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Iron-based nanomaterials as effective additives can enhance the quality and safety of compost. However, their influence on organic carbon fractions changes and greenhouse gas emissions during composting remains unclear. This study demonstrated that iron-based nanomaterials facilitate the conversion of light organic carbon fraction into heavy organic carbon fraction, with the iron-based nanomaterials group showing a significantly higher heavy organic carbon fraction content (41.88%) compared to the control group (35.71%). This shift led to an increase in humic substance content (77.5 g/kg) and a reduction in greenhouse gas emissions, with CO 2 , CH 4 , and N 2 O emissions decreasing by 20.5%, 39.7%, and 55.4%, respectively. Additionally, CO 2 -equivalent emissions were reduced by 42.9%. Microbial analysis revealed that iron-based nanomaterials increased the abundance of Bacillus and reduced the abundance of methane-producing archaea such as Methanothermobacter and Methanomassiliicoccus. These results indicated that the role of iron-based nanomaterials in regulating reactive oxygen species production and specific microbial communities involved in humification process. This study provides a practical strategy for improving waste utilization efficiency and mitigating climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited 1-3 . Here we used a base editor-enabled DNA barcoding system 4 to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent cell lineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Social ties play a crucial role in determining the health and wellbeing of individuals. However, it remains unclear whether the capacity to process social information distinguishes well-connected individuals from their less-connected peers. This study explored how an individual's social network structure influences the dynamic processing of group norms, utilizing event-related potentials (ERPs)., Methods: The study involved 43 university students from the same class who participated in a social network study measuring metrics such as real-life social network size, in-degree, out-degree, and betweenness centrality. Subsequently, 27 students participated in an EEG study assessing their willingness to engage in various exercises after being exposed to peer feedback or in its absence., Results: The results indicate that an individual's social network structure is significantly associated with the dynamic processing of group norms. Notably, well-connected individuals exhibited larger ERP amplitudes linked to feedback (e.g., N200, P300, and LPP), greater functional segregation within the brain network (e.g., local efficiency and clustering coefficient), and enhanced synchronization within frontal area and across different brain areas., Discussion: These findings highlight that well-connected individuals possess enhanced sensitivity and efficiency in processing social information, pointing to potential areas for further research on the factors influencing social network evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Han, Liu, Xie, Lin, Hao, Ge, Hu, Zhu and Yang.)

Cancer is an evolutionary process shaped by selective pressure from the microenvironments. However, recent studies reveal that certain tumors undergo neutral evolution where there is no detectable fitness difference amongst the cells following malignant transformation. Here, through computational modeling, we demonstrate that negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is highly similar to neutral evolution. Crucially, NFDS promotes high antigenic heterogeneity and early immune evasion in hypermutable tumors, leading to poor responses to immune checkpoint blockade (ICB) therapy. Our model also reveals that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, this unique feature of NFDS is common in the whole-exome sequencing (WES) datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy and a non-small cell lung cancer (NSCLC) WES dataset (327 tumor samples from 100 patients). Altogether, our study provides quantitative evidence supporting the theory of NFDS in cancer, explaining the high prevalence of neutral-looking tumors. These findings also highlight the critical role of frequency-dependent selection in devising more efficient and predictive immunotherapies., (© 2024. The Author(s).)

