Effect of Different Cooking Methods on the Aroma and Taste of Chicken Broth.

A single combi oven, known for its versatility, is an excellent choice for a variety of chicken soup preparations. However, the impact of universal steam ovens on the flavor quality of chicken soup remains unclear. This study aimed to explore the impact of different cooking methods on the aroma and taste of chicken soup. Three cooking methods with various stewing times were compared: ceramic pot (CP), electric pressure cooker (EPC), and combi oven (CO). Analyses were conducted using electron-nose, electron-tongue, gas chromatography-ion mobility spectrometry (GC-IMS), automatic amino acid analysis, and chemometric methods. A total of 14 amino acids, including significant umami contributors, were identified. The taste components of CP and CO chicken soups were relatively similar. In total, 39 volatile aroma compounds, predominantly aldehydes, ketones, and alcohols, were identified. Aldehydes were the most abundant compounds, and 23 key aroma compounds were identified. Pearson's correlation analyses revealed distinct correlations between various amino acids (e.g., glutamic acid and serine) and specific volatile compounds. The aroma compounds from the CP and CO samples showed similarities. The results of this study provide a reference for the application of one-touch cooking of chicken soup in versatile steam ovens.

A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family.

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a female proband carrying a novel mutation in the DMD gene with non-random X-chromosome inactivation in a large pedigree with pseudohypertrophic muscular dystrophy. METHODS: Clinical information of the female proband, her monozygotic twin sister, and other family members were collected. Potential pathogenic variants were detected with Multiplex Ligation-dependent Probe Amplification (MLPA) and whole-exome sequencing (WES). Methylation-sensitive restriction enzyme (HhaI) was employed for X-chromosome inactivation analysis. RESULTS: The proband was a female over 5 years old, displayed clinical manifestations such as elevated creatine kinase (CK) levels and mild calf muscle hypertrophy. Her monozygotic twin sister exhibited normal CK levels and motor ability. Her uncle and cousin had a history of DMD. WES revealed that the proband carried a novel variant in the DMD (OMIM: 300,377) gene: NM_004006.3: c.3051_3053dup; NP_003997.2: p.Tyr1018*. In this pedigree, five out of six female members were carriers of this variant, while the cousin and uncle were hemizygous for this variant. X-chromosome inactivation analysis suggested non-random inactivation in the proband. CONCLUSION: The c.3051_3053dup (p.Tyr1018*) variant in the DMD gene is considered to be the pathogenic variant significantly associated with the clinical phenotype of the proband, her cousin, and her uncle within this family. Integrating genetic testing with clinical phenotype assessment can be a valuable tool for physicians in the diagnosis of progressive muscular dystrophies, such as Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD).

Smartphone dependency and mental health among Chinese rural adolescents: the mediating role of cognitive failure and parent-child relationship.

Background: With the widespread use of smartphones in daily life, smartphone dependency has become a global problem, especially among adolescents. Existing research studies have supported the association between smartphone dependency and the mental health of Chinese rural adolescents, but the underlying mechanism is still unclear. Objective: The present study used a survey to test whether smartphone dependency may be associated with mental health in Chinese rural adolescents. The mediating role of cognitive failure and parent-child relationship was also examined. Materials and methods: In total, 941 adolescents (45.91% male; mean age = 14.05, SD = 1.04) in rural areas of mainland China were recruited to complete four scales, including the Mobile Phone Dependence Scale (MPDS), Cognitive Failures Questionnaire (CFQ), Family Adaption and Cohesion Evaluation Scales (FACES), and Mental Health of Middle School Students Scale. Results: The results showed that both cognitive failure and parent-child relationship acted as mediators in the effect of smartphone dependency on mental health among Chinese rural adolescents, and smartphone dependency also affected parent-child relationship by influencing cognitive failure, thus affecting mental health among Chinese rural adolescents indirectly. Conclusion: The present study suggests that improving parent-child relationships and reducing cognitive failure can reduce the impact of smartphone dependency on the mental health of Chinese rural adolescents.

Platelets in the tumor microenvironment and their biological effects on cancer hallmarks.

