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Studies of both, microbiota and target therapy associated with gene mutations in colorectal cancer, (CRC) have attracted increasing attention. However, only a few of them analyzed the combined effects on CRC. we analyzed differences in intestinal microbiota of 44 colorectal cancer patients and 20 healthy controls (HC) using 16S rRNA gene sequencing of fecal samples. For 39 of the CRC patients, targeted Next Generation Sequencing (NGS) was carried out at formalin fixed paraffin embedded (FFPE) samples to identify somatic mutation profiles. Compared to the HC group, the microbial diversity of CRC patients was significantly lower. In the CRC group, we found a microbiome that was significantly enriched for strains of Bifidobacterium, Bacteroides, and Megasphaera whereas in the HC group the abundance of Collinsella, Faecalibacterium, and Agathobacter strains was higher. Among the mutations detected in the CRC group, the APC gene had the highest mutation rate (77%, 30/39). We found that the KRAS mutant type was closely associated with Faecalibacterium, Roseburia, Megamonas, Lachnoclostridium, and Harryflintia. Notably, Spearman correlation analysis showed that KRAS mutations were negatively correlated with the existence of Bifidobacterium and positively correlated with Faecalibacterium. By employing 16S rRNA gene sequencing, we identified more unique features of microbiota profiles in CRC patients. For the first time, our study showed that gene mutations could directly be linked to the microbiota composition of CRC patients. We hypothesize that the effect of a targeted colorectal cancer therapy is also closely related to the colorectal flora, however, this requires further investigation.
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Neoplasias Colorretais , Microbiota , Neoplasias Colorretais/genética , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Ribossômico 16S/genéticaRESUMO
Background Intravenous sufentanil-midazolam and inhalational sevoflurane are widely used for anesthetic induction in children undergoing cardiac surgery. However, knowledge about their effects on hemodynamics and cardiac efficiency remains limited due largely to the lack of direct monitoring method. We used minimally invasive technique pressure recording analytical method (PRAM) to directly monitor hemodynamics and cardiac efficiency and compared the effects of the two anesthetic regimens in children undergoing ventricular septal defect repair. Methods Forty-Four children (2.3±0.9 years) were randomly divided into two groups to receive either intravenous sufentanil (1 µg/kg) and midazolam (0.2 mg/kg) (Group SM) or 2.0 minimal alveolar concentration (MAC) sevoflurane (Group S) to complete induction after sedation was obtained with 2.0 MAC sevoflurane. Systemic hemodynamic data recorded by PRAM included heart rate (HR), systolic (SBP) and mean (MBP) blood pressure, stroke volume index (SVI), cardiac index (CI), systemic vascular resistance index (SVRI), the maximal slope of systolic upstroke (dp/dtmax) and cardiac cycle efficiency (CCE) after sedation obtained, 1, 2, 5 min after induction achieved, 1, 2, 5 and 10 min after intubation. Results HR, SVRI showed a decrease in Group SM but an increase in Group S (Ptime*group<0.0001) in the study period. SVI and CCE showed an increase in Group SM but a decrease in Group S (Ptime*group<0.0001). SBP, MBP and CI were related to time after polynomial transformation, and showed an increase after intubation in Group SM but a decrease in Group S (Ptime2*group<0.0001). Conclusion PRAM provides meaningful and direct monitoring of hemodynamics and cardiac efficiency during the dynamic period of anesthetic induction in children undergoing cardiac surgery. As compared to inhalational sevoflurane, intravenous sufentanil-midazolam exerts more favorable effects on systemic hemodynamics and cardiac efficiency during anesthetic induction in this group of patients.
