Outcomes of a Double-Cup Construct to Treat Paprosky 3A and 3B Acetabular Defects at a Mean of 39 Months.

BACKGROUND: Modular reconstruction systems based on porous tantalum (PT) prosthetic components have been increasingly used for the treatment of complex acetabular bone defects in revision total hip arthroplasty. We report a novel technique that applies a revision cup as a "super-augment" to form a "double-cup" construct for Paprosky type III defects. METHODS: A retrospective review was conducted on revision total hip arthroplasty cases, comparing those treated with double-cup constructs (DC group, n = 48) to those treated with PT shells and augments (PT group, n = 48). All procedures were performed at the same institute between 2017 and 2022. Clinical outcome evaluation utilized the Harris Hip Score, Oxford Hip Score, and the 36-Item Short Form Survey. Preoperative and postoperative radiographic assessments measured hip center of rotation (COR) position and leg length discrepancy. Additionally, postoperative complications and implant survivorship were monitored during the follow-up period. RESULTS: The clinical outcomes improved substantially in both groups, which showed no significant difference in the Harris Hip Score (P = .786), the Oxford Hip Score (P = .570), and the 36-Item Short Form Survey (P = .691). Compared to the PT group, the reconstruction COR was significantly closer to the anatomic COR (vertical distance: 2.630 versus 7.355 mm, P = .0034; horizontal distance: 1.881 versus -6.413 mm, P < .0001) in Paprosky 3B type defects. Additionally, postoperative leg length discrepancy was less in the DC group (-8.252 versus -1.821 mm, P = .0008). Dislocation was the main complication in the DC group, and only 1 patient received re-revision due to repeated dislocation. The cumulative survival rate of the DC group (100%; 95% confidence interval 100) was better than the PT group (83.4%; 95% confidence interval 70.5 to 98.6) when re-revisions for aseptic loosening were the endpoint (P = .046). CONCLUSIONS: The DC is a reliable revision technique for the reconstruction of Paprosky type III bone defects. Although dislocation remains challenging, the biomechanically superior restoration achieved by this technique lowers the risk of aseptic loosening.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Nomograms for prognostic risk assessment in glioblastoma multiforme: Applications and limitations.

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer. Prognosis evaluation is of great significance in guiding individualized treatment and monitoring of GBM. By integrating different prognostic variables, nomograms simplify the statistical risk prediction model into numerical estimates for death or recurrence, and are hence widely applied in prognosis prediction. In the past two decades, the application of high-throughput profiling technology and the establishment of TCGA database and other public data deposits have provided opportunities to identify cancer-related molecules and prognostic biomarkers. As a result, both molecular features and clinical characteristics of cancer have been reported to be the key factors in nomogram model construction. This article comprehensively reviewed 35 studies of GBM nomograms, analyzed the present situation of GBM nomograms, and discussed the role and significance of nomograms in personalized risk assessment and clinical treatment decision-making. To facilitate the application of nomograms in the prognostic prediction of GBM patients, a website has been established for the online access of nomograms based on the studies of this review, which is called Consensus Nomogram Spectrum for Glioblastoma (CNSgbm) and is accessible through https://bioinfo.henu.edu.cn/nom/NomList.jsp.

The association between meat consumption and the metabolic syndrome: a cross-sectional study and meta-analysis.

The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.

Cardiac glycosides from the roots of Streblus asper Lour. with activity against Epstein-Barr virus lytic replication.

Cardiac glycosides (CGs) show potential broad-spectrum antiviral activity by targeting cellular host proteins. Herein are reported the isolation of five new (1-5) and eight known (7-13) CGs from the roots of Streblus asper Lour. Of these compounds 1 and 7 exhibited inhibitory action against EBV early antigen (EA) expression, with half-maximal effective concentration values (EC50) being less than 60 nM, and they also showed selectivity, with selectivity index (SI) values being 56.80 and 103.17, respectively. Preliminary structure activity relationships indicated that the C-10 substituent, C-5 hydroxy groups, and C-3 sugar unit play essential roles in the mediation of the inhibitory activity of CGs against EBV. Further enzyme experiments demonstrated that these compounds might inhibit ion pump function and thereby change the intracellular signal transduction pathway by binding to Na+/K+-ATPase, as validated by simulated molecular docking. This study is the first report that CGs can effectively limit EBV lytic replication, and the observations made in this study may be of value for lead compound development.

Comparison of foreign language anxiety based on four language skills in Chinese college students.

