high pre-treatment PLR was a bio-predictor of short OS in patients with pancreatic cancer, suggesting that PLR could be used to predict prognosis of patients with pancreatic cancer before treatment. However, additional well-designed and large-scale studies are necessary.

Comparison of transanal endoscopic microsurgery with or without neoadjuvant therapy and standard total mesorectal excision in the treatment of clinical T2 low rectal cancer: a meta-analysis.

Some clinical trials demonstrated local resection for clinical T1 rectal cancer was safe and effective. But for clinical T2 rectal cancer, the results were controversial. Neoadjuvant therapy (NT) is proven to reduce the opportunity of advanced rectal cancer recurrence in various researches. The objective of this Meta-Analysis was to evaluate the oncological outcomes of transanal endoscopic microsurgery (TEM) with or without NT comparing with conventional total mesorectal excision (TME) for the treatment of clinical T2 rectal cancer.To search for the relevant studies, an electronic search was done from the databases of Pubmed, Embase, and the Cochrane Library in this meta-analysis. We compared the effectiveness of transanal endoscopic microsurgery with or without NT and standard total mesorectal excision in the treatment of T2 Rectal Cancer. 1RCT and 3nRCTs including 121 TEM patients (TEM + NT: 59, TEM: 62) and 174 TME patients with T2 rectal cancer were retrieved. Compared with TME, there were no significant differences in the outcomes of local recurrence, overall recurrence, overall survival between TEM + NT group. However in compassion with TME, TEM without NT was associated with an increased local recurrence, overall recurrence, and a shorter overall survival, with individual ORs being 3.04 (95% Cl: 1.17-7.90; I2 = 0%), 5.67 (95% Cl: 1.58-20.38; I2 = 0%) and 0.12 (95% Cl: 0.02-0.65; I2 = 0%), respectively. Compared with TME, TEM after NT may be a feasible and safe organ preservative approach for patients with clinical T2 low rectal cancer. But for those without NT, TEM always seem be associated with worse oncological outcomes.