Background: Spinal cord stimulation (SCS) is a surgical technique used in patients with chronic intractable pain, and its effectiveness and safety have been validated by multiple studies. However, to maintain an optimal and steady long-term effect is still challenging. Here, we report a new management paradigm integrating smartphone application and remote programming. Chronic pain patients with SCS implants can monitor their pain status on the phone and change stimulation parameters accordingly. The PreMaSy study is a randomized controlled trial to evaluate the clinical effectiveness and safety of this precise management system., Methods: Patients with chronic intractable pain will be screened for eligibility, and 82 participants are anticipated to be enrolled in this trial. After the electrode implantation, the stimulation effectiveness will be tested. Participants with a reduction of more than 50% in the visual analog scale (VAS) will receive implantation of an implantable pulse generator and randomized (1:1) into the experimental group or control group. All participants will be asked to take online follow-ups and complete assessments using a smartphone application. Daily pain characteristic assessments and monthly quality of life questionnaires are integrated into the App, and participants will be required to complete these assessments. The daily VAS for pain intensity will be monitored and a threshold will be set based on baseline VAS score. The interventional appointment will be scheduled once the threshold is reached. The primary outcome is the health condition and quality of life assessed by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). Utility values of EQ-5D-5L will be assessed at baseline and 1, 3, and 6 months post-operative., Discussion: The PreMaSy study aims to evaluate the effectiveness and safety of a novel App-based, patient-centered, self-assessment management system for chronic intractable pain. A randomized controlled trial is designed to test the non-inferiority of this precise management system compared to the monthly online follow-ups. It is also expected to yield valuable experiences regarding precision medicine., Trial Registration: ClinicalTrials.gov NCT05761392. Registered on March 07, 2023., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Incomplete lineage sorting (ILS) makes ancestral genetic polymorphisms persist during rapid speciation events, inducing incongruences between gene trees and species trees. ILS has complicated phylogenetic inference in many lineages, including hominids. However, we lack empirical evidence that ILS leads to incongruent phenotypic variation. Here, we performed phylogenomic analyses to show that the South American monito del monte is the sister lineage of all Australian marsupials, although over 31% of its genome is closer to the Diprotodontia than to other Australian groups due to ILS during ancient radiation. Pervasive conflicting phylogenetic signals across the whole genome are consistent with some of the morphological variation among extant marsupials. We detected hundreds of genes that experienced stochastic fixation during ILS, encoding the same amino acids in non-sister species. Using functional experiments, we confirm how ILS may have directly contributed to hemiplasy in morphological traits that were established during rapid marsupial speciation ca. 60 mya., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Alleles that cause advantageous phenotypes with positive selection contribute to adaptive evolution. Investigations of positive selection in protein-coding genes rely on the accuracy of orthology, models, the quality of assemblies, and alignment. Here, based on the latest genome assemblies and gene annotations, we present a comparative analysis on positive selection in four great ape species and identify 211 high-confidence positively selected genes (PSGs). Even the differences in population size among these closely related great apes have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments, we found that they experienced comparable numbers of positive selection. We also uncovered that more than half of multigene families exhibited signals of positive selection, suggesting that imbalanced positive selection resulted in the functional divergence of duplicates. Moreover, at the expression level, although positive selection led to a more non-uniform pattern across tissues, the correlation between positive selection and expression patterns is diverse. Overall, this updated list of PSGs is of great significance for the further study of the phenotypic evolution in great apes.

The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases 1 . Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research 2,3 . The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome-much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 × 10 -8 per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system.

Objectives: Due to the impact of COVID-19 epidemic, face-to-face follow-up treatments for patients with chronic pain and implanted spinal cord stimulation (SCS) devices are forced to be delayed or stopped. This has led to more follow ups being done remotely. Meanwhile, with the development of 4G/5G networks, smartphones, and novel devices, remote programming has become possible. Here, we investigated the demand and utility of remote follow-ups including remote programming for SCS for patients with chronic pain., Materials and Methods: A questionnaire including questions on demographic characteristics, pain history, postimplantation life quality, standard follow-up experience, remote follow-up, and remote programming experience was sent to patients diagnosed as chronic intractable pain and treated with SCS during January 2019 to January 2020., Results: A total of 64 participants completed the questionnaire. About 70% of participants expressed demands for remote follow-ups due to the inconvenience, high costs, and time consumption of traditional follow-up visits. Nearly 97% of participants have attempted remote follow-ups, and about 81% of participants have further tried remote programming. Approximately, 96% of them recognized the benefits., Conclusions: The remote programming was in high demand among participants. Most of the participants have tried remote follow-ups or even remote programming. The remote programming appeared to be more efficient, economic and were widely recognized among participants., (© 2021 International Neuromodulation Society.)