BACKGROUND: Numerous studies have established that foreign language anxiety (FLA) has a significant impact on learners' language acquisition and performance. FLA is a unique form of anxiety that occurs in response to a certain circumstance. Even though a growing amount of research has extended to the examination of skill-based anxiety in specific, such as listening, speaking, reading, and writing, little used corresponding skilled-based FLA scales to assess learners' skill-based FLA at one group of learners. To fill a void in this line of research, the study aimed to explore learners' primary FLA by comparing their four language skill-specific FLAs with four different skill-based FLA scales. Additionally, we wished to investigate the variables that influence learners' FLA. METHODS: All participants in the study were first-year medical students. Individual instructors delivered and collected a total of 1023 questionnaires using an open questionnaire platform during normal English lessons in the mid-semester. SPSS 24.0 (Statistical Package for Social Science 24 version) was used to analyze all statistics. Internal validity tests were undertaken on each scale to ascertain the component structure of certain modified scales. The study employed the independent sample t-test and a statistical description to investigate students' major FLA and its variables. RESULTS: With a mean value of 106.863, the predominant FLA arouses from English listening anxiety. English reading anxiety was the lowest, with a mean score of 62.726. Male and female students both demonstrated the greatest degree of FLA in English listening and the least anxiety in English reading. However, their mean difference was not statistically significant (t = 1.220). By comparing the mean scores for four skill-based FLAs across language proficiency groups, it became clear that the scores for the medium were much higher than the average, with average scores of ESA: 91.988, ELA: 106.864, EWA: 74.157, ERA: 62.726, respectively, and the higher-level group scored lower than the average. Students' prior English learning achievements are negatively connected with their FLA, with r values of -.207 (ELA), -.143 (EWA), and - .204 (ERA). The self-evaluation of students' English listening, writing, and reading abilities was considerably adversely connected with FLA, but the self-evaluation of their English-speaking abilities was favorably correlated with FLA. CONCLUSION: A comparison of students' FLA revealed that the primary skill-based FLA is related to English listening anxiety. Regardless of gender or language proficiency level, FLA was mainly driven by foreign language listening anxiety in all individuals. Prior language achievement and students' self-evaluation are associated with their FLA.

A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma.

Blood group antigen is a class of heritable antigenic substances present on the erythrocyte membrane. However, the role of blood group antigens in cancer prognosis is still largely unclear. In this study, we investigated the expression of 33 blood group antigen genes and their association with the prognosis of 30 types of cancers in 31,870 tumor tissue samples. Our results revealed that blood group antigens are abnormally expressed in a variety of cancers. The high expression of these antigen genes was mainly related to the activation of the epithelial-mesenchymal transition (EMT) pathway. High expression of seven antigen genes, i.e., FUT7, AQP1, P1, C4A, AQP3, KEL and DARC, were significantly associated with good OS (Overall Survival) in six types of cancers, while ten genes, i.e., AQP1, P1, C4A, AQP3, BSG, CD44, CD151, LU, FUT2, and SEMA7A, were associated with poor OS in three types of cancers. Kidney renal clear cell carcinoma (KIRC) is associated with the largest number (14 genes) of prognostic antigen genes, i.e., CD44, CD151, SEMA7A, FUT7, CR1, AQP1, GYPA, FUT3, FUT6, FUT1, SLC14A1, ERMAP, C4A, and B3GALT3. High expression of SEMA7A gene was significantly correlated with a poor prognosis of KIRC in this analysis but has not been reported previously. SEMA7A might be a putative biomarker for poor prognosis in KIRC. In conclusion, our analysis indicates that blood group antigens may play functional important roles in tumorigenesis, progression, and especially prognosis. These results provide data to support prognostic marker development and future clinical management.

Nonglandular prickle formation is associated with development and secondary metabolism-related genes in Rosa multiflora.

Roses are among the most economically important ornamental plants worldwide. But prickles on the stem and leaves cause difficulties for cultivation or inconveniences during harvest and transportation, thus are an undesirable horticultural character. However, little is known about the molecular mechanisms of prickle development. In this study, we sought to develop Rosa multiflora (in the family Rosaceae) as a model plant to study prickle formation. The morphology, structure, and ontogeny of prickles were characterized, and transcriptome analysis of prickly and prickleless R. multiflora genotypes was performed. Morphological observation and microscopic analyses revealed that prickles of R. multiflora were non-glandular prickles (NGPs) and their maturation went through five developmental stages, which was accompanied by the accumulation of secondary metabolites such as lignin and anthocyanins. Comparative transcriptome analysis identified key pathways and hub genes potentially involved in prickle formation. Interestingly, among the differentially expressed genes (DEGs), several notable development and secondary metabolism-related transcription factors (TFs) including NAC, TCP, MYB, homeobox, and WRKY were up-regulated in prickly internodes. KEGG enrichment analysis indicated that DEGs were enriched in the pathways related to biosynthesis of secondary metabolites, flavonoids, and phenylpropanoids in the prickly R. multiflora. Our study provides novel insights into the molecular network underlying the regulation of prickle morphogenesis in R. multiflora, and the identified candidates might be applied to the genetic improvement of roses.