The interplay between platelets and tumors has long been studied. It has been widely accepted that platelets could promote tumor metastasis. However, the precise interactions between platelets and tumor cells have not been thoroughly investigated. Although platelets may play complex roles in multiple steps of tumor development, most studies focus on the platelets in the circulation of tumor patients. Platelets in the primary tumor microenvironment, in addition to platelets in the circulation during tumor cell dissemination, have recently been studied. Their effects on tumor biology are gradually figured out. According to updated cancer hallmarks, we reviewed the biological effects of platelets on tumors, including regulating tumor proliferation and growth, promoting cancer invasion and metastasis, inducing vasculature, avoiding immune destruction, and mediating tumor metabolism and inflammation.

[Advances in albicidin].

Xanthomonas albilineans (Ashby) Downson is a quarantine pest for importing plants to China that causes leaf scald bacterial disease on sugarcane. X. albilineans produces a potent phytotoxin/antibiotic called albicidin. As a pathogenic factor, albicidin causes typical white leaf stripes by inhibiting plastid DNA gyrase and disturbing chloroplast differentiation. Meanwhile, the antibacterial activity of albicidin gives X. albilineans a competitive advantage against rival bacteria during their colonization. Furthermore, albicidin has a rapid bactericidal activity against a variety of Gram-positive and Gram-negative pathogenic bacteria of human species at nanomolar concentrations, making it a potential antimicrobial drug for clinical application. This article reviews the advances of albicidin from the aspects of its molecular structure, traditional extraction methods, mechanism of action, biosynthetic genes and processes, chemical synthesis method and improvement, in order to provide insights into the prevention and treatment of the sugarcane leaf scald disease, and the development of new antibiotics.

The Relation Between Numerical Magnitude Processing and Mathematical Performance in d/Deaf and Hard of Hearing Children: The Influence of Fluency.

Pursuant to the criterion of fluency, two types of mathematical achievement tests were used in the present study: simple subtraction (to measure mathematical fluency) and number series completion (to serve as a nonfluency mathematics test). A cohort of 223 d/Deaf and hard of hearing (d/Dhh) students in grades 3-9 in special education schools took a series of cognitive and mathematical tests. After outlying data were considered, the sample was reduced to 198 students; the findings were consistent with expectations: The numerical magnitude processing did not add significantly to the prediction of mathematical reasoning (nonfluency mathematics) but did make a significant contribution to the prediction of arithmetic computation (fluency mathematics) after demographic variables and general cognitive processing were controlled for. The findings suggest that the effect of numerical magnitude processing on d/Dhh children's mathematical performance can be influenced by mathematical fluency.

Evolution analysis of FRIZZY PANICLE (FZP) orthologs explored the mutations in DNA coding sequences in the grass family (Poaceae).

FRIZZY PANICLE (FZP), an essential gene that controls spikelet differentiation and development in the grass family (Poaceae), prevents the formation of axillary bud meristems and is closely associated with crop yields. It is unclear whether the FZP gene or its orthologs were selected during the evolutionary process of grass species, which possess diverse spike morphologies. In the present study, we adopted bioinformatics methods for the evolutionary analysis of FZP orthologs in species of the grass family. Thirty-five orthologs with protein sequences identical to that of the FZP gene were identified from 29 grass species. Analysis of conserved domains revealed that the AP2/ERF domains were highly conserved with almost no amino acid mutations. However, species of the tribe Triticeae, genus Oryza, and C4 plants exhibited more significant amino acid mutations in the acidic C-terminus region. Results of the phylogenetic analysis showed that the 29 grass species could be classified into three groups, namely, Triticeae, Oryza, and C4 plants. Within the Triticeae group, the FZP genes originating from the same genome were classified into the same sub-group. When selection pressure analysis was performed, significant positive selection sites were detected in species of the Triticeae and Oryza groups. Our results show that the FZP gene was selected during the grass family's evolutionary process, and functional divergence may have already occurred among the various species. Therefore, researchers investigating the FZP gene's functions should take note of the possible presence of various roles in other grass species.

How do international faculty at Japanese universities view their integration?

The purpose of the study is to explore how international faculty at Japanese universities view their integration. An exploratory study of semi-structural interviews with 40 full-time international faculty hired in Japanese universities with various backgrounds was conducted. The key findings indicate that international faculty perceived their integration as a beneficial longstanding two-way process of acquiring equality, developing engagement, and forming a feeling of attachment towards Japan. Meanwhile, their actual practices towards their integration appear to be diverse, which can be summarized into three broad categories, namely, preventive, occasional, and promotional. The study suggests a disjunction between international faculty's attitudes and their actual practices towards their integration, which is influenced by the overall host environment from a macro perspective, work role from a meso perspective, and personal intention, origin of country, and previous experience in Japan from a micro perspective. Theoretical and practical implications drawn from the key findings are provided to not only better understand the integration of international faculty at Japanese universities, but also to better serve and support them in practice.