As COVID-19 rampages throughout the world and has a major impact on the healthcare system, non-emergency medical procedures have nearly come to a halt due to appropriate resource reallocation. However, pain never stops, particularly for patients with chronic intractable pain and implanted spinal cord stimulation (SCS) devices. The isolation required to fight this pandemic makes it impossible for such patients to adjust the parameters or configuration of the device on site. Although telemedicine has shown a great effect in many healthcare scenarios, there have been fewer applications of such technology focusing on the interaction with implanted devices. Here, we introduce the first remote and wireless programming system that enables healthcare providers to perform video-based real-time programming and palliative medicine for pain patients with a SCS implant. During the COVID-19 pandemic from January 23, 2020, the date of lockdown of Wuhan, to April 30, 2020, 34 sessions of remote programming were conducted with 16 patients. Thirteen of the 16 patients required programming for parameter optimization. Improvement was achieved with programming adjustment in 12 of 13 (92.3%) cases. Eleven of the 16 (68.8%) patients reported that the system was user-friendly and met their needs. Five patients complained of an unstable connection resulting from the low network speed initially, and three of these patients solved this problem. In summary, we demonstrated that a remote wireless programming system can deliver safe and effective programming operations of implantable SCS device, thereby providing palliative care of value to the most vulnerable chronic pain patients during a pandemic., Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03858790., Competing Interests: JW and GW have received research support from Beijing PINS Medical Co., (donated SCS devices for pain). LL reports personal fees from Beijing Pins Medical Co., outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Lu, Xie, Zhang, Dong, Zhang, Yu, Wang, Wang and Li.)

New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies 1-3 . For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database 4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies 5 are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus 6 , a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far.

Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity 1-4 . Sparse taxon sampling has previously been proposed to confound phylogenetic inference 5 , and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.

Objective: To compare the cumulative live birth rates (cLBRs) after the first assisted reproductive technology (ART) cycle using flexible gonadotropin releasing hormone (GnRH)-antagonist protocol vs. standard long GnRH agonist protocol for controlled ovarian stimulation (COS) in infertile women with different ages and ovarian reserve. Methods: Women who underwent ART treatment at our center between June 1st, 2015 and December 31st, 2018 were screened. Among them, only women who underwent their first COS cycle with flexible GnRH antagonist protocol or standard long GnRH agonist protocol were included in this study. The main outcome measurement was cLBR. Results: A total of 4,402 patients were eligible for the analysis, of whom, 2,762 patients used the GnRH agonist protocol and 1,640 patients used the GnRH antagonist protocol. The cLBRs of women in the antagonist protocol group and long agonist protocol group were 45.3 and 50.0%, respectively. Subgroup multivariable regression analysis showed that, in patients with low ovarian reserve (AFC ≤ 7), the cLBR was significantly lower in the antagonist group than in the long agonist protocol group [OR (95% CI) 0.62 (0.41, 0.94)], which effect was more robust in younger patients (<30 y) [OR (95% CI) 0.29 (0.11, 0.74)]. The analysis also revealed remarkably lower cLBR in patients above 40 years regardless of their AFC, although the difference was not statistically significant. However, in patients with high ovarian reserve (AFC >24), the cLBR was higher in cycles with antagonist protocol than with the long agonist protocol [OR (95% CI) 1.43 (0.96, 2.12)], and the effect was of statistical significance in younger patients (< 30 y) [OR (95% CI) 1.78 (1.07, 2.96)]. Conclusion: The present study suggests that the flexible GnRH antagonist protocol might not be suitable for patients with low ovarian reserve (AFC ≤ 7) or patients aged over 40 years. However, flexible GnRH antagonist protocol might be strongly recommended for patients under 30 years old and with high ovarian reserve (AFC > 24). For the rest groups of patients in the present cohort, antagonist protocol was slightly favored because it had lower OHSS in general and in patients with poly-cystic ovarian syndrome (PCOS) according to previous publications., (Copyright © 2020 Zhang, Xie, Zhang, Huang, Xiao, Wang, Tong, Miao and Wang.)