Evidence for the 'rate-of-living' hypothesis between mammals and lizards, but not in birds, with field metabolic rate.

Longevity, an important life-history trait, is determined by extrinsic and/or intrinsic causing mortality. Here, we used body mass (BM), field metabolic rate (FMR), longevity, and female maturity data reported from 300 amniote species to test whether 1) longevity was related to BM, FMR and female maturity, and 2) FMR, female maturity, or both, had a direct effect on longevity and whether an indirect effect of FMR on female maturity improved model fit. The results showed that BM was positively correlated with longevity and FMR, but negatively correlated with mass-specific FMR (mFMR) in amniotes. Phylogenetic confirmatory path analysis showed that, in the best model, longevity had a direct negative correlation with mFMR in lizards, and an indirect negative correlation with mFMR through female maturity in mammals. However, longevity had a direct positive correlation with mFMR in birds. Furthermore, longevity was positively correlated with female maturity in endotherms (birds and mammals) but weakly correlated with female maturity in ectotherms (lizards). Thus, our results are consistent with the life-history theory and the "rate-of-living" hypothesis in lizards and mammals but not support them in birds.

Retropharyngeal internal carotid artery: a potential risk factor during nasotracheal intubation.

PURPOSE: To investigate the potential risk of the retropharyngeal internal carotid artery (RICA) during nasotracheal intubation (NTI). METHODS: We retrospectively surveyed 2028 patients and 90 healthy controls (HC) with neck computed tomography angiography (CTA). The incidence of RICA was analyzed, as well as the correlation between the average minimum carotid-pharyngeal distance (CPD) and the carotid-median plane distance (CMD). We also compared CPD between RICA and HC. RESULTS: RICA was observed in 91 out of the 2028 patients, reaching an incidence of 4.5% (91/2028). RICA in female patients was 65.9% (60/91) compared to 34.1% (31/91) in male patients. The incidence of RICA at nasopharynx (NP), oropharynx (OP), and hypopharynx (HP) was 31.9% (29/91), 61.5% (56/91), and 6.6% (6/91), respectively. The incidence of the mucosal eminence of the posterior wall of the pharynx in RICA was 30.8% (28/91). In 15 cases, RICA caused the pharyngeal cavity to become narrow, with an incidence of 16.5% (15/91). Moreover, CPD and CMD was positively correlated (r = 0.56, p < 0.01). The average minimum CPD of RICA was only 2.25 ± 1.26 mm, which was much shorter than HC (17.62 ± 1.98 mm) (t = 62.46, p < 0.01). Some CPD of RICA was even less than 1 mm, with an incidence of 20.9% (19/91). CONCLUSION: RICA is not uncommon in asymptomatic adults. It is very close to the midline and posterior wall of the pharynx and is more likely to occur in the nasopharynx (NP) and oropharynx (OP). RICA tear is likely to occur during NTI.

The phosphatidylethanolamine biosynthesis pathway provides a new target for cancer chemotherapy.