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Anestesia Geral/métodos , Comunicação Interventricular/cirurgia , Hemodinâmica/fisiologia , Monitorização Intraoperatória/métodos , Sevoflurano/administração & dosagem , Sufentanil/administração & dosagem , Analgésicos Opioides , Anestésicos Inalatórios/administração & dosagem , Pré-Escolar , Feminino , Seguimentos , Comunicação Interventricular/fisiopatologia , Humanos , Injeções Intramusculares , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVE: Neuromuscular blocking agents are routinely used in laparoscopic surgery to optimize operative conditions. We compared the effect of a deep and moderate neuromuscular blockade (NMB) on surgical conditions and postoperative outcomes in children undergoing major laparoscopic surgery. METHODS: Sixty children aged 2-14 years scheduled to undergo major laparoscopic surgery were randomly allocated to deep (post-tetanic count 1-2 twitches) or moderate (train-of-four 1-2 twitches) NMB groups. The anesthesia was maintained with propofol and remifentanil, and the NMB was maintained with a rocuronium continuous infusion. At the end of the operation, the NMB were antagonized with sugammadex. The intra-abdominal pressure, airway pressure, Leiden Surgical Rating Scale, intraoperative hemodynamics, drug usages, duration of surgery, postoperative recovery time, pain, and complications were compared between the groups. RESULTS: The maximum and mean intra-abdominal pressure, the peak inspiratory pressure, and mean airway pressure were significantly lower in the deep NMB group than in the moderate NMB group (p < 0.001). The Leiden Surgical Rating Scale and the dosage of rocuronium were significantly higher in the deep NMB group than the moderate NMB group (p < 0.001). The intraoperative hemodynamics, duration of surgery, post-operative recovery time, pain, and the incidence rate of complications were not significantly different between the groups (p > 0.05). CONCLUSIONS: A deep NMB provided better operative conditions and similar recovery profiles compared with a moderate NMB as reversed with sugammadex in children undergoing major laparoscopic surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2100053821.
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Laparoscopia , Bloqueio Neuromuscular , Rocurônio , Humanos , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Criança , Bloqueio Neuromuscular/métodos , Masculino , Feminino , Pré-Escolar , Adolescente , Rocurônio/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Período de Recuperação da Anestesia , Remifentanil/administração & dosagem , Propofol/administração & dosagem , Sugammadex/administração & dosagemRESUMO
Developing an efficient drug delivery system to mitigate the harm caused by root-knot nematodes is crucial. In this study, enzyme-responsive release abamectin nanocapsules (AVB1a NCs) were prepared using 4, 4-diphenylmethane diisocyanate (MDI) and sodium carboxymethyl cellulose as response release factors. The results showed that the average size (D50) of the AVB1a NCs was 352 nm, and the encapsulation efficiency was 92 %. The median lethal concentration (LC50) of AVB1a NCs for Meloidogyne incognita activity was 0.82 mg L-1. Moreover, AVB1a NCs improved the permeability of AVB1a to root-knot nematodes and plant roots and the horizontal and vertical soil mobility. Furthermore, AVB1a NCs greatly reduced the adsorption of AVB1a by the soil compared to AVB1a emulsifiable concentrate (EC), and the effect of the AVB1a NCs on controlling root-knot nematode disease was increased by 36 %. Compared to the AVB1a EC, the pesticide delivery system significantly reduced the acute toxicity to the soil biological earthworms by approximately 16 times that of the AVB1a and had a lower overall impact on the soil microbial communities. This enzyme-responsive pesticide delivery system had a simple preparation method, excellent performance, and high level of safety, and thus has great application potential for plant diseases and insect pests control.
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Nanocápsulas , Praguicidas , Solanum lycopersicum , Tylenchoidea , Animais , Carboximetilcelulose Sódica/farmacologia , Praguicidas/farmacologia , Solo , Sódio/farmacologiaRESUMO
PURPOSE: The aim of this study was to investigate the function and mechanisms of ELABELA (ELA) in the aerobic exercise-induced antiapoptosis and angiogenesis of ischemic heart. METHODS: The myocardial infarction (MI) model of Sprague-Dawley rat was established by the ligation of the left anterior descending coronary artery. MI rats underwent 5 wk of Fc-ELA-21 subcutaneous injection and aerobic exercise training using a motorized rodent treadmill. Heart function was evaluated by hemodynamic measures. Cardiac pathological remodeling was evaluated by Masson's staining and the calculation of left ventricular weight index. Cell proliferation, angiogenesis, and Yes-associated protein (YAP) translocation were observed by immunofluorescence staining. Cell apoptosis was analyzed by TUNEL. Cell culture and treatment were used to elucidate the molecular mechanism of ELA. Protein expression was detected by Western blotting. Angiogenesis was observed by tubule formation test. One-way or two-way ANOVA and Student's t -test were used for statistical analysis. RESULTS: Aerobic exercise stimulated the endogenous ELA expression. Exercise and Fc-ELA-21 intervention significantly activated APJ-Akt-mTOR-P70S6K signaling pathway, kept more cardiomyocytes alive, and increased angiogenesis, so as to inhibit the cardiac pathological remodeling and improved the heart function of MI rats. Fc-ELA-32 also had the cellular and functional cardioprotective activities in vivo . In vitro , ELA-14 peptide regulated the phosphorylation and nucleoplasmic translocation of YAP and activated the APJ-Akt signaling pathway so as to increase the proliferation of H9C2 cells. Moreover, the antiapoptosis and the tubule formation of HUVECs were also enhanced by ELA-14, whereas the inhibition of Akt activity weakened such effects. CONCLUSIONS: ELA is a potential therapeutic member that plays a key role through APJ-Akt/YAP signaling axis in aerobic exercise-induced cardioprotection of MI rats.