Objective: The study aimed to investigate the impact of the peak E2 level during controlled ovarian hyperstimulation (COS) on the cumulative live birth rate (cLBR) in non-PCOS women with normal ovarian reserve., Materials and Methods: Women between 20 and 39 years were included. Donor cycles and patients who never experienced embryo transfer were excluded. Multivariable regression and smooth curve fitting were applied for statistical analysis., Results: A total of 1141 patients were included. The mean age, basal AFC, peak E2 level, and number of retrieved oocyte were 30.0 ± 3.7 years old, 16.8 ± 6.7, 3911.0 ± 1302.9 pg/ml, and 13.6 ± 5.5, respectively. In the overall population of the cohort, cLBR, miscarriage rate, and preterm birth rate were 66.9%, 7.4%, and 13.7%, respectively. The results of multivariable regression analysis failed to show the impact of peak E2 on the cLBR [OR (95%CI) 0.995 (0.982, 1.009), P = 0.486]. However, the result of smooth curve fitting indicated that when the peak E2 was lower than 2185 pg/ml, the cLBR increased about 12% with 100 pg/ml increasing of the peak E2. When the peak E2 was higher than 6136 pg/ml, the cLBR decreased about 10% with 100 pg/ml increasing of the peak E2., Conclusion: We concluded that the peak E2 level on hCG trigger day is associated with the cLBR in a segmental pattern. There should be an appropriate range of the peak E2 level during COS to achieve a relative best cLBR in non-PCOS patients using stimulating protocol mainly based on GnRH agonist; however, the cutoff value must vary in different centers.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women. Multiple susceptible gene as well as environmental factors and their interaction each other are contributed to the PCOS risk. Several case-control studies have researched the associations of the vitamin D receptor gene (VDR) polymorphisms with PCOS susceptibility, but the jury is still out. Here, we carried out a meta-analysis to clarify polymorphisms between ApaI (C/A) (rs7975232), BsmI (G/A) (rs1544410), FokI (C/T) (rs10735810), TaqI (T/C) (rs731236) and Tru9I (G/A) (rs757343) in the VDR gene and PCOS susceptibility based on relative lager sample size., Methods: English database of PubMed and Embase, and Chinese database of Wanfang and China National Knowledge Infrastructure (CNKI) databases were retrivaled for the relationship between VDR gene variates and PCOS susceptibility published before 31th, May 2018. Crude odds ratios (ORs) and its 95% confidence intervals (95% CIs) in different comparisons were used to detected the strength of the association. All the statistical analyses of the present meta-analysis were performed by STATA version 12.0 software., Results: Totally, 3587 (PCOS group 1922; control group 1665) participants from 13 studies were included which met our inclusion criteria. A statistically significant association between VDR ApaI (rs7975232) polymorphism and PCOS susceptibility (C vs. A: OR = 1.19, 95%CI = 1.06~1.34, P = 0.004) was found in the overall population. After stratified by ethnicity, we showed that there is a significant association between VDR ApaI (rs7975232) polymorphism and susceptibility to PCOS in the Asian (C vs. A: OR = 1.21, 95%CI = 1.04~1.42, P = 0.016) population, but this association was not found in the Caucasian population. Additionally, a significant relationship between VDR BsmI (rs1544410) variates with PCOS susceptibility in the Asian (G vs. A: OR = 1.27, 95%CI = 1.06~1.53, P = 0.011) population, but this association was not found in the Caucasian population. We didn't find any association between VDR FokI (rs2228570), VDR TaqI (rs731236), VDR Tru9I (rs757343) and PCOS susceptibility in the overall and the subgroup populations., Conclusions: Our findings demonstrated that VDR ApaI (rs7975232) and VDR BsmI (rs1544410) polymorphisms are correlated with susceptibility to PCOS in the Asian population and VDR TaqI (rs731236), VDR FokI (rs2228570), VDR Tru9I (rs757343) did not reveal a relationship with the PCOS susceptibility.

Objective: To investigate the role of endometrial macrophages in embryo implantation and in regulating the expression of vascular endothelial growth factor A (VEGFA) in mouse endometrium during the peri-implantation period., Method: At D3.5 (D0.5 defined as the morning when a vaginal plug was observed), pregnant mice were divided randomly into experimental group, control group and blank group. In the experimental group, the mice were subjected to intrauterine injection of clodronate liposomes on the left side of uterus to eliminate the macrophages, and PBS liposomes on the right side. PBS liposomes and PBS were administered in the control and blank groups, respectively. The uterine tissues were collected on D5.5 and stained with trypan blue to show the implantation sites. Flow cytometry was performed to examine the percentage of F4/80(+) CD11b(+) macrophages macrophages in the uterus. F4/80(+) macrophage population within the endometrium and ovary and changes in VEGFA expression at the implantation and non-implantation sites were examined using immunohistochemistry., Results: Endometrial F4/80(+) CD11b(+) macrophages macrophages were significantly reduced by 74% following intrauterine injection of clodronate liposomes (P<0.05). The number of macrophages in the ovaries showed no significant difference among the 3 groups. In the experimental group, the left side of the uterine showed imcomplete cavity closure with a lower number of implantation site than the right side (2.20∓1.81 vs 5.10∓1.91, P<0.05). VEGFA expression at the implantation site were significantly decreased in the endometrium on the left side with macrophage suppression as compared with that on the right side (P<0.05)., Conclusion: Endometrial macrophages appear to modulate uterine receptivity by regulating the expression of VEGFA to affect embryo implantation, suggesting the important role of macrophages in embryo implantation.