Mathematics anxiety and mathematical calculation in deaf children: A moderated mediation model of mathematics self-efficacy and intelligence.

BACKGROUND: Previous studies have shown the relationship between mathematics anxiety and math performance in deaf students, but their inner influencing mechanism remains unclear. AIM: To examine a moderated mediation model between mathematics anxiety and mathematical calculation, with intelligence as a moderator, and mathematics self-efficacy as a mediator. METHODS: A sample of 247 deaf children from 2 special education schools and 247 hearing children (matched in intelligence) from one mainstream school in China completed computerized tests of intelligence and mathematical calculation and self-report questionnaires of mathematics anxiety and mathematics self-efficacy. Simple mediation analyses and moderated mediation analyses were conducted using PROCESS, and a simple slopes method was employed to plot the conditional indirect effects. RESULTS: There was a significant negative correlation between mathematics anxiety and mathematical calculation, and between mathematics anxiety and mathematics self-efficacy in deaf children and hearing children. However, mathematics self-efficacy was positively associated with mathematical calculation in deaf children but not in hearing children, and the significantly negative relationship between mathematics anxiety and intelligence was observed only in deaf children but not in hearing children. Mathematics self-efficacy partially mediated the association between mathematics anxiety and mathematical calculation in deaf children; and the indirect effect between mathematics anxiety and mathematical calculation via mathematics self-efficacy was moderated by intelligence in deaf children but not in hearing children. CONCLUSIONS: The results were discussed to illuminate the mechanism in relation to the practical implication for the intervention and early development of mathematics performance in deaf children.

Numerical Magnitude Processing in Deaf Adolescents and Its Contribution to Arithmetical Ability.

Although most deaf individuals could use sign language or sign/spoken language mix, hearing loss would still affect their language acquisition. Compensatory plasticity holds that the lack of auditory stimulation experienced by deaf individuals, such as congenital deafness, can be met by enhancements in visual cognition. And the studies of hearing individuals have showed that visual form perception is the cognitive mechanism that could explain the association between numerical magnitude processing and arithmetic computation. Therefore, we examined numerical magnitude processing and its contribution to arithmetical ability in deaf adolescents, and explored the differences between the congenital and acquired deafness. 112 deaf adolescents (58 congenital deafness) and 58 hearing adolescents performed a series of cognitive and mathematical tests, and it was found there was no significant differences between the congenital group and the hearing group, but congenital group outperformed acquired group in numerical magnitude processing (reaction time) and arithmetic computation. It was also found there was a close association between numerical magnitude processing and arithmetic computation in all deaf adolescents, and after controlling for the demographic variables (age, gender, onset of hearing loss) and general cognitive abilities (non-verbal IQ, processing speed, reading comprehension), numerical magnitude processing could predict arithmetic computation in all deaf adolescents but not in congenital group. The role of numerical magnitude processing (symbolic and non-symbolic) in deaf adolescents' mathematical performance should be paid attention in the training of arithmetical ability.

Guizhi Fuling Capsule Exhibits Antidysmenorrhea Activity by Inhibition of Cyclooxygenase Activity.

Guizhi Fuling capsule (GZFLc) is a modern preparation from traditional Chinese Medicine. Guizhi Fuling was first prescribed by Zhang Zhongjing almost two thousand years ago for the treatment of primary dysmenorrhea. It has also been used to treat uterine fibroids, dysfunctional uterine bleeding, and endometriosis. Although effective against dysmenorrhea clinically, there are limited information on the mechanism of its action. The major components responsible for the activity are not well defined. The aim of this study has been to elucidate a mechanism that may facilitate the development of a bioactivity-based assay for quality control during drug formulation and manufacturing. Using an oxytocin-induced mouse dysmenorrhea model, we showed that oral administration of GZFLc at 150 and 300 mg/kg, dosages relevant to clinic usages, significantly suppressed oxytocin-induced writhing response. The antidysmenorrhea effect was also demonstrated by a rotarod assay. We showed that GZFLc treatment significantly prolonged the hanging time of mice on the rotating rod. Histological studies showed that GZFLc treatment reduced lamina propria edema, while no effect on COX2 expression was detected. GZFLc instead exhibited direct inhibitory effect against COX2, a critical enzyme that catalyzes arachidonic acid conversion to prostaglandins. By HPLC profiling, we showed that paeoniflorin, paeonol, and cinnamaldehyde are the major components from the corresponding plants. At 5 and 10 mg/kg, both paeoniflorin and paeonol were active against induced dysmenorrhea. The study not only links GZFLc antidysmenorrhea activity to COX2 inhibition but also uncovers a mechanism of action by which an assay can be developed for bioefficacy evaluation of GZFLc.