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Infarto do Miocárdio , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Infarto do Miocárdio/prevenção & controle , Transdução de Sinais , Miócitos Cardíacos/metabolismoRESUMO
BACKGROUND: Some traditional pesticide formulations are inefficient, leading to excessive use and abuse of pesticides, which in turn effects environment. Intelligent release pesticide formulations are ideal for improving pesticide utilization and persistence while reducing environmental pollution. RESULTS: We designed a benzil-modified chitosan oligosaccharide (CO-BZ) to encapsulate avermectin (Ave). Ave@CO-BZ nanocapsules are prepared based on a simple interfacial method via cross-linking of CO-BZ with diphenylmethane diisocyanate (MDI). The Ave@CO-BZ nanocapsules have an average particle size of 100 nm and exhibited a responsive release performance for ROS. The cumulative release rate of nanocapsules at 24 h with ROS increased by about 11.4% compared to that without ROS. The Ave@CO-BZ nanocapsules displayed good photostability. Ave@CO-BZ nanocapsules can penetrate root-knot nematodes more easily and exhibited better nematicidal activity against root-knot nematodes. The pot experiment showed that the control effect of Ave CS at low concentration was 53.31% at the initial stage of application (15 d), while Ave@CO-BZ nanocapsules was 63.54%. Under the same conditions, the control effect of Ave@CO-BZ nanocapsules on root-knot nematodes was 60.00% after 45 days of application, while Ave EC was only 13.33%. The acute toxicity experiments of earthworms showed that the toxicity of nanocapsules was significantly lower than that of EC. CONCLUSION: The ROS-responsive nanocapsules can improve the utilization of pesticides and non-target biosafety. This modified chitosan oligosaccharide has great potential as a bio stimuli-responsive material, and this simple and convenient method for preparing Ave@CO-BZ nanocapsules provides a direction for the effective utilization of pesticides. © 2023 Society of Chemical Industry.
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Quitosana , Nanocápsulas , Praguicidas , Praguicidas/toxicidade , Espécies Reativas de Oxigênio , OligossacarídeosRESUMO
Background: Previous studies have reported that children who were admitted to the ICU experienced a significant decrease in sleep quality compared to home. We investigated the effects of dexmedetomidine as an adjunct to sufentanil on the sleep in children admitted to the ICU on the first night after major surgery. Methods: This is a prospective study From January to February 2022. Clinical trial number: ChiCTR2200055768, http://www.chictr.org.cn. Fifty-four children aged 1-10 years old children undergoing major laparoscopic surgery were recruited and randomly assigned to either the DEX group, in which intravenous dexmedetomidine (0.3 ug/kg/h) and sufentanil (0.04 ug/kg/h) were continuously infused intravenously for post-operative analgesia; or the SUF group, in which only sufentanil (0.04 ug/kg/h) was continuously infused. Patients were monitored with polysomnography (PSG) on the first night after surgery for 12 h. PSG, sleep architecture, physiologic variables and any types of side effects related to anesthesia and analgesia were recorded. The differences between the two groups were assessed using the chi-square and Wilcoxon rank-sum tests. Results: Fifty-four children completed data collection, of which thirty-four were 1-6 years old and twenty were aged >6 years. Compared to the SUF group, subjects in the DEX group aged 1-6 years displayed increased stage 2 sleep duration (P = 0.02) and light sleep duration (P = 0.02). Subjects aged >6 years in the DEX group also displayed increased stage 2 sleep duration (P = 0.035) and light sleep duration (P = 0.018), but decreased REM sleep percentage (P = 0). Additionally, the heart rate and blood pressure results differed between age groups, with the heart rates of subjects aged >6 years in DEX group decreasing at most time points compared to SUF group (P < 0.05). Conclusion: Dexmedetomidine prolonged N2 sleep and light sleep duration in the pediatric ICU after surgery but had different effects on the heart rate and blood pressure of subjects in different age groups.