BACKGROUND & AIMS: Since human induced pluripotent stem cells (iPSCs) develop into hepatic organoids through stages that resemble human embryonic liver development, they can be used to study developmental processes and disease pathology. Therefore, we examined the early stages of hepatic organoid formation to identify key pathways affecting early liver development. METHODS: Single-cell RNA-sequencing and metabolomic analysis was performed on developing organoid cultures at the iPSC, hepatoblast (day 9) and mature organoid stage. The importance of the phosphatidylethanolamine biosynthesis pathway to early liver development was examined in developing organoid cultures using iPSC with a CRISPR-mediated gene knockout and an over the counter medication (meclizine) that inhibits the rate-limiting enzyme in this pathway. Meclizine's effect on the growth of a human hepatocarcinoma cell line in a xenotransplantation model and on the growth of acute myeloid leukemia cells in vitro was also examined. RESULTS: Transcriptomic and metabolomic analysis of organoid development indicated that the phosphatidylethanolamine biosynthesis pathway is essential for early liver development. Unexpectedly, early hepatoblasts were selectively sensitive to the cytotoxic effect of meclizine. We demonstrate that meclizine could be repurposed for use in a new synergistic combination therapy for primary liver cancer: a glycolysis inhibitor reprograms cancer cell metabolism to make it susceptible to the cytotoxic effect of meclizine. This combination inhibited the growth of a human liver carcinoma cell line in vitro and in a xenotransplantation model, without causing significant side effects. This drug combination was also highly active against acute myeloid leukemia cells. CONCLUSION: Our data indicate that phosphatidylethanolamine biosynthesis is a targetable pathway for cancer; meclizine may have clinical efficacy as a repurposed anti-cancer drug when used as part of a new combination therapy. LAY SUMMARY: The early stages of human liver development were modeled using human hepatic organoids. We identified a pathway that was essential for early liver development. Based upon this finding, a novel combination drug therapy was identified that could be used to treat primary liver cancer and possibly other types of cancer.

OSpaad: An online tool to perform survival analysis by integrating gene expression profiling and long-term follow-up data of 1319 pancreatic carcinoma patients.

Pancreatic carcinoma (PC) is a type of highly lethal malignant tumor that has unfavorable outcomes. One major challenge in improving clinical outcomes is to identify novel biomarkers for prognosis. In this study, we developed an online consensus survival tool for pancreatic adenocarcinoma (OSpaad), which allows researchers and clinicians to analyze the prognostic value of selected genes in PC. OSpaad contains 1319 unique PC cases that have both gene expression data and correspondent clinical data from seven individual cohorts and provides four survival terms including overall survival, disease-specific survival, disease-free interval, progression-free interval for prognosis evaluation. To meet the different research needs, OSpaad allows users to limit survival analysis in subgroups by selecting different terms of clinical confounding factors such as TNM stage, sex, smoking time, lymph invasion, and race. Moreover, we showed that 97% (116 out of 120) previously reported prognostic biomarkers, including ERBB2, TP53, EGFR and so forth, were validated and confirmed their prognostic significance in OSpaad, demonstrating the well performance of survival analysis in OSpaad. OSpaad is a user-friendly online tool with a straightforward interface allowing clinicians and basic research scientists with even a limited bioinformatics background to easily screen and evaluate the prognostic value of genes in a large PC cohort. This online tool can be accessed at http://bioinfo.henu.edu.cn/PAAD/PAADList.jsp.

OSuvm: An interactive online consensus survival tool for uveal melanoma prognosis analysis.

Uveal melanoma (UM) is a rare, aggressive, but the most frequent primary intraocular malignancy in adults, and up to 50% of patients develop a tendency of liver metastases. Great efforts have been made to develop biomarkers that facilitate diagnosis, prediction of the risk, and response to treatment of UM. However, a biologically informative and highly accurate gold standard system for prognostic evaluation of UM remains to be established. To facilitate assessment of the prognosis of UM patients, we established a user-friendly Online consensus Survival tool for uveal melanoma, named OSuvm, by which users can easily estimate the prognostic values of genes of interest by the Kaplan-Meier survival plot with hazard ratio and log-rank test. OSuvm comprises four independent cohorts including 229 patients with both gene expression profiles and relevant clinical follow-up information, and it has shown great performance in evaluating the prognostic roles of previously reported biomarkers. Using OSuvm enables researchers and clinicians to rapidly and conveniently explore the prognostic value of genes of interest and develop new potential molecular biomarkers for UM. OSuvm can be accessed at http://bioinfo.henu.edu.cn/UVM/UVMList.jsp.

Crossed cerebellar diaschisis after stroke detected noninvasively by arterial spin-labeling MR imaging.