Complete Genome Sequence Reveals Evolutionary and Comparative Genomic Features of Xanthomonas albilineans Causing Sugarcane Leaf Scald.

Leaf scald (caused by Xanthomonas albilineans) is an important bacterial disease affecting sugarcane in most sugarcane growing countries, including China. High genetic diversity exists among strains of X. albilineans from diverse geographic regions. To highlight the genomic features associated with X. albilineans from China, we sequenced the complete genome of a representative strain (Xa-FJ1) of this pathogen using the PacBio and Illumina platforms. The complete genome of strain Xa-FJ1 consists of a circular chromosome of 3,724,581 bp and a plasmid of 31,536 bp. Average nucleotide identity analysis revealed that Xa-FJ1 was closest to five strains from the French West Indies and the USA, particularly to the strain GPE PC73 from Guadeloupe. Comparative genomic analysis between Xa-FJ1 and GPE PC73 revealed prophage integration, homologous recombination, transposable elements, and a clustered regulatory interspaced short palindromic repeats (CRISPR) system that were linked with 16 insertions/deletions (InDels). Ten and 82 specific genes were found in Xa-FJ1 and GPE PC73, respectively, and some of these genes were subjected to phage-related proteins, zona occludens toxin, and DNA methyltransferases. Our findings highlight intra-species genetic variability of the leaf scald pathogen and provide additional genomic resources to investigate its fitness and virulence.

Essential oils from Inula japonica and Angelicae dahuricae enhance sensitivity of MCF-7/ADR breast cancer cells to doxorubicin via multiple mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelicae dahurica (Hoffm.) Benth. & Hook.f.ex Franch. & Sav combined with Pueraria and Gastrodia elata Bl. combined with Inula japonica Thunb. are widely used in herb-pairs of traditional chinese medicine. Previous studies have shown that Angelicae dahuricae essential oil (ADO) enhanced puerarin internalization into ABCB1-overexpressed Caco-2 cells. These findings suggest the possibility that essential oils may enhance the absorption via certain mechanisms related to ABCB1 and reverse multidrug resistance (MDR). AIM OF THE STUDY: ADO and essential oils from Inula japonica (IJO) may reverse ABCB1-mediated MDR, but this ability has not been investigated in detail in the well-established cancer cell lines. In this study, the underlying molecular mechanisms were further investigated to examine how IJO and ADO reverse MDR in the resistant human breast cancer cell line of MCF-7/ADR. Also this work may help uncover the conceivable compatibility mechanisms of above herb-pairs involved in ABCB1. MATERIALS AND METHODS: The MDR human breast cancer MCF-7/ADR cells were treated with IJO, its sesquiterpene component isoalantolactone (ISO) or ADOat non- cytotoxic concentrations. The MDR ability was examined by measuring the sensitivity to doxorubicin (DOX), DOX accumulation and efflux, ABCB1 ATPase activity, ABCB1 expression, membrane fluidity, and stability and localization of lipid rafts and caveolae. Finally, the molecular modeling was performed to postulate how ISO interacts with ABCB1. RESULTS: Treating MCF-7/ADR cells with IJ oil, ISO or AD oil reversed MDR 2- to 3-fold, without affecting the sensitivity of the non-MDR parental cell line. Mechanistic studies showed that these oils down-regulated mRNA and protein expression of ABCB1, and reduced the stability of lipid rafts in the cell membrane, which has previously been shown to reduce ABCB1-mediated transport. On the other hand, IJO, ISO and ADO did not inhibit ABCB1 ATPase activity, and fluorescence polarization experiments showed that low concentrations of the oils did not appear to alter membrane fluidity, unlike some MDR-reversing agents, ISO showed a higher docking score than verapamil but lower than dofequidar and tariquidar. CONCLUSIONS: Our results suggest that IJO, ISO and ADO could reverse MDR by down-regulating ABCB1 expression and reducing lipid raft stability. These findings may be useful for developing safer and effective MDR reversal agents and also help find out the compatibility mechanisms.