Objective: To investigate the effect of prostaglandins E2 (PGE2) in enhancing vascular endothelial growth factor (VEGF) expression in a rat macrophage cell line and the effect of the media from PGE2-inuced rat macrophages on angiogenetic ability of human umbilical vein endothelial cells (HUVECs) in vitro., Methods: Western blotting and qPCR were employed to investigate the expressions of VEGF protein and mRNAs in rat macrophage cell line NR8383 stimulated by PGE2 in the presence or absence of EP2 receptor inhibitor (AH6809) and EP4 receptor inhibitor (AH23848). Conditioned supernatants were obtained from different NR8383 subsets to stimulate HUVECs, and the tube formation ability and migration of the HUVECs were assessed with Transwell assay., Results: PGE2 stimulation significantly enhanced the expression of VEGF protein and mRNAs in NR8383 cells in a dose-dependent manner. The supernatants from NR8383 cells stimulated by PGE2 significantly enhanced tube formation ability of HUVECs (P<0.05) and promoted the cell migration. Such effects of PGE2 were blocked by the application of AH6809 and AH23848., Conclusion: PGE2 can dose-dependently increase VEGF expression in NR8383 cells, and the supernatants derived from PGE2-stimulated NR8383 cells can induce HUVEC migration and accelerate the growth of tube like structures. PGE2 are essential to corpus luteum formation by stimulating macrophages to induce angiogenesis through EP2/EP4.

Background: The use of antibiotics is considered a major determinant of the development of resistance in organisms. This study assessed current patterns of antibiotic prescription and provides background for quality improvement in general hospitals in Hubei, China., Methods: A point-prevalence study was performed in November 2008. All inpatients on the day of the survey were included in the analysis., Results: On the day of the study, 6904 patients (56%) were receiving antibiotic therapy; the highest rate occurred in the ICU (90%), and the lowest occurred in the medical wards (39%). The most commonly used antibiotics were β-lactam antibiotics, including cephalosporins (40%) and piperacillin (19%), followed by fluoroquinolones (14%)., Conclusions: Our data indicated a high rate of antibiotic use in Chinese hospitals. These findings suggest important areas for intervention and the implementation of antibiotic stewardship policies in Chinese hospitals. A multi-faceted strategy should be implemented at the national level in China and should include education, regulation, and greater financial support from the government., (Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