BACKGROUND: As a noninvasive perfusion-weighted MRI technique, arterial spin-labeling (ASL) was becoming increasingly used to evaluate cerebral hemodynamics in many studies. The relation between ASL-MRI and crossed cerebellar diaschisis (CCD) was rarely discussed. In this study, the aim of our study was to assess the performance of ASL-MRI in the detection of crossed cerebellar diaschisis after stroke in compared with single-photon emission CT (SPECT). RESULTS: 17 of 51(33.3%) patients revealed CCD phenomenon by the SPECT method. In CCD-positive group, CBFASL of ipsilateral cerebellar were significantly increased compared with contralateral cerebellar (p < 0.0001) while no significant differences (p = 0.063, > 0.001) in the CCD-negative group. Positive correlation was detected between admission National institute of health stroke scale (NIHSS) and asymmetry index of SPECT (AISPECT) (r = 0.351, p = 0.011), AIASL (r = 0.372, p = 0.007); infract volume and AISPECT (r = 0.443, p = 0.001), AIASL (r = 0.426, p = 0.002). Significant correlation was also found between cerebral blood flow of SPECT (CBFSPECT) and CBFASL, AISPECT and AIASL (r = 0.204, p = 0.04; r = 0.467, p = 0.001, respectively). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AIASL was 0.829. CONCLUSIONS: CBF derived from ASL-MRI could be valuable for assessment of CCD in supratentorial stroke patients. Additionally, CCD was significantly associated with larger ischemic volume and higher initial NIHSS score.

Pharmacokinetic and pharmacodynamic profiling of four antimicrobials against Acinetobacter baumannii infection.

BACKGROUND: The aim of this study was to evaluate common antimicrobial regimens used in eradicating Acinetobacter baumannii in Shenyang, China. METHODS: Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) for imipenem, cefoperazone/sulbactam (2:1), tigecycline and colistin methanesulfonate. RESULTS: For the results of PTAs, imipenem following administration of 0.5 g q6 h, 1 g q8 h, and 1 g q6 h for both 0.5 h and 2 h infusion achieved＞90% PTAs when MIC was 8 µg/ml; cefoperazone/ sulbactam (2:1) following administration of 4.5 g q6 h and 6 g q6 h achieved＞90% PTAs when MIC was 64µg/ml; tigecycline following administration of 50 mg q12 h and 100 mg q12 h achieved＞90% PTAs when MIC was 1 µg/ml; colistin methanesulfonate with high dosages (3MU q8 h) could provide high PTA (95.13%) in patients with CLCr＜60 ml/min when MIC was 2 µg/ml. As for CFR values of four antibiotics, imipenem achieved the lowest CFR values. For cefoperazone/sulbactam (2:1) and tigecycline, with simulated regimens improvement, the CFR values were both increased, and there were obviously increasing CFR values against Acinetobacter baumannii. For colistin methanesulfonate, the most aggressive dosage of 3MU q8 h could provide satisfactory CFR values (≥86.94%) against Acinetobacter baumannii in patients at various CLCr. CONCLUSION: This study suggested that measurement of MICs, individualized therapy and therapeutic drug-level monitoring should be considered together to achieve the optimal drug exposure. That will provide the best chance of achieving the highest probability of a successful clinical or microbiological response, and avoiding the induced resistance.

OSskcm: an online survival analysis webserver for skin cutaneous melanoma based on 1085 transcriptomic profiles.

BACKGROUND: Cutaneous melanoma is one of the most aggressive and lethal skin cancers. It is greatly important to identify prognostic biomarkers to guide the clinical management. However, it is technically challenging for untrained researchers to process high dimensional profiling data and identify potential prognostic genes in profiling datasets. METHODS: In this study, we developed a webserver to analyze the prognostic values of genes in cutaneous melanoma using data from TCGA and GEO databases. The webserver is named Online consensus Survival webserver for Skin Cutaneous Melanoma (OSskcm) which includes 1085 clinical melanoma samples. The OSskcm is hosted in a windows tomcat server. Server-side scripts were developed in Java script. The database system is managed by a SQL Server, which integrates gene expression data and clinical data. The Kaplan-Meier (KM) survival curves, Hazard ratio (HR) and 95% confidence interval (95%CI) were calculated in a univariate Cox regression analysis. RESULTS: In OSskcm, by inputting official gene symbol and selecting proper options, users could obtain KM survival plot with log-rank P value and HR on the output web page. In addition, clinical characters including race, stage, gender, age and type of therapy could also be included in the prognosis analysis as confounding factors to constrain the analysis in a subgroup of melanoma patients. CONCLUSION: The OSskcm is highly valuable for biologists and clinicians to perform the assessment and validation of new or interested prognostic biomarkers for melanoma. OSskcm can be accessed online at: http://bioinfo.henu.edu.cn/Melanoma/MelanomaList.jsp.

Limonoids and tricyclic diterpenoids from Azadirachta indica and their antitumor activities.