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Skeletal muscle in patients with heart failure (HF) exhibits altered structure, function and metabolism. Myocardial infarction (MI) is the most common cause of HF. Oxidative stress and cell apoptosis are involved in the pathophysiology of MI/HF-induced skeletal muscle atrophy. It is well recognized that aerobic exercise (AE) could prevent skeletal muscle atrophy after MI, but the underlying mechanism and molecular targets are still not fully clarified. In this study, Fndc5-/- and Alcat1-/- mice were used to establish the MI model and subjected to six weeks of moderate-intensity AE. C2C12 cells were treated with H2O2 and recombinant human Irisin (rhIrisin), or transduced with a lentiviral vector to mediate the overexpression of ALCAT1 (LV-Alcat1). Results showed that MI reduced Irisin expression and antioxidant capacity of skeletal muscle, increased ALCAT1 expression, induced protein degradation and cell apoptosis, which were partly reversed by AE; Knockout of Fndc5 further aggravated MI-induced oxidative stress and cell apoptosis in skeletal muscle, and partly weakened the beneficial effects of AE. In contrast, knockout of Alcat1 reduced MI-induced oxidative stress and cell apoptosis and strengthened the beneficial effects of AE. rhIrisin and AICAR intervention inhibited ALCAT1 expression, oxidative stress and cell apoptosis, which induced by H2O2 or LV-Alcat1 in C2C12 cells. These findings reveal that AE could alleviate the levels of oxidative stress and apoptosis in skeletal muscle following MI, partly via up-regulating Irisin and inhibiting ALCAT1 expression.
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Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Humanos , Camundongos , Apoptose , Exercício Físico , Fibronectinas/genética , Fibronectinas/metabolismo , Insuficiência Cardíaca/metabolismo , Peróxido de Hidrogênio/metabolismo , Camundongos Knockout , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Estresse OxidativoRESUMO
Background: Compared with traditional diagnostic methods (TDMs), rapid diagnostic methods for infectious diseases (IDs) are urgently needed. Metagenomic next-generation sequencing (mNGS) has emerged as a promising diagnostic technology for clinical infections. Methods: This retrospective observational study was performed at a tertiary hospital in China between May 2019 and August 2022. The chi-square test was used to compare the sensitivity and specificity of mNGS and TDMs. We also performed a subgroup analysis of the different pathogens and samples. Results: A total of 435 patients with clinical suspicion of infection were enrolled and 372 (85.5%) patients were finally categorized as the ID group. The overall sensitivity of mNGS was significantly higher than that of the TDMs (59.7% vs. 30.1%, P < 0.05). However, there was no significant difference in the overall specificity between the two methods (83.3% vs. 89.6%, P = 0.37). In patients with identified pathogens, the positive rates of mNGS for detecting bacteria (88.7%), fungi (87.9%), viruses (96.9%), and Nontuberculous mycobacteria (NTM; 100%) were significantly higher than those of TDMs (P < 0.05). The positive rate of mNGS for detecting Mycobacterium tuberculosis was not superior to that of TDMs (77.3% vs. 54.5%, P = 0.11). The sensitivity rates of mNGS for pathogen identification in bronchoalveolar lavage fluid, blood, cerebrospinal fluid, pleural fluid, and tissue were 72.6%, 39.3%, 37.5%, 35.0% and 80.0%, respectively. Conclusion: With the potential for screening multiple clinical samples, mNGS has an overall advantage over TDMs. It can effectively identify pathogens, especially those that are difficult to identify using TDMs, such as NTM, chlamydia, and parasites.