The objective of this study is to examine the change in macrophage numbers, inducible form of NO synthase (iNOS), and vascular endothelial growth factor (VEGF) expression both before and after embryo implantation in the uterine tissue of mice. In order to explore the mechanism of macrophages in endometrial angiogenesis, 8-week-old female mice were divided into three groups: pregnant group, pseudopregnant group (mated to male mice that had been vasectomized), and estrous group (unmated). Individuals from these three groups were sacrificed at time intervals D1.5 to D6.5. Formalin-fixed paraffin-embedded tissue was used for immunocytochemical localization of Mφ, iNOS, and VEGF utilizing standard methodology. The proportion of macrophages in the peripheral blood was determined by flow cytometry, and the relationship between macrophage, iNOS, and VEGF expression was analyzed. The proportion of peripheral blood macrophages in the pregnancy group was significantly higher than that in the other groups. The results of immunohistochemistry determined that the macrophages exhibited changes in both numbers and distribution. The number of macrophages in the endometrium of the pregnancy and pseudopregnancy groups was significantly higher than that in the control (estrous) group. In the pregnancy group, macrophage numbers dramatically decreased and gradually transferred to the perimetrium on D4.5. Immunostaining revealed strong staining in the pregnancy group and weaker staining in the pseudopregnant and control groups for both iNOS and VEGF. There was strong, dense immunostaining at the implantation site for both iNOS and VEGF, whereas light immunostaining was seen in interimplantation tissues on D5.5 to D6.5. In the pregnant group, peripheral blood and uterine macrophage proportions were negatively correlated, whereas the amount of macrophages, iNOS, and VEGF expression in the endometrium were positively correlated. The expression of iNOS and VEGF in the endometrium also displayed a strong positive correlation. In conclusion, during embryo implantation, macrophages levels decreased in the uterus, whereas the number of peripheral macrophages increased, suggesting that macrophages may migrate into the peripheral blood and uterus to adapt for pregnancy. Additionally, an increase in the expression of iNOS and VEGF was observed during the implantation window, implying that iNOS and VEGF may play an important role in promoting embryo implantation. The positive correlation between macrophages, iNOS, and VEGF in the implanting uterus implied that macrophages might regulate iNOS and VEGF during the implantation process., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of spermatozoa from different sources on normal fertilization of oocytes, embryo quality and embryo developmental potential in intracytoplasmic sperm injection (ICSI) cycles., Methods: A retrospective analysis was conducted among 197 patients undergoing ICSI cycles in our center. The patients were classified into 3 groups according to the sources of semen, namely ejaculated spermatozoa group (n=102), percutaneous epididymal sperm aspiration (PESA) group (n=68), and testicular sperm aspiration (TESA) group (n=27). The ejaculated spermatozoa group was further classified into oligoasthenoteratozoospermia (n=67) and cryptozoospermia (n=35) subgroups. The normal fertilization, high-quality embryo, implantation and clinical pregnancy rates were compared among the groups; the rate of high-quality blastocyst formation in in-vitro culture of non-top quality embryos was also observed., Results: The patients with PESA showed significantly higher normal fertilization rate (75.6%) than those in oligoasthenoteratozoospermia (64.8%), cryptozoospermia (62.1%), and TESA (61.6%) groups (P<0.05). No significant differences were found in the high-quality embryo, implantation, and clinical pregnancy rates among the groups (P>0.05). The rate of high-quality blastocyst formation in the in-vitro culture of non-top quality embryos was also comparable among the groups (P>0.05)., Conclusion: Although spermatozoa obtained with by PESA is associated with a higher normal fertilization rate, the sources of spermatozoa do not significantly affect the embryonic quality and developmental potential in ICSI cycles.

Successive point-prevalence surveys were conducted annually from 2007 to 2011 to monitor the prevalence of healthcare-associated infections (HAIs) in a university hospital in Hubei Province in China. The surveys used the case definition criteria established by the Ministry of Health of the People's Republic of China. In the 5 surveys, the overall frequency of HAIs was 3.16% (301/9533). No significant differences were identified in the point prevalence measurements of HAIs in any of the years from 2007 to 2011. Of all the cases, proportionally, the most frequent infection site was the respiratory tract (2.34%), followed by surgical sites (0.43%) and urinary tract sites (0.28%). Gram-negative aerobic bacilli were the most common organisms mentioned; the most frequently isolated organism was Pseudomonas aeruginosa, followed by Escherichia coli and Acinetobacter baumannii. Approximately one-half of the patients were receiving antibiotics at the time of the surveys. Cephalosporin, penicillin, and quinolone were most commonly used for treatment or prevention. The differences found in HAI prevalence data across the 5 surveys given in the hospital were not statistically significant. In conclusion, this successive point-prevalence survey provides information about the trend of HAI prevalence, epidemical character, and the use of antibiotics among the university hospital's in-patients. This information allows us to initiate targeted programs for infection prevention and control., (Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