The chemical constituents of the roots, seeds, and bark of Azadirachta indica var. siamensis were investigated, leading to the isolation of six tricyclic diterpenoids and five limonoids, including two new compounds (2, 5). The structures were elucidated based on NMR spectroscopic techniques, mass spectrometry and single-crystal X-ray diffraction as well as comparison with the literature. Moreover, the cytotoxicity activities of the isolates were evaluated. The results indicated that the compounds 1-3, 5-9 exhibited cytotoxicities against one or more cancer cell lines tested, with IC50 values in the range of 1.7-88.1 µM. The mechanism of action studies indicated that the most active compound, compound 5, could induce the apoptosis of AZ521 cells. Furthermore, the Western blot analysis showed that compound 5 could reduce the expression levels of procaspases-3, -8, -9 and promote the expression of Bid and AIF.

OScc: an online survival analysis web server to evaluate the prognostic value of biomarkers in cervical cancer.

Aim: To establish a web server that can mutually validate prognostic biomarkers of cervical cancer. Methods: Four datasets including expression profiling and relative clinical follow-up data were collected from Gene Expression Omnibus and The Cancer Genome Atlas. The web server was developed by R software. Results: The web server was named OScc including 690 patients and can be accessed at http://bioinfo.henu.edu.cn/CESC/CESCList.jsp. The Kaplan-Meier survival curves with log-rank p-value and hazard ratio will be generated of interested gene in OScc. Compared with previous predictive tools, OScc had the advantages of registration-free, larger sample size and subgroup analysis. Conclusion: The OScc is highly valuable to perform the preliminary assessment and validation of new or interested prognostic biomarkers for cervical cancer.

Different progestin-primed ovarian stimulation protocols in infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection: an analysis of 1188 cycles.

PURPOSE: To evaluate the efficacy in suppressing the premature LH surge, embryo quality and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocols using medroxyprogesterone acetate versus utrogestan in women of all ages undergoing in vitro fertilization or intracytoplasmic sperm injection. METHODS: 1188 patients were enrolled in the retrospective study, of which 1002 patients were treated with medroxyprogesterone acetate (M group) and recombinant follicle-stimulating hormone (r-FSH)simultaneously from day 3 of the cycle until trigger day, while 186 patients were treated with utrogestan (U group) and r-FSH instead. Viable embryos were cryopreserved for later transfer in both groups. Differences in baseline characteristics, ovarian stimulation characteristics, endocrinological characteristics, embryo development and clinical outcome between two groups were assessed. Statistical analyses were performed stratified by age and number of oocytes retrieved. RESULTS: No significant differences were observed in the baseline characteristics, ovarian stimulation characteristics and clinical outcome of patients between groups. However, blastulation rate in the U group was significantly higher than that in the M group (49.4% vs. 32.9%, P < 0.001). During ovarian stimulation, LH levels remained steady in both groups. Higher percentage of premature LH surge was found in the U group (2.4% vs. 10.2%, P < 0.001), especially for patients aged more than 35 years or who had three oocytes or less retrieved. CONCLUSIONS: Both the administration of medroxyprogesterone acetate and utrogestan in PPOS were sufficient to prevent an untimely LH rise, while for patients with poor ovarian response or aged above 35 years, MPA may result in a more satisfactory LH level. PPOS protocol using medroxyprogesterone acetate or utrogestan was comparable in terms of oocytes and pregnancy outcome, whereas the administration of utrogestan may result in an improved blastulation than medroxyprogesterone acetate, which needs further exploration.

A Single Mutation Increases the Thermostability and Activity of Aspergillus terreus Amine Transaminase.

Enhancing the thermostability of (R)-selective amine transaminases (AT-ATA) will expand its application in the asymmetric synthesis of chiral amines. In this study, mutual information and coevolution networks of ATAs were analyzed by the Mutual Information Server to Infer Coevolution (MISTIC). Subsequently, the amino acids most likely to influence the stability and function of the protein were investigated by alanine scanning and saturation mutagenesis. Four stabilized mutants (L118T, L118A, L118I, and L118V) were successfully obtained. The best mutant, L118T, exhibited an improved thermal stability with a 3.7-fold enhancement in its half-life (t1/2) at 40 °C and a 5.3 °C increase in T5010 compared to the values for the wild-type protein. By the differential scanning fluorimetry (DSF) analysis, the best mutant, L118T, showed a melting temperature (Tm) of 46.4 °C, which corresponded to a 5.0 °C increase relative to the wild-type AT-ATA (41.4 °C). Furthermore, the most stable mutant L118T displayed the highest catalytic efficiency among the four stabilized mutants.