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Exsudatos e Transudatos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Centros de Atenção Terciária , China , Líquido da Lavagem Broncoalveolar , Metagenômica , Micobactérias não Tuberculosas , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Increasing pesticide retention on crop leaves is a key approach for guaranteeing efficacy when products are applied to foliage. Evidently, the formulation plays an important role in this process. Microcapsules (MCs) are a promising formulation, but whether and how their adhesion to the leaf surface affects retention and efficacy is not well understood. RESULTS: In this study, we found that the incorporation of polyethylene glycol (PEG) with different molecular weights into the MC shell affects the release profile of MCs and the contact area of these MCs to leaves by changing their softness. The cumulative release rates of pyraclostrobin (Pyr) MCs fabricated with PEG200, PEG400, PEG800 and PEG1500 were 80.61%, 90.98%, 94.07% and 97.40%, respectively. Scanning electron microscopy observations showed that the flexibility of the MCs increased with increasing PEG molecular weight. The median lethal concentration (LC50 ) of the MCs with different PEG to the zebrafish were 12.10, 8.10, 3.90 and 1.46 mg L-1 , respectively, which also indirectly reflected their release rate. Rainwater had less influence on the retention of the MCs prepared with PEG1500 than with the other PEG, which indicates a better adhesion to the target leave surfaces. MCs with the highest residual efficacy had better control efficacy on peanut leaf spot in field trials. CONCLUSION: Overall, adding PEG with an appropriate molecular weight to the MC shell can regulate the structure of the MC shell to improve the affinity between the MCs and leaves, which further improves the utilization of pesticides and reduces the environmental risks of pesticides. © 2021 Society of Chemical Industry.
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Fungicidas Industriais , Praguicidas , Animais , Cápsulas , Fungicidas Industriais/farmacologia , Polímeros , Peixe-ZebraRESUMO
Genetic mapping of F(2) progeny (n = 225) of hybrids between the Sobano variety of common buckwheat (Fagopyrum esculentum Moench) and the Homo wild accession (F. esculentum var. homotropicum) was carried out using randomly amplified polymorphic DNA (RAPD), sequence-tagged site (STS) and seed protein subunit markers, and three morphological traits. Ten linkage groups were identified, involving 87 RAPD markers, 12 STS markers, four seed protein subunit (PS(62)/PS(59), PS(49.8)/PS(51.4), PS(44)/PS(42.9), and PS(39.9)/PS(37.8)) markers, and three morphological alleles controlling homo/long style (H/s), shattering habit (Sht/sht), and acute/obtuse achene ridge (Ac/ac), covering a total of 655.2 cM.
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Mapeamento Cromossômico/métodos , DNA de Plantas/genética , Fagopyrum/genética , Proteínas de Plantas/genética , Alelos , Cromossomos de Plantas/genética , Fagopyrum/anatomia & histologia , Fagopyrum/classificação , Hibridização Genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Sementes/metabolismo , Sitios de Sequências RotuladasRESUMO
BACKGROUND: Several studies have been conducted to explore the prognostic value of miR-183 in different types of cancer; however, their results were controversial. Therefore, the present meta-analysis was conducted to comprehensively evaluate the prognostic value of miR-183 expression level in cancer. METHODS: A comprehensive literature search was carried out by searching PubMed and EMBASE database between January 1966 and April 2017. Fixed effect and random effect models were used to evaluate the pooled hazard risk (HR) and the relevant 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also carried out. RESULTS: A total of 12 studies published between 2011 and 2017 were included in the present meta-analysis. The meta-analysis result indicated that there was a significant association between miR-183 expression level and overall survival (HRâ=â2.642; 95%CI: 2.152-3.245), and there was a significant association between miR-183 expression level and tumor progression (HRâ=â2.403; 95%CI: 1.267-4.559). In subgroup analysis, we found that high expression level was significantly associated with poor prognosis in most cancers (HRâ=â2.824, 95%CI: 2.092-3.813); however, low miR-183 level was significantly associated with poor prognosis in melanoma and pancreatic ductal adenocarcinoma (HRâ=â2.322, 95%CI: 1.337-4.031). CONCLUSIONS: The results of our meta-analysis indicated that the highly expressed miR-183 might predict poor survival of patients with most cancer types, whereas the downregulated miR-183 level might be associated with poor prognosis in patients with melanoma and pancreatic ductal adenocarcinoma.
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Biomarcadores Tumorais/metabolismo , MicroRNAs/metabolismo , Neoplasias/genética , Progressão da Doença , Humanos , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Taxa de SobrevidaRESUMO
RATIONALE: Teratomas commonly arise in the gonads, including ovary and testis. The kidney is one of the most rare regions of primary teratoma. To date, about 19 cases of renal teratoma have been reported, and only 3 articles have reported renal immature teratoma; however, all of them occur in infant or children. In the present study, we reported a renal inmature teratoma in a male adult. PATIENT CONCERNS: The present patient was a middle-aged man with aching pain in the left waist, and contrast-enhanced CT showed a lump in the left kidney with mild-to-moderate enhancement, and a low density small necrotic area was seen in the center. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: The patient underwent radical nephrectomy. Based on postsurgical histopathology, the final diagnosis of this case was renal immature teratoma. Postoperative chemotherapy was carried out, and the patient has been followed-up for 18 months without tumor recurrence. LESSONS: Adult renal immature teratoma is rare, and the diagnosis is mainly based on the pathological findings.