Succinate dehydrogenase subunit B inhibits the AMPK-HIF-1α pathway in human ovarian cancer in vitro.

BACKGROUND: Ovarian carcinoma is one of the most common gynecological cancers with high mortality rates. Numerous evidences demonstrate that cancer cells undergo metabolic abnormality during tumorigenesis in tumor microenvironment and further facilitate tumor progression. Succinate dehydrogenase (SDH or Complex II) is one of the important enzymes in the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase subunit B (SDHB) gene, which encodes one of the four subunits of SDH, has been recognized as a tumor suppressor. However the role of SDHB in ovarian cancer is still unclear. METHODS: Using the SDHB specific siRNA and overexpression plasmid, the expression of SDHB was silenced and conversely induced in ovarian cancer cell lines SKOV3 and A2780, respectively. The possible role of SDHB in ovarian cancer was investigated in vitro, using proliferation, migration and invasion assays. To explore the mechanism, proliferation and migration related proteins such as Bcl-2, cleaved caspase 3, p-ERK, MMP-2, and p-FAK were examined by western blot. P-P38, p-AMPKα, and HIF-1α were also examined by western blot. CoCl2 was used to induce HIF-1α expression in SKOV3 and A2780 cells. RESULTS: SDHB silencing promoted cell proliferation, invasion, and migration, but inhibited apoptosis of SKOV3 and A2780 cells. In contrast, overexpression of SDHB inhibited cell proliferation, invasion, migration, and promoted apoptosis in SKOV3 cells. It was observed that up-regulation of Bcl-2 and MMP-2, activation of p-P38, p-ERK, and p-FAK, inhibition of cleaved caspase 3 in SDHB-silenced cells. Meanwhile, decreased Bcl-2 and MMP-2, inhibition of p-P38, p-ERK, and p-FAK, activation of cleaved caspase 3 were shown in SDHB-overexpressed SKOV3 cells. HIF-1α, an essential factor in tumor progression, was up-regulated in SDHB-silenced cells with the activation of p-AMPKα and down-regulated in SDHB-overexpressed cancer cells with the decreased p-AMPKα. And SDHB was proved to be decreased due to upregulation of HIF-1α expression in CoCl2-treated cancer cells. CONCLUSIONS: Our results firstly revealed that SDHB played a key role in cell proliferation, invasion, migration, and apoptosis of human ovarian carcinoma via AMPK-HIF-1α pathway. SDHB-overexpression might be a new approach to inhibit tumor progression in human ovarian carcinoma.

Citrate synthase expression affects tumor phenotype and drug resistance in human ovarian carcinoma.

Citrate synthase (CS), one of the key enzymes in the tricarboxylic acid (TCA) cycle, catalyzes the reaction between oxaloacetic acid and acetyl coenzyme A to generate citrate. Increased CS has been observed in pancreatic cancer. In this study, we found higher CS expression in malignant ovarian tumors and ovarian cancer cell lines compared to benign ovarian tumors and normal human ovarian surface epithelium, respectively. CS knockdown by RNAi could result in the reduction of cell proliferation, and inhibition of invasion and migration of ovarian cancer cells in vitro. The drug resistance was also inhibited possibly through an excision repair cross complementing 1 (ERCC1)-dependent mechanism. Finally, upon CS knockdown we observed significant increase expression of multiple genes, including ISG15, IRF7, CASP7, and DDX58 in SKOV3 and A2780 cells by microarray analysis and real-time PCR. Taken together, these results suggested that CS might represent a potential therapeutic target for ovarian carcinoma.

MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer.

Metastasis is major cause of mortality in patients with ovarian cancer. MiR-373 has been shown to play pivotal roles in tumorigenesis and metastasis; however, a role for miR-373 in ovarian cancer has not been investigated. In this study, we show that the miR-373 expression is down-regulated in human epithelial ovarian cancer (EOC) and inversely correlated with clinical stage and histological grade. Ectopic overexpression of miR-373 in human EOC cells suppressed cell invasion in vitro and metastasis in vivo, and the epithelial-mesenchymal transition process. Silencing the expression of miR-373 resulted in an increased migration and invasion of EOC cells. Using integrated bioinformatics analysis, gene expression arrays, and luciferase assay, we identified Rab22a as a direct and functional target of miR-373 in EOC cells. Expression levels of miR-373 were inversely correlated with Rab22a protein levels in human EOC tissues. Rab22a knockdown inhibited invasion and migration of EOC cells, increased E-cadherin expression, and suppressed the expression of N-cadherin. Moreover, overexpression of Rab22a abrogated miR-373-induced invasion and migration of EOC cells. Taken together, these results demonstrate that miR-373 suppresses EOC invasion and metastasis by directly targeting Rab22a gene, a new potential therapeutic target in EOC.