A multicentre prospective cohort study was performed in 17 intensive care units (ICUs) in tertiary care hospitals in Hubei Province, China. Ventilator-associated pneumonia (VAP) was defined according to modified criteria from the published literature. Among 4155 ventilated patients, the crude incidence and incidence rate of VAP were 20.9% and 28.9 cases per 1000 ventilator-days. Multivariate analysis using logistic regression revealed risk factors including male sex [risk ratio (RR): 1.5; P<0.001], coma (RR: 2.1; P<0.001), chronic obstructive pulmonary disease (RR: 1.4; P<0.001), infections at other sites (RR: 1.6; P=0.001), serious disease predating the onset of VAP (RR: 1.6; P<0.001) and interventions including antacid treatment (RR: 1.4; P<0.001), antimicrobial treatment (RR: 5.1; P<0.001), bronchoscopy (RR: 1.5; P=0.041) and tracheostomy (RR: 1.4; P=0.014). The most frequently isolated causative pathogens were Pseudomonas aeruginosa and Acinetobacter baumannii. Of all Staphylococcus aureus isolates, 45.7% were meticillin resistant. Rates, risk factors and causal pathogens of VAP in ICUs in Hubei differ from those reported from developed countries. These data show the need for more effective infection control interventions in Hubei, China., (Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the major risk factors and their interactions of ischemic stroke (IS) and to develop a classification tree model to predict the incidence risk of IS for a Chinese population., Methods: Exhaustive Chi-squared Automatic Interaction Detection (Exhaustive CHAID) algorithm of classification tree method was applied to build a prediction model for the incidence risk of IS under the design of 1:1 matched case-control study. The statistics of misclassification risk was used to evaluate the fitness of the model., Results: In the prediction model, six variables of physical exercise, history of hypertension, tea drinking, HDL-c level, smoking status and educational level were in turn selected as the predictors of IS incidence risk. In the subgroup of lacking of physical exercise, individuals who had history of hypertension would have a significantly higher IS risk (92%) than that of the ones who had no history of hypertension (64%). The misclassification risk estimate of the prediction model was 0.21 with the standard error of 0.02, indicating that 79% of the cases could be classified correctly based on current prediction model., Conclusions: Lacking of physical exercise and history of hypertension are identified to be the prominent predicting variables of IS risk for a hospital population of southern China. Although CHAID analysis could provide detailed information and insight about interactions among risk factors of IS, we still need to validate our model and improve the vascular risk prediction for Chinese subjects in further studies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate Chinese medical interns' cancer knowledge and associated factors, focusing on cancer screening., Methods: A questionnaire survey was conducted in ten leading Chinese medical schools from June to July in 2011. Medical interns were invited to fill the questionnaire., Results: Out of the 1350 copies sent, 1135 eligible responses were returned. Around 50% of interns had positive attitude toward oncology, but the knowledge score was low, particularly in screening. The percentages of scores were 44.8% (8.95/20) for overall and only 29.6% (2.07/7) for screening. The majority of internship length in oncology department was eight to fourteen days. Screening and prevention was ranked as third most taught, following diagnosis and treatment. Multivariate analysis showed that positive attitude to oncology correlated with positive self-evaluated overall (OR = 1.76, 95% CI (1.45, 2.12)) and screening (OR = 1.62, 95% CI (1.35, 1.95)) competence, but unexpectedly predicted lower screening score (OR = 0.77, 95% CI (0.61, 0.97)). Interns with positive self-evaluated screening competence were not found to possess higher cancer screening knowledge., Conclusion: Current medical education in Chinese medical schools fails to equip interns with optimal cancer knowledge, particularly in screening, even in interns who hold positive view to oncology. Interns' self-evaluated competence is not proportional to their knowledge scores.

Background: Metabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis., Methodology/principal Findings: To investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48-2.54) for CC genotype compared with TT genotype. In two-factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78-7.34), 3.18 (95%CI: 1.73-5.82) and 1.97 (95%CI: 1.27-3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18-fold (95%CI:0.89-fold to 1.58-fold), 1.87-fold (95%CI: 1.38-fold to 2.54-fold) and 4.39-fold (95%CI: 2.75-fold to 7.01-fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P(trend) <0.0001)., Conclusions/significance: Our results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI.

Successive point prevalence surveys were conducted in November 2007 and 2008 to monitor the prevalence of healthcare-associated infection (HCAI) in 13 grade III, 1st class hospitals in Hubei Province of China, using the case definition criteria established by the Ministry of Health in the People's Republic of China. In total, of 20 350 patients surveyed, 833 (4.09%) HCAIs were observed in 790 (3.88%) patients. There was no significant difference between the overall prevalence of HCAI in 2007 (4.14%) and 2008 (3.72%). Respiratory tract infection was the most common HCAI (63.15%), followed by surgical site infection (9.60%) and urinary tract infection (8.64%). Only 35.29% (294/833) of HCAI patients had positive microbiology results. Gram-negative bacteria were isolated most frequently and the most frequent organism was Pseudomonas aeruginosa, followed by Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Antibiotic use was documented for 10,344 (50.83%) patients, and cephalosporins, penicillins, and quinolones were the most commonly used agents for treatment or prophylaxis., (Copyright 2010. Published by Elsevier Ltd.)