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Neoplasias Renais/patologia , Teratoma/patologia , Humanos , Rim/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Strigolactones (SLs) are involved in the nutrient-dependent control of plant root and shoot architecture. The total sufficient uptake of nitrogen (N), and also its appropriate distribution, is essential for the normal growth and development of plants; however, the effect of SLs on N translocation in plants remains unknown. Here, the SL-signaling mutant dwarf 3 (d3), the biosynthesis mutant dwarf 10 (d10), and wild-type (WT) rice (Oryza sativa ssp. Japonica cv. Nipponbare) were used to investigate the relationship between N nutrition and the regulatory role of SLs. Relative to WT, the d10 mutant had a higher N concentration in older leaves but a lower N concentration in younger leaves, while the d3 mutant showed a considerably lower N concentration, especially in its younger leaves under normal N levels. By contrast, both d3 and d10 mutants contained higher N in their leaves under N-deficient conditions. The 15N uptake and distribution analysis revealed that the significantly different N concentrations among the d3, d10, and WT plants only occurred in their leaves, not in their roots. Moreover, when provided with an external supply of GR24, the synthetic SLs altered the leaf N distribution of the d10 mutant but not those of the d3 mutant and WT. Together, these results suggested that the effect of SLs on plant growth and development may be linked to N translocation to different shoot tissues.
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Lactonas/farmacologia , Nitrogênio/metabolismo , Oryza/efeitos dos fármacos , Transporte Biológico , Mutação , Oryza/genética , Oryza/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/genética , Brotos de Planta/metabolismoRESUMO
BACKGROUND: The relationship of vasectomy to prostate cancer has great public health significance. However, the results of observational studies were conflicting. To determine whether vasectomy is associated with the risk of prostate cancer, we performed a meta-analysis of cohort studies. METHODS: A literature search was carried out using Pubmed, Embase, Cochrane Libraryl, and China National Knowledge Infrastructure (CNKI) between January 1966 and July 2013. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of nine cohort studies contributed to the analysis. There was heterogeneity among the studies but no publication bias. Pooled results indicated that vasectomy was not associated with a significant increase of total prostate cancer risk (RR = 1.07, 95% CI [0.79, 1.46]). When stratified the various studies by geographic location, we found a significant association between vasectomy and increased PCa risk among studies conducted in the USA (RR = 1.54, 95% CI [1.23, 1.93]), however, there was no significant association between vasectomy and PCa risk among studies conducted in non-USA countries (RR = 0.74, 95% CI [0.50, 1.09]). Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSIONS: In conclusion, the present meta-analysis of cohort studies suggested that vasectomy was not associated with increased risk of prostate cancer. More in-depth studies are warranted to report more detailed results, including stratified results by age at vasectomy, tumor grade, and tumor stage.
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OBJECTIVE: Several observational studies have shown that metformin therapy may modify the risk of prostate cancer. We carried out a meta-analysis of relevant studies evaluating the effect of metformin therapy on prostate cancer risk. METHODS: We searched pubmed database (January 1966-February 2014) for case-control and cohort studies that assessed metformin therapy and prostate cancer risk. Two authors independently assessed eligibility and extracted data. Summary RRs was calculated using fixed-effects model or random-effects model. Heterogeneity among studies was examined using Q and I(2) statistics. RESULTS: We included six cohort studies and four case-control studies in the present meta-analysis, comprising 863,769 participants and 39,073 prostate cancer cases. The pooled RR of prostate cancer in relation to metformin therapy was 0.92 (95% CI: 0.84-1.02, P = 0.112). When we stratified the various studies by study type, we found that metformin therapy was associated with a significant reduced risk of prostate cancer among cohort studies (RR = 0.92, 95% CI [0.87, 0.96], P<0.001); however, no significant association was detected among case-control studies (RR = 0.95, 95% CI [0.78, 1.16], P = 0.632). There was also no indication of publication bias as suggested by Begg's test (P = 0.421) and Egger's test (P = 0.627). CONCLUSION: Our findings indicate that metformin therapy is not significantly associated with lower prostate cancer risk.