FOXM1 modulates cisplatin sensitivity by regulating EXO1 in ovarian cancer.

Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional factor FOXM1 has been reported to be overexpressed in ovarian cancer. In this study, we aimed to investigate the potential role of FOXM1 in ovarian cancers with chemoresistance to cisplatin. Our results indicate that FOXM1 is upregulated in chemoresistant ovarian cancer samples, and defends ovarian cancer cells against cytotoxicity of cisplatin. FOXM1 facilitates DNA repair through regulating direct transcriptional target EXO1 to protect ovarian cancer cells from cisplatin-mediated apoptosis. Attenuating FOXM1 and EXO1 expression by small interfering RNA, augments the chemotherapy efficacy against ovarian cancer. Our findings indicate that targeting FOXM1 and its target gene EXO1 could improve cisplatin effect in ovarian cancer, confirming their role in modulating cisplatin sensitivity.

Cisplatin-alginate conjugate liposomes for targeted delivery to EGFR-positive ovarian cancer cells.

Systemic side effects and low aqueous solubility have limited the clinical use of cisplatin (CDDP) in ovarian carcinoma and have contributed to failures in developing effective drug delivery systems. In order to develop a novel drug delivery system with enhanced efficacy and minimal adverse effects, we exploited the properties of sodium alginate (SA) to synthesize CDDP-SA conjugate (CS), which is highly soluble and readily incorporated into liposomes (CS-PEG-Lip). Epidermal growth factor receptor (EGFR) is overexpressed in many ovarian cancers, therefore we modified EGF on the liposomes (CS-EGF-Lip) to specifically target EGFR-expressing tumors, thereby increasing the bioavailability and efficacy of CDDP. In vitro experiments confirmed that EGF-Lip selectively recognized EGFR-positive SKOV3 cells and effectively penetrated tumor spheroids. We demonstrated that CS-EGF-Lip possessed satisfactory size distribution and exhibited significantly improved encapsulation and loading efficiency. Furthermore, CS-EGF-Lip sustained release of CDDP in vitro, suggesting that CS-EGF-Lip may retain the antitumor activity of CDDP. Inhibition of proliferation and migration was also greater with CS-EGF-Lip compared to CDDP. In vivo xenograft experiments revealed that administration of CS-EGF-Lip enhanced delivery of CDDP into ovarian tumor tissues and improved the antitumor efficacy of CDDP, while reducing nephrotoxicity and body weight loss in mice. These results suggest that CS-EGF-Lip may offer a promising strategy for CDDP delivery in the treatment of EGFR-positive ovarian carcinoma or similar tumors, with enhanced efficacy and fewer adverse effects.

Progesterone receptor PROGINS and +331G/A polymorphisms confer susceptibility to ovarian cancer: a meta-analysis based on 17 studies.

Progesterone and its receptor, progesterone receptor (PGR), have been widely studied for their roles in the onset and development of ovarian cancer. Although numerous epidemiological studies have focused on the association of PGR PROGINS and +331G/A polymorphisms with ovarian cancer susceptibility, presently, available results remain controversial, in part due to low sample sizes. Thus, a meta-analysis is required to evaluate this association. A literature search of PubMed, Embase, Web of Science, CNKI, and CBM databases was performed to retrieve eligible studies published before August 15, 2013. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of this association. All analyses were done using STATA 12.0 software (Stata Corp., College Station, TX, USA). Seventeen case-control studies with a total of 6,365 cases and 9,998 controls were identified. While no statistically significant association between the PROGINS allele and ovarian cancer risk was found in an overall analysis, a stratified analysis revealed that for Caucasians, never-oral contraceptive (OC) users, and serous tumor patients, there were statistically significant ORs for ovarian cancer risk associated with the mutated PROGINS allele. No significant association, however, between the +331G/A polymorphism and ovarian cancer susceptibility was observed in the overall analyses and subgroup analyses based on ethnicity and histological type. This meta-analysis provides evidence that the PROGINS allele occurs more frequently in ovarian cancer patients and especially in non-OC users and serous cancer patients, indicating that PROGINS may be a risk modifier. No significant association between the +331G/A polymorphism and ovarian cancer was found, even in stratified analyses by ethnicity and histological type. More detailed and well-designed studies are still needed to confirm the role of the PROGINS allele in ovarian cancer development.

Pharmacokinetic comparison of two nicotine transdermal systems, a 21-mg/24-hour patch and a 25-mg/16-hour patch: a randomized, open-label, single-dose, two-way crossover study in adult smokers.

BACKGROUND: A comparison of the 21-mg NiQuitin patch with other marketed nicotine patches reported significant differences in pharmacokinetic profiles, even among patches of the identical labeled dose strength. The 25-mg Nicorette Invisi patch became available in the United Kingdom at the end of 2008. No published studies have directly compared the pharmacokinetic profile of this new patch with that of the 21-mg NiQuitin patch. OBJECTIVES: This study was conducted to compare the single-dose pharmacokinetics of the 21-mg/24-hour patch and the 25-mg/16-hour patch. To determine whether any pharmacokinetic differences might be related to differences in wear time, a post hoc exploratory analysis evaluated the nicotine delivery profiles of the patches under the assumption that the 21-mg patch was removed after 16 rather than 24 hours. METHODS: This was a single-center, randomized, open-label, single-dose, 2-way crossover study in healthy adults who smoked >10 cigarettes per day in the 6 months before the study. Eligible subjects were housed at the study center for 2 baseline and 2 treatment sessions; no smoking was permitted during the baseline or treatment sessions. Subjects were allocated to receive either the 21-mg patch (removed after 24 hours) or the 25-mg patch (removed after 16 hours) during the first treatment session, after which they crossed over to the alternative sequence in the second treatment session. Blood samples were obtained at predetermined time points before and after patch application. The primary pharmacokinetic parameter was the AUC(0-infinity), an indication of total nicotine exposure. Secondary pharmacokinetic parameters included AUC(0-t), C(max), and T(max). Post hoc exploratory parameters were the AUC(0-16) and the AUC(0-infinity) assuming a 16-hour application time for the 21-mg patch. The differences in AUC(0-infinity), AUC(0-t), Cmax, AUC(0-16), and AUC(0-infinity) assuming a 16-hour application time for the 21-mg patch were considered significant if the lower limit of the 90% CI for the geometric mean ratio (21 mg:25 mg) was >100%. T(max) values were compared using a signed-rank test. Adverse events were elicited using a standard open-ended question on each day of confinement; spontaneously reported events were also captured. The topical effects of the patch (erythema; edema; extent of erythema/papules/pustules; self-reported pruritus) were assessed by study staff before patch application and 1 and 8 hours after patch application using a 4-point rating scale; any topical effects were recorded as adverse events. RESULTS: Fifty otherwise healthy smokers (29 men, 21 women) were enrolled; 47 (94%) were white. Their mean (SD) age was 31.5 (9.57) years (range, 20-53 years), mean weight was 70.24 (9.56) kg (range, 51.0-95.9 kg), and mean height was 173.0 (8.02) cm (range, 156-194 cm). Subjects reported smoking between 11 and 40 cigarettes per day before the study. The AUC(0-infinity) was significantly higher for the 21-mg patch worn for 24 hours than for the 25-mg patch worn for 16 hours (382.36 vs 243.69 ng/mL . h, respectively; geometric mean ratio: 156.90%; 90% CI, 148.10%-166.23%; P < 0.001). T(max) was reached significantly sooner with the 21-mg patch than with the 25-mg patch (6.0 vs 12.0 hours; P < 0.001). C(max) was significantly higher for the 21-mg patch compared with the 25-mg patch (18.34 vs 16.56 ng/mL; geometric mean ratio: 110.72%; 90% CI, 104.82%-116.94%; P < 0.01). The exploratory analyses suggested that the 21-mg patch applied for 16 hours may provide greater total nicotine exposure than the 25-mg patch applied for 16 hours. Although most subjects reported adverse events (75.0% with the 21-mg patch, 89.8% with the 25-mg patch), the majority of these events were mild. CONCLUSIONS: In this single-dose study in adult smokers, the 21-mg patch was associated with significantly greater nicotine exposure compared with the 25-mg patch. The 21-mg patch provided a maximal nicotine concentration faster than did the 25-mg patch.